209-Hematology Review _ Case Studies

8/3/2019 209-Hematology Review _ Case Studies

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Hematology Review 2009

Kim Auriemma, MSN, APRN-BC, AOCN

Nurse Practitioner

Georgia Cancer Specialists


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Complete Blood Count

CBC or Hemogram: one of the most commonly orderedlab tests. It assesses:

White blood cells (WBC)

Red blood cells (RBC)

Platelets (PLT)

WBC Differential


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The Complete Blood Cell Count

TABLE 1The Complete Blood Cell CountParameter Normal adult range Indications

HemoglobinMale: 14.0 17.4 mg/dLFemale: 12.0 16.0 mg/dL

Low: AnemiaHigh: Polycythemia

HematocritMale: 42% 52%

Female: 35%

48%

Low: Anemia

High: Polycythemia

RBC countMale: 4.5 5.5 x 106/LFemale: 4.0 5.0 x 106/L

Low: AnemiaHigh: Polycythemia

WBC count 5.0 10.0 x 103/LLow: LeukopeniaHigh: Leukocytosis

Platelet count 140 400 x 103/LLow: ThrombocytopeniaHigh: Thrombocytosis

Reticulocyte count0.5% 1.5%25 85 x 103/L

Low in anemia: Low marrow outputHigh: RBC loss

RBC, red blood cell; WBC, white blood cell. Data extracted from: Fischbach FT.A Manual of Laboratory and Diagnostic Tests. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:47.


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Blood cells


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Blood

Blood makes up about 7% of a bodys weight

An average adult has 14-18 pints of blood

Four main blood types: A, O, B, AB

Rh positive or negative

Universal Donor: O-

Universal Recipient: AB +


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Red Blood Cells

Red blood cells transport oxygen from the lungs to theorgans and peripheral tissues, then return to thelungs carrying carbon dioxide to be exhaled. RBCsare pliable and designed to traverse the small

capillary beds. RBCs contain the oxygen carryingprotein Hemoglobin (HGB). Hematocrit measures the% of RBC mass in 100ml blood.

Normal RBC life span = 120 days


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Red Blood Cells

Reticulocytes: immature RBCs

Number helps to determine causes of anemia. Normalretic count is 1.0-2.0%

Low retic 2% = indicates anemia caused by RBC

loss


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Normal RBC


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Red Cell Morphology

TABLE 2Red Cell Morphology

Possible findings Significance

Burr cells Uremia, low potassium, artifact, stomach cancer, peptic ulcer disease

Spur cells Liver disease, abetalipoproteinemia

Stomatocyte Hereditary condition, alcoholic liver disease

Spherocyte Hereditary condition, immune hemolytic anemia, water dilution, posttransfusion

Schistocyte, helmetThrombotic thrombocytopenic purpura, disseminated intravascular coagulation, vasculitis,myelophthisic glomerulonephritis, prosthetic heart valve

Elliptocyte, ovalocyte Hereditary, iron deficiency, megaloblastic anemias

Teardrop cells Iron deficiency, myelophthisic, megaloblastic anemias

Sickle cells Sickle cell disease

Target cells

Postsplenectomy thalassemia, hemoglobinopathy

Parasites Malaria, babesiosis

Basophilic stippling Thalassemia, lead toxicity

Bite cells G6PD deficiency

G6PD, glucose-6-phosphate dehydrogenase.Data extracted from: Fischbach FT.A Manual of Laboratory and Diagnostic Tests. Philadelphia, Pa: Lippincott Williams & Wilkins; 2003:84-86.


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Anemia of Decreased Marrow

ProductionWhen the marrow slows production due to insufficient

erythropoietin (EPO), lack of other vital elements inRBC production including iron, folate, B12, or attack

on the bone marrow by a virus, toxin or cancer.

The mean corpuscular volume (MCV) is the most usefulparameter to evaluate a low retic count anemia


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Anemia

Microcytic anemias

have low MCV (< 80)

most common type of anemia encountered in

primary care

Differential diagnosis: Iron deficiency anemia,thalassemia, anemia of chronicdisease/inflammation, sideroblastic anemia


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Microcytic Anemia

TABLE 3Laboratory Findings in Microcytic Anemias

Red cell

morphology

Serum iron

level

Total iron-binding

capacityPercent saturation Serum ferritin level

Iron deficiencyanemia

Microcytic,hypochromic

Decreased Increased < 16% Decreased

Anemia ofchronic

inflammation

Normocytic,microcytic

Decreased Decreased 10% 20% Increased

Sideroblastic

anemia

Microcytic,hypochromic

Increased Normal 50% 100% Increased

ThalassemiaMicrocytic, targetcells

Normal orincreased

Normal 30% 100% Normal or increased

Data extracted from: Massey. Med Clin North Am. 19929; Adamson JW. Iron deficiency and other hypoproliferative anemias. In: Kasper DL, Braunwald E, Fauci A, et al,eds. Harrisons Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Professional; 2004:660-666.


