Subscribe to RSS
Mode of Delivery Does Not Influence Postpartum Hypercoagulability Measured by Thrombin Generation or ThromboelastometryFunding The work presented in this article was supported by an unrestricted researcher-initiated grant from Covidien/Medtronic/Cardinal Health as successive owners of the Kendall SCD Compression product line.
17 May 2019
19 November 2019
07 January 2020 (online)
Introduction Venous thromboembolism (VTE) is a significant cause of maternal mortality with the greatest risk postpartum. Mode of delivery influences VTE risk, with emergency caesarean section (CS) associated with the highest risk (CS). Thromboprophylaxis is recommended for selected women to reduce the risk of VTE.
We aimed to investigate the impact of mode of delivery and thromboprophylaxis on hypercoagulability as measured by thromboelastometry (TEM) and thrombin generation (TG) in women at high VTE risk.
Materials and Methods Blood was collected from 99 pregnant women with VTE risk factors at up to five time points from pre- (T1) and post (T2)-delivery to 6 weeks postpartum (T5). Multiple linear regression was utilised to compare TG and TEM between those with vaginal delivery (VD) and CS at each time point. Paired sample t-test with post hoc Bonferroni correction was utilised to compare laboratory markers over time.
Results Women in both groups had a median of three postpartum VTE risk factors, with higher body mass index and parity post-VD. In both the groups, TG and TEM parameters suggested hypercoagulability at T2 compared with T1, with resolution at T5. There were minimal differences between groups, apart from T2 with shorter clot formation time and higher maximum clot firmness in the VD group.
Conclusion TG and TEM illustrate hypercoagulability associated with pregnancy and delivery. The pattern of postpartum hypercoagulability seen in women with VTE risk factors was similar irrespective of mode of delivery. Further research is required to establish the effect of labour on TG/TEM in the absence of low molecular weight heparin use.
Keywordsenoxaparin - vaginal delivery - caesarean section - thrombin generation - thromboelastometry
- 1 Knight M, Kenyon S, Brocklehurst P, Neilson J, Shakespeare J, Kurinczuk JJ. , eds. on behalf of MBRRACE. Saving Lives, Improving Mothers' Care - Lessons Learned to Inform Future Maternity Care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009–12. National Perinatal Epidemiology Unit, University of Oxford, Oxford; 2014
- 2 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton III LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143 (10) 697-706
- 3 Royal College of Obstetrics & Gynaecology, Reducing the Risk of Thrombosis and Embolism during Pregnancy and the Puerperium, in Greentop guideline 37; 2009
- 4 Royal College of Obstetrics & Gynaecology. Reducing the risk of Venous Thromboembolism during the Pregnancy and Puerperium, Greentop guideline 37a, in Greentop guidelines; 2015
- 5 Liu S, Liston RM, Joseph KS, Heaman M, Sauve R, Kramer MS. ; Maternal Health Study Group of the Canadian Perinatal Surveillance System. Maternal mortality and severe morbidity associated with low-risk planned cesarean delivery versus planned vaginal delivery at term. CMAJ 2007; 176 (04) 455-460
- 6 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
- 7 Armstrong S, Fernando R, Ashpole K, Simons R, Columb M. Assessment of coagulation in the obstetric population using ROTEM® thromboelastometry. Int J Obstet Anesth 2011; 20 (04) 293-298
- 8 Huissoud C, Carrabin N, Benchaib M. , et al. Coagulation assessment by rotation thrombelastometry in normal pregnancy. Thromb Haemost 2009; 101 (04) 755-761
- 9 van Rheenen-Flach LE, Zweegman S, Boersma F, Lenglet JE, Twisk JW, Bolte AC. A prospective longitudinal study on rotation thromboelastometry in women with uncomplicated pregnancies and postpartum. Aust N Z J Obstet Gynaecol 2013; 53 (01) 32-36
- 10 Chowdary P, Adamidou D, Riddell A. , et al. Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring. Br J Haematol 2015; 168 (05) 719-727
- 11 Dargaud Y, Hierso S, Rugeri L. , et al. Endogenous thrombin potential, prothrombin fragment 1+2 and D-dimers during pregnancy. Thromb Haemost 2010; 103 (02) 469-471
- 12 Patel JP, Patel RK, Roberts LN. , et al. Changes in thrombin generation and D-dimer concentrations in women injecting enoxaparin during pregnancy and the puerperium. BMC Pregnancy Childbirth 2014; 14: 384
