The aim of this study is to investigate thrombogenesis and the hypercoagulable changes in pregnant women affected by thrombophilia who received low-molecular-weight heparin (LWMH) prophylaxis. We included 21 pregnant women affected by thrombophilia treated with LWMH and 20 nontreated normal pregnant women as the control group. The sample group of thrombophilic pregnant women included different conditions (factor V Leiden mutation, protein C deficiency, protein S deficiency, antiphospholipid antibodies syndrome, and combined defects). Three blood samples were collected during pregnancy (i.e., at 16, 20, and 24 weeks) and tested for activated partial thromboplastin time and prothrombin fragment F1 + 2 (F1 + 2); anti-FXa activity was tested only in treated thrombophilic pregnant women. F1 + 2 levels progressively increased during pregnancy in both study groups. However, the F1 + 2 increase in women exposed to heparin prophylaxis was significantly lower than that in normal pregnant women in all 3 measurements carried out during gestation (p < 0.05); a statistically significant inverse correlation between F1 + 2 levels and anti-Xa activity (R = -0.8575, p < 0.05) was observed in treated women during pregnancy. Our findings suggest that F1 + 2 in addition to anti-Xa measurement could be used to adjust LWMH prophylaxis, at least in high-risk pregnant women.

1.
Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S: Coagulation and fibrinolysis changes in normal pregnancy: increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997;73:31-36.
2.
Brack MJ, More RS, Hubner PJ, Gershlick AH: Prothrombin fragment F1 + 2 concentrations for monitoring anticoagulation therapy with heparin. Int J Cardiol 1993;38:57-61.
3.
Royal Collage of Obstetricians and Gynaecologists: Thrombosis and embolism during pregnancy and the puerperium: reducing the risk - guidelines. https://www.rcog.org.uk/ (accessed August 20, 2015).
4.
Sergi C, Al Jishi T, Walker M: Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet 2015;291:671-679.
5.
Mutlu I, Mutlu MF, Biri A, Bulut B, Erdem M, Erdem A: Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history. Blood Coagul Fibrinolysis 2015;26:267-273.
6.
O'Connell MP, O'Leary M, MacKeogh L, Murphy K, Keane DP: Is the monitoring of anti-Xa activity necessary in pregnant women undergoing thromboprophylaxis? Eur J Obstet Gynecol Reprod Biol 2004;114:12-14.
7.
Paskaleva I, Karagiozova Zh, Doncheva E, Dineva D: Monitoring of low-molecular-weight heparins in pregnant women with inherited thrombophilic disorders. Akush Ginekol (Sofiia) 2014;53:3-10.
8.
Chowdary P, Adamidou D, Riddell A, Aghighi S, Griffioen A, Priest P, Moghadam L, Kelaher N, Huq FY, Kadir RA, Tuddenham EG, Gatt A: Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring. Br J Haematol 2015;168:719-727.
9.
Ota S, Wada H, Abe Y, Yamada E, Sakaguchi A, Nishioka J, Hatada T, Ishikura K, Yamada N, Sudo A, Uchida A, Nobori T: Elevated levels of prothrombin fragment 1 + 2 indicate high risk of thrombosis. Clin Appl Thromb Hemost. 2008;14:279-285.
10.
Wexels F, Haslund A, Dahl OE, Pripp AH, Gudmundsen TE, Laszlo F, Seljeflot I, Borris LC, Lassen MR: Thrombin split products (prothrombin fragment 1 + 2) in urine in patients with suspected deep vein thrombosis admitted for radiological verification. Thromb Res 2013;131:560-563.
11.
Catena C, Zingaro L, Casaccio D, Sechi LA: Abnormalities of coagulation in hypertensive patients with reduced creatinine clearance. Am J Med 2000;109:556-561.
12.
Patel JP, Patel RK, Roberts LN, Marsh MS, Green B, Davies JG, Arya R: Changes in thrombin generation and D-dimer concentrations in women injecting enoxaparin during pregnancy and the puerperium. BMC Pregnancy Childbirth 2014;14:384.
13.
Hoke M, Kyrle PA, Philipp K, Pabinger I, Kaider A, Schönauer V, Quehenberger P, Eichinger S: Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin. Thromb Haemost 2004;91:935-940.
14.
Lovely RS, Moaddel M, Farrell DH: Fibrinogen gamma' chain binds thrombin exosite II. J Thromb Haemost 2003;1:124-131.
15.
Davie EW, Kulman JD: An overview of the structure and function of thrombin. Semin Thromb Hemost 2006;32(suppl 1):3-15.
16.
Gallwitz M, Enoksson M, Thorpe M, Hellman L: The extended cleavage specificity of human thrombin. PLoS One 2012;7:e31756.
17.
Bajzar L, Manuel R, Nesheim ME: Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem 1995;270:14477-14484.
18.
Abou-Nassar K, Kovacs MJ, Kahn SR, Wells P, Doucette S, Ramsay T, Clement AM, Khurana R, Mackinnon K, Blostein M, Solymoss S, Kingdom J, Sermer M, Rey E, Rodger M; TIPPS Investigators: The effect of dalteparin on coagulation activation during pregnancy in women with thrombophilia: a randomized trial. Thromb Haemost 2007;98:163-171.
19.
Shapiro NL, Kominiarek MA, Nutescu EA, Chevalier AB, Hibbard JU: Dosing and monitoring of low-molecular-weight heparin in high-risk pregnancy: single-center experience. Pharmacotherapy 2011;31:678-685.
20.
Parco S, Vascotto F, Simeone R: Thromboprophilaxis in neurological conditions in pregnancy: a clinical dilemma or a methods dilemma? Minerva Ginecol 2016;68:95-96.
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.