Uncomplicated heparinization for cardiopulmonary bypass in a patient with antiheparin antibodies

Abstract

THE SYNDROME of heparin-induced thrombocytopenia (HIT) is now recognized to consist of two distinct clinical entities.1-3 HIT type I is characterized by a mild thrombocytopenia (.100 3 109/L) usually occurring within 48 hours of initiating heparin, which is not associated with thrombotic or bleeding complications and which resolves spontaneously even with continued heparin administration. HIT type II is associated with a more profound thrombocytopenia (,100 3 109/L or ,50% of preheparin count) beginning 5 to 8 days after initiating heparin and follows a more malignant course. Patients with a diagnosis of HIT type II are at high risk for proximal vein or arterial thrombosis, pulmonary embolism, amputation, and death. HIT type I is believed to represent a direct aggregating effect of heparin resulting in increased clearance of platelets from the circulation. HIT type II is a result of antibody production to the complex formed by heparin and platelet factor 4 (PF 4). The pathogenic antibody is of the IgG class and can bind with Fc receptor sites on platelets and endothelial cells, resulting in activation and production of a prothrombotic state. Reaching a diagnosis of HIT type II has been assisted by the development of several laboratory assays for antiheparin antibodies. Although the assay techniques vary considerably, they can all be described generally as either physiologic or immunologic. The physiologic assays involve the detection of platelet activation when heparin is added to the patient’s serum. The 14C-serotonin release assay (SRA) is the archetypic physiologic assay and is considered the gold standard by many authors for the laboratory diagnosis of HIT type II. The cost, technical expertise, and requirement for radioactive materials, however, have limited the access to this test to large reference laboratories. The immunologic assays involve direct detection of antibodies in the patient’s serum to the heparin-PF 4 complex, most often by an enzyme-linked immunosorbent assay (ELISA). The commercial availability of an ELISA kit now provides wider access to serologic testing for HIT type II. Traditionally, a diagnosis of HIT type II was thought to be an absolute contraindication to heparin exposure. More recently, the safe conduct of cardiopulmonary bypass (CPB) with anticoagulation with single-dose heparin was reported for heart transplant patients with a diagnosis of HIT type II when antiheparin antibodies were no longer detectable by SRA.4 Although alternative anticoagulation techniques are available for CPB, the abandonment of well-established heparin protocols carries considerable risk and should be undertaken only when this approach clearly provides the safest course. A case is presented that shows the uncertainties in diagnosing HIT type II and the factors that must be considered before CPB.