Unselected women with elevated levels of factor VIII:C or homocysteine are not at increased risk for obstetric complications

Saskia Middeldorp; Marlène H. van de Poel; Ivan Bank; Karly Hamulyák; Eduard J. Libourel; Maria M.W. Koopman; Martin H. Prins; Jan van der Meer; Harry R. Büller

doi:10.1160/TH04-03-0198

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 787-790
DOI: 10.1160/TH04-03-0198

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Unselected women with elevated levels of factor VIII:C or homocysteine are not at increased risk for obstetric complications

Saskia Middeldorp

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

,

Marlène H. van de Poel

²Department of Hematology, Division of Hemostasis, Thrombosis, and Rheology, University Hospital Groningen, The Netherlands

,

Ivan Bank

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

,

Karly Hamulyák

³Department of Haematology, University Hospital of Maastricht, Maastricht, The Netherlands

,

Eduard J. Libourel

²Department of Hematology, Division of Hemostasis, Thrombosis, and Rheology, University Hospital Groningen, The Netherlands

,

Maria M.W. Koopman

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

,

Martin H. Prins

⁴Department of Clinical Epidemiology and Medical Technology Assessment, University Hospital of Maastricht, Maastricht, The Netherlands

,

Jan van der Meer

²Department of Hematology, Division of Hemostasis, Thrombosis, and Rheology, University Hospital Groningen, The Netherlands

,

Harry R. Büller

¹Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

› Author Affiliations

Abstract

Summary

Acquired and hereditary thrombophilias are associated with obstetric complications such as (pre-)eclampsia, HELLP syndrome and fetal loss. Our objective was to assess the risk of obstetric complications in women with elevated levels of FVIII:C or hyperhomocysteinemia, as compared with their relatives who had normal FVIII:C or homocysteine levels. From a large family study of patients with venous thromboembolism or premature atherosclerosis and elevated levels of FVIII:C or hyperhomocysteinemia (propositi), the obstetric histories of female first degree relatives, who had been pregnant at least once, were studied. Levels of FVIII:C and homocysteine (both fasting and post-methionine loading) were determined. The number of obstetric complications was calculated and compared in women with normal and elevated levels of FVIII:C, and normal and elevated levels of homocysteine. Women with elevated levels of FVIII:C had a 15.4% risk for toxicosis, preeclampsia, or HELLP syndrome and a 23.9% for fetal loss. This was not statistically different from women with normal levels of FVIII:C. Women with hyperhomocysteinemia tended to have a lower risk for toxicosis, pre-eclampsia, or HELLP syndrome (8.0%, RR 0.6, 95% CI 0.2-1.7) and fetal loss (22.0%, RR 0.8, 95% CI 0.5-1.5) as compared to relatives with normal levels, although these differences did not reach statistical significance. If the analysis was limited to comparing extremes, the results did not materially differ. Unselected women with elevated plasma levels of FVIII:C or hyperhomocysteinemia are not at increased risk for obstetric complications as compared to their relatives with normal levels.

Keywords

Heparin - low molecular weight heparin - bone - osteoblastogenesis - adipogenesis

Full Text

References

References
1 Alfirevic Z, Roberts D, Martlew V. How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review. Eur J Obstet Gynecol Reprod Biol 2002; 101: 6-14.
2 Sanson BJ, Friederich PW, Simioni P. et al. The risk of abortion and stillbirth in antithrombin-, protein C-, and protein S-deficient women. Thromb Haemost 1996; 75: 387-8.
3 Preston FE, Rosendaal FR, Walker ID. et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-6.
4 Meinardi JR, Middeldorp S, de Kam PJ. et al. Increased risk for fetal loss in carriers of the factor V Leiden mutation. Ann Int Med 1999; 130: 736-9.
5 Bank I, Libourel EJ, Middeldorp S. et al. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications: a family study. Arch Int Med. 2004 In press..
6 Marietta M, Facchinetti F, Sgarbi L. et al. Elevated plasma levels of factor VIII in women with early recurrent miscarriage. J Thromb Haemost 2003; 01: 2536-9.
7 Nelen WL, Blom HJ, Steegers EA. et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000; 74: 1196-9.
8 van der Molen EF, Verbruggen B, Novakova I. et al. Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy. BJOG 2000; 107: 785-91.
9 Ronnenberg AG, Goldman MB, Chen D. et al. Preconception homocysteine and B vitamin status and birth outcomes in Chinese women. Am J Clin Nutr 2002; 76: 1385-91.
10 El Khairy L, Vollset SE, Refsum H. et al. Plasma total cysteine, mortality, and cardiovascular disease hospitalizations: the Hordaland Homocysteine Study. Clin Chem 2003; 49: 895-900.
11 Stirrat GM. Recurrent miscarriage. Lancet 1990; 336: 673-5.
12 Wilcox AJ, Weinberg CR, O’Connor JF. et al. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189-94.
13 Regan L, Rai R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 839-54.
14 Kraaijenhagen RA, Anker PS, Koopman MMW. et al. High plasma concentration of factor VIIIc: a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5-9.