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Definition, Etiology, PathogenesisTop
Disorders of platelets may be caused by abnormal platelet counts (thrombocytopenia, rarely thrombocythemia) or abnormal platelet function.
1. Thrombocytopenia is usually defined as a platelet count <150,000/microL. It may be classified as:
a) Inherited: Rare, sometimes familial, it may present in childhood. Examples include Bernard-Soulier syndrome, Fanconi anemia, Alport syndrome.
b) Acquired: More frequent, it may be caused by drugs (myelosuppressive agents, thiazide diuretics, estrogens, interferons), alcohol and other toxins, viral infections, cobalamin and/or folate deficiency, bone marrow disorders (leukemia, lymphoid neoplasm, myelodysplastic syndrome, cancer metastasis, Gaucher disease, tuberculosis, myelofibrosis), aplastic anemia, radiation, selective megakaryocytic aplasia, or cyclic thrombocytopenia (regular decreases in platelet counts every 21-39 days, most frequently in young women).
2) Thrombocytopenia caused by excess destruction of platelets and decreased platelet production; this is termed immune thrombocytopenia (ITP).
a) Immune: Caused by transfusion, drugs (eg, heparin [nonimmune thrombocytopenia caused by heparin is usually asymptomatic, while immune heparin-induced thrombocytopenia – HIT – is associated with thrombosis, not bleeding], abciximab, quinidine, sulfonamides, nonsteroidal anti-inflammatory drugs, antibiotics, gold compounds), infections, autoimmune diseases (eg, systemic lupus erythematosus, antiphospholipid syndrome), non-Hodgkin lymphomas, or treatment with antilymphocyte immunoglobulin or antithymocyte immunoglobulin, among many other causes.
b) Nonimmune: Thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), sepsis, disseminated intravascular coagulation (DIC), Kasabach-Merritt syndrome, cyanotic congenital heart disease, and others.
4) Thrombocytopenia caused by sequestration of platelets: Hypersplenism (see Splenomegaly).
5) Thrombocytopenia caused by dilution developing after transfusion of several units of packed red blood cells without concomitant transfusions of platelet concentrate.
6) Pregnancy (platelet counts are usually >70,000/microL; the condition requires no treatment and resolves spontaneously after delivery).
Pseudothrombocytopenia is a laboratory artifact caused by in vitro platelet agglutination in the blood collected in a tube containing ethylenediaminetetraacetic acid (EDTA); it can cause significant underestimation of platelet counts; however, most automated analyzers will recognize platelet clumping and not report a falsely reduced level. Platelet counts in the blood collected in tubes containing heparin or citrate are usually accurate.
2. Thrombocytosis is defined as a platelet count >400,000/microL:
1) Primary thrombocytosis (essential thrombocythemia) is a myeloproliferative neoplasm (see Primary Myelofibrosis).
2) Secondary (reactive) thrombocytosis may be caused by surgery, solid tumors, iron deficiency anemia, hemolytic anemia, chronic inflammatory or infectious diseases, acute blood loss, splenectomy, chronic alcohol abuse, or multiple blood donations. It is usually asymptomatic, causes no bleeding or thrombosis, and resolves after successful treatment of the underlying condition.
3. Qualitative disorders of platelet function cause prolonged bleeding times and impaired platelet aggregation as assessed using aggregometry in patients with normal or slightly decreased platelet counts:
1) Inherited: Rare abnormalities of platelet surface receptors, membrane, cytoskeleton, or degranulation.
2) Acquired: Most commonly drug-induced (acetylsalicylic acid, ticlopidine, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa antagonists, fibrinolytic agents, or other drugs) or caused by uremia, myeloproliferative neoplasms, acute leukemia, or monoclonal gammopathy.
Note: In patients with severe bleeding you may use desmopressin 0.3 microg/kg or platelet concentrate (usually in patients not responding to desmopressin). The effects will vary. Repeated doses of desmopressin are limited by tachyphylaxis and potentially hyponatremia. Neither of these agents has been validated in clinical trials as effective.
Cutaneous and mucosal bleeding: petechiae on the skin of extremities, trunk (rarely the face), and oral mucosa; gingival bleeding; epistaxis; menorrhagia and urinary and/or genital bleeding. Life-threatening gastrointestinal or intracranial hemorrhages may occur, and excessive bleeding after tissue injury may be observed. In patients with thrombocytopenia bleeding usually occurs with platelet counts <20,000/microL.