Journal of Thrombosis and Thrombolysis

, Volume 43, Issue 1, pp 105–111 | Cite as

Adjustment of therapeutic LMWH to achieve specific target anti-FXa activity does not affect outcomes in pregnant patients with venous thromboembolism

  • Brendan P. McDonnell
  • Kate Glennon
  • Aoife McTiernan
  • Hugh D. O’Connor
  • Colin Kirkham
  • Barry Kevane
  • Jennifer C. Donnelly
  • Fionnuala Ni Áinle


Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality in the developed world. Low molecular weight heparins (LMWH) are routinely used to provide therapeutic anticoagulation during pregnancy for women with VTE, with measurement of plasma anti-FXa activity used to guide dosing in certain patient groups. There is limited evidence to support the use of anti-FXa monitoring in pregnant patients. This study seeks to ascertain whether anti-FXa monitoring of pregnant patients with VTE influences patient outcomes. We performed a single-centre case series including two consecutive groups of pregnant patients treated with LMWH for VTE sustained in the index pregnancy with and without monitoring of anti-FXa levels. 35,394 patients delivered during the study period in a large urban stand-alone maternity hospital, with 26 cases of VTE eligible for inclusion. There was no significant difference between the two groups in any clinical outcome; including maternal blood loss at delivery, recurrent thromboembolic events or rates of planned delivery. These data provide clinical evidence to support current international guideline recommendations that measurement of plasma anti-FXa activity in the majority of patients receiving therapeutic-intensity antenatal LMWH is not warranted.


Factor Xa Low molecular weight heparin Pregnancy Tinzaparin Venous thrombosis 


Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.


  1. 1.
    Knight M, Kenyon S, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ (2014) on behalf of MBRRACEUK. Saving lives, improving mothers’ care lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity. Oxford: National perinatal epidemiology unit, University of oxford 2009–2012Google Scholar
  2. 2.
    Stain M, Schönauer V, Minar E, Bialonczyk C, Hirschl M, Weltermann A et al (2005) The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease. J Thromb Haemost 3:2671–2676CrossRefPubMedGoogle Scholar
  3. 3.
    Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM (2012) Vandvik PO; American college of chest physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest 141:e691S–e736SCrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hirsh J, Levine MN (1992) Low molecular weight heparin. Blood 79:1–17PubMedGoogle Scholar
  5. 5.
    Baglin T, Barrowcliffe TW, Cohen A, Greaves M (2006) British committee for standards in haematology. guidelines on the use and monitoring of heparin. Br J Haematol 133:19–34CrossRefPubMedGoogle Scholar
  6. 6.
    McCoy AJ, Pei XY, Skinner R, Abrahams JP, Carrell RW (2003) Structure of beta-antithrombin and the effect of glycosylation on antithrombin’s heparin affinity and activity. J Mol Biol 326:823–833CrossRefPubMedGoogle Scholar
  7. 7.
    Huntington JA (2003) Mechanisms of glycosaminoglycan activation of the serpins in hemostasis. J Thromb Haemost 1:1535–1549CrossRefPubMedGoogle Scholar
  8. 8.
    Johnson DJ, Langdown J, Li W, Luis SA, Baglin TP, Huntington JA (2006) Crystal structure of monomeric native antithrombin reveals a novel reactive center loop conformation. J Biol Chem 281:35478–35486CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gomez K, McVey JH, Tuddenham E (2005) Inhibition of coagulation by macromolecular complexes. Haematologica 90:1570–1576PubMedGoogle Scholar
  10. 10.
    Langdown J, Belzar KJ, Savory WJ, Baglin TP, Huntington JA (2009) The critical role of hinge-region expulsion in the induced-fit heparin binding mechanism of antithrombin. J Mol Biol 386:1278–1289CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R et al (2001) Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 119:64S–94SCrossRefPubMedGoogle Scholar
  12. 12.
    Bates SM, Weitz JI (2005) Coagulation assays. Circulation 112:e53–e60CrossRefPubMedGoogle Scholar
  13. 13.
    Garcia DA, Baglin TP, Weitz JI, Samama MM (2012) American college of chest physicians parenteral anticoagulants: antithrombotic therapy and prevention of Thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest 141:e24S–e43SCrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Harenberg J (2004) Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes. J Thromb Haemost 2:547–550CrossRefPubMedGoogle Scholar
  15. 15.
    Bounameaux H, de Moerloose P (2004) Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No. J Thromb Haemost 2:551–554CrossRefPubMedGoogle Scholar
  16. 16.
    The acute management of thrombosis and embolism during pregnancy and the puerperium. Royal College of Obstetricians and Gynaecologists Green-top Guideline No. 37b (2007)Google Scholar
  17. 17.
    Romualdi E, Dentali F, Squizzato A, Ageno W (2013) Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature: a reply to a rebuttal. J Thromb Haemost 11:788–789CrossRefPubMedGoogle Scholar
  18. 18.
    Barbour LA, Oja JL, Schultz LK (2004) A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol 191:1024–1029CrossRefPubMedGoogle Scholar
  19. 19.
    Gibson PS, Newell K, Sam DX, Mansoor A, Jiang X, Tang S et al (2013) Weight-adjusted dosing of tinzaparin in pregnancy. Thromb Res 131:71–75CrossRefGoogle Scholar
  20. 20.
    O’Connell MP, O’Leary M, MacKeogh L, Murphy K, Keane DP (2004) Is the monitoring of anti-Xa activity necessary in pregnant women undergoing thromboprophylaxis? Eur J Obstet Gynecol Reprod Biol 114:12–14CrossRefPubMedGoogle Scholar
  21. 21.
    Crowther MA, Spitzer K, Julian J, Ginsberg J, Johnston M, Crowther R et al (2000) Pharmacokinetic profile of a low-molecular weight heparin (reviparin) in pregnant patients: a prospective cohort study. Thromb Res 98:133–138CrossRefPubMedGoogle Scholar
  22. 22.
    Norris LA, Bonnar J, Smith MP, Steer PJ, Savidge G (2004) Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy: a pharmacokinetic study. Thromb Haemost 92:791–796PubMedGoogle Scholar
  23. 23.
    Greer I, Hunt BJ (2005) Low molecular weight heparin in pregnancy: current issues. Br J Haematol 128:593–601CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Brendan P. McDonnell
    • 1
  • Kate Glennon
    • 1
  • Aoife McTiernan
    • 1
  • Hugh D. O’Connor
    • 1
  • Colin Kirkham
    • 1
  • Barry Kevane
    • 2
  • Jennifer C. Donnelly
    • 1
  • Fionnuala Ni Áinle
    • 2
    • 3
    • 4
  1. 1.Department of ObstetricsRotunda HospitalDublin 1Ireland
  2. 2.Department of HematologyRotunda HospitalDublin 1Ireland
  3. 3.Department of HematologyMater Misericordiae University HospitalDublin 7Ireland
  4. 4.School of Medicine and Medical SciencesUniversity College DublinDublin 4Ireland

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