Conclusion

Argatroban, a synthetic DTI, is an effective anticoagulant with a predictable dose-response effect. This agent offers several theoretical advantages as an anticoagulant for patients with HIT: it inhibits free and bound thrombin, it does not cross-react with HIT antibodies, and its anticoagulant effects are rapidly active and also rapidly reversible. Further, upon prolonged or repeated administration, argatroban is well tolerated, with no alteration in anticoagulant response and no induction of drug-specific antibodies.

In clinical studies, argatroban therapy, compared with historical controls, improves outcomes of HIT, particularly thrombosis and its sequelae, without increasing bleeding risk. Argatroban also provides safe and effective anticoagulation in patients with a history of HIT requiring acute anticoagulation. No intracranial hemorrhage has occurred during argatroban infusion in over 900 patients with HIT, including many with stroke, who have received argatroban during clinical trials. These benefits are achieved when argatroban is administered iv at 2 mg/kg/min, titrated to achieve an aPTT 1.5-3.0 times baseline. Although no initial dosage adjustment is required for patients with renal impairment, an initial dose of 0.5 mg/kg/min is recommended for hepatically impaired patients and may be prudent in patients with conditions associated with hepatic congestion. Also in clinical studies, argatroban at higher doses (25 mg/kg/min, titrated to achieve an ACT of 300-450 s) provides safe and adequate anticoagulation during PCI in patients with or risk of HIT. Lower doses of argatroban in combination with a GPIIb/IIIa antagonist also provide safe and adequate anticoagulation during PCI. The recommended dosing schedules for the approved uses of argatroban in the United States, i.e., prophylaxis or treatment of thrombosis in HIT and during PCI for patients with or at risk for HIT, are summarized in Table 4.

Patients with or at risk of HIT have also successfully undergone hemodialy-sis using argatroban anticoagulation, and although not studied in prospective clinical trials, peripheral intervention, cardiovascular surgery, and ECMO. Arga-troban therefore offers a versatile therapeutic option for the management of patients with or at risk of HIT in diverse clinical settings.

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