REPLY
Recurrence of Venous Thromboembolism after Unfractionated Heparin Therapy
Stuart K. Sutton, MD
15 December 1996 | Volume 125 Issue 12 | Page 1013
IN RESPONSE:
Drs. Kormas and Manoharan provide useful information that, as they indicate, is especially relevant for patients discharged soon after completion of intravenous heparin therapy. Recent actuarial guidelines imply that only 4 inpatient days are required to treat deep venous thrombosis (although 5 days seems to be the absolute minimum on the basis of the need for adequate overlap of warfarin and heparin therapy). In such an environment, clinicians must have an optimal understanding of these subtleties of disease management.
The results of Kormas and Manoharan's study updates the work of Thomas and colleagues [1], who showed the influence of heparin on measures of warfarin activity. This study showed that the effect of heparin on warfarin therapy (as measured by the British corrected ratio) was related to both the heparin dose and the initial British corrected ratio. More recently, Solomon and colleagues [2] reported the marked variability of the effect of heparin on the INR depending on which thromboplastin reagent was used to determine the prothrombin time.
Kormas and Manoharan did not specify the duration of warfarin therapy in their study. This information would be important because INRs markedly vary during the first 4 days of warfarin therapy [3]. Consequently, if a similarly short course of concomitant heparin and warfarin therapy occurred in this study, then the relative effect of heparin cessation on the change in INR cannot be reliably determined.
Litin and Gastineau [4], recognizing the effect of heparin on the INR, recommend stopping the heparin infusion for 4 hours before measuring the final INR on the day of hospital discharge. Data on heparin pharmacokinetics support this suggestion [5]. However, Solomon and colleagues provide perhaps the best suggestion: Certain thromboplastins are relatively insensitive to heparin and should provide more reliable INRs if used in these settings.
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Author and Article Information
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Health Services Association of Central New York, Syracuse, NY 13224.
1. Thomas P, Fennerty A, Backhouse G, Bentley DP, Campbell IA, Routledge PA. Monitoring effects of oral anticoagulants during treatment with heparin. BMJ. 1984; 288:191.
2. Solomon HM, Randall JR, Simmons VL. Heparin induced increase in the international normalized ratio. Am J Clin Pathol. 1995; 103:735-9.
3. Hirsh J, Poller L. The international normalized ratio: a guide to understanding and correcting its problems. Arch Intern Med. 1994; 154:282-8.
4. Litin SC, Gastineau DA. Concise review for primary-care physicians: current concepts in anticoagulant therapy. Mayo Clin Proc. 1995; 70:266-72.
5. Lutomski DM, Bottorff M, Sangha K. Pharmacokinetic optimisation of the treatment of embolic disorders. Clin Pharmacokinet. 1995; 28:67-92.
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