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Iron Deficiency Anemia

Definition: anemia occurs when body iron stores aredepleted by prolonged bleeding withoutreplacement. Other causes can include inadequateiron stores due to poor dietary intake and or poorabsorption or utilization

Incidence: common, seen in up to 20% of women, 50%

of pregnant women and 3% of menLab findings: anemia, low retic, low MCV and low MCHC

low ferritin, low % iron saturation, elevated TIBC,possible thrombocytosis

Signs and Symptoms: fatigue, pallor, pica, blood lossExam findings: pallor, pale conjunctiva, koilonychia,

angular stomatitis, glossitis. More severe anemiamay see tachycardia, tachypnea


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Iron deficiency anemia

Management:

first must identify etiology

GI bleeding

Menorrhagia Pregnancy

Poor intake

Lack of absorption


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Repletion of iron Oral Iron

Ferrous Sulfate 320mg bid-tid (most common, GIside effects)

Ferrous Gluconate 325 mg bid-tid(bettertolerated)

Niferex 150 mg qd Repliva 1 po qd (taken 21 of 28 days)

Vitamin C aids absorption of iron. Milk/calciumproducts hamper absorption

* Will need 3-6 months of oral iron to repletestores. If no response, or unable to tolerate orabsorb, refer to hematology for intravenous irontherapy (Infed, Ferrlicit, Venofur)


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hypochromic


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Hemolytic anemia

Hemolytic anemia occurs when the bone marrow isunable to make up for premature destruction of redblood cells by increasing their production. Hemolysiscan be triggered by infection, medications, auto-immune responses, inherited disorders(hemoglobinopathies)

Treatment depends on cause

Folate (folic acid) is used in all hemolytic anemias tohelp stabilize the RBC membrane and decreasedestruction


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Hemolytic Anemia

Auto-immune hemolytic anemia - Cause is oftenunknown

Signs and Symptoms: usually very acute and seriouswith sudden rapid drop in Hgb leading to fatigue,weakness, SOB. Patient is usually hospitalized

Exam findings: pallor, tachycardia, tachypnea,

jaundice, splenomegalyLabs: low Hgb/Hct, + direct Coombs, elevated bilirubin,

elevated LDH, low serum haptoglobin, elevated reticcount

Diff Dx: anemia secondary to blood loss,hemoglobinopathy


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Auto-Immune Hemolytic anemia

Treatment:Steroids, usually Prednisone at high dose (1mg/kg) to

help suppress the immune system. Gradual taperover weeks to months. Splenectomy is oftenconsidered followed by other types of immune

modulation if hemolysis is not improving. Bloodtransfusions can be used to off set severe anemiahowever there is increased risk for antibodydevelopment and reactions

This can be a chronic relapsing disease


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Hemoglobinopathies

Hemoglobinopathy: defined as a genetic defect thatresults in an abnormal structure of one or both of theglobin chains of the hemoglobin molecule

These disorders are hereditary and some such as sickle

cell trait and G6PD deficiency once offered anevolutionary advantage over time by providingimmunity to malaria

There are hundreds of types of hemoglobinopathies andmost are not clinically apparent


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Thalassemia Syndromes

Definition: inherited genetic disorders that causedecreased production of normal Hgb A.

Three types:

Beta Thalassemia major

Beta Thalassemia minor

Alpha ThalassemiaIncidence: In b thalassemia can be as high as 1 in 10 in

certain Mediterranean populations. In the US approx2 million people have some form of thalassemia traitor disease. Thalassemia is the most common genetic

disorder worldwide.


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Thalassemia Major

Most severe form. Also known as Cooleys anemia.Lab findings: Hgb electropheresis would show increase

in Hgb A2 and F with no normal Hgb ASigns and symptoms usually present in infants prior to

6 months of age including irritability, poor feeding,pallor

Physical findings: severe anemia, jaundice andhepatosplenomegaly, as well as growth retardation

Management includes life long chronic bloodtransfusions to replace abnormal Hgb with normalHgb. Chronic transfusions lead to iron overload whichmust be removed from the body with chelation

therapy (Desferol, Exjade) to avoid liver and heartfailure.


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Thalassemia Minor

Definition: less severe form of thalassemia whereby ptdoes produce some normal Hgb A

Labs: Hgb electropheresis shows decreased Hgb A andincreased Hgb A2 and F. Peripheral smear oftenshows target cells and basophilic stippling. Iron

studies are normalSigns and Symptoms are usually absent

Physical exam: normal or may have splenomegaly

Management: no specific therapy is required. Ironsupplements are not recommended unless ironstudies confirm iron deficiency with low ferritin


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Thalassemia

Definition: Genetic disorder of the A-globin chain. 4 lociof alpha globin and severity of disease depends onnumber of alpha globin chains genetically affected.

Incidence: Most common thalassemia with highestincidence in those of Southeast Asian, Mediterranean

and African decent.Labs: Microcytic RBC, with or without anemia. May haveelevated RBC count. Hgb electropheresis may benormal

Signs and Symptoms: none to mild symptoms ofanemia including pallor, fatigue to most severe form

causing fetus with hydrops fetalis and stillbirth.


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Thalassemia

Physical findings: none to more severe form of disordercausing splenomegaly to most severe form in whichall 4 alpha globin chains are affected. This is notcompatible with life

Management: most often there is no specific therapy.Genetic counseling recommended for families withhistory of thalassemias prior to pregnancy


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RBC Target Cells


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Target Cells


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Sickle cell anemia

Sickle cell anemia genetic disorder whereby red bloodcells in a stressful environment become abnormallyshaped like a sickle and cause hemolysis, anemiaand veno-occlusion. This leads to end-organ damagein the spleen, kidneys and liver.

Incidence: More than 70,000 Americans have sickle cell

disease. About 2 million Americans, 1 in 12 AfricanAmericans - have sickle cell traitEthnic groups with sickle cell anemia are usually African

descendants although those of Mediterraneandecent can also be affected.

Labs: CBC shows anemia, adult sickle cell anemia

patients usually have elevated WBC and plateletcount, elevated retic, elevated bilirubin, Hgbelectropheresis shows abnormal Hgb SS (moresevere disease) or Hgb SC or S-beta thalassemia


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Sickle cell anemia

Signs and symptoms: anemia occurs as abnormalRBC have a shortened life span of only about 15 dayscompared to the usual 120 days. The RBCs are alsofragile and lack flexibility leading to veno-occlusionand resulting pain crises, as well as risk for CVA andpriapism. Sickle cell veno-occlusive crises can betriggered by infection, dehydration, temperaturechanges and other stressors to the body.

