Risk Factors for Pregnancy Associated Venous Thromboembolism

Summary

In an attempt to reduce the incidence of pregnancy associated venous thromboembolism (PA-VTE), some researchers have advocated screening of all women for the factor V^Leiden mutation during early pregnancy. We have conducted a large retrospective study (over 72,000 deliveries) to determine if this would be useful. Sixty-two objectively confirmed venous thrombotic events (51 DVT, 11 PE) were recorded at two maternity units in the UK. The incidence of DVT was 0.71 per 1000 deliveries (95% CI 0.5-0.9) with 0.50 occurring in the antenatal period (95% CI 0.34-0.66) and 0.21 in the puerperium (95% CI 0.11-0.31). The incidence of PE was 0.15 per 1000 deliveries (95% CI 0.06-0.24), 0.07 antenatal (95% CI 0.01-0.13) and 0.08 in the puerperium (95% CI 0.02-0.14). Of these 62,50 attended for follow-up and thrombophilia screening. 28% of all episodes of PA-VTE had no CIinical risk factor for thrombosis or an identifiable thrombophilic abnormality. Deficiency of antithrombin was identified in 12% of individuals (95% CI 3-21) and the factor V^Leiden mutation in 8% (95% CI 0.5-15.5). Based on estimates of the prevalence of the factor V^Leiden mutation in the population, we estimate that the thrombotic risk for a woman during pregnancy or the puerperium with the defect is approximately 1 in 400-500. This figure would not lend support to the idea of random screening for the mutation in early pregnancy.

