ACQUIRED DISORDERS OF PLATELET FUNCTIOII



Aspirin and other nonsteroidal anti-inflamma­tory drugs inhibit platelet cyclooxygenase, the key enzyme in transformation of platelet arachi-donic acid to products that induce platelet aggre­gation, the cyclic endoperoxides and thrombox­ane A2. These substances mediate the normal platelet release reaction initiated by platelet ag­onists such as ADP, epinephrine, or collagen. After contact with aspirin or similar drugs, plate-letsexhibit impaired aggregation and release, the bleeding time is moderately prolonged, and the number of microaggregates of platelets detectable in the blood is diminished. The duration of these platelet effects of the nonsteroidal anti-inflam­matory drugs varies widely. Only aspirin, by vir­tue of covalent acetylation of cyclooxygenase at its active site, has a prolonged effect on platelet function (since platelets do not synthesize en­zymes as they circulate, one dose of aspirin in­hibits platelet function for up to a week); other nonsteroidal anti-inflammatory drugs have anti­platelet effects lasting less than 24 hours. Throm-bin-induced platelet activation is unaffected by aspirin or similar drugs, accounting for the lim­ited hemorrhagic tendency produced by these agents. However, when a second defect of he-mostasis exists, such as hemophilia, thrombocy­topenia, or anticoagulant therapy, ingestion of as­pirin may lead to serious bleeding.

Acquired defects in platelet function can ac­company several types of systemic diseases. Ure­mia produces a hemorrhagic tendency with ep-istaxes, ecchymosis, and gastrointestinal bleeding related to platelet dysfunction and often to throm­bocytopenia. Platelet aggregation and platelet pro-coagulant activity are both abnormal and the bleeding time is prolonged. Accumulation of toxic metabolites in the plasma may be partly respon­sible for these dysfunctions, as may be an inad­equate synthesis of thromboxane. Hemodialysis tends to improve platelet function. Infusion of cryoprecipitate or administration of estrogens has been reported to correct the hemostatic abnor­malities. Paraproteinemias such as multiple mye­loma can induce bleeding by coating the platelet surface with monoclonal immunoglobulin, which prevents platelet-platelet interaction, and by interfering with fibrin polymerization. In leuke­mics and myeloproliferative syndromes, defects in platelet function are common. In DIC, the presence of fibrin split products in the cir­culating blood also can impair platelet function .

Laboratory findings distinguish vascular pur­puras from purpuras directly involving the com­ponents of the hemostatic mechanism. The typi­cal findings in vascular purpura include an abnormal tourniquet test (positive Rumpel-Leede test), indicating increased capillary fragility, and prolonged bleeding time in the presence of a nor­mal platelet count, normal platelet function, and normal coagulation screen. Congenital vascular purpura is found in inherited diseases of connec­tive tissue. Acquired vascular purpura can occur in paraproteinemias, scurvy, Cushing’s disease or corticosteroid treatment, in association with other drugs, or in old age. In children, Henoch-Schonlein purpura is an allergic-type vasculitis manifested by abdominal pain, hematuria and glomerulonephritis, hemorrhagic urticaria and arthralgias.

Bleeding in hereditary hemorrhagic telangiec­tasia (Osler-Weber-Rendu disease) results from fragile, easily bleeding mucosal telangiectases. This disorder is inherited as an autosomal dom­inant trait in which the vascular abnormalities continue to form throughout life, becoming more prominent after puberty. All mucosal surfaces may be involved, with bleeding commonly orig­inating from the nose and from the respiratory, gastrointestinal, and genitourinary .tracts. Pul­monary arteriovenous fistulae are common (15 per cent). Telangiectases may or may not be present on the skin. The mainstays of treatment are cauterization of accessible lesions, vigorous iron replacement therapy to correct continual blood loss, and efforts at maintaining local he-mostasis.