Background: Normal pregnancy is characterized by numerous changes in the hemostatic system, creating the hypercoagulable state which increases the risk of venous thromboembolic event (VTE) occurrence. The risk is further increased by the presence of inherited or acquired thrombophilia. Objective: In this study, we aimed to determine the prevalence of different types of thrombophilia in women with pregnancy-related VTE, and to investigate the possible connection between the type of thrombophilia and localization of VTE as well as the gestational age of VTE occurrence. Participants and Methods: Two hundred and two women with the first episode of pregnancy-related VTE and 130 controls were investigated. The antithrombin, protein C and protein S activity, APC resistance, FVG1691A, and FIIG20210A were determined. None of the investigated women was pregnant at the time of thrombophilia testing, and none was using oral contraceptives. Results: Thrombophilia was diagnosed in 95 patients (47%) and 7 controls (5.4%). The prevalence of FV Leiden, FIIG20210A mutations, antithrombin, PC and PS deficiencies taken together and combined thrombophilia was 22.3, 10.4, 6.9 and 6.9%, respectively. Significantly more frequent antepartum occurrence of VTE (11 vs. 3, p < 0.05) was found in women with natural coagulation inhibitor deficiency. Pulmonary embolism occurred more frequently in nonthrombophilic women (25 vs. 3, p < 0.001). Conclusion: Inherited thrombophilia was found to be considerably more frequently present in women with pregnancy- and puerperium-related VTE compared to healthy controls. Women with thrombophilia are at higher risk of developing thromboses localized in the iliacofemoral region, and women without thrombophilia are at higher risk of developing pulmonary embolism. Deficiency in natural coagulation inhibitors is associated with antepartum VTE occurrence.

1.
Bonnar J: Haemostasis and coagulation disorders in pregnancy; in Bloom AL, Thomas DP (eds): Haemostasis and Thrombosis. Edinburgh, Churchill Livingstone, 1987, pp 570–584.
2.
Bremme K: Haemostasis in normal pregnancy; in Brenner B, Marder VJ, Conard J (eds): Women’s Issues in Haemostasis and Thrombosis. London, Martin Dunitz, 2002, pp 151–165.
3.
McColl MD, Ramsay JE, Tait RC, Walker ID, McCall F, Conkie JA, Carty MJ, Greer IA: Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997;78:1183–1188.
4.
Eldor A: Thrombophilia, thrombosis and pregnancy. Thromb Haemost 2001;86:104–111.
5.
Arkel YS, Ku DW: Thrombophilia in pregnancy: review of the literature and some original data. Clin Appl Thromb Hemost 2001;7:259–268.
6.
Greer IA: Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999;353:1258–1265.
7.
McColl MD, Ellison J, Greer IA, Tait RC, Walker ID: Prevalence of the postthrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol 2000;108:272–274.
8.
Blanco-Molina A, Trujillo-Santos J, Criado J, Lopez L, Lecumberri R, Gutierrez R, Monreal M: Venous thromboembolism during pregnancy or postpartum: findings from the RIETE registry. Thromb Haemost 2007;97:186–190.
9.
Gherman RB, Goodwin TM, Leung B, Byrne J, Nethumumi R, Montoro M: Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstetr Gynecol 1999;94:730–734.
10.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM: A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698–3703.
11.
Djordjevic V, Rakicevic LJ, Gagic M, Nikolic A, Savic A: Simultaneous detection of factor V Leiden and factor IIG20210A variant by a multiplex PCR on whole blood. Balc J Med Gen 2001;4:15–17.
12.
Djordjevic V, Rakicevic LJ, Spasic M, Miljic P, Mikovic D, Kovac M, Radojkovic D: FV Leiden, FII G20210A, MTHFR C677t mutations and first venous thromboembolism during pregnancy and puerperium. Vojnosanitet Pregl 2004;62:201–205.
13.
Martinelli I, De Stefano V, Taioli E, Paciaroni K, Rossi E, Mannucci PM: Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium. Thromb Haemost 2002;87:791–795.
14.
Gerhardt A, Scharf RE, Beckmann MW, Struve S, Bender HG, Pillny M, Sandmann W, Zotz RB: Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and puerperium. N Eng J Med 2000;342:372–380.
15.
Hellgren M, Svensson PJ, Dahlback B: Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 1995;173:210–214.
16.
Djordjevic V, Rakicevic LJ, Mikovic D, Kovac M, Miljic P, Radojkovic D, Savic A: Prevalence of Factor V Leiden, Factor V Cambridge, Factor II G20210A and methylenetetrahydrofolate reductase C677T mutations in healthy and thrombophilic Serbian population. Acta Haematol 2004;112:227–229.
17.
Samama MM, Conard J, Mathieux V, Gerotziafas GT, Horellou MH, Elalamy I: Heritable thrombophilia and pregnancy associated thrombosis. Turk J Haematol 2002;19:445–451.
18.
Bjorgell O, Nilsson PE, Nilsson JA, Svensson PJ: Location and extent of deep vein thrombosis in patients with and without FV:R506Q mutation. Thromb Haemost 2000;83:648–651.
19.
Martinelli I, Battaglioli T, Razzari C, Mannucci PM: Type and location of venous thromboembolism in patients with factor V Leiden or prothrombin G20210A and in those with no thrombophilia. J Thromb Haemost 2007;5:98–101.
20.
Bounameaux H: Factor V Leiden paradox: risk of deep vein thrombosis but not of pulmonary embolism. Lancet 2000;356:182–183.
21.
McColl MD, RamsayJE, Tait RC, Walker ID, McCall F, Conkie JA, Carty MJ, Greer IA: Superficial vein thrombosis: incidence in association with pregnancy and prevalence of thrombophilic defects. Thromb Haemost 1998;79:741–742.
22.
Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, Mackie I, Makris M, Nokes T, Perry D, Tait RC, Walker I, Watson H: Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010;149:209–220.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.