Correspondence
Thrombophilia
N Engl J Med 2001; 345:697-699August 30, 2001
- Article
To the Editor:
Seligsohn and Lubetsky (April 19 issue)1 justify not routinely testing white women for inherited thrombophilia before prescribing oral contraceptives, since “it would deny contraceptives to about 5 to 10 percent of white women . . . while preventing very few fatal thromboembolisms.” This is not acceptable. No woman should die unnecessarily from complications of contraceptive use, nor should any woman be subjected to a possible stroke, pulmonary embolism, or deep venous thrombosis when the occurrence of these complications could have possibly been prevented by a simple and accurate blood test. Other acceptable forms of birth control are available. Not offering women an informed choice and thus perhaps significantly increasing their risk of a preventable complication associated with substantial morbidity should not be the standard of care.
1 ReferencesNina Caplin, M.D.
Mount Sinai School of Medicine, Elmhurst, NY 11373
ninacaplin@aol.com Laurie Edelman, M.D.
Mount Sinai School of Medicine, New York, NY 100291
Seligsohn U ,Lubetsky A . Genetic susceptibility to venous thrombosis. N Engl J Med 2001;344:1222-1231
Full Text | Web of Science | Medline
To the Editor:
Seligsohn and Lubetsky propose an algorithm for identifying a congenital state of hypercoagulability in patients with thromboembolic disease. When my colleagues and I used this algorithm in 87 patients with venous thrombosis and thrombophilia, 12 cases were not detected, in 4 because the process was limited to superficial veins and in 8 because the patients had distal deep-vein thrombosis after surgery or immobilization (Table 1Table 1
Risk Factors Associated with Hypercoagulability in 87 Patients with Venous Thrombosis and Thrombophilia.). Although subclavian thrombosis is not mentioned in the article, we found three patients with this condition, in all three cases secondary to venous-catheter implantation or effort. A history of superficial thrombophlebitis is not rare in patients with thrombophilia. Thus, we recommend extending testing for thrombophilia to all patients with secondary distal deep-vein thrombosis, secondary subclavian thrombosis, or extended superficial-vein thrombosis.1 1 ReferencesFrancesc J. Casals Sole, M.D.
Hospital Clinic, 08036 Barcelona, Spain
casals@compuserve.com To the Editor:
Seligsohn and Lubetsky define criteria for assessing the likelihood of inherited thrombophilia. According to these criteria, thrombophilia is likely in a patient 45 years of age or older in whom proximal-vein thrombosis has been provoked by surgery, trauma, or immobilization. Most patients with a first episode of venous thrombosis meet these criteria, but in such cases the thrombosis is due to underlying diseases.1-3 Therefore, these patients should be categorized as unlikely to have thrombophilia, without the need for further testing. Doing so would improve the diagnostic yield of thrombophilia screening and would reduce costs.
In addition, the authors recommend lifelong oral anticoagulant therapy for a subgroup of patients who are characterized by a high risk of recurrence. At present, however, no clinical trials support such a treatment regimen. With regard to the risk of major bleeding complications that is directly related to the duration of anticoagulant therapy,4 we suggest restricting the initial treatment period to five years, even in these high-risk patients. Thereafter, the decision as to whether warfarin therapy should be continued or stopped should be reconsidered.
4 ReferencesBernd Pötzsch, M.D.
University of Bonn, 53105 Bonn, Germany
bernd.poetzsch@ukb. uni-bonn. de Katharina Madlener, M.D.
Kerckhoff Clinic, 61231 Bad Nauheim, Germany1
Baron JA ,Gridley G ,Weiderpass E ,Nyren O ,Linet M . Venous thromboembolism and cancer. Lancet 1998;351:1077-1080[Erratum, Lancet 2000;355:758.]
CrossRef | Web of Science | Medline2
White RH ,Gettner S ,Newman JM ,Trauner KB ,Romano PS . Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 2000;343:1758-1764
Full Text | Web of Science | Medline3
Heit JA ,Silverstein MD ,Mohr DN ,Petterson TM ,O'Fallon WM ,Melton LJ III . Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000;160:809-815
CrossRef | Web of Science | Medline4
Beyth RJ ,Quinn LM ,Landefeld CS . Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998;105:91-99
CrossRef | Web of Science | Medline
To the Editor:
Seligsohn and Lubetsky present decision trees that may help clinicians who are caring for patients with thrombophilia. However, some points need clarification. In Figure 2A of their article, the distinction between patients in whom thrombophilia is “highly likely” and those in whom it is “likely” is not clear. In particular, when thrombosis occurs during pregnancy in a woman less than 45 years old (as is the case in general), do the authors consider thrombophilia “likely” or “highly likely”? We think it is reasonable to screen for a deficiency of antithrombin, protein C, or protein S in such a situation. In Figure 2B, some considerations regarding therapy do not meet standard recommendations. For instance, the recommended duration of treatment in patients with cerebral-vein thrombosis, in the absence of thrombophilia, is six months.1 Do the authors have evidence to support a prolongation of this duration?
