Thrombocytopenia Platelet disorders are caused by a decrease in the number of platelets (thrombocytopenia) or a decrease in their function (platelet insufficiency) leading to poor thrombosis and bleeding. Platelet counts are below the normal range of 140,000 to 400,000/μl. Thrombocytopenia may result from insufficient platelet production, splenic ramps "Mi naoquat? Increased destruction or utilization and dilution of platelets (Table 133-1). Severe thrombocytopenia, regardless of the cause, can result in typical bleeding: multiple petechiae, most commonly on the lower legs, or small scattered petechiae at sites of minor trauma; mucocutaneous hemorrhages (rhinorrhea, gastrointestinal and genitourinary tracts, and vaginal hemorrhages); and massive postoperative hemorrhages. Gastrointestinal hemorrhage and central nervous system hemorrhage can be life-threatening. Thrombocytopenia, however, does not present with intraorganic hemorrhage (e.g., deep visceral hematomas or joint hemorrhages) in the same way as it does when secondary to coagulopathies (e.g., hemophilia, see Section 131). Diagnosis A thorough history of the patient's medications must be obtained to exclude drugs that increase platelet destruction in sensitive patients. Thrombocytopenia occurs in approximately 5% of heparin-treated patients (see Heparin-induced thrombocytopenia, below), and can occur even with minimal heparin flushing in order to keep the arterial catheter open. Thrombocytopenia is less commonly induced by other drugs, such as quinidine, quinine, sulfonamides, oral antidiabetics, gold salts, and rifampin. Other important elements of the history may include symptoms suggestive of an underlying immune disorder (e.g., joint pain, Raynaud's phenomenon, fever of unknown origin); signs and symptoms suggestive of thrombotic thrombocytopenia (see TTP-HUS, below); a blood transfusion within 10 days suggesting post-transfusion purpura; and heavy alcohol consumption suggesting alcohol-induced thrombocytopenia. 5% of pregnant women may develop mild thrombocytopenia during labor. Mild thrombocytopenia can occur in 5% of pregnant women during labor. Because thrombocytopenia is common in patients with human immunodeficiency virus (HIV) infection, it can be differentiated from idiopathic thrombocytopenic purpura (see ITP); this can lead to other risk factors for symptoms of HIV infection and medical history. Physical examination is also important in the diagnosis: (1) Fever is usually present in thrombocytopenia secondary to infectious or active systemic lupus erythematosus (SLE) and thrombotic thrombocytopenias (TTP), but not in idiopathic thrombocytopenic purpura (ITP) or drug-related purpura. (2) The spleen is not enlarged on palpation in patients with thrombocytopenia due to increased platelet destruction (e.g., idiopathic thrombocytopenic purpura, drug-related immune thrombocytopenia, thrombotic thrombocytopenic purpura), whereas the spleen is mostly palpable in patients with thrombocytopenia secondary to platelet retention by the spleen, as is the case in patients with thrombocytopenia secondary to lymphoma or myeloproliferative disease. The same is true for patients with thrombocytopenia secondary to lymphoma or myeloproliferative disease. (3) Other signs of chronic liver disease are also diagnostic, such as spider nevi, jaundice, and liver palms. (4) Thrombocytopenia is often associated with late pregnancy. A peripheral blood count is a key test to determine the severity of thrombocytopenia, and a blood smear can provide clues to its etiology (Table 133-2). Screening tests for hemostasis (see Section 131) are normal if the thrombocytopenia is not associated with other disorders that affect hemostasis (e.g., liver disease or disseminated intravascular coagulation). Bone marrow imaging is indicated if abnormalities other than thrombocytopenia are seen on the blood smear. This test provides information on the number and morphology of megakaryocytes and determines the presence or absence of diseases causing bone marrow failure (e.g., myelodysplasia). Antiplatelet antibody testing is not clinically significant. HIV antibody testing should be performed if the patient's history or examination provides evidence of risk for HIV infection. The treatment of thrombocytopenia varies with the cause and severity of the disease and requires rapid identification of the cause and possible correction (e.g., discontinuation of heparin in heparin-associated thrombocytopenia). Because repeated platelet transfusions can produce homologous platelet antibodies, which may reduce the efficacy of the therapy, intermittent use is necessary to prevent the production of these antibodies. If thrombocytopenia is due to platelet depletion, platelet transfusions should be reserved for the treatment of fatal or central nervous system hemorrhage. If thrombocytopenia is due to bone marrow failure, platelet transfusions should be reserved for the treatment of acute hemorrhage or severe thrombocytopenia (e.g., platelet count <10,000/μl). Idiopathic (immune) thrombocytopenic purpura is a hemorrhagic disorder without systemic lesions, which is chronic in adults and acute and self-limiting in children. In adults, idiopathic (immune) thrombocytopenic purpura (ITP) is due to the production of antibodies (autoantibodies) against structural platelet antigens, whereas in children, the synthesis of antibodies is triggered by viral antigens. The antibody reacts with the viral antigen attached to the platelet surface. Diagnosis Physical examination is negative except for petechiae, purpura, and mucosal bleeding (mild or profuse). Peripheral blood tests are normal except for a decreased platelet count. Bone marrow examination is usually normal except for a normal or increased number of megakaryocytes. Treatment In adults, treatment is usually initiated with oral corticosteroids (e.g., prednisone 1 mg/kg daily). If effective, platelet counts will return to normal within 2 to 6 weeks, followed by a gradual taper of corticosteroids. However, the majority of patients have a less than satisfactory outcome or have a relapse when the dose of adrenal steroids is reduced. Splenectomy provides relief in 50% to 60% of patients. The efficacy of other medications in patients who are refractory to treatment with steroids and splenectomy has not been demonstrated. Because of the long duration of chronic ITP and the low mortality rate in patients with chronic ITP, the advantages and disadvantages of treatment must be carefully weighed. The efficacy of immunosuppressive therapy with synthetic androgens (danazol) or with azathioprine, vincristine, cyclophosphamide, or cyclosporine has been inconsistent. In patients with lethal bleeding associated with ITP, immunoglobulin infusion (IVIg) may be used, which inhibits the platelet-clearing effect of encapsulated antibodies by mononuclear macrophages. IVIg is given at a dose of 1 g/kg for 1 day or for 2 consecutive days. The patient's platelet count often rises within 2 to 4 days, but remains elevated for only 2 to 4 weeks. High-dose methylprednisolone at 1 g/(kg.d) IV for 3 days results in a rapid rise in platelet counts and is slightly less costly than IVIg. Platelet transfusions should also be given to patients with fatal bleeding. Platelet transfusions should not be given prophylactically in patients with ITP because glucocorticosteroids or IVIg may be expected to be effective within a few days. Treatment of children is the reverse of that for adults. The use of corticosteroids or IVIg rapidly restores platelet counts but does not improve clinical outcomes. Because most children recover spontaneously from severe thrombocytopenia within days or weeks, supportive therapy alone is sometimes recommended. Splenectomy should be delayed for at least 6 to 12 months in children with chronic ITP who have failed to respond to corticosteroids or IVIg, due to the increased risk of severe infections in splenic children and the fact that most children spontaneously remit, even after years of illness.