To the Editor: The first case vignette in Guttmacher and Collins'sprimer on genomic medicine (Nov. 7 issue)1 is not a good exampleof the value of genomic medicine; rather, it may be an exampleof excessive laboratory testing. Heparin prophylaxis duringpregnancy would be indicated for Kathleen, the woman describedin the vignette, on the clinical basis of her prior estrogen-relateddeep venous thrombosis, even if she were not heterozygous forthe factor V Leiden mutation.2 Conversely, although she is heterozygousfor the factor V Leiden mutation, heparin prophylaxis wouldnot be indicated if she had never had an episode of deep venousthrombosis.3,4 Therefore, knowing that she is heterozygous forthe factor V Leiden mutation is neither necessary nor sufficientfor guiding her clinical care. There may come a time when wecan generate an adequately sensitive and specific genomic profileof coagulation, but even then, before ordering a test, we shouldconsider whether the result will have any bearing on the patient'sclinical care.
Harrison G. Weed, M.D. Mitchell A. Medow, M.D., Ph.D. Ohio State University College of Medicine Columbus, OH 43210 weed-2{at}medctr.osu.edu
References
Guttmacher AE, Collins FS. Genomic medicine -- a primer. N Engl J Med 2002;347:1512-1520. [Free Full Text]
Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001;119:Suppl:122S-131S. [Free Full Text]
Clark P, Twaddle S, Walker ID, Scott L, Greer IA. Cost-effectiveness of screening for the factor V Leiden mutation in pregnant women. Lancet 2002;359:1919-1920. [CrossRef][Web of Science][Medline]
Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med 2002;162:2357-2360. [Free Full Text]
The authors reply: Weed and Medow raise an interesting point.They are correct in suggesting that the translation of evenprecise genomic information from the laboratory to the clinicmay not always be clear-cut. We certainly agree with their assertionthat, absent her history of deep venous thrombosis while takingoral contraceptives, knowledge of Kathleen's factor V Leidenmutation would not indicate a need for heparin prophylaxis andthus would contribute nothing to her care (and would mean extracosts). However, it was because of that history and becauseof her family history that testing for factor V Leiden was ordered,and we believe that her physician was correct to do so.
Weed and Medow's assertion that heparin prophylaxis is indicatedfor Kathleen regardless of her genetic status is, however, debatable.A recent multicenter, prospective study of 125 pregnant womenwith a history of a single episode of deep venous thrombosisfound that "the risk of recurrent antepartum venous thromboembolismin women with a history of venous thromboembolism is low, andtherefore routine antepartum prophylaxis with heparin is notwarranted."1 It is because of such data that a recent reviewsuggested that "prophylactic heparin is not required [in theantepartum period] among women without a detectable inheritedor acquired thrombophilia in whom a previous venous thromboticevent was associated with a nonrecurring risk factor."2 We believethat Kathleen's management illustrates the value, not the excesses,of genomic medicine.
Alan E. Guttmacher, M.D. Francis S. Collins, M.D., Ph.D. National Human Genome Research Institute Bethesda, MD 20892-2152 guttmach{at}mail.nih.gov
References
Brill-Edwards P, Ginsberg JS, Gent M, et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000;343:1439-1444. [Free Full Text]
Lockwood CJ. Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol 2002;99:333-341. [CrossRef][Web of Science][Medline]
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