Use of Bivalirudin for Suspected Heparin-Induced Thrombocytopenia during Lower Extremity Revascularization
- Volume 2 - Issue 6 - Nov/Dec 2005
- Posted on: 9/5/08
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Jay G. Robison, MD, Fred Crawford, Jr., MD, Walter Uber, PharmD
Advantages of various direct thrombin inhibitors, a modified dosing schedule for bivalrudin, and experience with monitoring parameters are described. These advantages may form the basis for consideration when alternative anticoagulation to heparin is desired during peripheral vascular procedures.
An 82-year-old, 65 kg, white male underwent evaluation for progressive fatigue and shortness of breath. He had undergone a Hancock porcine mitral valve replacement in conjunction with a one-vessel coronary artery bypass 12 years previously. He also had a history of chronic atrial fibrillation, requiring warfarin therapy. After evaluation confirmed significant mitral regurgitation, he was admitted for heparinization and cessation of warfarin therapy prior to “re-do” valve replacement. His preoperative platelet count was 162K/cu mm. He underwent an uncomplicated procedure using a #27 Carpentier-Edwards mitral valve with a concomitant carotid endarterectomy and Dacron patch angioplasty for asymptomatic critical left internal carotid stenosis. Aspirin was begun soon postoperatively. His immediate postoperative platelet count was 80K/cu mm and continued to remain low through the second postoperative day (POD) at 64K/cu mm. Subcutaneous heparin was restarted at 5000 units every eight hours in the evening of POD 2. The platelet count remained low at 68 K/cu mm on POD 3, but his platelet factor 4 (PF4) assay was negative. Coumadin was begun on POD 5, the heparin was discontinued, and a repeat PF4 assay was again negative. By POD 6, the platelet count had increased to 148K/cu mm, and his prothrombin time was 15.5 sec (nl 12.6–15.2); international normalized ratio (INR) was 1.19.
On the seventh POD with an INR of 1.21, he developed sudden onset of the left foot, numbness and calf pain during physical therapy. Initial evaluation suggested a viable functioning limb with no change in pulse status and an audible Doppler signal. However, by the following morning (on POD 8), symptoms had not only progressed but, only a femoral pulse was palpable in the symptomatic limb, which remained cold but appeared viable. Femoral and pedal pulses were palpable in the asymptomatic limb. There was no evidence of aortic or peripheral aneurysms, and the ankle brachial index was reduced to 0.71, but no toe pressure was discernable on the symptomatic extremity.
Though an echocardiogram showed the mitral valve to be well seated without thrombus, a thromboembolic event was suspected, and he was taken directly to the operating room for exploration and angiography without reversal of anticoagulation. Despite previous negative PF4 assays and no serologic evidence of heparin-induced thrombocytopenia (HIT), previous diminished platelet counts and the sudden onset of acute leg ischemia heightened clinical concern about the possibility of serologically negative HIT, as well as concern about using heparin during any attempt at lower extremity revascularization.
Because of these concerns, bivalirudin was used for intraoperative anticoagulation. Evaluation of the patients’ underlying renal function was calculated using the Cockcroft-Gault equation (serum creatinine: 1.1 mg/dl), and was estimated to be approximately 48 ml/min at the time of operation. Since experience using bivalirudin for anticoagulation in patients undergoing off-pump coronary artery bypass operations, percutaneous coronary, and peripheral interventions has been described,1–3 we chose to use a modified version of these dosing strategies to target a lower level of anticoagulation for this open surgical procedure. A bolus dose of bivalirudin 0.5 mg /kg was given intravenously over 10–20 seconds, followed by a continuous infusion of 1.0 mg/kg/hr to achieve and maintain an activated clotting time (ACT), approximately twice baseline (range: 225–250 seconds). Activated clotting times were measured intraoperatively at baseline, 5 minutes after the loading dose given, and then approximately every 15 minutes throughout the procedure. Activated partial thromboplastin time, PT, INR and platelet count were also monitored periodically during the procedure (Table 1). Documentation of an ACT in the predetermined range was confirmed prior to the placement of arterial clamps and the interruption of flow at the femoral level.
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