Exam findings: scleral icteris, jaundice, splenomegalyin children (adults usually have either required

splenectomy in childhood or have infarcted the spleencausing loss of spleneic function by adult age).


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Sickle cell disease

Normal adult spleen is11cm in craniocaudallength.

This picture illustrates a

spleen that has infarcteddue to sickle cell diseaseand shrunk to 4.5cm inlength. This spleen wouldnot be functional.

Auto-splenectomy


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Sickled red blood cells


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Pathophysiology of sickle cell disease


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Parasite


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Sickle cell anemia

Diff Dx: other hemoglobinopathies

Treatment: no cure for sickle cell disease other thanallogeneic bone marrow transplant which carriessignificant risk for morbidity and mortality.

Management of this chronic disease includesavoidance of known triggers of veno-occlusive crisis,daily folic acid. Analgesics for painful crisis patientsare often hospitalized for pain crisis for IV narcoticanalgesics, hydration with D5W (need free water),

anti-inflammatories.


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Sickle cell disease

Hydrea is sometimes used to treat sickle cell diseaseand decrease frequency of pain crises andhospitalizations in adult sickle cell patients. Thoughtto work by increasing fetal hgb and decreasingtendency for RBC to sickle.

Vaccination with pneumococcal vaccine q5 years inadults is recommended since spleneic function isimpaired.

Blood transfusions with exchange transfusion is used inserious cases of acute chest syndrome or priapism

and are also used in children with sickle cell diseaseas prophylaxis to reduce risk of CVA.


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G6PD deficiency

Glucose-6-phosphate dehydrogenase deficiency ahereditary enzyme deficiency that leads to hemolysiswhen certain drugs are ingested that induce oxidantstress on RBCs.

Incidence - Most common human enzyme deficiencyaffecting 400 million people worldwide. X-linkedrecessive disorder with more males affected thanfemales. Occurs more often in blacks

Signs and symptoms: none unless hemolysis occurscausing anemia with fatigue, SOB, dark urine


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G6PD deficiency

Exam findings: none specific unless having activehemolysis

Drugs to be avoided with G6PD def:

Elitec (rasburicase), Methylene blue, Pyridium,Sulfacetamide, Sulfasalazine, Isobutyl nitrite,Nitrofuratoin, Primaquine, Sulfamethoxazole(Bactrim), Toluidine blue

*G6PD deficient patient are also allergic to fava beans


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G6PD deficiency

Labs: show evidence of hemolysisElevated bilirubin levels

Elevated serum LDH

Low serum haptoglobin

Hemoglobinuria

Elevated retic count

Low RBC count and hemoglobin

Heinz bodies present on examination of the peripheralblood smear using special stains

Methylene blue test

Methemoglobin reduction test used for diagnosis


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Anemia of Chronic Disease

Definition: anemia caused by inflammatory processesoccurring due to long-standing infection, neoplasticdisease and other inflammatory disorders includingrheumatoid arthritis, SLE. These processes block irontransportation from storage sites to the bone marrowfactory. Can also be associated with renal failure anddecreased erythropoietin production

Incidence: second most common anemia behind irondeficiency anemia

Lab findings: CBC showing anemia, low or normal MCV,

normal iron studies or low % iron saturation withnormal to low TIBC, elevated CRP or sed rate,elevated BUN/creatinine


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Anemia of Chronic Disease

Signs and Symptoms: fatigue, pallor or asymptomatic ifpatient has long standing history of RA, SLE, otherinflammatory disease, chronic renal failure

Physical findings: none specific

Management: Treat underlying disease

If unable to determine causative factor, refer to

hematology for bone marrow biopsy


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Sideroblastic Anemia

Definition: anemia characterized by ringed-sideroblasts.Caused by an enzyme disorder in which the body hasadequate iron but is unable to incorporate it intohemoglobin. Iron enters the developing red blood cellwhere iron accumulates in the mitochondria giving aringed appearance to the nucleus (ie: ringedsideroblast). Can be caused by genetic defect, toxinexposure or idiopathic.

Lab findings: microcytic anemia, basophilic stipplingon peripheral smear, usually normal iron studies.Bone marrow biopsy needed if this anemia issuspected based on presentation and peripheralsmear. Check blood ETOH, lead levels


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Sideroblastic anemia


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Sideroblastic anemia

Signs and Symptoms: depend on cause. May havehistory of ETOH abuse, have altered mental status,abdominal pain or neuropathy, history of treatmentfor TB, fatigue, pallor, family history

Physical findings: pallor, abnormal neuro exam withdecreased sensory perception, tender abdomen,evidence of ETOH, enlarged spleen or liver, cardiacarrhythmia

Management: refer to hematology for management.Sometimes treated as a Myelodysplastic syndromewith epo growth factors. May progress to aplastic

anemia requiring bone marrow transplant


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Macrocytic Anemias

Definition: macrocytosis or megaloblastic anemia ischaracterized by anemia with elevated MCV

Incidence: fairly common, seen more in the elderly andthose with history of GI pathology or surgeries

Differential Dx:B12 deficiency, folate deficiency, historyof GI disorder or surgery, chemotherapy, chronicalcoholism, hypothyroidism, liver disease (hepatitis),splenectomy (loss of filtration through spleen leadsto larger RBCs)


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Macrocytic RBC


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B12 deficiency anemia

Definition: anemia caused by inadequate B12. Can bedue to inadequate dietary intake in vegans or morecommonly as a result of loss of intrinsic factor whichleads to inability to absorb B12 (pernicious anemia)

Lab findings: anemia on CBC, MCV elevated usually >95. Normal or low serum B12 with elevatedmethylmalonic acid, normal or elevatedhomocysteine, anti-intrinsic factor antibodies


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B12 deficiency

Signs and Symptoms: fatigue, pallor, neuropathy,dizziness, hair loss, memory loss/dementia inelderly, history including chronic gastritis, bariatricsurgery, auto-immune disorder.