- 13 Rosenkranz A, Hiden M, Leschnik B. , et al. Calibrated automated thrombin generation in normal uncomplicated pregnancy. Thromb Haemost 2008; 99 (02) 331-337
- 14 Bagot CN, Marsh MS, Whitehead M. , et al. The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy. J Thromb Haemost 2010; 8 (08) 1736-1744
- 15 Hemker HC, Giesen P, Al Dieri R. , et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (01) 4-15
- 16 Bennett SA, Bagot CN, Appiah A. , et al. Women with unexplained recurrent pregnancy loss do not have evidence of an underlying prothrombotic state: experience with calibrated automated thrombography and rotational thromboelastometry. Thromb Res 2014; 133 (05) 892-899
- 17 Maybury HJ, Waugh JJS, Gornall A, Pavord S. There is a return to non-pregnant coagulation parameters after four not six weeks postpartum following spontaneous vaginal delivery. Obstet Med 2008; 1 (02) 92-94
- 18 Saha P, Stott D, Atalla R. Haemostatic changes in the puerperium ‘6 weeks postpartum’ (HIP Study) - implication for maternal thromboembolism. BJOG 2009; 116 (12) 1602-1612
- 19 Rossetto V, Spiezia L, Dabrilli P, Gavasso S, Simioni P. Effect on thrombin generation of the “in vitro” addition of low-dose LMWH to plasma of healthy pregnant and nonpregnant women. Clin Appl Thromb Hemost 2012; 18 (03) 331-333
- 20 Epiney M, Boehlen F, Boulvain M. , et al. D-dimer levels during delivery and the postpartum. J Thromb Haemost 2005; 3 (02) 268-271
- 21 Green L, Lawrie AS, Patel S. , et al. The impact of elective knee/hip replacement surgery and thromboprophylaxis with rivaroxaban or dalteparin on thrombin generation. Br J Haematol 2010; 151 (05) 469-476
- 22 Ismail SK, Norris L, Muttukrishna S, Higgins JR. Thrombin generation post elective caesarean section: effect of low molecular weight heparin. Thromb Res 2012; 130 (05) 799-803
- 23 van Veen JJ, Gatt A, Makris M. Thrombin generation testing in routine clinical practice: are we there yet?. Br J Haematol 2008; 142 (06) 889-903
- 24 van Hylckama Vlieg A, Baglin CA, Luddington R, MacDonald S, Rosendaal FR, Baglin TP. The risk of a first and a recurrent venous thrombosis associated with an elevated D-dimer level and an elevated thrombin potential: results of the THE-VTE study. J Thromb Haemost 2015; 13 (09) 1642-1652
- 25 Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 (04) 397-402
- 26 Lutsey PL, Folsom AR, Heckbert SR, Cushman M. Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study. J Thromb Haemost 2009; 7 (10) 1639-1648
- 27 Tripodi A, Legnani C, Chantarangkul V, Cosmi B, Palareti G, Mannucci PM. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008; 6 (08) 1327-1333
- 28 Besser M, Baglin C, Luddington R, van Hylckama Vlieg A, Baglin T. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 2008; 6 (10) 1720-1725
- 29 Dargaud Y, Trzeciak MC, Bordet J-C, Ninet J, Negrier C. Use of calibrated automated thrombinography +/- thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006; 96 (05) 562-567
- 30 Haidl H, Cimenti C, Leschnik B, Zach D, Muntean W. Age-dependency of thrombin generation measured by means of calibrated automated thrombography (CAT). Thromb Haemost 2006; 95 (05) 772-775
- 31 Roberts LN, Patel RK, Chitongo P, Bonner L, Arya R. African-Caribbean ethnicity is associated with a hypercoagulable state as measured by thrombin generation. Blood Coagul Fibrinolysis 2013; 24 (01) 40-49
- 32 Omunakwe HE, Roberts LN, Patel JP, Subramanian D, Arya R. Re: a comparison of the recommendations for pharmacologic thromboembolism prophylaxis after caesarean delivery from the major guidelines: impact on thromboprophylaxis rates of implementing Royal College of Obstetricians and Gynaecologists' guidance for reducing the risk of ante- and postnatal venous thromboembolism. BJOG 2017; 124 (05) 831-832
- 33 de Lange NM, van Rheenen-Flach LE, Lancé MD. , et al. Peri-partum reference ranges for ROTEM(R) thromboelastometry. Br J Anaesth 2014; 112 (05) 852-859
- 34 Griffiths S, Woo C, Mansoubi V. , et al. Thromboelastography (TEG®) demonstrates that tinzaparin 4500 international units has no detectable anticoagulant activity after caesarean section. Int J Obstet Anesth 2017; 29: 50-56
- 35 Chow L, Carr A, MacKenzie L, Walker A, Archer D, Lee A. The effect of dalteparin on thromboelastography in pregnancy: an in vitro study. Int J Obstet Anesth 2016; 28: 22-27
- 36 Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MSV. Risk of a thrombotic event after the six week post-partum period. N Engl J Med 2014; 370: 1307-1315