Clinical Presentation of HIT. Part 4
A number of investigators have adapted the enzyme-linked immunosorbent assay (ELISA) technique to devise diagnostic tests for HIT. The most recent of these uses immobilized PF4 bound to heparin as a target for the HIT antibody. Initial studies reported PF4 ELISA to be at least as sensitive as both the 14C-serotonin release and HIPA assays, although discrepant results occur in up to 25% of patients, indicating that the different assays recognize different patient cohorts. Two recent studies evaluating this assay in patients after cardiopulmonary bypass surgery have reported the heparin-associated antibody to be detectable in .50% of patients by the time of hospital discharge. The presence of antibody was not predictive of either thrombocytopenia or thromboembolic complications, suggesting that the increased sensitivity may be of limited clinical utility in this setting. Further evaluation of this assay will be required before its integration into routine clinical practice.
Prevention
The most important principle of prevention is to minimize the exposure to heparin. In patients with established venous thrombosis, early commencement of warfarin shortens the duration of heparin therapy, thus minimizing the likelihood of developing thrombocytopenia without affecting efficacy. Most investigators stress the importance of maintaining a high index of suspicion and performing regular platelet counts in all patients receiving heparin therapy. This has been predicated on the retrospective observation that prompt diagnosis of the condition with abrupt withdrawal of the drug can substantially reduce the complication and mortality rates. However, in a more recent retrospective analysis, patients with a diagnosis of HIT had a subsequent 30-day risk of thrombosis .50%, despite cessation of heparin therapy with or without institution of warfarin therapy, suggesting that additional alternative anticoagulant therapy may be necessary in this patient group.
Treatment
HIT type I. Asymptomatic patients developing mild thrombocytopenia in the absence of the heparin-dependent antibody do not require specific treatment. However, it may be difficult to distinguish this condition from early type II; these patients should be closely monitored, and if there is any doubt, heparin should be discontinued.
HIT type II. In patients who develop thrombocytopenia with a positive laboratory test for the heparin-dependent antibody, the cornerstone of therapy is the absolute discontinuation of heparin. It is imperative that all potential sources of heparin be avoided, a task that can be difficult given the ubiquity of the drug in the hospital setting. Platelet transfusions are not recommended, both because bleeding complications are uncommon and thrombotic events can follow the transfusions. Once heparin is discontinued, the platelet count should begin to increase within 24 to 48 h and reach normal levels by 4 to 5 days. For patients with confirmed venous or arterial thrombosis, the selection of substitute anticoagulant therapy is particularly problematic in the United States at present, as there is currently no readily available, effective, alternative antithrombotic drug. If long-term anticoagulation is required, treatment with warfarin should be commenced. However, warfarin may precipitate venous limb gangrene in patients with deep venous thrombosis complicating HIT by producing protein C deficiency without simultaneous inhibition of thrombin generation, so it should not be administered without concomitant use of a rapidly acting anticoagulant agent.