Molecular Weight Heparin In Patients Research Articles

Use of low molecular weight heparin in patients with heparin-induced thrombocytopenia undergoing carotid endarterectomy.

(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

Angiogenic effects of low molecular weight heparin in patients with stable coronary artery disease: A pilot study

Objectives. The study was designed to assess the feasibility of conducting a trial to investigate whether exercise and low molecular weight heparin therapy with dalteparin sodium (Fragmin) would improve collateral function to the ischemic myocardium in patients with coronary artery disease.Background. The severity of myocardial ischemia in patients with coronary artery disease is at least partly dependent on the status of the collateral circulation. Therefore, improvement in collateral function would potentially provide a unique way of alleviating myocardial ischemia. Because the combination of ischemia and heparin has previously been demonstrated to enhance collateral growth, we studied the anti-ischemic effects of combined treatment with dalteparin sodium and exercise-induced ischemia in patients with coronary artery disease.Methods. Twenty-three patients with stable coronary artery disease were randomized to receive either subcutaneous dalteparin sodium or placebo for a 4-week period. Patients received either placebo or 10,000 IU of dalteparin sodium by subcutaneous injection once daily for weeks 1 and 2 and 5,000 IU daily for weeks 3 and 4. During the 1st 2 weeks, patients were exercised to ischemia three times a day. At baseline and 4 weeks after treatment, treadmill exercise testing, exercise radionuclide ventriculography nd 48-h ambulatory ST segment monitoring were performed.Results. Eight (80%) of the 10 dalteparin sodium-treated patients compared with 4 (31%) of 13 placebo-treated patients (p < 0.02) had an increased rate-pressure product at the onset of 1 mm of ST segment depression. The duration of exercise to ischemia increased in all patients treated with low molecular weight heparin and in 62% of placebo-treated patients (p < 0.03). The number and duration of episodes of ST segment depression during ambulatory monitoring decreased by 30% and 35%, respectively (p < 0.05), in the dalteparin sodium group but were unchanged in the placebo group. The decrease in left ventricular ejection fraction with exercise was lower in 80% of dalteparin sodium-treated patients compared with 54% of placebo-treated patients (p = 0.06). When all five factors reflecting collateral function were considered together in a multivariate analysis of variance, there was a significant improvement in low molecular weight heparin-treated patients compared with placebo-treated patients (p = 0.014).Conclusions. This study provides preliminary evidence suggesting that exercise and low molecular weight heparin therapy with dalteparin sodium lessen myocardial ischemia and that the improvement is likely to be mediated by enhanced collateral function.

Prevention of Post-Operative Thrombosis by Low Molecular Weight Heparin in Patients Undergoing Hip Replacement

Prevention of Post-Operative Thrombosis by Low Molecular Weight Heparin in Patients Undergoing Hip Replacement

Prevention of Postoperative Venous Thrombosis: A Randomized Trial Comparing Unfractionated Heparin with Low Molecular Weight Heparin in Patients Undergoing Total Hip Replacement

A double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

Pharmacokinetic studies of standard heparin and low molecular weight heparin in patients with chronic renal failure.

The disappearance of the anticoagulant activities of a standard commercial heparin and of a low molecular weight (LMW) heparin (PK 10169), administered as single intravenous injections, was studied in patients with chronic renal failure. Heparin and LMW heparin anticoagulant activities were determined by activated partial thromboplastin time (APTT) and chromogenic assays of anti-Xa and anti-IIa activities. Following heparin injection, a fast initial decay of anticoagulant activities preceded a slow convex disappearance curve, in semilogarithmic plots. These experimental data are in agreement with a model based on a predominant saturable mechanism of elimination of heparin in patients with renal failure. The disappearance of LMW heparin anti-Xa activity was obviously different, with linear or concave elimination curves, and longer apparent half-life. Taken together, our kinetic data and those previously reported in normal subjects strongly suggest that the mechanism of elimination of the LMW heparin studied is not saturable (at least for the tested dosages), and that the kidneys play a minimal role in the elimination.