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

Abstract

SummaryA 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.

Bleeding complications after systematic switch of routine thromboprophylaxis for major orthopaedic surgery

“…The overall bleeding rate of 2% after major orthopaedic surgery is comparable with the clinical outcome of large randomized trials (10). The rate of symptomatic DVT and PE during the hospitalization was even lower than expected, confirming the high efficacy of thromboprophylaxis with LMWH in daily clinical practice.…”

“…Randomized controlled trials confirmed that thromboprophylaxis with low-molecular-weight heparins (LMWH) substantially reduces the rate of DVT and PE (7)(8)(9). The rate of bleeding complications after major orthopedic surgery with thromboprophylaxis approximates 2% (10). However, because of the different pharmacodynamic properties, LMWH are not interchangeable for the various indications.…”

Blood Loss in Cemented THA is not Reduced with Postoperative Versus Preoperative Start of Thromboprophylaxis

“…Some researchers use a decrease in hemoglobin greater than 2 g/dL in the definition of major bleeding [11], and the rate of major bleeding frequently is reported as a safety outcome in trials of thromboprophylaxis [9,13,16,23]. We found such a decrease in hemoglobin for the majority of patients until the first postoperative injection (83% versus 90%) and the day after surgery (93% versus 90%), which indicates a decrease in hemoglobin is a poor parameter for defining major bleeding in patients undergoing THA.…”

“…Type of antithrombotic drug, dosage, and timing of the first dose may influence bleeding and development of thrombosis. Low-molecular-weight heparins (LMWHs) are widely used antithrombotics because of their favorable efficacy-to-safety profiles [9,23], but the best timing of the first dose remains controversial [24,28]. Preoperative initiation 12 hours before surgery has been based on the premise that DVT starts during surgery and that preoperative initiation is necessary to optimize antithrombotic effectiveness [17,27].…”

Absence of Transplacental Passage of the Low Molecular Weight Heparin Enoxaparin

“…Since there is no clear recommendation regarding the dose of LMWHs in pregnancy, we used 40 mg of enoxaparin, as this is the recommended dose either for prophylaxis in patients at high risk of VTE (major orthopedic surgery [19] or cancer surgery [20], acutely ill medical patients [21]), or, according to some authors [4], for obstetric thromboprophylaxis. The timing of fetal blood sampling (3 h after the enoxaparin injection) corresponds to the time of peak blood levels of enoxaparin in the mother [8] and also to the peak of placental blood flow, allowing most drugs capable of crossing the placenta to do so in a very short period of time [16].…”