Collaboration Report for Exercise: Survey 2010-2 ... · PDF fileNumber of Participants: 84 Number of Cases: 5 Report Generated: Saturday, January 22, 2011 7:26 PM Collaboration Report

Number of Participants: 84

Number of Cases: 5

Report Generated: Saturday, January 22, 2011 7:26 PM

Collaboration Report for Exercise: Survey 2010-2

Case: 2010-2 Case 6

Add comments on other abnormalities:Guide: There is deaggregation after the minimal initial aggregation response to ADP and

thromboxane analogue.

Scored: Not Scored

Reviewer:

Increased WBC, Decreased RBC, macrocytic, decreased H/H Submitted:

EID Number: 1161

Scored: Not Optimal

Reviewer:

The platelet aggregation is decreased with all agonists including ADP, collagen, epinepherine, arachidonic acid, and U46619. The ristocetin induced platelet aggregation shows a normal dose response. The findings are suggestive of an intrinsic platelet dysfunction, possibly associated with myelodysplastic syndrome. The platelet ATP (dense granule) release study is suggested.

Reviewed by: Dr Heesun Rogers 12/15/2010

Submitted:

EID Number: 1163

Scored: Not Scored

Reviewer:

Add comments on other abnormalities. Submitted:

EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165


Page 1 of 97

Scored: Not Yet Reviewed

Reviewer:


EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Correct

Reviewer:

Add comments on other abnormalities.Apparent loss of release reaction (could be acquired or inherited). Decreased TXA2 production?

Submitted:

EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Not Scored

Reviewer:


EID Number: 1170

Scored: Correct

Reviewer:

Maximal aggregation is reduced with 2.5uM and 5.0uM concentration ADP, low concentration (1.25 ug/mL) Collagen, Epinephrine, Arachidonic Acid, and U46619. Maximal aggregation is normal is with high concentration (5 ug/mL) Collagen, and low (0.5 mg/mL) and high (1.25 mg/mL) Ristocetin.

Submitted:

EID Number: 1171

Scored: Incorrect

An aspirin -like defect is excluded by the abnormal response to thromboxane analogue. No mention of possible dense granule secretion defect.

Reviewer:

If the U46619 was normal, this would be consistent with aspirin or NSAID ingestion or aspirin like defect.

Submitted:

EID Number: 1172


Page 2 of 97


Reviewer:


EID Number: 1173

Scored: Not Scored

Reviewer:


EID Number: 1176

Scored: Not Scored

Reviewer:


EID Number: 1178

Scored: Not Scored

Reviewer:

Low haemoglobin, macrocytes high white cell count

Submitted:

EID Number: 1179


Reviewer:


EID Number: 1180


Reviewer:


EID Number: 1183

Scored: Correct

Reviewer:

Absent aggregation with arachidonic acid, low concentration of collagen and epinephrine. Reduced aggregation with both concentrations of ADP and U46619.

Submitted:

EID Number: 1188


Reviewer:

Macrocytic anemia. Submitted:

EID Number: 1196


Page 3 of 97

Scored: Not Scored

Reviewer:

Moderate macrocytic anemia with an increased RDW suggesting RBC anisocytosis. Mild leukocytosis with mild neutrophilia and monocytosis.

Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201

Scored: Not Scored

Reviewer:


EID Number: 1203

Scored: Not Scored

Reviewer:


EID Number: 1204

Scored: Not Scored

Reviewer:


EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213

Scored: Not Scored

Reviewer:


EID Number: 1214


Reviewer:

Macrocytic anemia with hyperleukocytosis. Submitted:

EID Number: 1218


Page 4 of 97


Reviewer:


EID Number: 1222

Scored: Not Scored

Reviewer:

Macrocytic anaemia, neutrophilia, normal platelet count Submitted:

EID Number: 1223

Scored: Not Scored

Reviewer:


EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Correct

Reviewer:

Overall interpretation: Platelet function defect, possibly involving the thromboxane receptor or signalling via thromboxane receptor or other secretion defect.Suggest lumi aggregation for further evaluation.

Submitted:

EID Number: 1230

Scored: Not Optimal

Reviewer:

Aggregation responses decreased to all agonists except to 5mcg/ml collagen and to ristocetin.

Submitted:

EID Number: 1231

Scored: Correct

Reviewer:

Immediate deaggregation with ADP 2.5 and 5.0 µM Submitted:

EID Number: 1233


Page 5 of 97

Scored: Correct

Reviewer:

The presence of a Macrocytic Anemia is definitely consistent with the possibility of Myelodysplastic Syndrome. Bone Marrow Aspirate and Biopsy are indicated along with Reticulocyte %, Absolute Reticulocyte Count, Reticulocyte Index, and Iron Studies including Ferritin level.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

There is abnormal deaggregation with thromboxane analogue and ADP. There is reduced primary and no secondary aggregation with epinephrine.

Submitted:

EID Number: 1235


Reviewer:

Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

Other abnormalities with two or more agonists. Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240

Scored: Not Scored

Reviewer:

Submitted:

EID Number: 1242


Reviewer:


EID Number: 1244


Page 6 of 97

Give your overall case interpretation:Guide: The overall interpretation expected is that there is a platelet function defect,

possibly due to a defect in secretion or signaling, with absent aggregation with epinephrine and arachidonic acid; reduced aggregation with thromboxane analogue and ADP, with deaggregation; and reduced aggregation with the low but not high concentration of collagen (with normal "shape change"); and normal aggregation with ristocetin. A platelet function defect due to Glanzmann thrombasthenia is excluded by the initial aggregation with ADP and thromboxane analogue and the normal response to high concentration of collagen. An aspirin- like defect is excluded by the abnormal response to thromboxane analogue.

Scored: Correct

Reviewer:

Aquired storage pool or granular release defect due to MDS. Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

The platelet aggregation is decreased with all agonists including ADP, collagen, epinepherine, arachidonic acid and U46619. The ristocetin induced platelet aggregation shows a normal dose response. The findings are suggestive of an intrinsic platelet dysfunction, possibly associated with myelodysplastic syndrome. The platelet ATP (dense granule) release study is suggested.

Reviewed by: Dr. Heesun Rogers

Submitted:

EID Number: 1163

Scored: Correct

Reviewer:

Results consistent with a platelet release defect, possibly a Storage Pool Defect. More than likely not a signaling defect since the Thromboxane analog response is abnormal.

Submitted:

EID Number: 1164

Scored: Correct

Reviewer:

Give your overall case interpretation. platelet function defect includes secretion , thromboxane receptor, and storage pool defect

Submitted:

EID Number: 1165

Scored: Correct

Reviewer:

Decreased aggregation with ADP, collagen, epinephrine, arachidonic acid and U46619. Normal ristocetin and high dose collagen response. No evidence of secondary waves suggests possible secretion defect consistent with myelodysplastic syndrome.

Submitted:

EID Number: 1166


Page 7 of 97

Scored: Correct

Reviewer:

Evident platelet qualitative deficiency, congenital or acquired. Unfortunately patient's gender and age are not available. If patient is a child or young adult, a congenital deficiency needs to be excluded. If patient is older than 50 years old, the abnormal results of platelet aggregation studies may be related to MDS, medication or other acquired conditions.

Submitted:

EID Number: 1167


Reviewer:

Give your overall case interpretation.Apparent loss of release reaction (could be acquired or inherited). Would consider SPD, uremia.

Submitted:

EID Number: 1168

Scored: Incorrect

A platelet function defect due to Glanzmann thrombasthenia is excluded by the initial aggregation with ADP and thromboxane analogue and the normal response to high concentration collagen.

Reviewer:

Give your overall case interpretation. Decreased platelet aggregation with multiple agonists. Normal response to ristocetin. May be compatible with Glanzmann's thrombasthenia. Given CBC abnormalities, cannot rule out acquired platelet disorder due to marrow disease (ie - MDS). Clinical correlation required, recommend repeat testing

Submitted:

EID Number: 1169

Scored: Correct

Reviewer:

Abnormal aggregation to ADP, Epinephrine, AA, and lower dose of collagen, with failure to acheive normal aggregation with thromboxane is suggestive of storage pool disorder or secretion defect.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

The finding of abnormal aggregation with multiple agonists is consistent with a congenital or acquired platelet function defect. The potential causes include a secretion defect, including dense granule deficiency, or a defect in the thromboxane receptor or thromboxane signaling pathways. Platelet function disorders have been reported in myelodysplastic syndromes.

Submitted:

EID Number: 1171


Page 8 of 97

Scored: Correct

Reviewer:

Most consistent with thromboxane signal transduction or receptor defect

Submitted:

EID Number: 1172

Scored: Incorrect

Reviewer:

The patient has MDS which is shown to be associated with abnormal platelet aggregometry. Decreased response to ADP, collagen, epinephin and arichidonic acid in addition to low response to thrombin is suggestive of thromboxan receptor defect.

Submitted:

EID Number: 1173


Reviewer:

This case is typical of a platelet dysfunction associated with MDS, with abnormal aggregation response to several agonisits and normal platelet agglutination to ristocetin (Girtovitis FI et al, Acta Haematol. 2007) . Several mechanisms have been proposed, including disruption in thromboxane A 2 synthesis, decreased density of agonist receptors on the platelet surface, and platelet storage pool deficiency. Ineffective hematopoiesis (including dysplastic megakaryocytes) largely accounts for the observed results.

Submitted:

EID Number: 1176

Scored: Correct

Reviewer:

Severe platelet dysfunction with markedly impaired production and/ or release of tromboxane.

Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Findings suggest platelet function disorder is present. Should be confirmed on a repeat sample if clinically indicated.

Platelet nucleotide or EM should be performed to rule out Storage pool disorder.

Submitted:

EID Number: 1179

Scored: Correct

Reviewer:

Acquired Thrombopathy (resembling tromboxane receptor defect) by Myelodysplastic Syndrome

Submitted:

EID Number: 1180


Page 9 of 97

Scored: Incorrect

An aspirin-like defect is excluded by the abnormal response to thromboxane analogue.

Reviewer:

Give your overall case interpretation. Asperin-like defect

Submitted:

EID Number: 1183


Reviewer:

The finding of abnormal aggregation with multiple agonists is compatible with a platelet function defect. In this case, the potential cause could be the myelodysplastic syndrome (defective megakaryopoesis, megakaryocyte originating from leukemic cell).

Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

Negligible aggregation of arachidnic acid and U46619 together with decreased aggregation to ADP, epinephrine, low dose collagen and normal aggregation to high dose collagen suggest thromboxane receptor deficiency or defect in the thromboxane induced pathway.

Submitted:

EID Number: 1196


Reviewer:

Reduced platelet response to all agonists except high concentration collagen and ristocetin in the context of a possible myelodysplastic/myeloproliferative syndrome.

Conclusion: acquired platelet dysfunction in the context of a myelodysplatic/myeloproliferative syndrome. It might be consistent with a storage pool disease, platelet granules abnormalities.

Submitted:

EID Number: 1197

Scored: Correct

Reviewer:

Thrombopathy, fitting with MDS. Submitted:

EID Number: 1201

Scored: Correct

Reviewer:

?MDS related platelet dysfunction. Submitted:

EID Number: 1203


Page 10 of 97

Scored: Correct

Reviewer:

Give your overall case interpretation. Agregation is normal only with Ristocetin and collagen 5. The findings suggest that a platelet function disorder is possible : see the drug use and repeat agregation testing.

Submitted:

EID Number: 1204


Reviewer:

Despite a normal platelet count and a capacity of aggregation in response to a high dose of collagen, the transduction pathways appear to be very disturbed mainly for Gi and Gq, a control of dense granule content can also be done (ATP release and/or electron microscopy of whole platelets). Myelodysplastic (probable) syndrome are known to present these aggregation defects to epinephrine, ADP, and arachidonate - biochemical characterization, western blot studies ...would to be achieve for the transduction pathway proteins.

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

The findings of abnormal aggregation with more than three agonists are consistent with a platelet function defect. In this case, the potential causes include a secretion defect, including dense granule deficiency, or a defect in the thromboxane receptor or thromboxane signaling pathways. It would be incorrect to interpret the findings as an aspirin like defect, due to the absent aggregation with thromboxane analogue. Due to the abnormal aggregation in both concentrations with ADP and a desaggregation you should concider a platelet ADP receptor defect. Exclude a drug-induced defect.

Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

An acquired platelet function disorder has to be excluded. Repeat platelet aggregation. ATP release can give more information.Findings should be confirmed on another sample. Drug-induced defects should also be excluded.

