Pharmacy & Therapeutics - November 2008 - (Page 647)

Heparin-Induced Thrombocytopenia continued from page 644 effects. Therefore, clinical HIT does not always develop in patients with a positive test result. The utility of the test can be improved with increased specificity to detect IgG antibodies to the heparin–PF4 complex rather than detecting a combination of IgG/IgA/IgM. In light of a positive ELISA and no confirmatory functional test, the pretest probability (the 4 T’s) consistent with clinical presentation should strengthen the diagnosis of HIT.11,12,18 MANAGEMENT If the diagnosis of HIT is strongly suspected (often prior to laboratory confirmation), heparin must be discontinued immediately. This includes heparin-bonded catheters and heparin flushes of intravascular catheters, which can occur as incidental exposures despite a clearly written order to discontinue heparin from the medical house staff. Recording “heparin allergy” in the patient’s record and posting signs at the bedside warning against the use of heparin products are other ways to prevent incidental exposures.23 Low-molecular-weight heparin (LMWH) should also be avoided because of its high potential for cross-reactivity with HIT antibodies, even though it is less likely to trigger antibodies than UFH upon initial administration. Because of the high risk of subsequent thrombosis (25% to 50%) that continues up to 30 days after heparin is discontinued,24 an alternative anticoagulant should be used until platelet counts recover. Examples include a direct thrombin inhibitor such as lepirudin (Refludan, Bayer), bivalirudin (Angiomax, Ben Venue) or argatroban (Novastan, GlaxoSmithKline), or a factor Xa inhibitor such as danaparoid (Orgaran, Organon) or fondaparinux (Arixtra, GlaxoSmithKline). This recommendation is based on the presence of thrombocytopenia whether or not thrombosis is present. Optimal alternative agents should differ in their mechanism of anticoagulation. They should lack cross-reactivity with the heparin–PF4 antibodies, should be fast-acting, and should have a short half-life. They should be easy to monitor and should be well tolerated with a low incidence of bleeding risk. Table 4 summarizes the current American College of Chest Physicians (ACCP) recommendations for the treatment of HIT. Table 5 depicts alternative agents to heparin anticoagulation in the setting of HIT—agents that are currently available in the U.S. The only two agents approved for management of HIT in the U.S. are the direct thrombin inhibitors lepirudin and argatroban. Direct Thrombin Inhibitors Lepirudin (Refludan) Lepirudin, a recombinant protein, is modified and derived from hirudin, a natural medicinal anticoagulant used for centuries and found in leech saliva. It is a potent ir reversible direct thrombin inhibitor that forms a 1:1 complex with throm- Table 4 Treatment of Heparin-Induced Thrombocytopenia (HIT)* Strategy Strongly suspected (or confirmed) HIT (with or without thrombosis) Recommendation (Grade) • Discontinue all heparin (UFH or LMWH, flushes) • Administer a non-heparin anticoagulant ° Lepirudin (1C) ° Argatroban (1C) ° Bivalirudin (2C) ° Fondaparinux (2C) • Routine ultrasonography of lower-limb veins (1C) • Vitamin K antagonist is not recommended until platelet count has recovered (at least 150 x 109/L) (1B) • Vitamin K antagonist should be given only during overlapping alternative anticoagulation (minimum five days) and started at a low dose (maximum: 5 mg warfarin) (1B) • Alternative anticoagulation should be continued until platelet count has reached stable plateau and the INR has reached the intended target range (1B) • Vitamin K should be given (10 mg orally or 5–10 mg intravenously) (1C) • Do not give (2C) Screening for DVT (whether or not clinical evidence is present) Management of DTI–vitamin K antagonist overlap Reversal of vitamin K antagonist anticoagulation (for patients receiving a vitamin K antagonist at the time of HIT diagnosis) Prophylactic platelet transfusions (in patients without active bleeding) DTI = direct thrombin inhibitor; DVT = deep vein thrombosis; INR = International Normalized Ratio; LMWH = low-molecular-weight heparin; UHF = unfractionated heparin. * Recommendations from the American College of Chest Physicians, 2008. Data based on text from Warkentin TE, Greinacher A, Koster A, et al. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 8th ed. Chest 2008;133(6 Suppl):342S–343S.13 Vol. 33 No. 11 • November 2008 • P&T® 647

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Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

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