Physical findings: pallor, tachycardia, abnormal sensory

neuro exam, tachypnea

Management:Cyanocobalamin 1000mcg IM weekly x 4 then monthly

usually for life

B12 is poorly absorbed by the oral route


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Folate Deficiency anemia

Definition: macrocytic anemia caused by lack of folicacid. Common in alcoholics

Lab findings: CBC with anemia, macrocytic with MCV >95. Elevated homocysteine with low or normal serumfolate

Signs and Symptoms: fatigue, pallor, unusual diet (nouncooked fruits and vegetables), alcoholism

Physical exam: none specific

Management: Folic Acid 1mg po qd

Repeat homocysteine in 3 months and if remainselevated, may increase folic acid to 2mg daily.Treatment usually long term.


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Increased marrow production

Elevated blood cells due toover production in themarrow. Can seeoverproduction of RBC,WBC, Platelets


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Erythrocytosis

Definition: Over production of red blood cells in thebone marrow.

Possible causes are:

Polycythemia Vera (PV) myeloproliferative disorderwhich leads to over production of red blood cells

(possibly also in WBC and Platelets) in the bonemarrow.

Incidence in the US: PV is relatively rare, occurring in0.6-1.6 persons per million. Occurs more in men.

Work up should be triggered for Hgb > 15 in womenand > 17 in men


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Polycythemia


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Polycythemia Vera

Lab tests would include RBC mass, serumerythropoietin levels (usually decreased), ABG, bonemarrow biopsy usually performed, JAK 2 mutationanalysis (JAK genes play important role inhematopoesis)

History and Exam findings: splenomegaly, red

complexion (plethora), fatigue, headache, dizziness,assess for clottingDiff Dx: elevated RBC from smoking, chronic cardiac or

lung disease, high altitude, dehydrationTreatment therapeutic phlebotomy 500ml weekly

until Hct < 45%, then usually maintenance

phlebotomy every 1-3 months. May requirereplacement IV fluids to avoid hypotension


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Secondary Erythrocytosis

Definition: elevated RBC count without other blood cellabnormality. Most common causes are smoking,dehydration and environment of chronic hypoxia

Lab findings: Elevated RBC with otherwise normal WBC,platelet count. Bone marrow biopsy would shownormal erythrocyte precursors, normal epo level

Diagnosis is often one of exclusion if polycythemia isruled out

Signs and symptoms depending on cause. May havesymptoms of chronic hypoxia, SOB, oxygenrequirement, current tobacco use. High altitude living

Management: treat underlying cause


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Thrombocytosis

Definition: elevated platelet count > 500,000Diff Dx includes: bone marrow myeloproliferative

disorder as in essential thrombocythemia (ET) orsecondary to iron deficiency, splenectomy, infection,malignancy or inflammatory disease

Incidence: little dataLab findings: CBC showing elevated platelet count. Iron

studies may show iron deficiency. JAK 2 mutationanalysis can be helpful

Signs and Symptoms: often asymptomatic and foundon routine CBC. ET patient may experience

headaches, TIAs


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Thrombocytosis

Physical findings: eval for evidence of infection,lymphadenopathy, bleeding, thrombosis

Bone marrow needed to evaluate for ET

Usually referred to hematology for work up

Management: treat underlying cause as applicable

For ET: usually no treatment unless patient issymptomatic with headaches, TIAs, thrombosis.Treatment usually consists of Anagrelide and orHydroxyurea. May consider at least ASA forasymptomatic patient with platelet count > 1 million.


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Platelets


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Thrombocytopenia

Definition: platelet count < 100,000.Differential Dx: bone marrow dysfunction, malignancy,

auto-immune response, medication, chemotherapy,acute bleeding, acute thrombosis, DIC, HIT, lab error

Incidence: ITP: 100 cases per million people per yearwith children accounting for half of those. Females

more likely to be affected.Lab/diagnostic studies: check CBC for other cytopenias,

HIT assay, platelet aggregation studies, anti-plateletantibodies, bleeding time, bone marrow biopsy wouldshow elevated megakaryocytes (platelet precursors)in destruction problem however low megakaryocytesin bone marrow production disorder. Check DICpanel. Check cultures of blood, CSF if evidence ofinfection. Radiographic studies for evidence ofDVT/PE. Spleneic ultrasound to eval for sequestration


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Thrombocytopenia

Signs and symptoms: bruising, bleeding, infectioussymptoms, abd pain, fever, recent history of heparin,medication use including recent chemo, thiazides,ethanol, estrogen, sulfonamides, quinine, quinidine,methyldopa, anti-epileptics

Physical findings: ecchymoses, bleeding, splenomegaly

with LUQ pain, SOB, hemoptysis (with PE), unilaterallower ext edema, + homans sign (with DVT),erythema, swelling or other evidence of infection,petechiae

Management: depending on causeFor ITP (idiopathic thrombocytopenia purpura) need to

suppress immune system since this is an auto-immune response. Usually treat with Prednisone1mg/kg qd until platelet count back to normal rangethen slowly taper. Often have relapse. Can also useIVIG, Monoclonal ab therapy with Rituxan. N-Plate


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Thrombocytopenia

For HIT (heparin induced thrombocytopenia) mustdiscontinue all Heparin use (considered Heparinallergic). This response causes patient to behypercoagulable despite low platelet count so patientmust be anti-coagulated with Refludan/Argatroban inhospital setting and then Warfarin as out patient for3-6 months under care of hematologist

