ArticlePharmacotherapy of heparin-induced thrombocytopenia: Therapeutic options and challenges in the clinical practices
Section snippets
Risk factors
Patients' exposure to heparin is the main risk factor and a critical step in the development of HIT (Table 1). A heparin source such as bovine lung is more immunogenic than those produced from porcine intestine,15 and the risk of HIT rises with the length and volume of exposure to heparin as well as the route of administration,16 and more likely with intravenous heparin than subcutaneous administration.17, 18, 19 Nevertheless, HIT can develop from any heparin exposure, including incidental
Pathophysiology
HIT is an autoimmune response caused by the formation of antibodies that activate platelets after heparin administration.27, 28 This response leads to an interaction with PF4, which is normally found on endothelial cells and platelets, and formation of immunogenic heparin–PF4 complexes that cause an immunologic response. Antibodies are generated resulting in a complex forming among antibodies, heparin, and PF4. This complex leads to further platelet activation, resulting in formation of
Clinical presentation and laboratory diagnosis
HIT may occur rapidly or with a delayed onset, depending on the presence of heparin–PF4 antibodies from a previous administration and sensitization of heparin and related molecules may induce rapid-onset HIT.33 In patients exposed to heparin for the first time, the onset of HIT may occurs 5–10 days after receiving heparin.4, 5, 12, 34 The thrombocytopenia in HIT is usually moderate in severity, with a median platelet count being between 50 and 80 × 109/L, although the nadir platelet count can
Renal replacement therapy
Renal replacement therapy is a term used to cover a large number of different procedures patients with renal failure such as hemodialysis procedures. The most commonly used anticoagulant in this setting is heparin to maintain the patency during these procedures. Argatroban and danaparoid have both been used and are recommended for patients with HIT who need renal replacement therapy74, 75, 76; the use of regional citrate is suggested for patients with a past history of HIT.4, 5
Pregnancy
Pregnant patients have a lower risk of developing HIT during pregnancy than in nonpregnant populations, especially when LMWH is used.77, 78 Nonheparin anticoagulants should be initiated once HIT is confirmed and heparin should be immediately discontinued. The evidence available on the efficacy and safety of nonheparin anticoagulants in this patient population is still very low. For pregnant women with acute or subacute HIT, danaparoid has been suggested and the use of lepirudin or fondaparinux
Switching to an oral anticoagulant
The risk for severe thrombotic complication of the microvasculature is associated with acute HIT. Avoidance of vitamin K antagonists (VKA) such as warfarin (which can induce skin necrosis owing to rapid depletion of protein C, a natural occurring anticoagulant) and variations in half-lives of vitamin K–dependent factors should be considered.79 Once HIT is confirmed, patient receiving VKA should be held and International Normalized Ratio (INR) should be reversed by vitamin K. Platelet recovery
Duration of anticoagulation for HIT
The risk of HIT for subsequent venous thromboembolism is reversible and transient. Therefore, anticoagulation duration is suggested to be continued for 4–6 weeks in patients with confirmed isolated HIT and for a minimum of 12 weeks in patients associated with thromboembolic events.4, 5, 81
Platelet administration
Because thromboembolic events are seen as complications for HIT more than bleeding diathesis and owing to the clinical concern that platelet administration may increase the risk of thromboembolic events, platelet administration is unnecessry.4, 5, 12
Conclusions and clinical considerations
The diagnosis of HIT requires clinical evaluation and laboratory confirmation. Platelet count monitoring should performed every 2 or 3 days in patient population with a risk of HIT >1%. When HIT is strongly suspected, management should include immediate discontinuation of all heparin formulations and the start of alternative, nonheparin anticoagulants. VKA should not be given. Instead, if VKA was given, reverse elevated INR by administering vitamin K and avoid platelet transfusions. A serotonin
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