Submitted:

EID Number: 1214


Page 11 of 97

Scored: Not Optimal

Glanzmann thrombasthenia is excluded by the initial aggretation with ADP adn thromboxane analogue and the normal response to high concentration of collagen.

Reviewer:

Presence of platelet function defect: possible Glanzmann Thrombasthenia Need 2nd aggregation testing to confirm. Cytometry investigation: CD41, CD61a, CD42b, CD62P. Check for platelet antibodies (anti-GPIIbIIIa...). Check for ATP release and if possible electron microscopy (dense granule investigation). Onco-hematological investigation (bone marrow aspiration...) after hemostasis check up. Molecular biology if confirmed by cytometry.

Submitted:

EID Number: 1218

Scored: Not Optimal

Reviewer:

Inconsistent findings associated with probable myeloproloiferative disorder.

Submitted:

EID Number: 1222

Scored: Correct

Reviewer:

?secretion/qualitative defect secondary to myelodysplasia. ?storage pool defect

Submitted:

EID Number: 1223

Scored: Correct

Reviewer:

Virtually no aggregation response with epinephrine, arachidonic acid, U46619 and the low collagen concentration. With both ADP concentration the first phase was decreased and the reaction was completely reversible. The 4x higher collagen concentration and the response to ristocetin was normal. This pattern with the severeness of the aggregation defect for epinephrine >collagen >arachidonic acid >ADP with some differences in the range of severity has been decribed several times fpr patients with myelodyplastic syndromes. In some it was due to an acquired storage pool defect and in 1 patient due to abormal interactions with GP VI. The bleeding tendency is mild in the majority of patients. The none-respose to arachidonic acid is not indicative for an ASS- intake.

Submitted:

EID Number: 1225


Page 12 of 97

Scored: Correct

Reviewer:

Aggregation abnormalities detected with several agonists, suggestive of a platelet secretion defect. The whole blood platelet count was 290,000 and the platelet rich plasma count was 250,000. Using provided reference intervals and tracings, there is reduced aggregation with ADP (2.5 um,5.0 um), collagen (1.25 u g/ml), epinephrine (6um), arachidonic acid (1.6mM), and the thromboxane analogue U46619 (1um). There is essentially normal aggregation to all other agonists including collagen (5ug/ml), and ristocetin (0.5 mg/ml, 1.25 mg/ml). The reduced aggregation with ADP, collagen, epinephrine, arachidonic acid, and U46619 may be suggestive of a platelet secretion defect and my represent an acquired defect due to an underlying myelodysplastic syndrome. Additional studies including platelet ATP release may be helpful to futher characterize these abnormal aggregation findings.

Submitted:

EID Number: 1228

Scored: Not Scored

Reviewer:

Give your overall case interpretation. Submitted:

EID Number: 1230

Scored: Correct

Reviewer:

Acquired platelet function abnormalities can occur with myelodysplasia. These include acquired secretion defects and dense granule deficiency.

Submitted:

EID Number: 1231

Scored: Correct

Reviewer:

Suggestive of a platelet function disorder. R/O drug effect may be secondary to MDS.

Submitted:

EID Number: 1233


Page 13 of 97

Scored: Not Optimal

A platelet function defect due to Glanzmann thrombasthenia is excluded by the initial aggregation with ADP and thromboxane analogue and the normal response to high concentration of collagen

Reviewer:

Results are most consistent with a Congenital or Acquired form of Glanzmann Thrombasthenia. In this case, if the personal and family bleeding history is negative, it would be considered to be an acquired form secondary to T cell dysregaulation of a Myelodysplastic Syndrome. We recommend Direct and Indirect Platelet Antibody Testing along with exclusion of Autoimmune, Lymphoproliferative, and Plasma Cell Disorders. In addition, we recommend ruling out an Acquired Storage Pool Disorder and/or Secretion Defect as these are also relatively common and have been reported in the literature in patients with Myelodysplastic and Myeloproliferative Disorders.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

There is reduced aggregation with all agonists except for 1.25 mg/mL ristocetin and 5 mcg/mL collagen. The response to the lower concentration of ristocetin is normal. The findings are consistent with a defect in platelet function and suggest a potential problem with signaling and/or secretion. Studies of dense granule secretion by ATP release and an assessment of platelet dense granules by electron microscopy may be helpful to further evaluate the abnormalities. Confirmation on another sample is recommended.

Submitted:

EID Number: 1235

Scored: Incorrect

A platelet function defect due to Glanzmann thrombasthenia is excluded by the initial aggregation with ADP and thromboxane analogue and the normal response to high concentration of collagen.

Reviewer:

Need to rule out that the patient is taking GP IIb/IIIa antagonists. Pattern similar to Glanzmann's with the exception of the normal Collagen. Use flow cytometry to rule of deficiency of GP IIb and/or IIIa

Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

The findings suggest that a platelet function disorder is present. The findings should be confirmed on another sample, if clinically indicated.

Submitted:

EID Number: 1239


Page 14 of 97

Scored: Incorrect


Reviewer:

Mild Glanzmann's Submitted:

EID Number: 1240

Scored: Incorrect


Reviewer:

Probable Glanzmann's Thrombastenia. Submitted:

EID Number: 1242

Scored: Not Optimal

No mention of platelet function defect. Reviewer:

Multiple agonist defects consistent with acquired defect (myelodysplasia).

Decreased U46619 is not indicative of aspirin effect. Ristocetin results do not identify VWD.

Submitted:

EID Number: 1244

Provide additional tests or additional comments:Guide: It would be reasonable to suggest testing for a dense granule secretion defect

and for dense granule deficiency. Cytogenetics might be interesting given the history of myelodysplasia.

Scored: Correct

Reviewer:

Suggest BM biopsy, EM of plt to look at granules Submitted:

EID Number: 1161

Scored: Not Scored

Reviewer:

Provide additional tests or additional comments. Submitted:

EID Number: 1163

Scored: Correct

Reviewer:

Recommend ATP release studies and/or Platelet EM evaulation for dense granule deficiency vs abnormality associated with MDS.

Submitted:

EID Number: 1164


Page 15 of 97

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Correct

Reviewer:

Recommend bone marrow biopsy, FISH, flow cytometry and platelet EM.

Submitted:

EID Number: 1166

Scored: Correct

Reviewer:

Definitive interpretation is somewhat hindered by limited clinical information. If a congenital deficiency is suspected, platelet EM studies or molecular studies may also be considered.

Submitted:

EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Not Scored

Reviewer:


EID Number: 1170

Scored: Correct

Reviewer:

Addtional tests to consider in the evaluation of the disorder include ATP release assays, electron microscopy, and consider testing for a thromboxane receptor defect.

Submitted:

EID Number: 1171

Scored: Incorrect

Reviewer:

Evaluate with a higher concentration of U46619 Submitted:

EID Number: 1172


Page 16 of 97

Scored: Not Scored

Reviewer:


EID Number: 1173

Scored: Correct

Reviewer:

Platelet secretion test may be considered. Submitted:

EID Number: 1176

Scored: Correct

Reviewer:

Consider additional release studies. Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Platelet nuceleotide quantification and EM microscopy if available Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183


Reviewer:

Further investigations on the possible myelodysplastic syndrome. Submitted:

EID Number: 1188

Scored: Not Scored

Reviewer:

It would have been a useful addaition to have data on the therapy of the patient.

Submitted:

EID Number: 1196


Page 17 of 97

Scored: Correct

Reviewer:

Examination of platelets on the blood smear might be informative. Platelets might display reduced alpha and delta granules, abnormal membranes and vary in size. If abnormal, EM might be performed.

Submitted:

EID Number: 1197


Reviewer:


EID Number: 1201

Scored: Not Scored

Reviewer:


EID Number: 1203


Reviewer:

Provide additional tests or additional comments. Retesting off drugs that inhibit platelet function Glycoprotein analysis by flow cytometry

Submitted:

EID Number: 1204

Scored: Correct

Reviewer:

Dense granules examination: ATP release and/or electron microscopy of whole platelets. Possible interference of drug information would be for this case.

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

It would be reasonable to consider ATP release assays, tests for dense granule deficiency (e.g. EM). It would also be acceptable to recommend investigations for a thromboxane receptor defect.

Maybe you should do a new platelet aggregation as well to confirm your findings.

If the patient have MDS the platelet defect could be a secondary effect.

Submitted:

EID Number: 1213


Page 18 of 97

Scored: Correct

Reviewer:

ADP receptor defect has to be excluded. Effect of drugs? Since also abnormal max. aggregation with low conc. collagen and thromboxan analogue, a platelet dysfunction has te be ruled out. ATP release and/or electron microscopy is advised. Aggregation with AA is abnormal, but also with thromboxan- analogue. Cannot be explained by aspirin. ATP release is advised.

Submitted:

EID Number: 1214

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Correct

Reviewer:

Would like to check platelet nucleotides, and possibly electron microscopy

Submitted:

EID Number: 1223


Reviewer:


EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Not Scored

Reviewer:


EID Number: 1230


Page 19 of 97

Scored: Correct

Reviewer:

Recommend investigation for dense granule deficiency and secretion defects: DG counts and ATP release.

Submitted:

EID Number: 1231

Scored: Not Scored

Reviewer:


EID Number: 1233

Scored: Not Scored

Reviewer:

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

We would assess this person for dense granule release and ATP release abnormalities as the findings and clinical history suggest a platelet function defect with myelodysplasia, which can be associated with a variety of platelet function abnormalities. Cytogenetics would be of interest. It would be important to confirm the abnormal platelet function on another sample in order to exclude a preanalytical defect.

Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:


EID Number: 1236

Scored: Correct

Reviewer:

Platelet ATP release and/or electron microscopy for dense granule deficiency.

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240


Page 20 of 97

Scored: Not Optimal

Reviewer:

Would like to view a blood smear to examine platelets for granules. Test for IIb IIIa receptor expression

Submitted:

EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244

Case: 2010-2 Case 7

Add comments on other abnormalities:Guide: It would be reasonable to comment that there is no secondary aggregation with

epinephrine.

Scored: Correct

Reviewer:

Normal platelet function with all antagonist. Submitted:

EID Number: 1161


Reviewer:

The platelet aggregation study shows normal aggregation to all agonists. The ristocetin induced platelet aggregation shows a normal dose response. The platelet count is normal. Further evaluation to exclude any coagulation abnormality including PT/PTT is suggested.

Reviewed by: Dr. Heesun Rogers 12/15/2010

Submitted:

EID Number: 1163

Scored: Not Scored

Reviewer:

Patient should be referred to OB-GYN for possible anatomic explanation of increased menses.

Submitted:

EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165


Page 21 of 97

Scored: Not Scored

Reviewer:


EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Not Scored

Reviewer:


EID Number: 1170


Reviewer:

Maximal aggregation is within normal limits for low and high concentration ADP, low and high concentration Collagen, Epinephrine, Arachidonic Acid, U46619, and low and high concentration Ristocetin.

Submitted:

EID Number: 1171

Scored: Not Scored

Reviewer:

None Submitted:

EID Number: 1172

Scored: Not Scored

Reviewer:


EID Number: 1173


Page 22 of 97

Scored: Correct

Reviewer:

The slope of epinephrine-induced aggregation is lower than expected. Submitted:

EID Number: 1176

Scored: Not Scored

Reviewer:


EID Number: 1178

Scored: Correct

Reviewer:

Platelet aggregation tracings normal Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183

Scored: Not Scored

Reviewer:

no comments Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

No abnormalities other than easy bruising, menorrhagia challange related bleeding in the patient's history.

Submitted:

EID Number: 1196

Scored: Not Scored

Reviewer:

No anemia. Mild lymphopenia. Submitted:

EID Number: 1197


Page 23 of 97


Reviewer:


EID Number: 1201

Scored: Not Scored

Reviewer:


EID Number: 1203

Scored: Not Optimal

Reviewer:

Add comments on other abnormalities. collagen 1.25 : Lag time too long Ristocetin 1.25 : slope 1 too slowly There is absent secondary aggregation with Epineprhin

Submitted:

EID Number: 1204

Scored: Not Scored

Reviewer:


EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213


Reviewer:

Aggregation with epinephrine is slightly reduced, although still normal. Anyway, single agonist abnormality is not diagnostic.

Submitted:

EID Number: 1214


Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222


Page 24 of 97

Scored: Not Scored

Reviewer:

Normal full blood count Submitted:

EID Number: 1223


Reviewer:

Because VWD was already ruled out, it can be assumed, that a screen for secondary (plasmatic) hemostasis has been performed beforehand.

