Laboratory and diagnostic workups. Immunologic assays (polyspecific ELISA, IgG-specific ELISA, and particle gel immunoassay) detect antibodies against the PF4 heparin complexes regardless of their capacity to activate platelets. These tests are highly sensitive but less specific for HIT because they also detect PF4-heparin antibodies in patients who do not have HIT; therefore, immunoassays have a lower positive predictive value but a high negative predictive value (>95%).5
Functional assays (serotonin release assay, heparin-induced platelet activation assay, and platelet aggregation test) detect antibodies that induce heparin-dependent platelet activation. These assays are highly sensitive and specific but are not available at many medical centers. The positive predictive value of these assays is higher (89% to 100%).5
Figure 1 provides a diagnostic and initial treatment algorithm for suspected HIT. Immunoassays to detect PF4-heparin antibodies are recommended when clinical probability of HIT is intermediate to high. In these patients, a negative result on serologic testing has a high negative predictive value and suggests that an alternative diagnosis is more likely. In patients with a positive serologic test and intermediate probability of HIT, a functional assay might be beneficial, as a positive result increases the probability of HIT. For patients with high probability of HIT and a positive immunologic assay, functional assays might not be indicated as the diagnosis is likely.
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Table 2. Approved nonheparin anticoagulants for HIT
Treatment. If the probability of HIT is intermediate to high based on the 4Ts scoring system, all heparin products, including heparin flushes, should be immediately discontinued and a laboratory investigation for HIT antibodies should be undertaken. An investigation for lower-limb DVT also should be pursued in patients with high probability of HIT, as the risk of thrombosis is more than 30-fold higher than controls, and studies show that approximately 25% of patients with HIT present with both thrombocytopenia and thrombosis.5 In addition, the presence of thrombosis might influence duration of anticoagulation.
Avoid platelet transfusions, as this might propagate thrombosis.
Anticoagulation. With a significant risk of thrombosis associated with this disorder, treatment with an alternative anticoagulant should be started. Vitamin K antagonists, such as warfarin, cannot be given in acute HIT because of the high risk of inducing skin necrosis and venous limb gangrene. Such anticoagulation should not be used until the platelet count increases to greater than 150×109/L. If warfarin already has been given, reversal with vitamin K is indicated.
Consequently, an alternative anticoagulant bridge to warfarin therapy must be used. Usually, the bridging agent will be one of two intravenous direct thrombin inhibitors (argatroban and lepirudin) approved for this purpose.6 Both are associated with a higher risk of bleeding. Argatroban is hepatically cleared; lepirudin is renally cleared. Table 2 summarizes dosing information for these agents. A third direct thrombin inhibitor, bivalirudin, is approved for treatment of HIT, but only during percutaneous coronary intervention.6
Finally, the recently FDA-approved oral direct thrombin inhibitor dabigatrin has not been studied in or approved for HIT.
Other rational therapies include the factor Xa inhibitors danaparoid and fondaparinux. However, only danaparoid is FDA-approved for use in the treatment of HIT. It can, in cases of low or moderate suspicion of HIT, be given in prophylactic doses, lowering the risk of major bleeding.
Duration of treatment. Whichever bridging anticoagulant is chosen, it should be continued until the platelet count has fully recovered. Further, prior to discontinuation, warfarin therapy should be administered for at least five days and the international normalized ratio (INR) should be therapeutic for approximately 48 hours.
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Figure 1. Evaluation and initial management algorithm