DVT Prophylaxis for Total Joint Arthroplasty
Low-Molecular-Weight Heparin

Rajiv Gandhi, M.D., FRCSC
Nizar N Mahomed, M.D., ScD, FRCSC
Division of Orthopaedic Surgery, Toronto Western Hospital, University of Toronto
Toronto, ON

The incidence of asymptomatic deep vein thrombosis (DVT) in joint replacement surgery ranges from 45 to 57% after total hip replacement (THR), and 40 to 84% after total knee replacement (TKR) in the absence of thromboprophylaxis1. Prophylaxis with low-molecular-weight Heparin (LMWH) decreases that incidence to about 15% in THR and 30 % in TKR2-5. The mortality from pulmonary embolism (PE) following joint replacement surgery is estimated at 0.5-2.0 %6-11.

It is generally agreed upon that patients need some sort of prophylactic regime following total joint replacement; however, the selection of a prophylactic regimen involves a balance between efficacy and safety.

The low-molecular-weight Heparins are prepared by either chemical or enzymatic

depolymerization of unfractionated Heparin. The mechanism of action of low-molecular-weight Heparin is through the inhibition of factor Xa12,13.

The low-molecular-weight Heparins have many clinical advantages as compared to unfractionated Heparin. They have a more predictable dose-response than standard Heparin because of reduced binding to plasma proteins and vascular endothelium. They also have a better bioavailability: 90% compared with 30% to 40% for standard Heparin. They also have a longer half-life as compared with standard Heparin14. A fixed consistent dose of LMWH can be used, and there is no need for laboratory monitoring as they don't increase the activated partial thromboplastin time.

Low-molecular-weight Heparin is metabolized in the kidney and therefore should be used with caution in patients with renal insufficiency. Originally, it was thought that LMWH was not associated with the development of thrombocytopenia, but this is not true15. It has been suggested that the platelet count of patients who are receiving low-molecular-weight Heparin for prophylaxis against deep venous thrombosis be checked at least once prior to discharge16.

The efficacy of LMWH has been proven in many studies to decrease the risk of proximal and distal DVT by at least 70% as compared to placebo7,17-19. LMWH has been compared with Warfarin in a number of multi-centre randomized clinical trials using venographically proven DVT as the outcome measure20-23. These studies have all shown that LMWH was more efficacious at preventing clots than Warfarin at the expense of a slightly greater bleeding risk (Table 1).

Table 1. Summary of data from randomized trials comparing LMWH and Warfarin for prevention of VTE


No. Patients

overall DVT Rate(%)

Proximal DVT rate(%)

PE rate(%)

Risk (%)

Hamulyak et al23






RD Group21
RD Heparin






Hull et al20






Francis et al22







NR- Not Reported

















The optimal timing for the first dose of LMWH prophylaxis is controversial. The largest randomized trial addressing this issue is the North American Fragmin Trial (NAFT) which showed that preoperative initiation of Fragmin (2 h preop) increased major bleeding without improved antithrombotic efficacy compared to the early postoperative regimen (mean 6 h postop)25. It is important to note that the first dose of Fragmin, whether started preop or postop, was a half dose at 2500U as compared to the recommended dose of 5000U to decrease the risk of bleeding.

With the increasing use of neuraxial anesthesia, the potential for spinal hematoma with preoperative administration of LMWH remains a concern. In the NAFT study, there were no cases of spinal hematoma among the 482 patients who received neuraxial anesthesia and were administered the modified regimens of Dalteparin (either preoperatively or postoperatively)25.

The recommendations from Chest26 are to begin prophylaxis 6 h after surgery. Starting Heparin 2 h preoperatively or within the first 6 h after surgery only increases the risk of bleeding without any beneficial effect on thromboembolic prophylaxis. Initiation 12-24 hours postoperatively may not be as effective as initiation at 6 h postoperatively. Further randomized trials that directly compare different times of postoperative initiation (eg, 6 h vs 12 h) of the same LMWH are required to establish definitively the timing of the first dose that optimizes the risk-benefit of this prophylaxis.

A literature review by Heit demonstrated that the optimal duration of prophylaxis for most patients should be 7-10 days27. Others have suggested a duration of prophylaxis of 10-14 days28. Prolonged therapy should be considered for those with a history of VTE or other risk factors.

The most effective prophylactic agents for hip and knee replacement patients include low-molecular-weight Heparin, Warfarin, and Fondaparinux, however the optimal prophylactic agent is not yet known. Future studies that stratify patients by risk may help determine the optimal therapeutic agent and the appropriate duration of treatment for each patient.


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