17 (44) 5(13) 4(10) 4(10) 2(5) 2(5) 1 (3) 1 (3) 1 (3) 1 (3) 1 (3)

Abbreviations: DVT, deep venous thrombosis; HIT, heparin-induced thrombocytopenia; PCI, percutaneous coronary intervention; PE, pulmonary embolism.

Source: Campbell et al., 2000a.

for, HIT. Forty-three tested positive for anti-PF4/polyanion antibodies, and 16 had thrombosis preceding bivalirudin treatment. Bivalirudin was given for an average of 8 days, with transition to warfarin (median overlap 4 days) performed in 44 of 52 patients. The authors noted minimal increase in the INR on bivalirudin alone (mean increase 0.33). Minor bleeding was seen in only a few patients and there were no amputations or deaths attributable to HIT.

Berilgen et al. (2003) treated 15 patients with multi-organ failure and suspicion for HIT with bivalirudin. Thirteen of the patients had renal and liver dysfunction, 10 were on dialysis, and eight required mechanical ventilation. Fourteen of the 15 had a positive PF4-dependent enzyme-immunoassay. One new catheter-related superficial thrombophlebitis developed and one patient with previous ischemic extremities required an amputation. Despite six deaths (not related to therapy), the authors concluded that bivalirudin can be safely and effectively administered in HIT patients with both renal and hepatic dysfunction. Dang et al. (2006) used bivalirudin, argatroban or lepirudin in 42 confirmed or presumed HIT patients. A composite of clinical outcomes (DVT, non-fatal MI, non-fatal stroke, limb amputation, and all-cause mortality) were similar in all three groups. The authors concluded that bivalirudin was a viable treatment alternative for the management of HIT.

There are several additional series of critically ill patients with acute HIT (or a history of HIT) with multiorgan failure who received bivalirudin. Ramirez et al. (2005) reported their experience with 42 patients, of whom 78.6% required an intensive care unit (ICU) stay and 14 who had renal or liver dysfunction or both. Nine of their patients with a history of HIT underwent an interventional procedure or surgery requiring bivalirudin administration. Transfusion was required in 28.6% of the patients, five died from multiorgan failure, and three suffered a new thrombotic event during therapy including a cephalic vein thrombosis, left ventricular thrombus, and an ischemic stroke (the latter occurred while the patient was on subtherapeutic doses of bivalirudin). There were no amputations and bivalirudin was felt to be safe and efficacious in both the ICU setting and critically ill individuals.

Similarly, Kiser and Fish (2006) evaluated the safety, effectiveness, and dosing of bivalirudin in 18 critically ill patients with hepatic and/or renal dysfunction (12 had both). The mean duration of bivalirudin therapy was 15 ± 17 days. The authors reported no clinically significant bleeding episodes, there were no amputations or deaths associated with a thrombotic event, and there was only one reported new thrombosis (a lower extremity DVT). Of note, however, three patients had blood clots form on the filters used for CVVH during treatment, and hepatic dysfunction had only a minimal effect on bivalirudin dosing.

There are several single case reports describing bivalirudin use for patients with HIT. Finks (2006) reported the successful use of bivalirudin as a primary anticoagulant during carotid endarterectomy; Robison et al. (2006) used it to maintain anticoagulation during femoral and tibial thromboembolectomy, while Alekshun et al. (2006) used bivalirudin in a patient with idiopathic giant-cell myocarditis requiring emergent biventricular assist device placement who had developed propagating clots in the chamber despite therapeutic heparin anticoagulation; both patients tested positive for anti-PF4/heparin antibodies. There is one report of long-term (2 mo) use of bivalirudin to treat serologically confirmed HIT complicated by recurrent left leg ischemia and arterial thrombosis while on LMWH (Bufton et al., 2002a). This patient received a continuous infusion of bivalirudin (22 mg/h [0.27 mg/kg/h]) using a continuous ambulatory drug delivery (CADD) pump.

Table 7 summarizes theoretical advantages of bivalirudin as a treatment for HIT.

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