Inherited Thrombophilia and First Venous Thromboembolism during Pregnancy and Puerperium

Ida Martinelli; Valerio De Stefano; Emanuela Taioli; Katia Paciaroni; Elena Rossi; Mannucci Mannuccio Pier

doi:10.1055/s-0037-1613085

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 87(05): 791-795
DOI: 10.1055/s-0037-1613085

Review Article

Schattauer GmbH

Inherited Thrombophilia and First Venous Thromboembolism during Pregnancy and Puerperium

Ida Martinelli

¹Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy

,

Valerio De Stefano

²Department of Hematology, Catholic University of Rome, Italy

,

Emanuela Taioli

³Epidemiology Unit, IRCCS Maggiore Hospital, University of Milan, Italy

,

Katia Paciaroni

²Department of Hematology, Catholic University of Rome, Italy

,

Elena Rossi

²Department of Hematology, Catholic University of Rome, Italy

,

Mannucci Mannuccio Pier

¹Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy

› Author Affiliations

Abstract

Summary

Venous thromboembolism is a rare but threatening complication of pregnancy. Little conclusive information is available on the actual risk of venous thromboembolism during pregnancy or puerperium in women with inherited thrombophilia, particularly in carriers of factor V Leiden and of the G20210A prothrombin gene mutation. To determine the pregnancy-related and puerperium-related risk of venous thromboembolism in women with inherited thrombophilia, we performed a case-control study on 119 women who had a first episode of deep vein thrombosis and/or pulmonary embolism during pregnancy or puerperium and 232 healthy women who had at least one pregnancy without thrombosis. Inherited thrombophilia was diagnosed in 47 patients (39.5%) and 15 controls (6.5%). The relative risk of venous thromboembolism was 10.6 (95% CI, 5.6-20.4) for heterozygous carriers of factor V Leiden, 2.9 (95% CI, 1.0-8.6) for heterozygous carriers of the prothrombin mutation and 13.1 (95% CI, 5.0-34.2) for those with antithrombin, protein C or protein S deficiency taken together. Sixty-eight of the 119 women (57%) had thrombosis after delivery, confirming the puerperium as a particularly high-risk period. When women were divided into two groups of those with antenatal or postnatal thrombosis, the relative risks associated with each type of inherited thrombophilia were of similar magnitude. In conclusion, women with inherited thrombophilia have an increased risk of venous thromboembolism during pregnancy. Among thrombophilic abnormalities, the prothrombin mutation was the weakest risk factor. Thrombosis occurred more frequently in puerperium than in pregnancy, whether or not thrombophilia was diagnosed.

