Notes- September 23 2013- Platelet Disorders

7/27/2019 Notes- September 23 2013- Platelet Disorders

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September 23, 2013- Platelet Disorders

1. Hemostasis depends on the interaction of vasculature, platelets, plasma coagulation factors,fibrinolytic system

a. Primary Hemostasis- problems with plateletsi. Mucosal/Cutaneous Bleeding

1. Easy bruising2. Epistatis3. Gingival bleeding4. Prolonged bleeding with tooth extraction5. Menorrhagia6. Purpura7. Petechiae

Qualitative Platelet Disorders- normal in number, non-functioning

8. Glandzmanns Thrombasthenia-a. Autosomal recessive geneb. Normal platelet countc. Normal adhesiveness and retention- no aggregation except with

ristocetin

d. Abnormal clot retraction- unique to this diseasee. + tourniquet testf. Increased bleeding timeg. Bleeding- severe, early onseth. Spontaneous/aggravated by traumai. Glycoprotein IIb IIIa missing from platelet membrane and decreased

thrombasthenin (causes abnormal clot retraction)

j. Treat with platelet concentrate9. Von Willebrands Disease-

a. Autosomal dominant gene on chromosome 12 (controls synthesis offactor VIII from megakaryocytes and endothelial cells)

b. Heterozygote- usually mild- begins in second decadec. Homozygote- moderately severe- begins early, severity decreases with

age

d. Decreased active VIII:C (need for intrinsic coag) and VIII:VWF (necessaryfor ristoceitin aggregation, and adhesion of platelets to subendothelium)

e. Treatment- cryoprecipitate (has both VIII:C and VIII:VWF, fibrinogen andXIII)- or DDAVP (deamino-8-d-arginine vasopressin- causes increased

synthesis but must have ability to synthesize VIII:VWF)

f. Platelet count normalg. Bleeding time increased- decreased VIII:VWF so cant adhere to collagenh. APTT increased- because theyre not activating VIII:C which is essential to

intrinsic coagulation


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i. Decreased platelet adhesionj. No aggregation with ristocetin (other agents its norma l)

10.Bernard-Soulier Syndromea. Autosomal recessive 1/1 million peopleb. Homozygous: moderate to severe bleedingc. Heterozygous: mild to moderate bleedingd. Thrombocytopenia (mild to moderate)e. Giant platelets size of lymphocytesf. Increased bleeding timeg. Decreased platelet adhesivenessh. Abnormal aggregation with ristocetin (other agents normal)i. Clot retraction normalj. Problem is that the platelets lack glycoprotein Ib on membrane- cant

bind to VIII:VWF to attach to collagen and cant utilize ristocetin, but can

attach to fibrin because doesnt require Ib

k. Treatment- platelet concentrate if bleeding11.May Hegglin Anomaly

a. Autosomal dominant geneb. Relatively rarec. Bizarre giant plateletsd. Basophilic inclusions in granulocytes- look sort of like Dohle bodies but

know they dont have infection

e. Thrombocytopeniaf. Normal number of megakaryocytes in bone marrow- something

happening to platelets once outside BM

g. Most patients clinically normal- have mild bleedingQUANTITAIVE ABNORMALITIES

ii. Thrombocytopenia-DECREASED AMOUNTS OF PLATLETSa. Deficient production in bone marrow of plateletsb. Excessive destructionc. Most common hemostatic problem come across with patientsd. Down to 20,000/uL can spontaneously hemorrhage so must do

preventative measures

2. Amegakaryocytic Thrombocytopenia-a. Congenital= rareb. Acquired=

i. long term nutritional deficiency


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ii. Aplastic anemiaiii. Chemotherapyiv. Ionizing radiation

3. Acute Idiopathic Thrombocytopenic Purpura (ITP)a. Antibody to plateletsb. Mostly in childrenc. History: respiratory infection, rubella, mumpsd. Sudden onsete. Two types:

i. Mucosal/Cutaneous Bleeding- milderii. Internal Bleeding- more serious

f. Usually benigng. Treatment= steroidsh. 10% progress to chronic

4. Chronic ITPa. Follows acute or long historyb. Insidious onsetc. Remissions/relapsesd. Treatment= steroid/splenectomy

5. Idiopathic Thrombocytopenic Purpura- (ITP)a. Acute or chronic

i. Strinking thrombocytopeniaii. Bleeding time increased

iii. Positive tourniquet testiv. APTT normalv. PT normal

6. Thrombotic Thrombocytopenic Purpura (TTP)a. Platelet thrombi throughout vasculature- white clots (platelet clumps)b. No activation of coagulation factorsc. Etiology: associated with viral disease, infections, pregnancy, drugs,

toxins, auto-immune

d. Regional tissue damage: CNS (most markedly effected)-strokes, kidneys-renal failure

e. Decreased ADAMTS13 vWF cleaving protease- without have largemolecules of vWF in blood will cause platelets to clump

i. Decreased levels associated with estrogen, certain medications,certain infections

f. Familial (inherit a defective enzyme) or acquired (developing an auto-abto the protease)


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g. Increased large molecules of vWF in blood, activate plateletsh. Thrombocytopenia, schistocytes- microangiopathic hemolytic anemiai. Increased bleeding timej. Treatment- fresh frozen plasma, plasma exchange (best option),

corticosteroids (didnt work very well however)

k. 90% mortality rate if not treated7. Hemolytic Uremic Syndrome- (HUS)

a. Mostly in childrenb. Platelet thrombi specific to renal vasculaturec. Thrombocytopenia- b/c have platelet clumpsd. Schistocytese. Reduced renal function- b/c thats where platelet clumps reside

Thrombocytosis and Thrombocythemia- INCREASED NUMBER OF PLATELETS

1. Platelet counts greater than 500,000/uL2. Severe bleeding or thrombosis3. If greater than 1 million cant predict if platelets will function correctly, will

either bleed or throw clots

4. Treatment= chemotherapya. Thrombocytosis-

i. Short-lived, often symptomlessii. Secondary to well defined clinical states:

1. Post splenectomy2. Major surgery- will increase 25-150% after surgery3. Acute hemorrhage4. Polycythemia vera (increase in RBC, WBC, platelets)5. CGL6. Underlying malignancy

b. Thrombocythemia-i. Primary problem (below)

ii. Increased megakaryocytes therefore increased plateletsiii. Platelets have qualitative defects also

Platelet Transfusions

1. Maintain at room temperature maximum of 72 hours with gentle agitation2. ABO Compatible, best compatible HLA type

a. Platelet Rich Plasma- (PRP)-i. Separate plasma from RBCs with light spin 2000 rpm for 3 minutes

ii. Yields ~250mL- of platelets in solutioniii. ~90% platelets in solution yieldediv. transfusion increases platelets about 10,000/uL in about an hour


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b. Platelet Concentrate-i. Take PRP

ii. Heavy spin (5000 rpm for 5 min)iii. Remove platelet poor plasma (supernatant) put in satellite bagiv. Left with platelet concentrate -Yields ~20-50 mL plasma with platelets

c. Plateletpharesis-i. Use heparin

ii. Blood returned to patientiii. Use within 24 hours

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Notes- September 23 2013- Platelet Disorders