For medication related drop discontinue offendingmedication and platelets should recover rapidly. Maybe an expected drop post chemotherapy if beingtreated for cancer

For consumption from acute thrombosis, patient needsto be anti-coagulated and platelets should recover


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Thrombocytopenia

Lab Error: can have platelet clumping due to EDTA tubethis may cause platelet count to appear falsely low peripheral smear examination can confirm normalplatelet count. Blood can be collected in NA citratetube and re-run to confirm normal count

For TTP (thrombotic thrombocytopenia purpura) thisrare disorder of the anticoagulation system will causepatient to require plasmapheresis to removeinhibitors of VW factor. Give pt FFP (fresh frozenplasma) to replace normal VW factor. This is a rare

but serious disease that requires care underhematologist. May see RBC schistocytes on smear


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Bleeding Disorders

HemophiliaDefinition: genetic disorder characterized by lack of

blood clotting factors.Hemophilia A: lack of factor VIII (most common). Sex

linked occurring in 1:10,000 malesHemophilia B: lack of factor IX (Christmas factor)

occurring in 1:100,000 malesLabs/diagnostic testing: diagnosed by checking factor

activity levels, CBC, PT/PTT, bleeding timeSigns and symptoms: easy bruising, prolonged

bleeding, painful joints due to hemarthrosis. Olderhemophiliacs likely to be infected with HIV due to

receiving contaminated factor products


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Bleeding Disorders

Von Willebrand disease (VWD)

Definition: bleeding disorder caused by lack of VonWillebrand factor which interferes with plateletfunction thereby increasing risk for bleeding. Most

forms of VWD are mildIncidence: most common blood clotting disorderoccurring in 1 in 800-1000 people

Labs: normal CBC, bleeding time (prolonged), VonWillebrand factor assay (reduced), plateletaggregation study (reduced), Ristocetin co-factor

(reduced)


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Von Willebrand Disease

Signs and symptoms: easy bruising, prolonged bleedingafter surgery, dental procedure, menorrhagia,epistaxis

Physical findings: may be normal or may seeecchymoses, petechiae, bleeding

Management:Desmopressin (DDAVP) nasal spray helps to increase

factor VIII and VW factor in the bloodFresh frozen plasma/cryoprecipitate in acute bleeding

or surgery


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White blood cells

Definition: blood cells thatfight infection. Produced inthe bone marrow.

Elevated = leukocytosis

Decreased = leukopenia.


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Leukopenia

Definition: total WBC < 4,300

Differential Dx: Infection including bacterial or viral,chemotherapy, other medications (anti-epileptics,penicillins, sulfonamides, cephalosporins, thiazides,cimetidine, ethanol, immunosuppressants),

hematologic malignancy, aplastic anemia,hypersplenism, auto-immune disorders, Feltyssyndrome. Low WBC can be normal in certainpopulations

Lab studies/diagnostic testing: CBC, differential, CMP,

bone marrow biopsy


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Leukopenia

Signs and Symptoms: maybe none, symptoms ofinfection, fever, lymphadenopathy, weight loss, nightsweats. Check medications

Physical findings: lymphadenopathy, splenomegaly,

may be asymptomatic

Management: determine underlying cause

Blacks can have asymptomatic leukopenia as baseline


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Leukocytosis

Definition: WBC > 10,800

Differential Dx: Infection, Chronic inflammation,Medications (steroids), Recovery post chemotherapy,WBC growth factors (Neupogen, Leukine, Neulasta)used in cancer therapies, hematologic malignancy

(leukemia) or bone marrow dysfunction

Lab/diagnostic tests: CBC with diff, UA/cx if urinarysymptoms, CXR if resp symptoms, blood cultures,LAP (leukocyte alkaline phosphotase elevated inleukomoid reaction, decreased in leukemias)


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Leukocytosis

Signs and Symptoms: may be asymptomatic, fever,infectious symptoms, cough, SOB, dysuria, skininfection/abcess, rash, weight loss, fatigue, nightsweats

Physical findings: may be none. Erythema, edema, skinrash, lymphadenopathy, cachexia,

hepatosplenomegaly, abnormal heart sounds,adventitious lung sounds

Management: determine underlying cause.

If unable to determine cause or if leukocytosis persists

or is rising after treating for infection, hematologyconsult for bone marrow biopsy


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Leukemia

Definition: hematologic malignancy of the bone marrowwhereby abnormal immature cells crowd out normalcells. WBC can be elevated or decreased in leukemia.RBC and platelets can be normal or decreased

Types of leukemia: most common

Acute Myelogenous Leukemia

Acute Lymphocytic Leukemia

Chronic Myelogenous Leukemia

Chronic Lymphocytic Leukemia


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Acute Leukemia

Incidence: about 7000 cases per year in US. 80% areAML, 20% ALL

Etiology is unknown for the most part. Risk factorsinclude exposure to benzene, radiation exposure andprior treatment with cytotoxic chemotherapy

Lab findings: CBC can show elevated, normal or lowWBC count. Often see anemia at presentation as wellas thrombocytopenia. Differential often showscirculating blasts (very immature WBCs). ElevatedLDH usually seen. Bone marrow biopsy diagnostic

Signs and Symptoms: pallor, fatigue, fever, anorexia,

weight loss, weakness, palpitations, dyspnea onexertion, infection, rash, bleeding, bruising


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Acute Leukemia

Physical findings: Ecchymoses, bleeding, pallor,tachycardia, tachypnea, hepatosplenomegaly,petechiae, scleral hemorrhage

