Bleeding may result from abnormalities of (1) platelets, (2) blood vessel walls, or (3) coagulation. Platelet disorders characteristically produce petechial and purpuric skin lesions and bleeding from mucosal surfaces. Defective coagulation results in ecchymoses, hematomas, and mucosal and, in some disorders, recurrent joint bleeding (hemarthroses).
Normal platelet count is 150,000–350,000/µL. Thrombocytopenia is defined as a platelet count <100,000/µL. Bleeding time, a measurement of platelet function, is abnormally increased if platelet count is <100,000/µL; injury or surgery may provoke excess bleeding. Spontaneous bleeding is unusual unless count <20,000/µL; platelet count <10,000/µL may be associated with serious hemorrhage. Bone marrow examination shows increased number of megakaryocytes in disorders associated with accelerated platelet destruction; decreased number in disorders of platelet production. Evaluation of thrombocytopenia is shown in Fig. 65-1.
Algorithm for evaluating the thrombocytopenic pt. DIC, disseminated intravascular coagulation; RBC, red blood cell; TTP, thrombotic thrombocytopenic purpura.
(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 most commonly caused by antibodies to ADAMTS13, a protease that normally cleaves von Willebrand factor (vWF); when vWF is not cleaved, it spontaneously binds and activates adherence of platelets.
Hemorrhage with extensive transfusion.
Platelet clumping usually secondary to collection of blood in EDTA (0.3% of pts). Examination of blood smear establishes diagnosis.