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Risks of Venous Thromboembolism After Cesarean Sections: A Meta-Analysis

  • Marc Blondon
    Correspondence
    CORRESPONDENCE TO: Marc Blondon, MD, Geneva University Hospitals, Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
    Affiliations
    Division of Angiology and Hemostasis, Department of Specialties of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland

    Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA
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  • Alessandro Casini
    Affiliations
    Division of Angiology and Hemostasis, Department of Specialties of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
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  • Kara K. Hoppe
    Affiliations
    Department of Obstetrics and Gynecology and of Maternal Fetal Medicine, University of Wisconsin, Madison, WI

    Department of Obstetrics and Gynecology, University of Washington, Seattle, WA
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  • Françoise Boehlen
    Affiliations
    Division of Angiology and Hemostasis, Department of Specialties of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
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  • Marc Righini
    Affiliations
    Division of Angiology and Hemostasis, Department of Specialties of Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
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  • Nicholas L. Smith
    Affiliations
    Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA

    Department of Epidemiology, University of Washington, Seattle, WA
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      Background

      Cesarean sections (CS) are believed to be associated with greater risks of postpartum VTE. Our objective was to systematically review the evidence on this association and on the absolute risk of VTE following CS.

      Methods

      We searched PubMed, Embase, and conference proceedings from 1980 to November 2015 for reports on the associations of delivery methods with postpartum VTE and on the incidence of VTE following CS. Studies on thrombophilia or recurrent VTE were excluded, and the search was restricted to prospective studies when assessing the incidence of VTE. Pooled relative and absolute risks were estimated with random effects models.

      Results

      The search retrieved 28 mostly retrospective observational studies comparing risks of VTE following CS and following vaginal deliveries (VD) (> 53,000 VTE events) and 32 prospective studies reporting risks of VTE following CS (218 VTE events). Compared with VD, the relative risk of VTE following CS ranged from 1 to 22, with a meta-analytic OR of 3.7 (95% CI, 3.0-4.6). Adjustment for age and BMI had a marginal influence on the estimated pooled OR. Associations were observed for both elective and emergency CS, with stronger estimates of associations for emergency CS. The pooled incidence was 2.6 VTE per 1,000 CS (95% CI, 1.7-3.5) and was greater in studies with a longer and better follow-up in the postpartum period (4.3 per 1,000 CS).

      Conclusions

      The risk of VTE was fourfold greater following CS than following VD; seemed independent of other VTE risk factors; and was greater following emergency CS than following elective CS. On average, three in 1,000 women will develop a VTE following CS.

      Key Words

      Abbreviations:

      CS (cesarean sections), MeSH (Medical Subject Headings), PE (pulmonary embolism), VD (vaginal deliveries)
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      References

        • Pomp E.R.
        • Lenselink A.M.
        • Rosendaal F.R.
        • Doggen C.J.
        Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study.
        J Thromb Haemost. 2008; 6: 632-637
        • Wik H.S.
        • Jacobsen A.F.
        • Sandvik L.
        • Sandset P.M.
        Prevalence and predictors for post-thrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study.
        J Thromb Haemost. 2012; 10: 840-847
        • Martin J.A.
        • Hamilton B.E.
        • Osterman M.J.
        Births in the United States, 2013.
        NCHS Data Brief. 2014; : 1-8
        • Jacobsen A.F.
        • Skjeldestad F.E.
        • Sandset P.M.
        Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study.
        J Thromb Haemost. 2008; 6: 905-912
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.
        JAMA. 2000; 283: 2008-2012
      1. Wells G, Shea B, O'Connell J, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed March 14, 2016.