Management: Rapid recognition of symptoms as those

of leukemia is crucial in acute leukemia as patientscan decline rapidly and die from infectiouscomplications or hemorrhage. Referral tohematologist for work up and chemotherapy


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Acute Leukemia


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Bone Marrow Biopsy


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Chronic Leukemia

Definition: differs from acute leukemia in thatsymptoms have lasted more than 3 months. ForCML, the natural history of the disease usuallyincludes a chronic phase lasting 2-4 yrs. Acceleratedphase can then occur leading to progressiveleukocytosis, anemia and thrombocytopenia.Eventually a blast crisis may ensue in which thedisease may behave more like AML requiringaggressive therapy and having a poor prognosis

Incidence: 4000 cases in US per year for CML


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Chronic Leukemia

Lab/diagnostic testing: CBC with diff shows elevatedWBC often with basophilia. Anemia often present.Platelets may be normal or low. Usually no peripheralblasts. Marrow blasts elevated or normal. LDHincreased. With very high WBC may seehyperkalemia and hypoglycemia. Ultrasound ofspleen often done as well as CT scans to help

differentiate between leukemia and lymphoma

Signs and Symptoms: may be subtle easy fatigability,malaise, anorexia, abd discomfort and early satietyfrom enlarged spleen.

Physical findings: may be none, orhepatosplenomegaly, pallor, ecchymoses

Diagnosis made with bone marrow biopsy


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Chronic Leukemia

Management:CLL: many times a watch and wait approach is takenand only treated if WBC doubling time is < 6m or ptbecomes symptomatic with progressive abnormalblood counts. At that point chemotherapy would beoffered, usually IV therapy depending on pts age andperformance status

CML: Most cases of CML have a genetic 9:22translocation (termed Philadelphia Chromosome).This type of CML is treated at this time with an oraltargeted chemotherapy agent called Gleevec takendaily. There are also new agents being studied forCML that work similar to Gleevec if Gleevec fails.


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Lymphoma

Definition: Hematologic malignancy involvinglymphadenopathy as well as possible bone marrowand other solid organ involvement.

Types: Hodgkins Lymphoma and Non-HodgkinsLymphoma (NHL)

Incidence: About 8000 new cases of Hodgkins disease

are diagnosed each year. Usually occurring in youngadults. NHL has an incidence of up to 90,000 newcases per year

Differential Dx: infections causing lymphadenopathy,cat scratch fever, viral infections (HIV), auto-immunedisorders, endocrine disorders, sarcoidosis

Lab/diagnostic testing: CBC with diff, CMP, LDH, Beta 2microglobulin, lymph node biopsy, bone marrowbiopsy, CXR, CT scans, PET scan


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Lymphoma

Risk factors for development of lymphoma: EBV, HHV-8, HTLV-1 viruses have a strong association withdevelopment of lymphoid tumors. h.Pylori is a riskfactor for development of gastric MALT (mucosaassociated lymphoid tissue) lymphoma. Inherited oracquired immunodeficiency disorders also predispose

individuals to lymphoma. Increase incidence of NHLin farmers and meat workers. Increased Hodgkinsdisease in wood workers.

Signs and symptoms: Painless adenopathy, fever, nightsweats, weight loss, fatigue (B-symptoms)

Physical findings: lymphadenopathy in one or morelymph node chains, hepatosplenomegaly, pallor


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Lymphoma

Staging: based on number of lymph node chainsinvolved and location above and or below diaphragm,bone marrow status, extra nodal sites of disease,absence or presence of B-symptoms

Stages from IA-IVB

Histiologic subtypes also important in determiningaggressiveness of disease which guides treatmentplan offered to patient

Less aggressive NHL: follicular center cell

More aggressive NHL: diffuse large cell


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Lymphoma

Management:

Based on stage, and subtype for Hodgkins diseaseusually IV chemotherapy +/- radiation therapy

NHL treatment can range from watch and wait approachto very strong IV chemotherapy for the aggressivesubtypes. Bone marrow transplant is sometimesneeded if patient fails initial chemotherapy foraggressive NHL.


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WBC Differential

Five subtypes of WBC noted in differential include:Neutrophils (segs + bands) AKA granulocytesthese are immature WBC. Important in fightingbacterial infections. Elevated neutrophils can becaused by acute infection, chemotherapy, stressreaction, burns, tissue necrosis, chronic

inflammatory disorders. Decreased neutrophils =neutropenia. Increased risk for infection ifneutrophils < 1000. Severe risk for infection if 10,000 is CLL.Lymphopenia can be caused by acute stressful illness(MI, pneumonia) as well as steroid therapy andlymphoma


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WBC Differential

Monocytes increased in infection, granulomatousdisease (sarcoid), collagen vascular disease.Decreased in acute stress reaction, pt on steroids,leukemia, chemo and immunosuppressant therapies

Eosinophils Increased in allergic diseases, parasiticinfections, collagen vascular diseases, from certainmedications, leukemia. Decreased in acute stressfulillness, steroids

Basophils Increased in allergic diseases, CML, chronic

inflammatory disorders.


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WBC differential cells


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Case Studies


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Case Study #1

History11 year old male.

Presented in emergency room with recentonset of easy bruising, bleeding gums, and

persistent epistaxis.Previously in excellent health. Mother stated

he was "never sick before in his entire life."