Submitted:

EID Number: 1225


Reviewer:


EID Number: 1228

Scored: Correct

Reviewer:

Add comments on other abnormalities. Overall interpretation: Normal Platelet function.Suggest lumi aggregation to rule out out a mild platelet function defect if clinically indicated.

Submitted:

EID Number: 1230

Scored: Not Scored

Reviewer:


EID Number: 1231


Reviewer:


EID Number: 1233


Page 25 of 97

Scored: Not Scored

Reviewer:


EID Number: 1234


Reviewer:

There is no secondary aggregation with epinephrine, which is a non-diagnostic finding.

Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:


EID Number: 1236

Scored: Not Scored

Reviewer:

None Submitted:

EID Number: 1239


Reviewer:


EID Number: 1240

Scored: Not Scored

Reviewer:

Submitted:

EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244


Page 26 of 97

Give your overall case interpretation:Guide: Nondiagnostic or normal aggregation findings. The lack of secondary aggregation

with epinephrine can be a normal variant.

The fact that there was no secondary aggregation with epinephrine (which can be a normal variant) could be commented on.

Scored: Correct

Reviewer:

Normal plt function. Evaluate for vWF deficiency and possible factor VIII and IX deficiency

Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

The platelet aggregation study shows normal aggregation to all agonists. The ristocetin induced platelet aggregation shows a normal dose response. The platelet count is normal. Further evaluation to exclude any coagulation abnormality including PT/PTT is suggested.


Submitted:

EID Number: 1163

Scored: Correct

Reviewer:

Platelet aggregation profile is entirely normal. No evidence of suboptimal response with any agonists.

Submitted:

EID Number: 1164

Scored: Correct

Reviewer:

Give your overall case interpretation. normal aggregation

Submitted:

EID Number: 1165

Scored: Correct

Reviewer:

Normal aggregation with all agonists. No evidence of platelet disorder. Submitted:

EID Number: 1166


Reviewer:

No laboratory evidence of a quantitative or qualitative platelet disorder. Submitted:

EID Number: 1167


Page 27 of 97

Scored: Correct

Reviewer:

Give your overall case interpretation.No evidence of a platelet abnormality. Would suggest checking vWF levels at a later date and rule out any type of vascular defect.

Submitted:

EID Number: 1168

Scored: Correct

Reviewer:

Normal platelet aggregation testing. . Submitted:

EID Number: 1169

Scored: Correct

Reviewer:

This patient showed normal aggregation response to all agonists, including ristocetin.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

Platelet aggregation study is within normal limits. Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Normal Submitted:

EID Number: 1172

Scored: Correct

Reviewer:

platelet aggregometry results are normal. This does not rule out a storage pool disorder which can be assesed by lumiaggregometry. A anamnesis is important and also a PFA-100 measurement or bleeding timemay be helpful. Analysis includes PT, aPTT, TT, FXIII, fibrinogen concentration, vWF for other causes of bleeding.

Submitted:

EID Number: 1173

Scored: Correct

Reviewer:

These aggregation tracings do not show marked aggregation abnormalities. The slope of epinephrine-induced aggregation may be considered as low (according to our experience) and this constellation may be related to storage pool deficiency (Nieuwenhuis KH et al, Blood 1987;70:620).

Submitted:

EID Number: 1176


Page 28 of 97

Scored: Correct

Reviewer:

No evidence for a platelet function disorder, however mild release disorders and/ or SPD are not excluded.

Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Platelet aggregation tracings are normal. This does not exclude storage pool disorder which requires measurement of platelet nucleotides.

Submitted:

EID Number: 1179

Scored: Correct

Reviewer:

No Trombocytopathie Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183

Scored: Correct

Reviewer:

Normal aggregation findings with all agonists. Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

No abnormality was detected by the aggregation study. Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Normal platelet function test. Submitted:

EID Number: 1197

Scored: Correct

Reviewer:

No abnormalities in platelet function Submitted:

EID Number: 1201


Page 29 of 97

Scored: Correct

Reviewer:

Severe case of normality. Submitted:

EID Number: 1203


Reviewer:

Give your overall case interpretation. History of bruising and menorrhagia suggest to repeat aggregation testing to confirm the anomalies of aggregation, with electron microscopy and PFA.

Submitted:

EID Number: 1204

Scored: Correct

Reviewer:

Patient having normal platelet count, normal platelet aggregations, and normal plasma von Willebrand level: the study of coagulation factors is strongly suggested.

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

The patient don´t seem to have any platelet defect. Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

Normal platelet aggregation. Additional tests have to be performed to exclude bleeding disorder.

Submitted:

EID Number: 1214

Scored: Correct

Reviewer:

No pathological platelet aggregation. Check for other coagulation abnormalities (PT, aPTT, Fibrinogen, Fibrinolysis). Control vWF:Ag; vWF:RCoF; FVIII:C even if normal on previous sample. Look for collagen pathologies (Ehlers-Danlos, Marfan...).

Submitted:

EID Number: 1218

Scored: Correct

Reviewer:

Normal aggregation results Submitted:

EID Number: 1222


Page 30 of 97

Scored: Correct

Reviewer:

No demonstrable abnormality in platelet aggregation. Currently nondiagnostic

Submitted:

EID Number: 1223

Scored: Correct

Reviewer:

There is a normal platelet aggregation pattern with all agonists. Because a relatively high portion of patients with a delta storage pool disease show no abnormalities in these aggregation tests, ATP-release or counting of the dense granules after labelling with mepacrine should be performed. On the othe hand the reported bleeding symtoms are not striking and can be found in frequently in the normal poulation, too.

Submitted:

EID Number: 1225

Scored: Correct

Reviewer:

Give your overall case interpretation.Normal aggregation responses. The whole blood platelet count was 224,000, and the platelet rich plasma count was 250,000. Using provided reference intervals and tracings, there is essentially normal aggregation with all agonists, which includes ADP (2.5 um, 5.0 um), collagen (1.25 ug/ml, 5 ug/ml), epinephrine (6 um), arachidonic acid (1.6 mM), the thromboxane analogue U46619 (1 um) and ristocetin (0.5 mg/ml, 1.25 mg/ml). These aggregation data are not supportive of an underlying platelet function defect.

Submitted:

EID Number: 1228

Scored: Not Scored

Reviewer:


EID Number: 1230


Reviewer:

Platelet aggregation studies are normal. Submitted:

EID Number: 1231

Scored: Correct

Reviewer:

Normal tracings for all agonists. Platelet agregation normal.

Submitted:

EID Number: 1233


Page 31 of 97

Scored: Correct

Reviewer:

Platelet Aggregation Studies appear to be normal. Consider specific secretion studies in order to completely rule out a secretion defect.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

Aggregation findings are nondiagnostic. The absent secondary aggregation with epinephrine can be a normal variant. If a platelet function defect is suspected, an evaluation for dense granule deficiency and ATP release abnormalities should be considered.

Submitted:

EID Number: 1235

Scored: Correct

Reviewer:

All aggregations normal Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

Normal Platelet Aggregation Submitted:

EID Number: 1239

Scored: Correct

Reviewer:

Within normal limits Submitted:

EID Number: 1240

Scored: Correct

Reviewer:

Normal platelet aggregation Submitted:

EID Number: 1242

Scored: Correct

Reviewer:

Normal PLT function study. Bleeding not due to platelet disorder.

Submitted:

EID Number: 1244


Page 32 of 97

Provide additional tests or additional comments:Guide: It would be reasonable to recommend testing for dense granule secretion and for

dense granule deficiency.

Scored: Not Optimal

Reviewer:

Suggest PT, aPTT testing, possible factor deficiency--FVIII, FIX, FXI vWF Multimers

Submitted:

EID Number: 1161

Scored: Not Scored

Reviewer:


EID Number: 1163


Reviewer:

Patient should be evaluated for possible diagnosis of Ehlers Danlos or other collagen vascular defects. Vit C deficiency shlould also be ruled out.

Submitted:

EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Not Scored

Reviewer:


EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Correct

Reviewer:

Provide additional tests or additional comments.Would suggest checking vWF levels at a later date and rule out any type of vascular defect.

Submitted:

EID Number: 1168


Page 33 of 97


Reviewer:


EID Number: 1169


Reviewer:


EID Number: 1170

Scored: Correct

Reviewer:

To further evaluate for a platelet disorder, consider ATP release assays and electron microscopy.

Submitted:

EID Number: 1171


Reviewer:

Further evaluation for coag abnormalities including VWD if not done previously

Submitted:

EID Number: 1172

Scored: Not Scored

Reviewer:


EID Number: 1173


Reviewer:

Platelet secretion test should be performed. Submitted:

EID Number: 1176

Scored: Correct

Reviewer:

Consider additional testing for release defects / mild storage pool disease. E.g. ATP release assays. Measurement of factor VIII,IX,XI and vwf.

Submitted:

EID Number: 1178


Page 34 of 97


Reviewer:

the laboratory tests suggest that platelet dependent haemostasi is normal. Other causes of a bleeding diathesis such as coagulation factor deficiencies should be excluded.

Submitted:

EID Number: 1179


Reviewer:


EID Number: 1180

Scored: Correct

Reviewer:

Provide additional tests or additional comments. repeat Von Willebrand

Submitted:

EID Number: 1183


Reviewer:

no additional comments Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

Investigation for vascular type bleeding and coagulaopathy is recommended.

Submitted:

EID Number: 1196


Reviewer:

Investigate family history and medication list. Check PT, APTT, fibrinogen level and platelet morphology on blood smear. How many times was VWF checked and what were the patient conditions at the time of the test(s)? If it was only once, I would suggest to repeat VWF measurement. I would also control FVIII level. FXIII and fibrinolysis might also be explored.

Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201


Page 35 of 97

Scored: Not Scored

Reviewer:


EID Number: 1203

Scored: Not Scored

Reviewer:


EID Number: 1204


Reviewer:

Level of plasma coagulation factors Submitted:

EID Number: 1209


Reviewer:

If the patient have severe problems she should consult a gynecologist.

Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

Screening for VWD (VWF ag, VWF activity, FVIII) should be repeated. Other causes of bleeding (factordeficienties) should be excluded.

Submitted:

EID Number: 1214

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222


Reviewer:

Would like to check platelet nucleotides Submitted:

EID Number: 1223


Page 36 of 97

Scored: Not Scored

Reviewer:


EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Not Scored

Reviewer:


EID Number: 1230

Scored: Correct

Reviewer:

Depending on clinical scenario repeat testing of VWF and platelet aggregation may be warranted.

Submitted:

EID Number: 1231

Scored: Not Scored

Reviewer:


EID Number: 1233

Scored: Not Scored

Reviewer:


EID Number: 1234

Scored: Correct

Reviewer:

We would recommend testing for dense granule secretion and for dense granule deficiency.

Submitted:

EID Number: 1235


Reviewer:


EID Number: 1236


Page 37 of 97

Scored: Not Scored

Reviewer:

None Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240

Scored: Not Optimal

Reviewer:

Would do protime and aptt screening tests. Submitted:

EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244

Case: 2010-2 Case 8

Add comments on other abnormalities:Guide: Agonist responses fall within the reference interval except for 0.5 mg/mL ristocetin.

Scored: Correct

Reviewer:

Large platelets, thrombocytopenia Increased results with Ristocetin

Submitted:

EID Number: 1161


Page 38 of 97


Reviewer:

Due to the patient's thrombocytopenia, the platelet aggregation is compared to diluted normal platelet-rich plasma. The platelet aggregation is decreased with ADP and collagen and normal with epinepherine, arachidonic acid and U44619. The ristocetin induced platelet aggregation is abnormally increased with low concentrations of ristocetin. The findings are suggestive of von Willebrand disease, probably type 2B or platelet type. However, an intrinsic platelet dysfunction needs to be excluded. Rechecking platelet aggregation and von Willebrand disease diagnostic panel is suggested.

Reviewed by: Dr Heesun Rogers 12/15/2010

Submitted:

EID Number: 1163

Scored: Not Scored

Reviewer:


EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Not Scored

Reviewer:


EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168


Page 39 of 97

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Correct

Reviewer:

Large Platelets and platelet clumping is consistent with type 2B vonWillebrand's disease

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

Thrombocytopenia and increased mean platelet volume suggesting the presence of megathrombocytes. The platelet rich plasma for the patient has a platelet count of 47x10^9/L. Maximal aggregation is within normal limits for the platelet count for low and high concentration ADP, low and high concentration Collagen, Epinephrine, Arachidonic Acid, U46619, and high concentration (1.25 mg/mL) Ristocetin. Maximal aggregation is increased for low concentration (0.5 mg/mL) Ristocetin.

Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Interpret with caution in thrombocytopenia Submitted:

EID Number: 1172


Reviewer:

Submitted:

EID Number: 1173

Scored: Not Scored

Reviewer:


EID Number: 1176

Scored: Not Scored

Reviewer:


EID Number: 1178


Page 40 of 97

Scored: Correct

Reviewer:

Low platelet count, slightly high MPV, Submitted:

EID Number: 1179

Scored: Correct

Reviewer:

Great platelets and decreased platelets Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183


Reviewer:

Thrombocytopenia with clumped platelets. Platelets show aggregation with low concentration of ristocetin, which should be absent in healthy persons. The results of the aggregation with epinephrine and low concentration of collagen are unsure because of the lack of reference values for low platelet counts.

Submitted:

EID Number: 1188


Reviewer:

Low platelet count. Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Thrombocytopenia, clumped platelets. Megathrombocytes. Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201


Page 41 of 97

Scored: Correct

Reviewer:

Platelet clumping on film is indicative of typeIIb vWD or platelet type vWD.

Submitted:

EID Number: 1203

Scored: Not Scored

Reviewer:


EID Number: 1204

Scored: Not Scored

Reviewer:


EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213


Reviewer:


EID Number: 1214

Scored: Correct

Reviewer:

Moderate thrombocytopenia with platelet clumps and slightly elevated MPV have to be taken in account.

Submitted:

EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Correct

Reviewer:

Mild thrombocytopenia with large platelets Submitted:

EID Number: 1223


Page 42 of 97

Scored: Not Scored

Reviewer:


EID Number: 1225


Reviewer:


EID Number: 1228

Scored: Correct

Reviewer:

Add comments on other abnormalities. Overall interpretation: Increased platelet response to low dose Ristocetin.Combined with thrombocytopenia and platelet clumping, these findings suggest Type IIB VWD.Suggest VWF panel with VWF multimer analysis for confirmation.Unable to fully evaluate platelet responses to other agonists due to thrombocytopenia.

Submitted:

EID Number: 1230


Reviewer:

Thrombocytopenia with clumped platelets noted on smear. Platelet aggregation performed on PRP with platelet count of 47 X 10e9/L. Platelet aggregation in response to ADP, 5mcg/ml collagen, AA, U46619 are within reference intervals for low platelet count samples and comparable to control PRP at equivalent platelet count. Increased response to low dose ristocetin. Normal response to standard dose ristocetin.

Submitted:

EID Number: 1231


Page 43 of 97

Scored: Correct

Reviewer:

Platelets moderately decreased with clumped platelets. Hyperaggregation with ristocetine 0.5 mg/mL. No interpretation for agonists: collagen 1.25 ug/mL, Epinephrin 6uM and Thromboxane analogue for this low PRP platelet count sample. aggregation responses within the 95% confidence interval for ADP, collagen 5 ug/mL, arachidonic acid and ristocetin 1.25 mg/mL for this low PRP platelet count.

Submitted:

EID Number: 1233


Reviewer:

Clumped Platetes could be an indication of issues in the Pre-Analytic Process. These Clumps could also be mediated by Anticoagulant, Temperature Dependent Antibodies, Presence of Platelet Specific Antibodies, Drugs, or due to a Type 2 or platelet-type von Willebrand Disorder.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

Agonist responses fall within the reference interval except for 0.5 mg/mL ristocetin. Submitted:

EID Number: 1235

Scored: Not Optimal

Since the patient had a low platelet count with clumping, the platelet count should be confirmed.

Reviewer:

Thrombocytopenia Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

Aggregation is abnormally increased with low concentrations of ristocetin.

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240


Page 44 of 97

Scored: Correct

Reviewer:

Platelet count is low and the platelets are clumped Submitted:

EID Number: 1242


Reviewer:


EID Number: 1244

Give your overall case interpretation:Guide: The patient has a low platelet count and as clumps were detected, it would be

reasonable to indicate that this should be confirmed. The aggregation studies were interpreted using reference intervals for low platelet count samples and the only notable abnormality is the increased aggregation with 0.5 mg/mL ristocetin. This abnormality suggests possible type 2B or platelet type von Willebrand disease, which should be further evaluated by von Willebrand factor testing (including multimers, if available) and genetic testing (if available). It would be reasonable to suggest further testing by adding the patient’s plasma to normal platelets determine if it causes increased aggregation with the lower concentration of ristocetin, as this patient’s plasma did.

Scored: Correct

Reviewer:

Type IIB vWF disease or Pseudo vWF disease Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

Due to the patient's thrombocytopenia, the platelet aggregation is compared to diluted normal platelet-rich plasma. The platelet aggregation is decreased with ADP and collagen and normal with epinepherine, arachidonic acid and U46619. The ristocetin induced platelet aggregation is abnormally increased with low concentrations of ristocetin. The findings are suggestive of von Willebrand disease, probably type 2B or platelet type. However, an intrinsic platelet dysfunction needs to be excluded.

Reviewed by: Dr. Heesun Rogers.

Submitted:

EID Number: 1163


Page 45 of 97

Scored: Correct

Reviewer:

The response to U46619 on the patietnhas to be disregarded becasue the normal control also failed to respond. The most striking abnormality is the low platelet count with a positive aggregation response to the low dose of Ristocetin typical of what is seen with Type IIB VWD.

Submitted:

EID Number: 1164

Scored: Correct

Reviewer:

Give your overall case interpretation. type 2B or platelet-type VWF

Submitted:

EID Number: 1165

Scored: Correct

Reviewer:

Reduced response to all agonists consistent with thrombocytopenia. Abnormaly increased response to low dose ristocetin consistent with VWD type 2B or pseudo-VWD.

Submitted:

EID Number: 1166


Reviewer:

Thrombocytopenia with aberrant 0.5mg/mL ristocetin induced platelet aggregation. These results are suggestive for possible type 2B VWD or a platelet type VWD due to gain of function mutation of GPIB-V-IX complex.

Submitted:

EID Number: 1167

Scored: Correct

Reviewer:

Give your overall case interpretation.Would consider vWD 2B or platelet-type vWD due to increase Ristocetin at 5 mg/nL, thrombocytopenia, and bleeding.

Submitted:

EID Number: 1168

Scored: Correct

Reviewer:

Abnormal platelet aggregation in response to low dose risrocetin and normal aggregation with other agonists. Results suggest von Willebrand disease type IIB or pseudo-VWD. To differentiate, recommend further investigation with RIPA mixing test.

Submitted:

EID Number: 1169


Page 46 of 97


Reviewer:

Probable type 2B vonWillebrand's disease. However based on the aggregation alone cannot rule out platelet-type (pseudo) vonWillebrand's.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

These findings are consistent with possible Type 2B or platelet-type von Willebrand disease.

Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Increased response to low dose ristocetin, rule out Type 2B VWD and less common pseudo VWD

Submitted:

EID Number: 1172

Scored: Correct

Reviewer:

The aggregation recordings are in accordance with the expected response obtained from a patient with low platelet count. However, the response to low dose ristocetin is abnormally high. This is suggestive of von willebrand disease type 2B or platelet type vWD. Analysis of vWF:Ag, vWF:RCo, multimer distribution is suggested. Genetic testing should be considered

Submitted:

EID Number: 1173

Scored: Correct

Reviewer:

At this low platelet count, all aggregation results are unsure or are at best to be interpret with caution. Of note a marked increase of platelet aggregation to low-dose ristocetin that suggests type 2B von Willebrand or platelet-type von Willebrand disease. The relative high aggregation result to the higher dose of ristocetin rules out BSS.

Submitted:

EID Number: 1176


Reviewer:

Von Willebrand IIB or platelet type von Willebrand. Submitted:

EID Number: 1178


Page 47 of 97

Scored: Correct

Reviewer:

Possible type 2B or platelet type von Willebrand disease Submitted:

EID Number: 1179

Scored: Correct

Reviewer:

vWF type 2B? Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183

Scored: Correct

Reviewer:

The aggregation findings are compatible with von Willebrand disease type IIb or platelet-type von Willebrand disease.

Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

The aggregation response to low dose ristocetin and the low platelet count suggest von Willebrand disease type IIb or platelet type von Willebrand disease.

Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Aggregation increased in response to low concentration ristocetin.

Response to other agonists have to be interpreted with caution or omitted.

Differential diagniosis: VWD type 2B platelet-type VWD

Submitted:

EID Number: 1197

Scored: Correct

Reviewer:

Results are consistent with Type IIb Von Willebrand Disease (reaction to low concentration ristocetin).

Submitted:

EID Number: 1201


Page 48 of 97

Scored: Correct

Reviewer:

Consistent with typeIIb vWD or platelet type vWD. Confirm with mixing studies.

Submitted:

EID Number: 1203

Scored: Correct

Reviewer:

Give your overall case interpretation. Aggregation is abnormally increased with low concentration of ristocetin and there are thrombocytopenia, clumped platelets and bleeding problems. Possible type 2B or platelet-type Von Willebrand disease.

Submitted:

EID Number: 1204


Reviewer:

Macrothrombocytopenia with predominantly an hyperaggregability to ristocetin, with no consistant defect to the other agonists: studies of plasma von Willebrand is strongly suggested first (antigen, ristocetin/collagen co-factors, multimers), if abnormal a search for mutations in vWF-exon28 and if no, a search for mutations in GPIBA is also suggested (most probably a IIB-VWF disease).

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

Complet with VWF analysis. The results suggest either a VWF type 2B or platelet VWF disease. Complet with genetic analysis.

Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

Possible type 2B or platelet-type Von Willebrand Disease Submitted:

EID Number: 1214


Reviewer:

Possible platelet type von Willebrand disease or vWD type 2B. Perform vWF:Ag; vWF:RCoF and FVIII:C. Perform new aggregation testing to confirm. Genetic testing if confirmed.

Interpretation is difficult because of the low amount of platelets avalaible for PRP even in comparison with adjusted control PRP

Submitted:

EID Number: 1218


Page 49 of 97

Scored: Correct

Reviewer:

Type 2B VWD or platelet type VWD Submitted:

EID Number: 1222

Scored: Correct

Reviewer:

Unexpectedly strong response to low dose ristocetin; all other agonists normal. With mild thrombocytopenia type 2B vWD suspected.

Submitted:

EID Number: 1223


Reviewer:

Isolated hyperresponse to low ristocetinc concentration. 0.5 mg/ml is an accepted threshold for hyperresponsiveness. Additionally low platelet count with some platelet aggregates in smear. Most probable diagnosis: von Willebrand disease typ 2B (mutation in the A1-domain of the VWF-gene). Differential diagnosis platelet type (pseudo-) von Willebrand disease (mutation in the GP Ib-gene, 3 different mutations described). A hyerresponsive RIPA-test with the PRP from the patient and with washed platelets from a normal donor and patient plasma should be sufficien to rule out platelet type VWD. Other possibility: genomic diagnosis.

Submitted:

EID Number: 1225

Scored: Correct

Reviewer:

Result: Abnormal findings. The whole blood platelet count was moderately decreased and estimated at 50,000-100,000. The platelet rich plasma count was 47,000. Using provided reference intervals, tracings and regression analysis, there is increased aggregation to ristocetin (0.5 mg/ml). There is essentially normal aggregation to all other agonists including ADP (2.5um, 5.0 um), collagen (5 um/ml), arachidonic acid (1.6 mM), U46619 (1uM), and ristocetin (1.25 mg/ml). Aggregation responses to collagen (1.25 ug/ml) and epinephrine (6um) are outside the reference interval for the control and will not be interpreted. The increased aggregation response with a low concentration of ristocetin may be suggestive of type II von Willebrand disease and if clinically indicated, complete evaluation including performance of a von Willebrand profile including FVIII activity, von Willebrand antigen, ristocetin cofactor activity, and von Willebrand factor multimers should be performed. However, impaired aggregation with a single agonist may represent a non-diagnostic finding and repeat testing is recommended.

Submitted:

EID Number: 1228


Page 50 of 97


Reviewer:


EID Number: 1230

Scored: Correct

Reviewer:

Results are consistent with von Willebrand Disease type 2B, or platelet -type VWD.

