Correspondence

Genomic Medicine

N Engl J Med 2003; 348:759-760February 20, 2003

Article

To the Editor:

The first case vignette in Guttmacher and Collins's primer on genomic medicine (Nov. 7 issue)1 is not a good example of the value of genomic medicine; rather, it may be an example of excessive laboratory testing. Heparin prophylaxis during pregnancy would be indicated for Kathleen, the woman described in the vignette, on the clinical basis of her prior estrogen-related deep venous thrombosis, even if she were not heterozygous for the factor V Leiden mutation.2 Conversely, although she is heterozygous for the factor V Leiden mutation, heparin prophylaxis would not be indicated if she had never had an episode of deep venous thrombosis.3,4 Therefore, knowing that she is heterozygous for the factor V Leiden mutation is neither necessary nor sufficient for guiding her clinical care. There may come a time when we can generate an adequately sensitive and specific genomic profile of coagulation, but even then, before ordering a test, we should consider whether the result will have any bearing on the patient's clinical care.

Harrison G. Weed, M.D.
Mitchell A. Medow, M.D., Ph.D.
Ohio State University College of Medicine, Columbus, OH 43210
weed-2@medctr.osu.edu

4 References

1. 1

   Guttmacher AE, Collins FS. Genomic medicine -- a primer. N Engl J Med 2002;347:1512-1520
   Full Text | Web of Science | Medline

2. 2

   Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy. Chest 2001;119:Suppl:122S-131S
   CrossRef | Web of Science | Medline

3. 3

   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

4. 4

   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
   CrossRef | Web of Science | Medline

Author/Editor Response

Weed and Medow raise an interesting point. They are correct in suggesting that the translation of even precise genomic information from the laboratory to the clinic may not always be clear-cut. We certainly agree with their assertion that, absent her history of deep venous thrombosis while taking oral contraceptives, knowledge of Kathleen's factor V Leiden mutation would not indicate a need for heparin prophylaxis and thus would contribute nothing to her care (and would mean extra costs). However, it was because of that history and because of 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 indicated for Kathleen regardless of her genetic status is, however, debatable. A recent multicenter, prospective study of 125 pregnant women with a history of a single episode of deep venous thrombosis found that “the risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.”1 It is because of such data that a recent review suggested that “prophylactic heparin is not required [in the antepartum period] among women without a detectable inherited or acquired thrombophilia in whom a previous venous thrombotic event was associated with a nonrecurring risk factor.”2 We believe that 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@mail.nih.gov

2 References

1. 1

   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
   Full Text | Web of Science | Medline

2. 2

   Lockwood CJ. Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol 2002;99:333-341
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Seth E Dobrin, Dietrich A Stephan. (2003) Integrating microarrays into disease-gene identification strategies. Expert Review of Molecular Diagnostics 3:3, 375-385
   CrossRef