No history of recent viral infection, and no

family history of bleeding disorders


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Case Study #1CBC

(with microscopic differential)RBC 4.52 x 1012/LHGB 13.4 g/dLHCT 37.2 %MCV 82.3 fLMCH 29.6 pgMCHC 35.9 g/dL

RDW 12.1WBC 5.3 x 109/LN 44 %L 39M 14E 1B 2

PLT


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Case Study #1

Morphologic AlterationsResults of the blood smear exam were:RBC morphology:

Normocytic, normochromic

WBC morphology:Within normal limits(one lymphocyte shown here)

PLT morphology:

Appear increased in size

d


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Case Study #1

1 giant platelet seen

C S d


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Case Study #1

Further Laboratory StudiesBone marrow biopsy:

Aspirate:Erythrocyte and granulocyte maturation within normallimits. Megakaryocytes appear normal in number andmorphology.

Sections:Slightly hypocellular for his age, with abundantmegakaryocytes.

Coagulation:INR 0.91 (RI 0.85-1.15)PTT 24.8 sec (RI 23-34)TT

15.8 sec (RI 13-18)

C S d #1


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Case Study #1

Physical ExamBleeding from the left nostril. Numerous

petechiae and purpura; mostly on theextremities.

No organomegaly.

C St d #1


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Case Study #1

What is the most likely diagnosis?

C St d #1


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Case Study #1

Diagnosis

Immune thrombocytopenic purpura

(ITP)

C St d #1


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Case Study #1

Clinical CourseThe patient was given standard therapy for ITP for

more than a month, but failed to respond. Hisplatelet counts did not improve and he continued tohave severe nosebleeds.

Because the patient's ITP was refractory to treatment,

it was decided to perform a splenectomy. During theprocedure, he received several units of platelets, andtolerated the surgery well.

His platelet count gradually recovered; after six monthsit was 289 x 109/L.

He is followed in Hematology Clinic, and continues to dowell.

C St d #2


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Case Study #2

33 year old female.Immigrated to the United States from Laos

four years prior to admission. Historyobtained through an interpreter.

Multiple transfusions and splenectomy twoyears prior to admission. Reason and/ordiagnosis unclear to patient.

Presented with flu-like symptoms of fever,

malaise, epigastric discomfort andnonproductive cough.

C St d #2


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Case Study #2

CBC(with microscopic differential)RBC 4.15 x 10[12]/LHGB 8.1 g/dLHCT 28.6 %MCV 68.9 fLMCH 19.5 pgMCHC 28.2 g/dL

RDW 22.3WBC (corrected) 8.0 x 10[9]/LN 51 %L 36M 7E 4B 2NRBC/100 WBC 83PLT 540 x

C St d #2


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Case Study #2

C St d #2


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Case Study #2

Morphologic AlterationsResults of the blood smear exam were:RBC morphology:

3+ hypochromasia1+ polychromasia2+ anisocytosis3+ target cells

occ spherocytes and fragmentsHowell Jolly bodies present

WBC morphology:Within normal limits

PLT morphology:

Within normal limits

Case St d #2


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Case Study #2

Hemoglobin electrophoresis:Hemoglobin E 80 %Hemoglobin F 5 %Other hemoglobins* 15 %*Identified as hemoglobin A2, hemoglobin Barts and a hemoglobin H

mutant.Iron studies:

Serum ferritin 3234 ng/mL(RI 12-86)Serum iron 140 g/dL

(RI 65-175)TIBC 152 g/dL

(RI 250-410)Saturation 92 %

(RI 20-55)

Case Study #2


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Case Study #2

DiagnosisHomozygous hemoglobin E disease and alpha

thalassemia

Clinical course

The patient's flu-like symptoms subsided; they werepresumed to be viral in origin.

She was referred to the Hematology Clinic, and placedon iron chelation therapy. After 18 months, herserum ferritin had fallen to 114 ng/mL. Herhemoglobin remained in the 7 to 9 g/dL range.Chelation was discontinued, with plans to monitor

the ferritin level every six months and resumetreatment when needed.

Case Study #3


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Case Study #3

History39 year old female.

History of fibrocystic breast disease.

Seen for routine work-up prior tobreast biopsy.

Physical Exam

Moderate splenomegaly.

No other organomegaly.

Case Study #3


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Case Study #3CBC

(with microscopic differential)

RBC 4.28 x 10[12]/L

HGB 13.4 g/dL

HCT 41.2 %

MCV 96.3 fL

MCH 31.3 pg

MCHC 32.5 g/dL

WBC 133.6 x 10[9]/LN seg 56 %

N band 15

N meta 13

N myelo 4

N pro 3

L 3

M 4E 1

B 1

PLT 417 x 10[9]/L

Case Study #3


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Case Study #3

Case Study #3


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Case Study #3

Morphologic AlterationsResults of the blood smear exam were:

RBC morphology:Normocytic, normochromic

WBC morphology:Mature stages and precursors all withinnormal morphologic limits

PLT morphology:

Within normal limits

Case Study #3


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Case Study #3

Bone marrow biopsy:Aspirate differential (1000 cells):

Erythroblasts 9.9%

Myeloblasts 1.1N

promyelocytes 1.4N and precursors71.7L 2.0M 2.8Eand precursors 2.2B and precursors8.9 Sections:

Markedly hypercellular with increased

megakaryocytes.

Case Study #3


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Case Study #3

Cytochemistry:Leukocyte alkaline phosphatase[LAP]

score: 3 (RI 64-176)Cytogenetics:

46,XX,t(9;22)(q34;q11)[Philadelphiachromosome]seen in all marrow cellsanalyzed.

Case Study #3


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Case Study #3

Diagnosis: Chronic Myeloid Leukemia (CML)

Clinical CourseFollowing the standard preparatory regimen, the patient received an

allogeneic bone marrow transplant. The donor was her HLA-matched brother.

Her post-transplant course went well, and 28 days later, herhemoglobin was 11.9 g/dL, WBC 2.0 x 10[9]/L, and PLT 84 x

10[9]/L. Her marrow showed evidence of good engraftment in allthree cell lines.Cytogenetics showed 46,XY normal karyotype in all marrow cells

analyzed. No 46,XX cells and no cells with a Philadelphiachromosome were seen.