Submitted:

EID Number: 1231

Scored: Correct

Reviewer:

Possible von Willebrand type 2B or platelet-type won Willebrand disease. Additionnal testing: Von Willebrand factor levels and consider genetic testing for type 2B or platelet-type von Willebrand disease.

Submitted:

EID Number: 1233

Scored: Correct

Reviewer:

Platelet Aggregation Studies demonstrate increased and abnormal aggregation to the low concentration Ristocetin. These results are most consistent with a Type 2 or Platelet-type Congenital or Acquired von Willebrand Disorder. We recommend repeat testing at a later point in time to exclude pre-analytic variables along with von Willebrand Factor Activity, von Willebrand Factor Antigen, vWF Ratios, vWF Multimer Studies, and Gene Sequencing. We also recommend Direct and Indirect Platelet Antibody testing.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

The platelet rich plasma had a low platelet count and results were interpreted using published reference ranges for low platelet samples. The responses to most agonists are normal, however, there is increase maximal aggregation with 0.5 mg/mL ristocetin, which suggests a gain-of-function abnormality, possibly due to type 2B or platelet-type von Willebrand disease. Correlation of the findings with the results of the von Willebrand factor screen and multimer analysis is recommended. Is there a family history of type 2B or platelet type von Willebrand disease?

Submitted:

EID Number: 1235


Reviewer:

Rule out vW subytype 2B Submitted:

EID Number: 1236


Page 51 of 97

Scored: Correct

Reviewer:

Possible type 2B or platelet-type von Willebrand disease. Submitted:

EID Number: 1239

Scored: Correct

Reviewer:

Von Willebrand's Submitted:

EID Number: 1240

Scored: Correct

Reviewer:

Probable Type 2B vWD or Platelet type vWD Submitted:

EID Number: 1242

Scored: Correct

Reviewer:

Increased response to low concentration of ristocetin consistent with VWD Type IIb or platelet-type VWD.

Study suboptimal due to low PLT CT and platelet clumping. Confirmatory testing (VWF: RCof, VWF:Ag & FVIII level; Platelet-VWF binding; and VWF multimeric analysis) recommended.

Submitted:

EID Number: 1244

Provide additional tests or additional comments:Guide: Laboratories should recommend testing for von Willebrand disease (antigen,

ristocetin cofactor, factor VIIIC, multimers if available), including genetic testing if available. It would be reasonable to suggest further testing by adding the patient’s plasma to normal platelets determine if it causes increased aggregation with the lower concentration of ristocetin, as this patient’s plasma did.

Scored: Correct

Reviewer:

Suggest vWF testing Submitted:

EID Number: 1161

Scored: Not Scored

Reviewer:


EID Number: 1163


Page 52 of 97

Scored: Correct

Reviewer:

Additonal testing needs to be performed for the VWF complex including VWF multimer analysis.

Submitted:

EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Correct

Reviewer:

Recommend VWD workup, including multimer analysis, possible vWF gene sequencing and RIPA with washed platelets and plasma.

Submitted:

EID Number: 1166

Scored: Correct

Reviewer:

Clinical and family history are important. RIPA with mixed donor platelet or plasma may be considered to differentiate the two possibilities.

Submitted:

EID Number: 1167


Reviewer:

Provide additional tests or additional comments.Control shows decreased aggregation for LD collagen, Arachidonic acid, U46619. Would consider vWD 2B or platelet-type vWD due to increase Ristocetin at 5 mg/nL, thrombocytopenia, and bleeding. Would consider further testing to rule out vWD. Generally don't test samples that are thrombocytopenic, but when comparing the patient to the control with an adjusted platelet count, it seems plausible.

Submitted:

EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169


Page 53 of 97

Scored: Correct

Reviewer:

Would recommend ordering F8, ristocetin cofactor activity, vwf antigen, and vwf multimer analysis. Would also recommend vWF 2B binding studies be performed.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

Recommend von Willebrand factor levels with multimer analysis and consider genetic testing for Type 2B or platelet-type von Willebrand disease.

Submitted:

EID Number: 1171

Scored: Not Scored

Reviewer:


EID Number: 1172

Scored: Not Scored

Reviewer:


EID Number: 1173

Scored: Correct

Reviewer:

Von Willebrand assay should be performed and, if required, multimeric analysis.

Submitted:

EID Number: 1176

Scored: Correct

Reviewer:

Measurement of von Willebrand activity, -antigen and multimers. Low dose ristocetin aggregation with mixing studies (donor platelets and patient plasma and mixing studies from patient platelets and donor plasma) to distinquise between IIB and platelet type VWF. Also gene mutation analysis can be considered. We only evaluated 3 out of 10 parameters according the given platelet count.

Submitted:

EID Number: 1178


Page 54 of 97

Scored: Correct

Reviewer:

Do VWF levels, consider genetic testing for type 2B VWD or platelet type VWD.

We would not normally report aggregation tracing results on agonists other than low dose ristocetin with this level of thrombocytopenia as we have not validated reference ranges for other agonists.

Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180


Reviewer:


EID Number: 1183

Scored: Correct

Reviewer:

Measure von Willebrand activity and antigen levels. Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

Addition of the patient's platelet poor plasma to normal platelets and molecular genetic testing could help in the differentiation between type IIb von Willebrand disease and platelet type von Willebrand disease.

Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Additional tests: APTT, VW Ag, ristocetin cofactor, FVIII, PFA-100. If consistent with VWD 2B or platelet-type VWD, mixing aggregation studies, multimers and genetic analyses.

Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201


Page 55 of 97


Reviewer:


EID Number: 1203

Scored: Correct

Reviewer:

Provide additional tests or additional comments. Von Willebrand factor levels (RCo, antigen, VIII, and multimers) Study the link of VWF to the platelets Consider Genetic testing fot type 2B or platelet-type Von Willebrand disease.

Submitted:

EID Number: 1204

Scored: Correct

Reviewer:

VWF antigen, ristocetin/collagen co-factors, multimers Submitted:

EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213

Scored: Correct

Reviewer:

Adjusted for platelet count, aggregation is normal for all agonists, except low concentration of ristocetin. AGGREGATION IS ABNORMALLY INCREASED WITH LOW CONC. OF RISTOCETIN. Additional tests are necessary: VWFag, VWFactivity, FVIII, VWF multimers, genetic testing for VWD (type 2B) or platelet-type VWD

Submitted:

EID Number: 1214

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222


Page 56 of 97

Scored: Correct

Reviewer:

No consensus reached before submission deadline; lab scientist interpretation of results. Would like to check VIII, vW:Ag, vW:RCo, vW:CB and multimers to exclude type 2B vWD.

Submitted:

EID Number: 1223

Scored: Correct

Reviewer:

additional tests for confirmation: VWF:Ag, VWF:RCo and VWF multimer analysis

therapy: VWF-containing FVIII concentrates; pure VWF-concentrates (only 1 French concentrate approved in Europe). DDAVP contraindicated in thrombocytopenic patients.

Submitted:

EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228


Reviewer:


EID Number: 1230

Scored: Correct

Reviewer:

Recommend testing for VWD: VWF antigen and activity assays, and multmer analysis. If supportive of diagnosis of VWD type 2B or platelet -type VWD, genetic analysis may be indicated.

Submitted:

EID Number: 1231

Scored: Not Scored

Reviewer:


EID Number: 1233


Page 57 of 97

Scored: Correct

Reviewer:

This case highlights some of the issues in samples with decreased Platelet Counts. We did not see a graph that represented a range of results based on platelet count for the low-dose Collagen. We were unsure of the significance a decreased Aggregation to U46619 would have in this patient as even patients with a normal platelet count can have a decreased aggregation to U46619 which could be conicidental or of undetermined significance on any single testing occasion. We did not see a graph for Epinephrine either but based on the fact that the patient's % aggregation was greater than the control and more importantly the fact that the normal reference % interval for patients with normal platelet counts is greater than 9%, we classified the result in this patient as normal.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

We would perform von Willebrand factor testing (including multimers). If it had not yet been done, we would send a sample for genetic testing for type 2B von Willebrand disease. ). We typically also test if adding the patient’s plasma to normal platelets causes increased aggregation with the lower concentration of ristocetin, as this is usually seen if the cause of the abnormality is type 2B von Willebrand disease.

Submitted:

EID Number: 1235

Scored: Correct

Reviewer:

VWF testing should be done to rule out Subtype 2B - consistent with low platelets and the presence of aggregation to low-dose ristocetin. High-molecular weight multimers would also be decreased in Subtype 2B- Would likely see a decreased ristocetin cofactor, VWF Ag and decreased/normal FVIII levels.

Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

von Willebrand factor levels. Consider genetic testing for type 2B or platelet-type von Willebrand disease.

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240


Page 58 of 97

Scored: Correct

Reviewer:

Would also do vWF antigen and activity, F8 assay, vwF mutimer analysis, vWF exon 28 sequence analysis, and 2B platlet vWD binding test.

Submitted:

EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244

Case: 2010-2 Case 9

Add comments on other abnormalities:Guide: None to report. There was minimal aggregation with epinephrine.


Reviewer:

Abnormal aggregation with epinephrine, epi response is mediated by adrenergic alpha2A receptor--some alpha2A receptor defects have been associated with bleeding disorders. Platelets are small

Submitted:

EID Number: 1161


Reviewer:

The platelet aggregation is decreased with epinepherine and normal with ADP, collagen, arachidonic acid and U46619. The ristocetin induced platelet aggregation shows a normal dose response. The pattern of platelet reactivity is non-specific and non-diagnostic. Rechecking the platelet aggregation is suggested, if indicated clinically.


Submitted:

EID Number: 1163

Scored: Not Scored

Reviewer:


EID Number: 1164


Page 59 of 97

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Not Scored

Reviewer:


EID Number: 1166

Scored: Not Optimal

Reviewer:

Need careful physical exam to exclude subtle albinism. Submitted:

EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168


Reviewer:


EID Number: 1169

Scored: Not Scored

Reviewer:


EID Number: 1170

Scored: Correct

Reviewer:

Normal platelet count with slightly decreased mean platelet volume. Maximal aggregation is decreased with a primary wave only for Epinephrine. Maximal aggregation is within normal limits for low and high concentration ADP, low and high concentration Collagen, Arachidonic Acid, U46619, and low and high dose Ristocetin.

Submitted:

EID Number: 1171


Page 60 of 97

Scored: Correct

Reviewer:

Isolated lack of response to epinephrine can be found in normal individuals and by itself is not diagnostic of a bleeding disorder

Submitted:

EID Number: 1172

Scored: Not Scored

Reviewer:


EID Number: 1173


Reviewer:

It seems that a second ristcetin-induced platelet aggregation to ristocetin 1.25 has been performed (but not reported in the summary table); this results in abnormal. This agonist shoul be retested.

Submitted:

EID Number: 1176

Scored: Not Scored

Reviewer:

There is a major difference between the two risto 1.25 measurements. One measurement is normal but the second measurement is abnormal. Therefore inconsistent results

Submitted:

EID Number: 1178

Scored: Not Scored

Reviewer:

slightly decreased HCT Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:

MPV low Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183

Scored: Correct

Reviewer:

Absent aggregation with epinephrine. Submitted:

EID Number: 1188


Page 61 of 97

Scored: Not Scored

Reviewer:

No other abnormalities. Submitted:

EID Number: 1196


Reviewer:

Low MPV. Mild lymphopenia. Submitted:

EID Number: 1197


Reviewer:


EID Number: 1201

Scored: Correct

Reviewer:

No primary or secondary aggregation with epinephrine. Submitted:

EID Number: 1203

Scored: Incorrect

Reviewer:

Add comments on other abnormalities. Collagen 1.25 : lag too long Ristocetin 1.25 : an error? aggregation to 84.1% and 11.2% to the other slide?

Submitted:

EID Number: 1204

Scored: Not Scored

Reviewer:


EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213


Reviewer:


EID Number: 1214


Page 62 of 97

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Not Scored

Reviewer:

Normal FBC Submitted:

EID Number: 1223

Scored: Not Scored

Reviewer:


EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Correct

Reviewer:

Add comments on other abnormalities.

Overall interpretation: Isolated decreased platelet response to epinephrine.This may represent a normal variant.Clinical significance uncertain.Suggest repeat study with lumi aggregation.

Submitted:

EID Number: 1230

Scored: Correct

Reviewer:

Decreased aggregation response to epinephrine only. Submitted:

EID Number: 1231


Page 63 of 97

Scored: Not Scored

Reviewer:


EID Number: 1233

Scored: Not Scored

Reviewer:


EID Number: 1234

Scored: Correct

Reviewer:

There is minimal aggregation with epinephrine. Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:

Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

Abnormalities seen with only one agonist (excluding collagen or ristocetin).

