(1) Production defects such as marrow injury (e.g., drugs, irradiation), marrow failure (e.g., aplastic anemia), marrow invasion (e.g., carcinoma, leukemia, fibrosis); (2) sequestration due to splenomegaly; (3) accelerated destruction—causes include:

• Drugs such as chemotherapeutic agents, thiazides, ethanol, estrogens, sulfonamides, quinidine, quinine, methyldopa.
• Heparin-induced thrombocytopenia (HIT) is seen in 5% of pts receiving >5 days of therapy and is due to in vivo platelet aggregation often from anti-platelet factor 4 antibodies. Arterial and occasionally venous thromboses may result. Despite the low platelets, HIT is a hypercoagulable state.
• Autoimmune destruction by an antibody mechanism; may be idiopathic or associated with systemic lupus erythematosus (SLE), lymphoma, HIV.
• Idiopathic thrombocytopenic purpura (ITP) has two forms: an acute, self-limited disorder of childhood requiring no specific therapy, and a chronic disorder of adults (esp. women 20-40 years). Chronic ITP may be due to autoantibodies to glycoprotein IIb/IIIa or glycoprotein Ib-IX complexes.
• Disseminated intravascular coagulation (DIC): platelet consumption with coagulation factor depletion [prolonged prothrombin time (PT), partial thromboplastin time (PTT)] and stimulation of fibrinolysis [generation of fibrin split products (FSPs)]. Blood smear shows microangiopathic hemolysis (schistocytes). Causes include infection (esp. meningococcal, pneumococcal, gram-negative bacteremias), extensive burns, trauma, or thrombosis; giant hemangioma, retained dead fetus, heat stroke, mismatched blood transfusion, metastatic carcinoma, acute promyelocytic leukemia.
• Thrombotic thrombocytopenic purpura (TTP): rare disorder characterized by microangiopathic hemolytic anemia, fever, thrombocytopenia, renal dysfunction (and/or hematuria), and neurologic dysfunction caused by failure to cleave von Willebrand factor (vWF) normally.
• Hemorrhage with extensive transfusion.