This patient continues to be followed in Hematology Clinic. At her lastvisit, ten years post-transplant, she was still doing well and hadno evidence of recurrent disease. Molecular diagnostic studiesperformed at that time were negative for BCR-abl transcripts.

Case Study #4


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Case Study #4

18 year old male student from Nigeria.Came to the emergency room with symptoms

of fever, shaking chills, nausea, andgeneralized malaise; occurring

intermittently over the past five days.Physical Exam

Fever of 103.3F.Tachycardia with a heart rate of 122.

Otherwise within normal limits

Case Study #4


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Case Study #4

CBC(with microscopic differential)

RBC 5.85 x 10[12]/L

HGB 13.3 g/dL

HCT 41.8 %

MCV 71.5 fL

MCH 22.7 pg

MCHC 31.8 g/dL

RDW 12.1

WBC 6.2 x 10[9]/L

N 89 %

L 8

M 2

E 1

B 0

PLT 102 x 10

Case Study #4


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Case Study #4

Case Study #4


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Case Study #4


RBC morphology:NormochromicNumerous red cells contain intraerythrocyticorganisms. Infected RBCs are enlarged; some are

oval shaped, others appear somewhat "fimbriated."Doubly infected cells are present, and severalmorphologic stages can be found, including ringforms, mature schizonts, and gametocytes.

WBC morphology:

Within normal limits(one lymphocyte shown here)

Case Study #4


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Case Study #4

PLT morphology:normal

RBC enzyme: G6PD 11.7 U/g Hgb

(RI 4.6-13.5)

Case Study #4


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Case Study #4

Diagnosis - MalariaUpon further questioning, the patient stated that he hadarrived in the United States from Nigeriaapproximately six months prior to this visit. Shortlyafter his arrival, he had experienced a similar illnessthat was diagnosed as malaria. Medication was

prescribed, but once he felt better he did notcontinue to take it.

Based on the blood smear morphology, the periodicpattern of his fever and chills, and his travel history,the causative organism was identified as Plasmodiumovale.

Case Study #4


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Case Study #4

Clinical CourseThe patient was hydrated with normal saline, andstarted on appropriate treatment for the erythrocyticstages of malaria. Several days later he began asecond course of therapy to eliminate theexoerythrocytic (hepatic) forms of the organism. He

completed the course of therapy, and on subsequentvisits was asymptomatic.

Note: On the basis of his low MCV, his relatively highRBC count, and his ethnic background, it is likelythat this patient also has alpha thalassemia trait.

Case Study #5


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Case Study #5

History:70 year old female.Symptoms of dyspnea on exertion, easy

fatigability, and lassitude for past 2 to 3months.

Denied hemoptysis, GI, or vaginal bleeding.Claimed diet was good, but appetite varied.Physical Exam:Other than pallor, no significant physical

findings were noted. Occult blood was

negative.

Case Study #5


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Case Study #5


RBC 3.71 x 10[12]/L

HGB 5.9 g/dL

HCT 20.9 %

MCV 56.2 fL

MCH 15.9 pg

MCHC 28.3 g/dL

RDW 20.2

WBC 5.9 x 10[9]/L

N 82 %

L 13

M 1

E 4

B 0

PLT 383 x 10[9]/

Case Study #5


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Case Study #5

Case Study #5


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Case Study #5

Morphologic Alterations

Results of the blood smear exam were:

RBC morphology:2+ hypochromasia3+ microcytosis2+ anisocytosis

2+ elliptocytes and target cellsocc teardrops and fragments

WBC morphology:Within normal limits(one lymphocyte shown here)

PLT morphology:Within normal limits

Case Study #5


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Case Study #5

Iron studies were performed, and resultswere:

serum ferritin


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Case Study #5

DiagnosisIron deficiency anemiaClinical CourseDiagnostic procedures included upper GI endoscopy,

colonoscopy, and small bowel biopsy. All werenegative.

The patient received packed RBC transfusions and wasstarted on iron therapy.She refused any further laboratory testing or other

procedures, and was discharged at her own request.She was lost to follow-up.

The etiology of her iron deficiency anemia could not be

determined, but it was most likely nutritional.

Case Study #6


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Case Study #6

History75 year old male.

Symptoms of severe headache andgeneralized pruritis.

Physical ExamSpleen palpable 10 cm. below left

costal margin. Liver palpable 3 cm.below right costal margin. The rest ofthe exam was within normal limits.

Case Study #6


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Case Study #6


RBC 7.70 x 10[12]/L

HGB 17.3 g/dL

HCT 54.3 %

MCV 97.1 fL

MCH 32.2 pg

MCHC 33.2 g/dL

RDW 16.4

WBC 18.3 x 10[9]/L

N seg 79 %

N myelocyte 5 %

L 9

M 4E 0

B 3

PLT 484 x 10

Case Study #6


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Case Study #6

Case Study #6


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Case Study #6


RBC morphology:Essentially normocytic, normochromic

WBC morphology:Within normal limits

PLT morphology:Within normal limits

Case Study #6


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Case Study #6

Further Laboratory StudiesBone marrow biopsy:Aspirate differential:

Within normal limitsSections:

Markedly hypercellular for age.Cytogenetics:46,XY. No numerical or structural

chromosome abnormalities detected.Pulmonary function:

Oxygen saturation: 97% (RI 94-100)

Case Study #6


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Case Study #6

DiagnosisPolycythemia vera

Clinical Course

The patient is being followed by hislocal physician, and treated withperiodic phlebotomy.


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Documents

209-Hematology Review _ Case Studies