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240

Scored: Not Scored

Reviewer:


EID Number: 1242


Reviewer:


EID Number: 1244


Page 64 of 97

Give your overall case interpretation:Guide: The overall interpretation should be reduced aggregation with epinephrine, which

is nondiagnostic and could represent a false positive. Given the family history, it would be reasonable to raise the possibility of Quebec platelet disorder - even if this was not suggested, nondiagnostic results were accepted as correct.

Scored: Correct

Reviewer:

Isolated abnormal aggregation with Epi, not diagnostic for inherited bleeding disorder.

Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

The platelet aggregation is decreased with epinepherine and normal with ADP, collagen, arachidonic acid and U46619. The ristocetin induced platelet aggregation shows a normal dose response. The pattern of platelet reactivity is non-specific and non-diagnostic. Rechecking the platelet aggregation is suggested, if indicated clinically.


Submitted:

EID Number: 1163

Scored: Correct

Reviewer:

The epinephrine response is the only aggregation abnormality noted and this defect alone doers not represent a known platelet function abnormality. Platelet agregation is consistent with normal individuals.

Submitted:

EID Number: 1164

Scored: Correct

Reviewer:

Give your overall case interpretation. question false positive aggregation with epi, or possible none responder to epi repeat agg

Submitted:

EID Number: 1165

Scored: Correct

Reviewer:

Reduced response to epinephrine. Single agonist aggregation defects are unlikely to be clinically significant. J Thr Haemost 2009, 7: 676.

Submitted:

EID Number: 1166


Page 65 of 97


Reviewer:

Abnormal epinephrine induced platelet aggregation is noted. Even though such an abnormal platelet response can be observed in about 10% general population, in light of patient's personal and family history bleeding, the possibility of a platelet storage pool disorder needs to be excluded. ATP release from dense bodies or platelet whole mount EM may be considered.

Submitted:

EID Number: 1167


Reviewer:

Give your overall case interpretation.No evidence of a platelet abnormality.

Submitted:

EID Number: 1168

Scored: Correct

Reviewer:

Decreased platelet aggregation to epinephrine. Single agonist abnormalities may represent false positive result. Recommend repeat testing.

Submitted:

EID Number: 1169

Scored: Correct

Reviewer:

Patient shows normal aggregation with all agonists except epinephrine. This is suggestive of a normal variant.

Submitted:

EID Number: 1170


Reviewer:

Aggregation study indicates a single agonist abnormality that is nondiagnostic and could represent a false-positive.

Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Normal Submitted:

EID Number: 1172


Page 66 of 97

Scored: Correct

Reviewer:

Besides low aggregation response to epinephrine, the test results are normal. Abnormality to only one agonist could be a false positive result. We suggest repeating platelet aggregometry and supplement with lumiaggregometry for platelet secretion and/or electron microscopy for platelet granule deficiency. Lacking of platelet alpha2-adrenergic recptor could also be considered.

Submitted:

EID Number: 1173

Scored: Not Optimal

Should also suggest nondiagnostic or false positive aggregation as possible diagnosis.

Reviewer:

Platelet aggregation tracings characterized by an isolated impaired epinephrine-induced platelet aggregation. The differential diagnostic includes a secretion defect but Gaucher disease should be strongly considered, even if there is no thrombocytopenia (Gillis S et al, Am J Hematol 1999;61:103).

Submitted:

EID Number: 1176


Reviewer:

According to the guidelines 1 abnormality should be considered as non diagnostic and could represent a false positive. Although a decreased platelet aggregation with epinephrine is described in Quebec Platelet Disorder.

Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Response to epinephrine very reduced at all concentrations. Abnormalities only seen with one agonist (epinephrine).

Results may indicate possible Quebec platelet disorder. However abnormal aggregation with a single agonist is non diagnostic and could represent a false positive result.

Submitted:

EID Number: 1179


Reviewer:

Medication? Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183


Page 67 of 97


Reviewer:

Abnormality of single agonist could be a non-diagnostic finding. This is also a physiologic finding in a part of the normal population. No aggregation with epinephrine could also be compatible with Quebec platelet disorder.

Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

The only abnormality is the lack of response to epinephrine, which could be a normal variant or could be due to too long storage of blood sample.

Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Normal platelet response to ADP, collagen, arachidonic acid, U46619 and ristocetin. Platelet aggregation slightly reduced in response to epinephrin. This might be an inherited or an acquired defect. It might be secondary to some medications. Not all subjects with isolated reduced platelet response to epinephrin have a bleeding history. It might be useful to be better informed regarding the family history of bleeding. For instance, mothers from boys with Wiskott Aldrich syndrome might have a defective platelet reponse to epinephrin. In addition, it has been reported that defective response to epinephrin might be due to reduced platelet alpha2 adrenergic receptors. This defect might also be part of a Quebec platelet syndrome.

Submitted:

EID Number: 1197

Scored: Correct

Reviewer:

No abnormalities of platelet function seen. Submitted:

EID Number: 1201


Reviewer:

Differential diagnosis may include: * Quebec platelet syndrome. * artefact from a poor collection - epinephrine is the most eratic and unreliable of all the agonists and these results may simply reflect a traumatic collection.

Submitted:

EID Number: 1203


Page 68 of 97

Scored: Incorrect

Reviewer:

Give your overall case interpretation. A platelet function disorder but repeat aggreagtion testing is need

Submitted:

EID Number: 1204

Scored: Correct

Reviewer:

Patient with normal platelet count and volume, with a family history of bleeding, the main defect is a total absence of platelet aggregation to epinephrine that could suggest a defect of alpha2 receptor, we observe also a tendency for longer latency to collagen, a moderate secondary wave to the low dose of ADP: a search for platelet alpha granule defect is suggested, mainly to u-PA first, plasmin and FV second, other granule proteins could also be characterized (FI, vWF, thrombospondin...) - this case is strongly suggestive of a Quebec platelet disorder.

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

It is only one single agonist that is abnormal. Maybe this is a false result. Do the test again on new samples. Do ATP release and E.M. If this does not show anything you might take samples and test for bleeding parameters. You can have abnormal aggregation on ephinidrine and still have normal platelet function.

Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

Not diagnostic, repeat aggregation Submitted:

EID Number: 1214

Scored: Correct

Reviewer:

Probably false positive result Possible storage pool disease. Consider 2nd aggregation testing to confirm. Complete with ATP release assays (mepacrin testing or lumiaggregometry) and if possible electron microscopy for dense granule aspect.

Submitted:

EID Number: 1218


Reviewer:

One agonist giving abnormal results is non diagnostic. ? false positive. Submitted:

EID Number: 1222


Page 69 of 97


Reviewer:

?release defect. Note positive family history Submitted:

EID Number: 1223

Scored: Correct

Reviewer:

The only abnormality is a consistent missing or severely decreased (maximal 5% which may be due to dilution by the agonist)epinephrine induced platelet aggregation. A completely absent aggregation has been decribed in patients with a very rare deficiency of the alpha-2- adrenergic receptor. On the other hand 16% of the japanese poulation showed a markedly reduced response to epinephrine without a bleeding tendency. In these patient the alpha-2-adrenoceptors were diminished (tested with 3H-yohimbine). Both setting may be familiar. There is no information given about the severity of bleedings in this family. The hematocrit is only slightly decreased which speaks againt a relevant bleeding diatheses. Im many patients with myeloproliferative diseases epinephrine induced aggregation is absent. But the blood count speaks against this differential diagnosis.

Submitted:

EID Number: 1225


Reviewer:

Give your overall case interpretation.Non-diagnostic findings. The whole blood platelet count was 182,000 and the platelet rich plasma count was 250,000. In addition, the mean platelet volume is slightly decreased 7.3 fL. Using provided reference intervals and tracings, there is reduced aggregation with epinephrine (6um). There is essentially normal aggregation to all other agonists including ADP (2.5 um, 5.0 um), collagen (1.25 ug/ml, 5 ug/ml), arachidonic acid (1.6 mM), the thromboxane analogue U46619 (1um), and ristocetin (0.5 mg/ml, 1.25 mg/ml). The reduced aggregation with the epinephrine without other abnormalities is of uncertain clinical significance and may represent a non-diagnostic finding; however, the finding of delayed and reduced response to epinephrine is seen in 10% of the normal population. Repeat testing is recommended.

Submitted:

EID Number: 1228

Scored: Correct

Overall interpretation is in the Other Abnormality category. But, the interpretation is correct, therefore, credit for correct interpretation was given.

Reviewer:


EID Number: 1230


Page 70 of 97

Scored: Correct

Reviewer:

Aggregation responses indicate a single agonist abnormality which is non-diagnostic. Recommend repeat aggregation studies.

Submitted:

EID Number: 1231

Scored: Correct

Reviewer:

Single agonist abnormality with epinephrin. Nondiagnostic. Repeat aggregation testing with ATP release (lumi-aggregation) for dense granule deficiency or electron microscopy testing.

Submitted:

EID Number: 1233

Scored: Correct

Reviewer:

Overall, Platelet Aggregation Appears Normal. However, based on the patient's positive family history, we recommend repeat testing to include secretion studies, Alpha2 Antiplasmin, Factor Assays including Factor XIII, and Thrombin Time and Reptilase Time to rule out dysfibrinogenia or hypofibrinogenemia. The presence of decreased Aggregation to a sigle agonist such as Epinephrine may or may not be significant as some normal patients do not respond well to Epinephrine. It would also be appropriate based on the patient's family history to rule out PAI-1 deficiency, Quebec Platelet Disorder, and vasculature disorders such as Ehlers-Danlos, Hereditary Hemorrhagic Telangiectasia, Marfan Syndrome, Pseudoxanthoma Elasticum, and Osteogenesis Imperfecta.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

The aggregation findings are nondiagnostic and shows minimal if any aggregation with epinephrine which could be a false positive or reflect a defect in platelet function as absent aggregation with epinephrine is typical for Quebec platelet disorder. If Quebec platelet disorder is suspected, genetic testing should be done to determine if the patient has the PLAU gene duplication mutation that is diagnostic of Quebec platelet disorder.

Submitted:

EID Number: 1235

Scored: Not Optimal

Reviewer:

Absent aggregation in response to epinephrine may be compatible with a chronic myeloproliferative disorder. Clinical and hematological correlation is essential.

Submitted:

EID Number: 1236


Page 71 of 97

Scored: Correct

Reviewer:

Aggregation responses indicate a single agonist abnormality which is nondiagnostic and could represent a false positive.

Submitted:

EID Number: 1239

Scored: Correct

Reviewer:

Probable normal variant. Submitted:

EID Number: 1240

Scored: Correct

Reviewer:

Only abnormal agonist is epinephrine platelet aggregation. This is a non-specific finding and is also present in many normals.

Submitted:

EID Number: 1242

Scored: Correct

Reviewer:

Single-agonist abnormality is not diagnostic for a platelet defect. Likely variation of normal, minimal drug effect, or technical artifact.

Submitted:

EID Number: 1244

Provide additional tests or additional comments:Guide: It would be reasonable to suggest additional tests such as screening for dense

granule deficiency, a release defect and for Quebec platelet disorder by genetic testing. In this case, dense granules and dense granule release was normal. The patient was verified to have the PLAU (uPA gene) duplication mutation of Quebec platelet disorder.

Scored: Incorrect

Reviewer:

Recommend checking vWF AG, PT, aPTT Submitted:

EID Number: 1161

Scored: Not Scored

Reviewer:


EID Number: 1163

Scored: Not Scored

Reviewer:


EID Number: 1164


Page 72 of 97

Scored: Not Scored

Reviewer:


EID Number: 1165


Reviewer:


EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Correct

Reviewer:

Provide additional tests or additional comments.No evidence of a platelet abnormality. Decreased percent aggregation seen with epinephrine might be considered as a potential false-positive or nondiagnostic finding since it is the only abnormal finding.

Submitted:

EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Not Optimal

Reviewer:

At our institution we would test this patient at a higher dose of epinephrine.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

Follow-up investigations to consider include repeat platelet aggregation testing, platelet ATP release studies, and electron microscopy.

Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Clinical correlation, further testing as indicated. Submitted:

EID Number: 1172


Page 73 of 97

Scored: Not Scored

Reviewer:


EID Number: 1173

Scored: Not Scored

Reviewer:


EID Number: 1176

Scored: Not Optimal

Reviewer:

Repeat measurement of ristocetin 1.25 and epinefrine in a new sample. Also measurements of von Willebrand factor activity should be performed.

Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Consider repeat aggregation testing and platelet nucleotide measurement.

Other bleeding diathesis such as coagulation factor deficiecies or VWD should be considered.

Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183

Scored: Not Optimal

Also consider testing for Quebec platelet disorder, as you mentioned in your interpretation.

Reviewer:

Repeat aggregation studies on another occasion. Submitted:

EID Number: 1188


Page 74 of 97

Scored: Not Scored

Reviewer:

No additional comments. Submitted:

EID Number: 1196

Scored: Not Scored

Reviewer:

I would like to have more informations regarding the family history of bleeding and the list of medications.

Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201

Scored: Not Scored

Reviewer:


EID Number: 1203


Reviewer:

Provide additional tests or additional comments. repeat aggregation testing

Submitted:

EID Number: 1204

Scored: Not Optimal

Should aldo mention evaluation for Quebec platelet disorder. Reviewer:

Platelet u-PA, FV levels, +others alpha granules contents if possible. Lymphopenia more low platelet count with a low mean platelet volume: a review of the granules by electron microscopy is also recommended for possible diagnosis of a Wiskott Aldrich syndrome.

Submitted:

EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213


Page 75 of 97

Scored: Correct

Reviewer:

Abnormality seen with one single agonist (epinephrine), is not diagnostic. Moreover, aggregation with epinephrine is variable in the normal population. Before additional testing (ATP release), repeat aggregation.

Submitted:

EID Number: 1214

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Correct

Reviewer:

Would like to measure platelet nucleotides Submitted:

EID Number: 1223


Reviewer:

It should be tried to measure the amount of the platelet alpha-2- adrenergic receptors on the platelet membrane. In the japanese population, epinephrine was still able to enhance ADP-induced platelet aggregation. Because this may give some evidence about the severity of the defect this test should be performed.

Submitted:

EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Not Scored

Reviewer:


EID Number: 1230


Page 76 of 97

Scored: Not Scored

Reviewer:


EID Number: 1231

Scored: Not Scored

Reviewer:


EID Number: 1233

Scored: Correct

Reviewer:

It is important to determine if the family bleeding history results from an autosomal dominant, recessive, or X-linked disorder and their diagnosis and cause of bleeding in order to asses the patient being evaluated against this information to determine whether it is consistent or inconsistent.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

We would normally screen for dense granule deficiency, a release defect and if clinically indicated, test for Quebec platelet disorder by genetic testing for the PLAU (uPA gene) duplication mutation of Quebec platelet disorder.

Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:


EID Number: 1236

Scored: Correct

Reviewer:

Repeat aggregation testing, platelet ATP release and /or electron microscopy for dense granule deficiency.

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240


Page 77 of 97

Scored: Not Optimal

The platelet aggregation may be a normal variant but there also may be dense granule deficiency or faulty release -- another consideration given the history, may be Quebec platelet disorder.

Reviewer:

Would to screening tests protime, aptt, possible other factor assays or vWD workup if warrented.

Submitted:

EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244

Case: 2010-2 Case 10

Add comments on other abnormalities:Guide: Aggregation is absent with all agonists except with 1.25 mg/mL ristocetin, which

shows a reduced response.

Scored: Correct

Reviewer:

Normal Platelet size and number, abnormal/absent response to all agonist.

Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

The platelet aggregation is nearly absent with all agonists including ADP, collagen, epinepherine, arachidonic acid and U46619.The ristocetin induced platelet aggregation is decreased. The findings can be seen with an intrinsic platelet dysfunction or non-aspirin drug effect. Glanzmann thrombasthenia cannot be excluded at this point. Rechecking the platelet aggregation study with platelet ATP (dense granule) release is suggested.


Submitted:

EID Number: 1163

Scored: Not Scored

Reviewer:


EID Number: 1164


Page 78 of 97

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Not Scored

Reviewer:


EID Number: 1166


Reviewer:


EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Not Scored

Reviewer:


EID Number: 1170

Scored: Correct

Reviewer:

Normal platelet count with mildly decreased mean platelet volume. Aggregation is present, but maximal aggregation is decreased with high concentration (1.25 mg/mL) Ristocetin. Platelet aggregation is absent with low and high concentration ADP, low and high concentration Collagen, Epinephrine, Arachidonic Acid, and U46619. Maximal aggregation is normal with low concentration (0.5 mg/mL) Ristocetin.

Submitted:

EID Number: 1171


Page 79 of 97

Scored: Not Scored

Reviewer:

None Submitted:

EID Number: 1172

Scored: Not Scored

Reviewer:


EID Number: 1173

Scored: Not Scored

Reviewer:


EID Number: 1176

Scored: Not Scored

Reviewer:


EID Number: 1178

Scored: Not Scored

Reviewer:

Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180

Scored: Not Optimal

Reviewer:

Add comments on other abnormalities. medication? repeat aggregation tests

Submitted:

EID Number: 1183

Scored: Correct

Reviewer:

Reduced MPV. Reduced aggregation with high dose ristocetin. Absent aggregation with all other agonists.

Submitted:

EID Number: 1188


Page 80 of 97

Scored: Not Scored

Reviewer:

No other abnormalities. Submitted:

EID Number: 1196

Scored: Not Scored

Reviewer:

Absence of anemia. Mild lymphopenia. Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201


Reviewer:


EID Number: 1203

Scored: Not Scored

Reviewer:


EID Number: 1204

Scored: Not Scored

Reviewer:


EID Number: 1209

Scored: Not Scored

Reviewer:


EID Number: 1213

Scored: Correct

Reviewer:

Aggregation with ristocetine is reduced, but present compared to other agonists (totally absent)

Submitted:

EID Number: 1214


Page 81 of 97


Reviewer:

No platelet aggregation for all agonist except for high level ristocetin with normal platelet count.

Submitted:

EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Correct

Reviewer:

Profound absence of a response to all agonists, except the weak response to high-dose ristocetin. Normal platelet count

Submitted:

EID Number: 1223

Scored: Not Scored

Reviewer:


EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Not Optimal

Should list differential diagnoses. Reviewer:

Add comments on other abnormalities. Overall interpretation: Absent platelet aggregation in response to all agonists, requiring GPIIb-IIIa. In addition, a markedly decreased GPIb mediated platelet agglutination is noted in response to high dose Ristocetin.Clinical history is required for interpretation.

Submitted:

EID Number: 1230

Scored: Correct

Reviewer:

Aggregation response absent to ADP, collagen, AA, U46619, and epinephrine. Decreased response to standard dose ristocetin.

Submitted:

EID Number: 1231


Page 82 of 97

Scored: Not Scored

Reviewer:


EID Number: 1233


Reviewer:


EID Number: 1234

Scored: Correct

Reviewer:

Aggregation is absent with all agonists except with 1.25 mg/mL ristocetin, which shows a reduced response.

Submitted:

EID Number: 1235


Reviewer:

Submitted:

EID Number: 1236

Scored: Correct

Reviewer:

Aggregation is present only with ristocetin. Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240

Scored: Not Scored

Reviewer:


EID Number: 1242

Scored: Not Scored

Reviewer:


EID Number: 1244


Page 83 of 97

Give your overall case interpretation:Guide: The findings of absent aggregation with all agonists suggest the diagnosis of

Glanzmann thrombasthenia, which can reflect inherited or acquired defects in the platelet fibrinogen receptor, alphaIIbbeta3. It would be reasonable to suggest additional investigations for an antibody inhibitor to this receptor, and to quantify receptor numbers. The case information provided suggests an acquired problem. It would also be reasonable to suggest that a drug-induced defect be excluded.

Scored: Correct

Reviewer:

Glanzmann's thrombosthenia Submitted:

EID Number: 1161

Scored: Correct

Reviewer:

The platelet aggregation is nearly absent with all agonists including ADP, collagen, epinepherine, arachidonic and U46619. The ristocetin induced platelet aggregation is decreased. The findings can be seen with an intrinsic platelet dysfunction or non-aspirin drug effect. Glanzmann thrombasthenia cannot be excluded at this point. Rechecking the platelet aggregation study with platelet ATP (dense granule) release is suggested.


Submitted:

EID Number: 1163


Reviewer:

The absent aggregation response to ADP, Epinephrine, Collagen, Arachidonic Acid and U46619 are classic findings of a GP IIb/IIa platelet receptor defect known as Glanzmans Thrombasthenia. The suboptimal response to 1.25 mg/ml of Ristocetin is not typical and warrants further evaluation of the VWF complex to be sure there is not a combined GT plus VWD disorder.

Submitted:

EID Number: 1164

Scored: Correct

Reviewer:

Give your overall case interpretation. Glanzmann thrombasthenia

Submitted:

EID Number: 1165

Scored: Correct

Reviewer:

No response to any agonist except ristocetin, reduced response to ristocetin. Suggests Glanzmann's thrombasthenia.

Submitted:

EID Number: 1166


Page 84 of 97

Scored: Correct

Reviewer:

Absent platelet aggregation response to AA, Col, Epi, U46619 and decreased response to 1.25mg/mL ristocetin.

There results are suggestive for possible Glanzmann thrombathenia (GT). Consider platelet GPIIbIIIa analysis by flow cytometric or molecular studies.

Submitted:

EID Number: 1167


Reviewer:

Give your overall case interpretation.The patient presents with new bruising and a history of heavy periods. Would consider an underlying vWD with a recent ingestion of thienopyridine-type drug.

Submitted:

EID Number: 1168


Reviewer:

Absent platelet aggregation with all agonists except ristocetin. May represent Glanzmann's thrombasthenia, however, with normal platelet and MPV, this is unlikely. Cannot exclude drug effect. Strongly recommend repeat testing.

Submitted:

EID Number: 1169

Scored: Correct

Reviewer:

Complete absence of aggregation to the ADP, collagen, epinephrine, AA, and thromboxane agonsits is suggestive of Glanzman's Thrombasthenia.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

These findings are consistent with possible congenital or acquired Glanzmann thrombasthenia.

Submitted:

EID Number: 1171

Scored: Correct

Reviewer:

Most consistent with Glanzmann's thrombasthenia although diminished response to Ristocetin (1.25 mg) is not consistent.

Submitted:

EID Number: 1172


Page 85 of 97

Scored: Correct

Reviewer:

absent response to all agonist besides ristocetin. Normal response in seen to ristocetin in low dosis, both decresed aggregation to higher dosis of ristocetin. This could be Glanzmann thrombastenia. Similar response may be due to GPIIb/IIIa receptor blocker ingestion. Drug information, and flowcytometry to further asses the GPIIb/IIIa receptor. Fibrinogen to exclude fibrinogen disorders

Submitted:

EID Number: 1173


Reviewer:

No aggregation to all agonists with impaired shape change. Glanzmann thrombastenia should be considered, although ristocetin aggregation test (1.25 mg/ml) is also abnormal. The differential diagnostic include severe hypo/dysfibrinogenemia. The reason for referal suggests an acquired disorder; and mixing studies (washed platelets resuspended in control plasma and vice-versa) should be performed to evidence a potential antibody directed to GPIIbIIIa and other platelet receptors. A clot retraction assay should be performed as well.

Submitted:

EID Number: 1176


Reviewer:

Possible Glanzman thrombasthemia. Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Aggregation is present only with ristocetin although the response to 1.25mg/mL is also reduced.

Possible Glanzmann's Thrombasthenia (inherited or acquired).

Submitted:

EID Number: 1179

Scored: Correct

Reviewer:

Glanzmann's trombobasthenia Submitted:

EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183


Page 86 of 97

Scored: Correct

Reviewer:

The results are compatible with Glanzmann's thrombasthenia. Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

The lack of response to all agonists but high dose ristocetin indicates inherited or acquired Glanzmann thrombasthenia.

Submitted:

EID Number: 1196

Scored: Correct

Reviewer:

Absent platelet aggregation in response to ADP, collagen, epinephrine, arachidonic acid, U46619. No agglutination at low concentration ristocetin. Reduced agglutination to high concentration ristocetin.

Differential diagnosis: Glanzmann Thrombasthenia (inherited, acquired), Afibrinogenemia.

Submitted:

EID Number: 1197

Scored: Correct

Reviewer:

Results consistent with Glanzman Submitted:

EID Number: 1201

Scored: Correct

Reviewer:

Results are consistent with Glanzmann's Thrombasthenia. Submitted:

EID Number: 1203

Scored: Correct

Reviewer:

Give your overall case interpretation. Aggregation is present only with ristocetin, possible Glanzmann thrombasthenia.