Keywords

Blood coagulation - factor V Leiden - prothrombin mutation - risk factors

Full Text

References

References
1 Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999; 54: 265-71.
2 Andersen BS, Steffensen FH, Sørensen HT, Nielsen GL, Olsen J. The cumulative incidence of venous thromboembolism during pregnancy and puerperium. Acta Obstet Gynecol Scand 1998; 77: 170-3.
3 Lindqvist P, Dahlbäck B, Marsál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94: 595-9.
4 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 Obstet Gynecol 1995; 173: 210-3.
5 Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstet Gynecol Scand 1983; 62: 239-43.
6 Treffers PE, Huidekoper BL, Weenink GH, Kloosterman GJ. Epidemiological observations of thrombo-embolic disease during pregnancy and in the puerperium, in 56,022 women. Int J Gynaecol Obstet 1983; 21: 327-31.
7 Martinelli I. Risk factors in venous thromboembolism. Thromb Haemost 2001; 86: 395-403.
8 Greer IA. Haemostasis and thrombosis in pregnancy. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. editors Haemostasis and thrombosis. Vol. 2. Edinburgh, Scotland: Churchill Livingstone; 1994: 987-1015.
9 Bonnar J. A review of the obstetrical aspects of haemostasis. Br J Haematol 1973; 25: 274-5.
10 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. New Engl J Med 1994; 330: 517-22.
11 Poort SR, Bertina RM, Vos HL. Rapid detection of the prothrombin 20210 A variation by allele-specific PCR. Thromb Haemost 1997; 78: 974-1163.
12 De Stefano V, Leone G, Mastrangelo S, Tripodi A, Rodeghiero F, Castaman G. et al. Thrombosis during pregnancy and surgery in patients with congenital deficiency of antithrombin III, protein C and protein S. Thromb Haemost 1994; 71: 799-800.
13 Conard J, Horellou MH, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiency in ATIII, protein C or protein S: study of 78 women. Thromb Haemost 1990; 63: 319-20.
14 Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C or protein S deficiency A cooperative, retrospective study. Arterioscl Thromb Vasc Biol 1996; 16: 742-8.
15 Hough R, Makris M, Preston F. Pregnancy in women with thrombophilia: incidence of thrombosis and pregnancy outcome. Br J Haematol. 1996 93. 01
16 Grandone E, Margaglione M, Colaizzo D, D’Andrea G, Cappucci G, Brancaccio V. et al. Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations. Am J Obstet Gynecol 1998; 179: 1324-8.
17 McColl MD, Ramsay JE, Tait RC, Walker ID, McCall F, Conkie JA. et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997; 78: 1183-8.
18 Hallak M, Senderowicz J, Cassel A, Shapira C, Aghai E, Auslender R. et al. Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy. Am J Obstet Gynecol 1997; 176: 889-93.
19 Dizon-Townson DS, Nelson LM, Jang H, Varner MW, Ward K. The incidence of the factor V Leiden mutation in an obstetric population and its relationship to deep vein thrombosis. Am J Obstet Gynecol 1997; 176: 883-6.
20 Bokarewa MI, Bremme K, Blomback M. Arg506-Gln mutation in factor V and risk of thrombosis during pregnancy. Br J Haematol 1996; 92: 473-8.
21 Hirsch DR, Mikkola KM, Marks PW, Fox EA, Dorfman DM, Ewenstein BM. et al. Pulmonary embolism and deep venous thrombosis during pregnancy or oral contraceptive use: prevalence of factor V Leiden. Am Heart J 1996; 131: 1145-8.
22 De Boer K, Büller HR, ten Cate JW, Levi M. Deep vein thrombosis in obstetric patients: diagnosis and risk factors. Thromb Haemost 1992; 67: 4-7.
23 McColl MD, Ellison J, Reid F, Tait RC, Walker ID, Greer IA. Prothrombin 20210 GβA, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy. Br J Obstet Gynecol 2000; 107: 565-9.
24 Gerhardt A, Scharf RE, Beckmann MW, Struve S, Bender HG, Pillny M. et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342: 374-80.
25 Friederich PW, Sanson BJ, Simioni P, Zanardi S, Huisman MV, Kindt I. et al. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med 1996; 125: 955-60.
26 McColl MD, Walker ID, Greer IA. The role of inherited thrombophilia in venous thromboembolism associated with pregnancy. Br J Obstet Gynecol 1999; 106: 756-66.
27 Ginsberg JS, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy From the Sixth ACCP Consensus Conference of Antithrombotic Therapy. Chest 2001; 119: 122S-31S.
28 Brill-Edwards P, Ginsberg JS, Gent M, Hirsh J, Burrows R, Kearon C. et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000; 343: 1439-44.
29 Porter JM. Reporting Standards in Venous Disease. J Vasc Surg 1988; 08: 172-82.
30 Frezzato M, Tosetto A, Rodeghiero F. Validated questionnaire for the identification of previous personal or familial venous thromboembolism. Am J Epidemiol 1996; 143: 1257-65.
31 de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
32 Ginsberg JS, Brill-Edwards P, Burrows RF, Bona R, Prandoni P, Buller HR. et al. Venous thrombosis during pregnancy: leg and trimester of presentation. Thromb Haemost 1992; 67: 519-20.
33 Sanson BJ, Lensing AWA, Prins MH, Ginsberg JS, Bakagan ZS, Lavenne-Pardonge E. et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668-72.