Correspondence

Low-Molecular-Weight Heparin in Patients with Deep-Vein Thrombosis

N Engl J Med 2001; 345:292-293July 26, 2001

Article

To the Editor:

The clinical importance of rapidly achieving a therapeutic activated partial-thromboplastin time with respect to the treatment of venous thromboembolism with unfractionated heparin has been underscored in various studies1 and reviews.2 Breddin et al. (March 1 issue)3 compared intravenous unfractionated heparin with subcutaneous weight-adjusted reviparin, given once or twice a day, as a therapy for deep-vein thrombosis. Reviparin (a low-molecular-weight heparin) was more effective than unfractionated heparin in reducing the size of the thrombus, and twice-daily administration of reviparin prevented recurrent thromboembolism better than did treatment with unfractionated heparin. The patients received fixed initial doses of unfractionated heparin, with the doses adjusted according to daily measurements of the activated partial-thromboplastin time. This approach led to an unacceptably high number of patients with a subtherapeutic activated partial-thromboplastin time after 48 hours (33 percent). A regimen involving doses of heparin adjusted for the patient's weight, as proposed by Raschke et al.,4 would probably have led more rapidly to therapeutic heparin levels and thus to fewer recurrent thromboembolic events. The statement that reviparin regimens are more effective than a regimen of unfractionated heparin can be considered true only in the context of a suboptimal heparin regimen.

Hans Stricker, M.D.
Giorgio Mombelli, M.D.
Regional Hospital, CH-6600 Locarno, Switzerland
hans.stricker@eoc.ch

4 References

1. 1

   Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med 1997;157:2562-2568
   CrossRef | Web of Science | Medline

2. 2

   Hirsh J. Heparin. N Engl J Med 1991;324:1565-1574
   Full Text | Web of Science | Medline

3. 3

   Breddin HK, Hach-Wunderle V, Nakov R, Kakkar VV. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis. N Engl J Med 2001;344:626-631
   Full Text | Web of Science | Medline

4. 4

   Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a “standard care“ nomogram: a randomized controlled trial. Ann Intern Med 1993;119:874-881
   Web of Science | Medline

To the Editor:

We would like to ask Breddin et al. to specify a detail of the treatment protocol. Reviparin was given either once or twice daily, at doses adjusted for body weight. Does this mean that the twice-daily group actually got twice the total daily dose received by the once-daily group, or was the total dose given in a 24-hour period the same — that is, the twice-daily group received half the dose per injection?

Christoph Pechlaner, M.D.
Walter Gritsch, M.D.
Innsbruck University Hospital, A-6020 Innsbruck, Austria
christoph.pechlaner@uibk.ac.at

Author/Editor Response

The authors reply:

To the Editor: Regarding the comments of Pechlaner and Gritsch: we stated that patients in both the reviparin groups received the same daily dose of reviparin, given either in two divided subcutaneous injections every 12 hours or as a single subcutaneous injection every 24 hours.

Regarding the comments of Stricker and Mombelli: we would like to point out that conventional practice is to administer unfractionated heparin by intravenous infusion, with the dose adjusted according to daily measurements of the activated partial-thromboplastin time to achieve a value 1.5 to 2.5 times the base-line level. To our knowledge, a randomized, controlled trial has never been performed comparing the efficacy of a heparin infusion adjusted for the activated partial-thromboplastin time with a weight-adjusted dose with the use of an objective method of assessing thrombus regression and recurrent thromboembolic events. Therefore, it remains speculative whether a weight-adjusted regimen of unfractionated heparin would be more effective in increasing thrombus regression and thus reducing the frequency of recurrent thromboembolism.

Hans Klaus Breddin, M.D.
Institute of Thrombosis and Vascular Diseases, D-60598 Frankfurt, Germany
breddin@em.uni-frankfurt.de

Vijay V. Kakkar, M.D.
Thrombosis Research Institute, London SW3 6LR, United Kingdom

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