Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin‐induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome associated with thrombosis. Alternative anticoagulation to heparin is needed for HIT patients during percutaneous coronary intervention (PCI). We evaluated argatroban, a direct thrombin inhibitor, for anticoagulation in this setting. Ninety-one HIT patients underwent 112 PCIs while on intravenous argatroban (25 microg/kg/min [350 microg/kg initial bolus], adjusted to achieve an activated clotting time of 300-450 sec). Primary efficacy endpoints were subjective assessments of the satisfactory outcome of the procedure and adequate anticoagulation during PCI. Among patients undergoing initial PCIs with argatroban (n = 91), 94.5% had a satisfactory outcome of the procedure and 97.8% achieved adequate anticoagulation. Death (zero patients), myocardial infarction (four patients), or revascularization (four patients) at 24 hr after PCI occurred in seven (7.7%) patients overall. One patient (1.1%) experienced periprocedural major bleeding. For patients who had subsequent hospitalizations (mean separation of 150 days) for repeat PCI using argatroban anticoagulation (n = 21), there were no unsatisfactory outcomes. Overall, outcomes were comparable with those historically reported for heparin. Argatroban therefore is a reasonable anticoagulant option in this setting, where current options are limited.

Treatment and Prevention of Heparin-Induced Thrombocytopenia

“…141 In these trials, 91 patients underwent PCI with a clinical success rate of 98% and an incidence of major bleeding of 1% 141 ( Table 17 ). Laboratory confi rmation of HIT was not required for these trials, so the proportion of patients who truly had HIT at the time of the procedure is uncertain.…”

Platelet Activity, Coagulation, and Fibrinolysis During Exercise in Healthy Males

“…19,20 Both thrombin inhibitors markedly reduced the coagulation profile and enhanced the fibrinolytic profile and fibrin gel permeability in samples taken at rest. Strenuous exercise induced platelet and leukocyte activation in vivo, augmented the responsiveness of platelets and leukocytes to agonist stimulation in vitro, and increased platelet-leukocyte aggregation.…”

“…Thereafter, the volunteers received enoxaparin (0.75 mg/kg intravenous injection followed by saline infusion; natriumklorid; Fresenius Kabi), 19 argatroban (350 g/kg intravenous bolus followed by 25 g/kg per minute of continuous infusion), 20 or placebo (saline bolus plus infusion). Infusions were administered, and activated clotting time was measured by an independent nurse who kept all other personnel blinded to the actual treatment given.…”

“…We did not assess the expression of platelet thrombin receptors (eg, PAR-1), which might influence exercise and treatment effects, and we did not perform a full evaluation of coagulation and fibrinolysis with measurements of individual components. The dosages of the thrombin inhibitors were chosen from clinical studies, 19,20 and dose-response studies with continuous infusion of the 2 drugs would further clarify their exact potencies regarding the presently evaluated effects.…”

How I treat heparin-induced thrombocytopenia and thrombosis

“…For patients who have received argatroban in this setting, the drug has been continued at reduced doses for a mean of 2 days after the procedure, in part, to prevent thrombosis due to an ongoing procoagulant process. 36 More experience is needed with the drug when used in combination with the inhibitors of the glycoprotein IIb/IIIa platelet receptors.…”