The question of the international normalized ratio in the antiphospholipid syndrome is also controversial and could have been addressed in the discussion. Finally, as mentioned by the authors, an increased level of homocysteine may be caused by vitamin B12 deficiency. This deficiency is rarely of dietary origin and most often reflects malabsorption of various causes.2
2 ReferencesBernard Goichot, M.D., Ph.D.
Emmanuel Andrès, M.D.
Hôpitaux Universitaires de Strasbourg, 67098 Strasbourg CEDEX, France
bernard.goichot@chru-strasbourg. fr 1
Bousser MG . Cerebral venous thrombosis: diagnosis and management. J Neurol 2000;247:252-258
CrossRef | Web of Science | Medline2
Andres E ,Goichot B ,Schlienger JL . Food cobalamin malabsorption: a usual cause of vitamin B12 deficiency. Arch Intern Med 2000;160:2061-2062
Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Caplin and Edelman should note that the estimated risk of fatal venous thromboembolism in women who are heterozygous for factor V Leiden and use contraceptives is 1 in 90,000.1 Thus, to prevent 1 death it would be necessary to test 1,800,000 women for factor V Leiden (assuming a prevalence of 5 percent in the population) and even more if testing for the prothrombin G20210A mutation were included. Furthermore, withholding oral contraceptives from 90,000 carriers would result in an increased number of unwanted pregnancies associated with complications and stigmatize persons bearing an inherited disorder, a result that could affect the cost of their health insurance. For these reasons, a consensus team recently recommended against screening for factor V Leiden in asymptomatic women contemplating the use of or using oral contraceptives, unless they have a personal or family history of thromboembolism or other risk factors.2
With regard to Casals Sole's comments: distal deep-vein thrombosis secondary to surgery, trauma, or immobilization is associated with a low rate of recurrence and therefore does not warrant testing for thrombophilia. Superficial-vein thrombosis is indeed one of the manifestations of inherited thrombophilia but is more frequently related to other causes. We limited our investigation to those patients who had recurrent events or an extension from the superficial to the deep veins. Upper-extremity venous thrombosis is relatively rare and in approximately 75 percent of cases is provoked by indwelling venous catheters, cancer, or an unusually strenuous effort. In approximately 25 percent of cases, the event is unprovoked; for these patients, we advocate high-priority and intermediate-priority tests. In one series, the prevalence of thrombophilia was 42 percent among patients with unprovoked cases and 15 percent among those with provoked cases.3
With regard to the comments of Pötzsch and Madlener: it has repeatedly been shown that approximately 50 percent of patients with inherited thrombophilia present with venous thrombosis after surgery, trauma, or immobilization. This rate is sufficiently high for these patients to be considered likely to have a thrombophilia and to undergo high-priority testing. We agree that only long-term, prospective, randomized studies will determine whether patients with a high risk of recurrence should be treated indefinitely or for five years.
We regard women less than 45 years old who present with an unprovoked venous thrombosis, whether or not they are pregnant or use female hormones, as highly likely to have a thrombophilia. As Goichot and Andrès suggest, such women should be examined for high-priority and intermediate-priority tests. No prospective studies have adequately addressed the issue of the desirable duration of oral anticoagulant therapy in patients with cerebral-vein thrombosis. In patients whose event is unprovoked or in patients who are affected by an inherited thrombophilia, we recommend indefinite treatment because of the 17 to 26 percent rate of recurrence of cerebral or noncerebral thrombotic events,4,5 particularly in patients bearing factor V Leiden.5
5 ReferencesUri Seligsohn, M.D.
Aharon Lubetsky, M.D.
Chaim Sheba Medical Center, Tel Hashomer 52621, Israel
zeligson@post.tau. ac. il 1
Creinin MD ,Lisman R ,Strickler RC . Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril 1999;72:646-651
CrossRef | Web of Science | Medline2
Grody WW ,Griffin JH ,Taylor AK ,Korf BR ,Heit JA . American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med 2001;3:139-148
CrossRef | Medline3
Heron E ,Lozinguez O ,Alhenc-Gelas M ,Emmerich J ,Fiessinger JN . Hypercoagulable states in primary upper-extremity deep vein thrombosis. Arch Intern Med 2000;160:382-386
CrossRef | Web of Science | Medline4
Preter M ,Tzourio C ,Ameri A ,Bousser MG . Long-term prognosis in cerebral venous thrombosis: follow-up of 77 patients. Stroke 1996;27:243-246
CrossRef | Web of Science | Medline5
Ludemann P ,Nabavi DG ,Junker R , et al. Factor V Leiden mutation is a risk factor for cerebral venous thrombosis: a case-control study of 55 patients. Stroke 1998;29:2507-2510
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
James Drife. (2002) Oral Contraception and the Risk of Thromboembolism. Drug Safety 25:13, 893-902
CrossRef
