(Gottlieb, Sprung) Staff Anesthesiologist, Department of General Anesthesiology.(Tabares, Levy) Fellow, Department of Vascular Medicine.(Kottke-Marchant) Staff member, Department of Clinical Pathology.Received from the Departments of General Anesthesiology, Vascular Medicine, and Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio. Submitted for publication February 29, 1996. Accepted for publication May 25, 1996.Address reprint requests to Dr. Gottlieb: Department of General Anesthesiology, E-31, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland. Ohio 44195. Address electronic mail to: gottlia@cesmtp.ccf.-org.Key words: Complications: heparin-dependent platelet antibody; heparin-induced thrombocytopenia. Drugs: low-molecular-weight heparin (enoxaparin); unfractionated heparin. Drug effect: anticoagulation. Surgery: carotid endarterectomy.CAROTID endarterectomy (CEA) is a common vascular surgical procedure for patients with severe carotid stenosis. [1]Heparin therapy, widely used during CEA, is not without risks and sometimes may be associated with a decrease in platelet count or thrombosis, a condition called heparin-induced thrombocytopenia (HIT). [2]This condition is believed to be immunologically mediated and involves the formation of heparin-dependent platelet antibodies (HDPA) [3]that recognize a complex of heparin and platelet factor 4. The estimated prevalence of HDPA in patients receiving heparin is 7.8%. [4]In patients with HIT who are candidates for CEA, a substitute for unfractionated heparin (UFH) should be used. Low molecular weight heparins (LMWHs) have a favorably high anti-factor Xa-to-anti-factor IIa activity ratio, which implies an improved antithrombotic potential with fewer bleeding side effects. The antithrombotic intravenous dose of LMWH (enoxapirin) [5]during CEA has not been established. We report the intraoperative use (dose and monitoring) of enoxaparin (Lovenox, Rhone-Poulenc Rorer Pharmaceuticals, Collegeville, PA) in three patients with documented HIT and HDPA who underwent four CEAs.Three patients who were 73, 76, and 78 yr old and had 80 to 99% stenosis of the internal carotid artery underwent elective CEA under general anesthesia. All had a history of severe coronary artery and peripheral vascular diseases and underwent multiple vascular reconstructions with repeated exposure to UFH, complicated by either thrombosis or thrombocytopenia. All patients had positive HDPA to UFH as documented by the platelet aggregation method. [6,7]Results of the patients' preoperative coagulation profiles were within normal limits (Table 1), and they had no history of bleeding tendencies immediately before these operations. Tests for HDPA to both UFH and LMWH were repeated before each CEA. In all cases, the test results were negative for LMWH. In two patients, repeated tests for HDPA to UFH became negative 4 (patient 1) and 12 months (patient 3) after the initial testing.Enoxaparin, which was used as an anticoagulant in all cases, was given intravenously 5 min before carotid artery clamping. In one patient with symptomatic carotid disease (patient 3), a continuous intravenous infusion of 2 mg *symbol* kg sup -1 *symbol* day sup -1 enoxaparin was administered before operation. This treatment was continued until carotid artery cross-clamping, when an additional intravenous bolus of 45 mg enoxaparin was given.The antithrombotic effect of enoxaparin was monitored with anti-factor-Xa activity assays (Dupont ACA, Wilmington, DE) before surgery, 5 min after injection of enoxaparin, after protamine sulfate administration (when used), and on the first postoperative day. At these times, we also obtained prothrombin time, activated partial thromboplastin time, a platelet count, fibrinogen concentration, and activated clotting time. Table 1lists all antithrombotic therapy and coagulation parameters. The operative and postoperative courses were uneventful and the patients had no thrombocytopenia, thrombosis, or bleeding. No hematoma formation was observed, and the average amount of neck drainage in the four operations was 25 ml, which is comparable to other CEAs.Thrombotic complications after heparin therapy may involve different systems and are associated with significant morbidity and death. [8-10]Unexplained recurrent thrombocytopenia, thrombotic events, or both, in patients receiving UFH should raise the suspicion for HIT, and testing for HDPA is strongly indicated in these patients. All of our patients had histories suggestive of HIT and all had documented HDPA by the platelet aggregation method. [6,7]Heparin-dependent platelet antibodies can be detected by several methods. A routinely used platelet aggregation method appears to be highly specific but has low sensitivity. [6,7]The14C-labeled serotonin-release assay, presumably the standard for HDPA testing, has high specificity and sensitivity [4]but involves the use of radioactive material and therefore is unavailable in many clinical laboratories. A recently developed platelet factor 4/heparin enzyme-linked immunosorbent assay produces results that correlate closely with those of the serotonin-release assay. [11]Two of our patients (patients 1 and 3) had negative antibody test before CEA after previously being diagnosed with positive HDPA. It was suggested that after a period of 3 to 6 months HDPA may either disappear [12]or become undetectable using14C-serotonin release. At the same time, platelet aggregation tests are less sensitive for detecting HDPA during even acute events [6,7]and may fail to detect low antibody titer present several months after the initial diagnosis. In this case, this
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May 1, 1997
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