Immune Thrombocytopenia.: Thrombocytopenia associated with increased peripheral destruction of platelets and shortened platelet survival caused by an antiplatelet antibody is seen in a number of diseases. In most cases a cause is identifiable.

Collagen vascular diseases, particularly systemic lupus erythematosus, may cause an antiplatelet antibody-related platelet decrease. Similar associations have been noted with leukemia and lymphoma, particularly lymphocytic lymphoma. All evaluations of suggested immune thrombocytopenia should include a complete blood count, peripheral smear, antinuclear antibody test, and bone marrow examination. A number of drugs have been associated with thrombocytopenia of immunologic origin. Quinine and quinidine are common offenders that affect platelets through an “innocent bystander” mechanism. The platelet is coated with a drug-antibody complex, complement is fixed, and intravascular platelet lysis occurs. Because of its relatively high frequency, heparin is an important cause of drug-induced thrombocytopenia in hospitalized patients. Platelets are activated by the formation of an immunoglobulin G (IgG)–heparin complex.

Low-molecular-weight heparin may be associated with less thrombocytopenia than standard, unfractionated heparin is; however, both forms of heparin demonstrate cross-reactivity.⁷ Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated side effect associated with heparin.^8,9 A meta-analysis including 7287 patients determined the incidence of HIT to be 2.6% for unfractionated heparin and 0.2% for low-molecular-weight heaprin.¹⁰ It usually occurs 5 to 7 days after the initiation of heparin treatment. Thrombus develops in approximately half the patients with HIT. The thrombotic complications can lead to loss of a limb in up to 20% and death in as many as 30%. The diagnosis is suggested in the presence of absolute thrombocytopenia or a greater than 50% reduction in platelets after the initiation of heparin. The most specific diagnostic tests for HIT are serotonin release assays, heparin-induced platelet aggregation assays, and solid-phase immunoassays. Platelet-associated IgG levels are commonly elevated, but this finding is less specific or sensitive than the other diagnostic tests. More concerning to the emergency physician is delayed-onset HIT. This form of HIT occurs a median of 14 days after the initiation of heparin, but it has been reported to occur up to 40 days after heparin is started.¹⁰ Arterial or venous thrombosis typically develops in patients with HIT after they receive heparin. The administration of heparin can result in the development of antibodies to the heparin and platelet factor 4 complex. The heparin–platelet factor 4–antibody complex is removed from the circulation, resulting in thrombocytopenia; however, this complex also results in the generation of microparticles that have procoagulant properties, which can lead to thrombus formation. Treatment of thrombotic complications in these patients involves the use of direct thrombin inhibitors (lepirudin, argatroban), factor Xa inhibitors (fondaparinux), or heparinoids (danaparoid).⁸

Digitoxin, sulfonamides, phenytoin, and aspirin are other drugs that may be associated with a thrombocytopenia. The patient has usually ingested the medication within 24 hours. An idiopathic thrombocytopenic purpura type of syndrome has been reported in intravenous cocaine users.¹¹ Clinical trials with platelet glycoprotein IIb/IIIa antagonists suggest that intravenous glycoprotein IIb/IIIa inhibitors may confer an increased risk for associated thrombocytopenia, independent of heparin therapy.¹² The platelet count may fall below 10,000/mm³ and be complicated by serious bleeding. Laboratory testing may confirm the presence of antibody, especially with the use of quinine and quinidine. After administration of the drug is stopped, the platelet count improves slowly during a period of 3 to 7 days. A short course of corticosteroid therapy, such as prednisone in a dose of 1 mg/kg with rapid tapering, may facilitate recovery.^13,14

Postinfectious immune thrombocytopenia is usually associated with viral diseases such as rubella, rubeola, and varicella. Although many cases associated with sepsis have a mechanical origin, some immune mechanisms have been demonstrated.¹³

Post-transfusion thrombocytopenia is a rare disorder that causes a precipitous fall in platelets approximately 1 week after the transfusion. In 90% of cases, its origin is linked to the 98% of the population carrying a PLA1 antigen on platelets. Despite the fact that 2% of blood recipients are mismatched with respect to this antigen, it is fortunately a rare occurrence. On transfusion into a PLA1 antigen–negative patient, the platelets with attached PLA1 antibodies provoke an anamnestic response, but the actual mechanism of platelet destruction remains unknown. The platelet count often falls precipitously below 10,000/mm³, with a significant risk for major bleeding. Intracranial hemorrhage occurs in approximately 10% of such cases. Patients are usually middle-aged women with a history of pregnancy who may have been previously sensitized to the PLA1 antigen during pregnancy. Plasma exchange therapy is an effective intervention.13,15