Submitted:

EID Number: 1204


Page 87 of 97

Scored: Correct

Reviewer:

Patient with normal platelet count and volume, no aggregation to common agonists, only an agglutination to ristocetin is observed: these results suggest a main defect of platelet IIbIIIa complexe such as a Glanzmann thrombasthenia, most probably of congenital origin, but an acquired form should not be excluded. An exploration by flow cytometry is suggested first in order to measure IIb, IIIa, and IIbIIIa complexe expressions on platelets, and second MAIPA.

Submitted:

EID Number: 1209

Scored: Correct

Reviewer:

This could be a accuired or congenital Glanzmann. Supplement with flow cytometri. Glycoprotein analysis to assess the platelet fibrinogen receptor αIIbβ3. Test for fibrinogen - afibrinogenemia. Autoantibodies against the receptor.

Submitted:

EID Number: 1213

Scored: Correct

Reviewer:

Possible Glanzmann thrombasthenia (acquired or inherited) Submitted:

EID Number: 1214

Scored: Correct

Reviewer:

Compatible with Glanzmann Thrombasthenia Need 2nd aggregation testing to confirm. Cytometry investigation: CD41, CD61a, CD42b, CD62P. Check for platelet antibodies (anti-GPIIbIIIa...). Molecular biology if confirmed by cytometry.

Submitted:

EID Number: 1218

Scored: Correct

Reviewer:

Possible Glanzmanns thrombastenia Submitted:

EID Number: 1222


Reviewer:

Glanzmann's Thrombasthenia Submitted:

EID Number: 1223


Page 88 of 97

Scored: Correct

Reviewer:

None of the agonists induced a normal aggregation pattern and only the high ristocetin concentration leads to any, but diminished aggregation. Even for Glanzmann´s thrombasthenia the aggregation defect is strikingly severe. I cannot see a shape change response with ADP, while with collagen it is clearly present. This pattern ist typical for thrombasthenia Glanzmann. The patient is not anemic. Thus the bleeding téndency seems not to be severe. The history speaks for both, inherited and acquired forms. Diagnostic tests for inherited morbus Glanzmann: Flow cytometry, molecular diagnosis Diagnostic tests for acquirded morbus Glanzmann: Flow cytometry, platelet anitbody tests (glycoprotein specific), mixing studies, immunofixation

Submitted:

EID Number: 1225


Reviewer:

Give your overall case interpretation.Aggregaton abnormalities suggestive of Glanzmann thrombasthenia. The whole blood platelet count was 197,000 and the platelet rich plasma count was 250,000. In addition, the mean platelet volume is slightly dereased 7.1 fL. Using established reference intervals and provided tracings, there is lack of aggregation with ADP (2.5 um, 5.0 um) collagen (5 ug/ml,) epinephrine (6um), arachidonic acid (1.6 mM), and the thromboxane analogue U46619 (1uM). There is decreased aggregation with ristocetin (1.25 mg/ml). There is essentially normal aggregation response to ristocetin (0.5 mg/ml). These aggregation findings are highly suggestive of a congenital platelet defect such as Glanzmann thrombasthenia. As a result, additional laboratory evaluation including analysis of platelet receptor glycoprotein GPIIb/IIIa expression by flow cytometry is recommended to confirm the above diagnosis.

Submitted:

EID Number: 1228


Reviewer:


EID Number: 1230

Scored: Not Optimal

Reviewer:

Poor response to all agonists suggests possibility of pre-analytical artifact. Recommend recollection, ensuring correct anticoagulant and handling.

Submitted:

EID Number: 1231


Page 89 of 97

Scored: Correct

Reviewer:

Possible acquired Glanzmann thrombasthenia. follow-up with gycoprotein analysis to assess the platelet fibrinogen receptor alphaIIb B 3.

Submitted:

EID Number: 1233


Reviewer:

Platelet Aggregation demonstrates decreased aggregation to Ristocetin with absence of aggregation to all other agonists tested. New bruising could indicate this is an acquired condition or it could indicate that a congenital condition has become more severe. We recommend repeat testing after patient has been off of any medications, herbals, and/or supplements for 10-14 days that may interfere with platelet function. Excluding pre-analytic variables, platelet aggregation pattern resembles a patient who might have Glanzmann Thrombasthenia and von Willebrand Disorder. As this would be extremely rare, ruling out medications including monoclonal antibody therapy as is used in some patients with cancer, monoclonal gammopathies, Autoimmune Disorders is of crucial importance. Antinuclear Antibodies (ANA), Direct and Indirect Platelet Antibody Testing, Protein Electrophoresis, von Willebrand Factor Activity, Antigen, and Multimers would be of benefit. Electron Microscopy and Platelet Glycoprotein Analysis would also be of use in resolving this case.

Submitted:

EID Number: 1234

Scored: Correct

Reviewer:

Aggregation is absent with all agonists except 1.25 mg/mL ristocetin, which shows reduced maximal aggregation. The findings suggest the diagnosis of Glanzmann thrombasthenia, which can be congenital or acquired, due to drugs or autoantibodies against the platelet fibrinogen receptor. Given the history of acquired bleeding problems, further testing should be considered, including glycoprotein analysis to determine if there is a deficiency of the platelet fibrinogen receptor, alphaIIbbeta3, and whether the patient has autoantibodies to this receptor. Clinical correlation is recommended, including a review of the patient’s current medications.

Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:


EID Number: 1236


Page 90 of 97

Scored: Correct

Reviewer:

Possible Glanzmann thrombasthenia (inherited or acquired). Submitted:

EID Number: 1239


Reviewer:

Glanzmann's Thrombasthenia Submitted:

EID Number: 1240


Reviewer:

Extremely abnormal platelet aggregation. Submitted:

EID Number: 1242

Scored: Correct

Reviewer:

Complete absence of aggregation with all agonists other than ristocetin is consistent with Glanzmann's thrombasthenia. Decreased ristocetin induced aggregation raises the possibility of concurrent VWD.

Repeat PLT AGG testing is recommended to verify this unusual combination of findings. Flow cytometry for GpIIb/IIIa is recommended for confirmation of Glanzmann's. FVIII, VWF:RCof and VWF:Ag are recommended for further VWD evaluation.

Submitted:

EID Number: 1244

Provide additional tests or additional comments:Guide: Tests for antibodies to alphaIIbbeta3, and flow cytometry (or other glycoprotein

assays) assays for the receptor would be reasonable to do. In this case, the plasma from the patient was found to inhibit control platelet aggregation, and she had detectable antibodies against alphaIIbbeta 3, with a receptor deficiency.


Reviewer:

Recommend fibrinogen level Submitted:

EID Number: 1161

Scored: Not Scored

Reviewer:


EID Number: 1163


Page 91 of 97

Scored: Not Optimal

Reviewer:

Platelet mapping for GP IIb/IIIa receptors should be done as well as evaluation of the VWF complex due the suboptimal Ristocetin response.

Submitted:

EID Number: 1164

Scored: Not Scored

Reviewer:


EID Number: 1165

Scored: Correct

Reviewer:

Suggest platelet flow cytometry and gene sequencing. Submitted:

EID Number: 1166

Scored: Not Scored

Reviewer:


EID Number: 1167

Scored: Not Scored

Reviewer:


EID Number: 1168

Scored: Not Scored

Reviewer:


EID Number: 1169

Scored: Correct

Reviewer:

Some patients with Glanzman's Thrombasthenia show decreased response to ristocetin. Would recommend platelet flow cytometry.

Submitted:

EID Number: 1170

Scored: Correct

Reviewer:

Follow-up investigations to consider include glycoprotein analysis to assess for glycoprotein IIb and IIIa and platelet aggregation mixing studies if an acquired disorder is suspected

Submitted:

EID Number: 1171


Page 92 of 97

Scored: Correct

Reviewer:

Flow cytometry to confirm. Submitted:

EID Number: 1172


Reviewer:


EID Number: 1173

Scored: Not Scored

Reviewer:


EID Number: 1176

Scored: Correct

Reviewer:

Glycoprotein analysis to assess the platelet fibrinogen receptor alfaIIbbeta3. Also measure fibrinogen levels and Willebrandfactor to exclude afibrinogenaemia and willebrand disease Remarkable ristocetin 1.25 respons is not mildly but more pronounced decreased, which is unusual in Glanzman patients.

Submitted:

EID Number: 1178

Scored: Correct

Reviewer:

Suggest flow cytometry of platelet glycoprotein Gp IIb/IIIa receptors. Submitted:

EID Number: 1179

Scored: Not Scored

Reviewer:


EID Number: 1180

Scored: Not Scored

Reviewer:


EID Number: 1183


Page 93 of 97


Reviewer:

Determine expression of glycoproteins on platelets (especially GPIIbIIIa)

Submitted:

EID Number: 1188

Scored: Correct

Reviewer:

It would be nice to know the age of the patient and the first onset of the symptoms. Flow cytometry for the detection of GPIIb, GpIIIa and their complex would be an additional test. The effect of patient's IgG on the aggregation of normal platelets would help differentiation between the inherited and acquired form.

Submitted:

EID Number: 1196


Reviewer:

Perform fibrinogen measurement. Provide the list of medications. Flow cytometry analysis (GPIIbIIIa).

Submitted:

EID Number: 1197

Scored: Not Scored

Reviewer:


EID Number: 1201

Scored: Not Scored

Reviewer:


EID Number: 1203

Scored: Correct

Reviewer:

Provide additional tests or additional comments. Glycoprotein analysis by flow cytometry to assess the platelet receptor GPIIbIIIa Von Willebrand Factor levels.

Submitted:

EID Number: 1204

Scored: Correct

Reviewer:

IIbIIIa glycoproteins status by flow cytometry Submitted:

EID Number: 1209


Page 94 of 97

Scored: Not Scored

Reviewer:


EID Number: 1213


Reviewer:

Additional testing for glycoprotein receptor IIbIIIa, presence and intensity (by flowcytometry CD 41/CD61).

Submitted:

EID Number: 1214

Scored: Not Scored

Reviewer:


EID Number: 1218

Scored: Not Scored

Reviewer:


EID Number: 1222

Scored: Correct

Reviewer:

Would like to check HLA type, and anti gpIIb-IIIa antibodies Submitted:

EID Number: 1223

Scored: Correct

Reviewer:

In case of an acquired form, an underlying disease should be investigated. An accidental mixing of blood or PRP with EDTA should be excluded.

Submitted:

EID Number: 1225

Scored: Not Scored

Reviewer:


EID Number: 1228

Scored: Not Scored

Reviewer:


EID Number: 1230


Page 95 of 97

Scored: Correct

Reviewer:

Although inherited or acquired thrombasthenia cannot be ruled out on the basis of this sample, the poor response to ristocetin makes this less likely.

Submitted:

EID Number: 1231

Scored: Not Scored

Reviewer:


EID Number: 1233

Scored: Correct

Reviewer:

It would be important to see if patient has been given or received ReoPro (Abciximab).

Submitted:

EID Number: 1234


Reviewer:

We would perform flow cytometry to assess for a deficiency of the platelet fibrinogen receptor, alphaIIbbeta3 and if an autoantibody was suspected, we would perform antigen capture assays to determine if the patient has autoantibodies to this receptor. It would also be interesting to determine if the patient’s plasma contains an inhibitor that induces similar function abnormalities after an incubation with control platelets.

Submitted:

EID Number: 1235

Scored: Not Scored

Reviewer:

Before reporting any agg. results on this patient I would verify that the instrument is working properly. The controls were always run in channel 1 and 2. I would want to run the controls in channel's 3 and 4 as well to confirm proper functioning of channels.

Submitted:

EID Number: 1236


Reviewer:

Glycoprotein analysis to assess the platelet fibrinogen receptor alphaIIbbeta3.

Submitted:

EID Number: 1239

Scored: Not Scored

Reviewer:


EID Number: 1240


Page 96 of 97

Scored: Correct

Reviewer:

Possible platelet antibody or some type of drug effect. Would like more patient history information, age-any meds or no meds patient is taking. Would repeat platelet aggregation studies at another date.

Submitted:

EID Number: 1242


Reviewer:


EID Number: 1244


Page 97 of 97

Documents

Collaboration Report for Exercise: Survey 2010-2 ... · PDF fileNumber of Participants: 84 Number of Cases: 5 Report Generated: Saturday, January 22, 2011 7:26 PM Collaboration Report