Correspondence

Reviparin after Leg Injury Requiring Immobilization

N Engl J Med 2003; 348:1061-1063March 13, 2003

Article

To the Editor:

Lassen et al. (Sept. 5 issue)1 note the high risk of venous thrombosis in patients with leg injury requiring immobilization, as well as previous studies of prophylaxis in this population. Given this high risk, none of the participants in their study should have been treated with placebo.

Hubertus P.A. Jersmann, M.D., Ph.D.
Royal Adelaide Hospital, Adelaide 5006, Australia
jersmann@iprimus.com.au

1 References

1. 1

   Lassen MR, Borris LC, Nakov RL. Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization. N Engl J Med 2002;347:726-730
   Full Text | Web of Science | Medline

To the Editor:

Lassen et al. did not address the possible influence of surgery on the incidence of thromboembolic events in their study. The surgical procedure itself and related factors, including the site, technique, and duration of the procedure, the type of anesthetic, and the presence of infection, may affect the risk of venous thrombosis.1 Could the authors provide data on the incidence of venous thromboembolism in patients who underwent surgical treatment and in those who did not?

Philippe Girard, M.D.
Institut Mutualiste Montsouris, 75014 Paris, France
philippe.girard@imm.fr

1 References

1. 1

   Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001;119:Suppl:132S-175S
   CrossRef | Web of Science | Medline

To the Editor:

Lassen et al. did not provide information on the race or ethnic group of the patients enrolled in their study. The indication for thromboprophylaxis may need to be tailored according to race or ethnic group.

It has been reported that Asians are at lower risk for pulmonary embolism and deep venous thromboembolism in the absence of prophylaxis (1 to 3 percent) than are whites.1,2 Routine thromboprophylaxis has not been used in Asian countries, and there have been no major clinical problems. The discrepancy may be attributable in part to genetic backgrounds. The most common inherited risk factors among whites, factor V Leiden and prothrombin G20210A, are rare among Asians.3

Hemorrhage, a common and potentially fatal complication of anticoagulation therapy, tends to occur more frequently in Asians than in whites.1 Its incidence reaches 6.6 percent per year among Asians receiving warfarin therapy with a goal of an international normalized ratio of 2.8.4

We would appreciate it if the authors could provide data on race or ethnic group for the patients in their study. Further investigation of the safety and efficacy of thromboprophylaxis among Asians as compared with whites will help guide clinical care.

Naoko Murashige, M.D.
Masahiro Kami, M.D.
Yoichi Takaue, M.D.
National Cancer Center Hospital, Tokyo 104-0045, Japan
nmurashi@ncc.go.jp

4 References

1. 1

   Ho YH, Seow-Choen F, Leong A, Eu KW, Nyam D, Teoh MK. Randomized, controlled trial of low molecular weight heparin vs. no deep vein thrombosis prophylaxis for major colon and rectal surgery in Asian patients. Dis Colon Rectum 1999;42:196-202
   CrossRef | Web of Science | Medline

2. 2

   Atichartakarn V, Pathepchotiwong K, Keorochana S, Eurvilaichit C. Deep vein thrombosis after hip surgery among Thai. Arch Intern Med 1988;148:1349-1353
   CrossRef | Web of Science | Medline

3. 3

   Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women: implications for venous thromboembolism screening. JAMA 1997;277:1305-1307
   CrossRef | Web of Science | Medline

4. 4

   Yamaguchi T. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation: a multicenter, prospective, randomized trial. Stroke 2000;31:817-821
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Jersmann believes that none of our patients should have been treated with placebo, which, from an ethical point of view, would be correct if thromboprophylaxis had been routinely offered to patients before the study was started. However, there was no existing recommendation for the use of prophylaxis in this patient population, because of the inconsistent results of previously reported studies. Also, when we started our study, no drug was approved for the indication, and therefore, no regimen was available for comparison. For this reason, three independent Danish ethics committees approved the study with the inclusion of the placebo group.

We agree with Dr. Girard that surgery might have an effect on the incidence of deep-vein thrombosis. Table 1Table 1Thrombotic Events According to the Type of Injury and Whether It Was Treated Surgically. shows the number of patients with thrombotic events according to the type of injury and whether surgery was performed. However, assessment of an interaction with surgery was not a prespecified analysis, and we did not perform statistical testing.

In response to Dr. Murashige and colleagues, all the patients in the study were white. We have not evaluated the patients for genetic mutations or polymorphisms. We agree that there may be a difference in the incidence of postoperative or post-traumatic thromboembolism according to race or ethnic group; however, it is still a controversial topic and the results of some studies suggest a higher incidence of postoperative thromboembolism in Asian patients than that cited by Murashige et al.1,2 We believe that the relative reduction of 50 percent in the incidence of deep-vein thrombosis in our study can be extrapolated to members of other racial and ethnic groups who are immobilized in plaster casts or braces after injury of the lower extremities, taking into account the small differences in the absolute prevalence of thromboembolic events.

Michael R. Lassen, M.D.
Hillerød Hospital, DK-3400 Hillerød, Denmark
mirula@fa.dk

Lars C. Borris, M.D.
Aarhus University Hospital, DK-8000 Aarhus, Denmark

Roumen L. Nakov, M.D., Ph.D.
Solvay Pharmaceuticals, 30173 Hannover, Germany

2 References

1. 1

   Dhillon KS, Askander A, Doraismay S. Postoperative deep-vein thrombosis in Asian patients is not a rarity: a prospective study of 88 patients with no prophylaxis. J Bone Joint Surg Br 1996;78:427-430
   Web of Science | Medline

2. 2

   Chan LY, Yuen PM, Lo WK, Lau TK. Symptomatic venous thromboembolism in Chinese patients after gynecologic surgery: incidence and disease pattern. Acta Obstet Gynecol Scand 2002;81:343-346
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Valerie L. Schade, Thomas S. Roukis. (2011) Antithrombotic Pharmacologic Prophylaxis Use During Conservative and Surgical Management of Foot and Ankle Disorders: A Systematic Review. Clinics in Podiatric Medicine and Surgery 28:3, 571-588
   CrossRef