Hemostasis: Platelet Disorders

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Quantitative disorders

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- decreased production
- increased consumption

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spontaneous bleeding risk

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<5,000 x 10^9/uL

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surgical risk

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<50,000 x 10^9/uL

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petechiae

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little red dots

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purpura

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bruise

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decreased production

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- hypoproliferation
- ineffective production

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hypoproliferation

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- decreased megakaryocytes
- from irradiation, chemotherapy, aplastic anemia, infiltrates (malignant cells), lupus erythematosis

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ineffective production

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- normal number of megakaryocytes
- megaloblastic anemia
- Iron deficiency anemia

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Idiopathic/immune thrombocytopenia purpura (ITP)

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- antibodies against plts, attach to plts and destroy

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3 types of idiopathic/immune thrombocytopenia purpura

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1.) Children
2.) Adults
3.) HIV patients

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Children ITP

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- peak age 5 years old, same for boys and girls, sudden onset, severe thrombocytopenia, spontaneous remission, no relapse (80%)

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Adult ITP

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- women greater than men, insidious slow onset, bleeding is rare (neocytes – new cells work better)
- Antibody directed against IIb/IIIa antibody may affect megakaryocytes and reduce both number and function

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HIV Patients ITP

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- antibody triggers a peroxidase pathway which causes direct cell
cell destruction
- mechanism seen in WBC with ingested bacteria
- never seen before in antibody mediated removal
- usually reticulo-endothelial removal or C’ destruction

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Treatment ITP

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- no plt transfusion, steriods, intravenous Ig, Rh immune globulin, splenectomy
- can't treat children

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Plt transfusion for ITP

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none, only extreme cases

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Steriods for ITP

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reduce circulating antibody, stop antibody production

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Intravenous immunoglobulins for ITP

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- 80% response rate but frequent relapse
- give antibodies to overwhelm them, so it won’t work as effective

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Rh immune globulin in D (Rh°) postitive patients for ITP

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- 85%
- blocks Fc receptors
on macrophages

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Splenectomy

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– 1/3 increase in circulating plts immediately
- decreased removal of antibody coated platelets

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Thrombotic Thrombocytopenia Purpura (TTP) symptoms and etiology

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1.)Proliferation of unusually HMW vWF
2.)Abnormal plt adherence aggregation and release
3.)Microemboli, hemolytic anemia and secondary fibrinolysis
4.)Lack of vWF cleaving protease

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Treatment of TTP

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- Plasma exchange w/ fresh frozen plasma, reduced mortality from 90% to 10-30%
- Removal of abnormal ULvWF, adding normal vWF
- Replacement of vWF cleaving protease, antibodies will still attack but it will also take out inhibitory antibody

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Hemolytic Uremic Syndrome

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- TTP w/ renal failure
- 2 variants: very old/young and adults

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HUS in very young/old

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- <3 yrs or >80 yrs following a long bout of bloody diarrhea typically triggered by infection, with E. coli.
- strain has an exotoxin called shiga thought to trigger the syndrome but it is unknown how

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HUS in adults

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observations of vHMW vWF and some decrease in the cleaving
protease has convinced some that adult HUS and TTP are variants of the same syndrome

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Treatment of HUS

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- plasma exchange
- antibiotics seem to aggravate rather than alleviate the condition

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Heparin induced thrombocytopenia/thrombosis (HITT)

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- Presence of both thrombocytopenia and thrombosis in heparin-sensitive patients teated with heparin
- Injected heparin reacts with plt factor 4 to create PF4-heparin complexes
- IgG antibodies react with complexes and form immune complexes
- Immune complexes bind to Fc receptors on circulating plts
- Plt activation releases PF4 from alpha granules
- Newly release PF4 binds to additional heparin, forming more immune complexes, and activating more plts to release more PF4, using more pltsthrombocytopenia
- Excess PF4 binds to heparin-like molecules on endothelial cells that provide targets for antibody binding, immune-mediated endothelia injurythrombosis

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Other reasons for decreased plts

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1.) Extracorporeal membrane oxygenation (ECMO) – heart lung machine, destroys plts
2.) Splenic pooling – decrease plt
- splenomegaly – more plt, less in circulation
- cirrhosis – hemorrhage
- lymphomas
- leukemias

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Hereditary qualitative disorders

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1.) Bernard-Soulier syndrome: normal aggregation, glycoprotein Ib adhesion defect
2.) Glanzmann’s Thrombasthenia: IIb/IIIa abnormal aggregation
3.) Storage pool deficit

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Acquired qualitative disorders

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1.) Uremia
2.) Paraprotein disorders Waldenstrom’s and other gamopathies
3.) Misc: SLE, FDPs especially fragments D and E - can interfere with plt function

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Uremia

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- kidney disease, excess of guanidinoscuccinic acid and/or hydroxypenolic acid, destroys plt function
- transfusion ineffective, dialysis

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Paraprotein disorders Waldenstrom’s and other gamopathies

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coats plt, prevents aggregation, clinical bleeding

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Increased Function

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Thrombocytosis: >500,000 usually >1,000,000
Associated: Myeloproliferative disorders and malignancies