DVT Prophylaxis for Total Joint Arthroplasty
Length of Prophylaxis

Muthu Ganapathi, MSc, FRCS(Ortho), Fellow in Joint Reconstruction
Pascal A. Vendittoli, MSc, FRCSC
Maisonneuve-Rosemont Hospital
Department of Surgery, Universit de Montral
Montral, QC

Although prophylaxis to prevent DVT following THA and TKR is universal in North America, there is a wide variation in the choice of the prophylaxis used as well as the duration of prophylaxis. With increasing trends towards shorter duration of hospital stay and emphasis on cost benefit relationship, it is important to base one's DVT prophylaxis regimen on the available scientific evidence.

Most of the studies reporting on the effectiveness of DVT prophylaxis show a significant decrease in the rate of asymptomatic DVT detected by universal screening methods. As the incidence of symptomatic VTE is much less, the number of patients needed to provide adequate power to detect a significant effect is much larger. It has been estimated >50,000 patients would be required to provide adequate power to show a risk reduction in fatal PE1. However, as reduction in the venography-detected asymptomatic DVT parallels, reduction in the symptomatic VTE, the former is generally considered to be a valid surrogate for the latter.

Various issues require consideration when selecting the optimal duration of prophylaxis. They include: 1) the possible variation in the evolution of VTE following THA and TKA, 2) the relevance of this variation in the relative effectiveness of the prophylaxis, 3) risk of complications (bleeding, haematoma and wound drainage) as well as 4) the cost benefit ratio.

While half of the symptomatic VTE occur within 17 days following THA, half of such events following TKA occur within seven days2 suggesting a possible difference in the pathophysiology. It may also be indicative of the greater soft tissue trauma occurring during TKA with resultant release of more prothrombotic factors. In addition, it has been found that without DVT prophylaxis, 50% to 60% of the DVT following THA occur in the proximal veins3 in contrast to TKA where 90% occur in the calf1.

Despite the difficulties in assessing the efficacy of DVT prophylaxis, evidence from meta-analysis of RCT's provide some information on which we can base our DVT prophylaxis strategy. Broadly, the length of the DVT prophylaxis has been categorized either as "short duration prophylaxis" (under two weeks) or "extended duration prophylaxis" (variably between three to six weeks).

A recent meta-analysis has been done on prospective studies which have investigated symptomatic outcomes following THA and TKA when "short duration prophylaxis" (seven to ten days) with either fixed dose LMWH or adjusted dose Warfarin was used4. It found that the incidence of symptomatic VTE was 2.5% following THA compared to 1.4% after TKA (p=0.02) with "short duration prophylaxis".

Another meta-analysis of nine RCTs comparing "extended duration prophylaxis" using un-fractionated Heparin or LMWH with placebo or untreated control provides support for "extended-duration prophylaxis" (30 to 42 days)5. The pooled estimate revealed a highly significant reduction in symptomatic VTE with "extended duration prophylaxis". This reduction was greatest in THA (1.4% versus 4.3%) when compared to TKA (1.0% versus 1.4%). Although the results for TKA were derived only from two studies, the difference in the relative risk reduction may be indicative of the differences in the natural history of VTE between the two procedures.

A further meta-analysis of six trials has also found that extending LMWH prophylaxis after discharge (19 to 29 days) was significantly more effective in reducing the overall DVT rate as well as the proximal DVT and symptomatic DVT when compared with out-of-hospital placebo in patients undergoing THA6.

Thus, evidence from the above studies suggests that "extended duration prophylaxis" following THA is beneficial, with reduced VTE incidence compared with "short duration prophylaxis". However, there is no evidence to show that "extended duration prophylaxis" beyond ten days is necessary after TKA5,7. It has also been suggested that in these cases, Aspirin may be considered beyond the ten days if there is no contraindication8.

A study analyzing the cost-effectiveness of "extended duration prophylaxis" has suggested that there is insufficient economic evidence to support extended thromboprophylaxis with LMWH following THA9. Although the cost-effectiveness of Warfarin was potentially quite favourable, this finding was based on limited clinical evidence. They have suggested that further research is warranted.

Our current DVT prophylaxis regimen is to use LMWH for four weeks following THA and for ten days following TKA. Aspirin may be considered for another three weeks for TKA if there is no contraindication, although the evidence for that is limited. In TKA patients with known risk factors for DVT, we use LMWH for four weeks.

While these recommendations are based on the current available evidence, further studies are warranted to evaluate alternative protocols which may be more cost-effective and with fewer side effects without compromising the efficacy. A randomized, Canadian multi-centre study, "EPCAT group" will be started in 2007 to compare the effect of Aspirin and LMWH when given after "short duration prophylaxis" with LMWH in THA patients. Further studies on risk stratification may also allow selecting high risk TKA patients for whom "extended duration prophylaxis" may be beneficial.

References

  1. Sculco T.P., Pellegrini V.D., Westrich G.H., Bottner F. Prophylaxis against venous thromboembolic disease in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 2002;84:466-77.
  2. White R.H., Romano P.S., Zhou H., Rodrigo J., Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty. Arch Intern Med 1998;158-14:1525-31.
  3. Westrich G.H., Sanchez P.M. Prevention and treatment of thromboembolic disease: an overview. Instr Course Lect 2002;51:471-80.
  4. Douketis J.D., Eikelboom J.W., Quinlan D.J., Willan A.R., Crowther M.A. Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes. Arch Intern Med 2002;162-13:1465-71.
  5. Eikelboom J.W., Quinlan D.J., Douketis J.D. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet 2001;358-9275:9-15.
  6. Hull R.D., Pineo G.F., Stein P.D., Mah A.F., MacIsaac S.M., Dahl O.E., Butcher M., Brant R.F., Ghali W.A., Bergqvist D., Raskob G.E. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001;135-10:858-69.
  7. Friedman R.J. Optimal duration of prophylaxis for venous thromboembolism following total hip arthroplasty and total knee arthroplasty. J Am Acad Orthop Surg 2007;15-3:148-55.
  8. Kearon C. Duration of venous thromboembolism prophylaxis after surgery. Chest 2003;124-6 Suppl:386S-92S.
  9. Skedgel C., Goeree R., Pleasance S., Thompson K., O'Brien B., Anderson D. The cost-effectiveness of extended-duration antithrombotic prophylaxis after total hip arthroplasty. J Bone Joint Surg Am 2007;89-4:819-28.

 

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