• References

• 1 Department of Health. Report on confidential enquiries into maternal death in the United Kingdom 1988-90. HMSO; London: 1994
• 2 Letsky EA, De SwietM. Thromboembolism in Pregnancy and Its Management. Br J Haematol 1984; 57: 543-552
• 3 Toglia MR, Weg JG. Thromboembolism During Pregnancy. N Engl J Med 1996; 335: 108-114
• 4 Greer IA. Haemostasis and thrombosis in pregnancy. In: Haemostasis and Thrombosis in Pregnancy. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Edinburgh: Churchill Livingstone; 1994. pp 0987-1015
• 5 Hellgren M, Blombäck MM. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. Gynaecological and Obstetrical Investigation 1981; 12: 141-154
• 6 The Royal College of Obstetricians and Gynaecologists. Report of the RCOG Working Party on Prophylaxis Against Thromboembolism in Gynaecology and Obstetrics 1995.
• 7 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de RondeH, van derVelden PA, Reitsma PH. Mutationin blood coagulation factor V associated with resistance to activated protein C [see comments]. Nature 1994; 369: 64-67
• 8 Bertina RM, Reitsma PH, Rosendaal FR, Vandenbroucke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis. Thromb Haemost 1995; 74: 449-453
• 9 Dahlbäck B, Hildebrand B. Inherited resistance to activated protein C is corrected by anticoagulant cofactor activity found to be a property of factor V. Proc Natl Acad Sci USA 1994; 91: 1396-1400
• 10 Dahlbäck B. Inherited resistance to activated protein C, a major cause of venous thrombosis, is due to a mutation in the factor V gene. Haemostasis 1994; 24: 139-151
• 11 Dahlbäck B. Factor V gene mutation causing inherited resistance to activated protein C as a basis for venous thromboembolism. Journal of Internal Medicine 1995; 237: 221-227
• 12 Dahlbäck B. New molecular insights into the genetics of thrombophilia Resistance to activated protein C caused by Arg 506 to Gin mutation in factor V as a pathogenic risk factor for venous thrombosis. Thromb Haemost 1995; 74: 129-148
• 13 Rees DC, Cox M, Clegg JB. distribution of factor V Leiden [see comments]. Lancet 1995; 346: 1133-1134
• 14 Bokarewa MI, Bremme K, Blombäck M. Arg 506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473-478
• 15 Hellgren M, Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obst Gynecol 1995; 173: 210-213
• 16 Ginsberg JS, Harish J. Use of antithrombotic agents during pregnancy. Chest 1995; 108: 305S-11S
• 17 Greer IA, De SwietM. Thrombosis prophylaxis in obstetrics and gynaecology. Br J Obst Gynaecol 1993; 100: 37-40
• 18 Walker ID, Colvin BT. On behalf of the haemostasis and thrombosis task force. Guidelines on the prevention, investigation and management of thrombosis associated with pregnancy. J Clin Pathol 1993; 16: 489-496
• 19 Macklon N, Greer I. Venous thromboembolic disease in Obstetrics and Gynaecology: The Scottish experience. Scot Med J 1996; 41: 83-86
• 20 De SwietM, Fidler J, Howell R, Letsky E. Thromboembolism in pregnancy. In: Advanced Medicine. Jewell D. ed. Pitman Medical; Tunbridge Wells: 1981. pp 309-317
• 21 Rutherford S, Montoro M, McGehee W, Strong T. Thromboembolic disease associated with pregnancy: an 11-year review. Am J Obstet Gynaecol 1991; 164: 286
• 22 Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstetrica et Gynecologica Scandinavica 1983; 62: 239-243
• 23 Treffers P, Huidekoper B, Weenink G, Kloosterman G. Epidemiological observations of thromboembolic disease during pregnancy and in the puerperium, in 56,022 women. Inti J Gynaecol Obst 1983; 21: 327-331
• 24 Friederich P, Sanson B, Simioni P, Zanaidi S, Huisman M, Kindt I, Prandoni P, Büller H, Girolami A, Prins M. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Annals Int Med 1996; 125: 955-960
• 25 Ginsberg JS, Brill-Edwards P, Burrows RF, Bona R, Prandoni P, Buller HR, Lensing A. Venous thrombosis during pregnancy: leg and trimester of presentation. Thromb Haemost 1992; 67: 519-520
• 26 Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency A cooperative, retrospective study. Ge-sellschaft fur Thrombose- und Hämostaseforschung (GTH) Study Group on Natural Inhibitors. Arteriosclerosis, Thrombosis & Vascular Biology 1996; 16: 742-748
• 27 Beauchamp NJ, Daly ME, Hampton KK, Cooper PC, Preston FE, Peake IR. prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis. Br J Haematol 1994; 88: 219-222
• 28 Tait RC, Walker ID, Perry DJ, Islam SI, Daly ME, McCall F, Conkie JA, Carrell RW. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 1994; 87: 106-112
• 29 Tait RC, Walker ID, Reitsma PH, Islam SI, McCall F, Poort SR, Conkie JA, Bertina RM. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995; 73: 87-93
• 30 Sanson JS, Friederich PW, Simioni P, Zanardi S, Huisman MV, Girolami A, ten CateJW, Prins MH. The risk of abortion and stillbirth in antithrombin, protein C, and protein S deficient women. Thromb Haemost 1996; 75: 387-388
• 31 Preston F, Rosendaal F, Walker I, Briet E, Bemtorp E, Conard J, Fontcuberta J, Makris M, Mariani G, Noteboom W, Pabinger I, Legnani C, Charrer I, Schulman S, van derMeer F. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348: 913-916
• 32 Conard J, Horellou MH, Van DredenP, Lecompte T, Samama M. Thrombosis and Pregnancy in Congenital Deficiencies in AT HI, Protein C or Protein S: Study of 78 women. Thromb Haemost 1990; 63: 319-320
• 33 Gandrille S, Greengard JS, Alhenc-Gelas M, Juhan-Vague I, Abgrall JF, Jude B, Griffin JH, Aiach M. Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM. Blood 1995; 86: 219-224
• 34 Koeleman BP, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031-1035
• 35 Koeleman BP, Van RumptD, Hamulyak K, Reitsma PH, Bertina RM. Factor V Leiden: an additional risk factor for thrombosis in protein S deficient families?. Thromb Haemost 1995; 74: 580-583
• 36 van BovenHH, Reitsma PH, Rosendaal FR, Bayston TA, Chowdhury V, Bauer KA, Scharrer I, Conard J, Lane DA. Factor V Leiden (FV R506Q) in families with inherited antithrombin deficiency. Thromb Haemost 1996; 75: 417-421