Nonheparin Anticoagulants for Heparin-Induced Thrombocytopenia
The following are 10 points to keep in mind about the clinical features and treatment of heparin-induced thrombocytopenia:
1. Heparin-induced thrombocytopenia is a prothrombotic disorder mediated by immunoglobulin G antibodies that bind to conformational epitopes on platelet factor 4 (PF4)-heparin complexes. These immune complexes initiate platelet activation and the coagulation cascade in a mechanism that involves the Fcγ receptor IIa.
2. When administered postoperatively, unfractionated heparin carries a higher risk (1.0% to 5.0%) of heparin-induced thrombocytopenia, compared to low molecular weight heparin, which is associated with a 0.1% to 1.0% risk.
3. Almost all patients with heparin-induced thrombocytopenia have anti-PF4-heparin antibodies, but most patients with anti-PF4-heparin antibodies do not have heparin-induced thrombocytopenia. The titer of the antibody, size of the PF4-heparin complexes, patient characteristics, and type of surgery impact the likelihood of developing pathogenic PF4-heparing antibodies.
4. The potential overdiagnosis of heparin-induced thrombocytopenia may be overcome by more discretionary testing limited to those populations with higher prevalence of disease and the use of clinical scoring systems (e.g., the 4T score or the HIT Expert Probability Score, both with their own advantages and limitations).
5. Two general types of serologic assays are used to diagnose heparin-induced thrombocytopenia: quantitative direct-binding assays that detect antibodies and functional assays that detect platelet activation induced by these antibodies. Direct binding assays are highly sensitive, but poorly specific (i.e., a negative test essentially rules out the diagnosis, but false positives are common). Functional assays (such as the serotonin-release assay), while both highly specific and sensitive, are limited by their availability and lack of standardization.
6. The most appropriate anticoagulant for use in patients with heparin-induced thrombocytopenia remains uncertain, but it should be immediate-acting, capable of interrupting the coagulation cascade at the level of thrombin or factor Xa, and associated with low bleeding risk.
7. Direct thrombin inhibitors and danaparoid (withdrawn from the US market in 2002) are favored treatments for heparin-induced thrombocytopenia in published guidelines, primarily because they have been evaluated in large, prospective studies.
8. The authors advocate the use of fondaparinux (although it is not Food and Drug Administration approved) for the treatment of heparin-induced thrombocytopenia in patients with normal renal function, based on emerging data on efficacy and bleeding risk. Argatroban (synthetic direct thrombin inhibitor) would be a reasonable option in those with impaired renal function.
9. Anticoagulants with short half-lives (e.g., argatroban) may be treatments of choice for the management of heparin-induced thrombocytopenia in patients who are likely to require invasive procedures.
10. The authors recommend that anticoagulation should be continued 4-6 weeks in patients with isolated heparin-induced thrombocytopenia, and for 3 months in patients with thrombosis. Warfarin should be introduced once the platelet count has normalized after an acute episode of heparin-induced thrombocytopenia.
Clinical Topics: Anticoagulation Management
Keywords: Immunoglobulin G, Polysaccharides, Chondroitin Sulfates, Heparin, Low-Molecular-Weight, Platelet Factor 4, Dermatan Sulfate, Pipecolic Acids, United States Food and Drug Administration, Thrombosis, Platelet Activation, Thrombocytopenia
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