        • Trinquart L.
        • Touze E.
        Pitfalls in meta-analysis of observational studies: lessons from a systematic review of the risks of stenting for intracranial atherosclerosis.
        Stroke. 2009; 40 (author reply e590): e586-e587
        • James A.H.
        • Jamison M.G.
        • Brancazio L.R.
        • Myers E.R.
        Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality.
        Am J Obstet Gynecol. 2006; 194: 1311-1315
        • Abbasi N.
        • Balayla J.
        • Laporta D.P.
        • Kezouh A.
        • Abenhaim H.A.
        Trends, risk factors and mortality among women with venous thromboembolism during labour and delivery: a population-based study of 8 million births.
        Arch Gynecol Obstet. 2014; 289: 275-284
        • Macklon N.S.
        • Greer I.A.
        Venous thromboembolic disease in obstetrics and gynaecology: the Scottish experience.
        Scott Med J. 1996; 41: 83-86
        • Treffers P.E.
        • Huidekoper B.L.
        • Weenink G.H.
        • Kloosterman G.J.
        Epidemiological observations of thrombo-embolic disease during pregnancy and in the puerperium, in 56,022 women.
        Int J Gynaecol Obstetrics. 1983; 21: 327-331
        • Galanaud J.P.
        • Cochery-Nouvellon E.
        • Alonso S.
        • et al.
        Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk factor for deep vein thrombosis during pregnancy.
        J Thromb Haemost. 2010; 8: 707-713
        • Hiltunen L.
        • Rautanen A.
        • Rasi V.
        • et al.
        An unfavorable combination of Factor V Leiden with age, weight, and blood group causes high risk of pregnancy-associated venous thrombosis: a population-based nested case-control study.
        Thromb Res. 2007; 119: 423-432
        • Jacobsen A.F.
        • Skjeldestad F.E.
        • Sandset P.M.
        Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium—a register-based case-control study.
        Am J Obstet Gynecol. 2008; 198: 233.e1-233.e7
        • Landon M.B.
        • Hauth J.C.
        • Leveno K.J.
        • et al.
        Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery.
        N Engl J Med. 2004; 351: 2581-2589
        • Virkus R.A.
        • Lokkegaard E.
        • Lidegaard O.
        • et al.
        Risk factors for venous thromboembolism in 1.3 million pregnancies: a nationwide prospective cohort.
        PloS One. 2014; 9: e96495
        • Abdul Sultan A.
        • Grainge M.J.
        • West J.
        • Fleming K.M.
        • Nelson-Piercy C.
        • Tata L.J.
        Impact of risk factors on the timing of first postpartum venous thromboembolism: a population-based cohort study from England.
        Blood. 2014; 124: 2872-2880
        • Blondon M.
        • Harrington L.B.
        • Righini M.
        • Boehlen F.
        • Bounameaux H.
        • Smith N.L.
        Racial and ethnic differences in the risk of postpartum venous thromboembolism: a population-based, case-control study.
        J Thromb Haemost. 2014; 12: 2002-2009
        • Colmorn L.B.
        • Ladelund S.
        • Rasmussen S.
        • Secher N.J.
        Risk of a venous thromboembolic episode due to caesarean section and BMI: a study in northern Denmark covering 2000-2010.
        J Obstet Gynaecol. 2014; 34: 313-316
        • Sultan A.A.
        • Tata L.J.
        • West J.
        • et al.
        Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom.
        Blood. 2013; 121: 3953-3961
        • Danilenko-Dixon D.R.
        • Heit J.A.
        • Silverstein M.D.
        • et al.
        Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.
        Am J Obstet Gynecol. 2001; 184: 104-110
        • Kierkegaard A.
        Incidence and diagnosis of deep vein thrombosis associated with pregnancy.
        Acta Obstet Gynecol Scand. 1983; 62: 239-243
        • Koroukian S.M.
        Relative risk of postpartum complications in the Ohio medicaid population: vaginal versus cesarean delivery.
        Medical Care Res Rev. 2004; 61: 203-224
        • Lindqvist P.G.
        • Torsson J.
        • Almqvist A.
        • Bjorgell O.
        Postpartum thromboembolism: severe events might be preventable using a new risk score model.
        Vasc Health Risk Manag. 2008; 4: 1081-1087
        • Kobayashi T.
        • Nakabayashi M.
        • Ishikawa M.
        • et al.
        Pulmonary thromboembolism in obstetrics and gynecology increased by 6.5-fold over the past decade in Japan.
        Circ J. 2008; 72: 753-756
        • Burrows L.J.
        • Meyn L.A.
        • Weber A.M.
        Maternal morbidity associated with vaginal versus cesarean delivery.
        Obstet Gynecol. 2004; 103: 907-912
        • Chan L.Y.
        • Tam W.H.
        • Lau T.K.
        Venous thromboembolism in pregnant Chinese women.
        Obstet Gynecol. 2001; 98: 471-475
        • Gherman R.B.
        • Goodwin T.M.
        • Leung B.
        • Byrne J.D.
        • Hethumumi R.
        • Montoro M.
        Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy.
        Obstet Gynecol. 1999; 94: 730-734
        • Simpson E.L.
        • Lawrenson R.A.
        • Nightingale A.L.
        • Farmer R.D.T.
        Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database.
        Br J Obstet Gynaecol. 2001; 108: 56-60
        • Won H.S.
        • Kim D.Y.
        • Yang M.S.
        • Lee S.J.
        • Shin H.H.
        • Park J.B.
        Pregnancy-induced hypertension, but not gestational diabetes mellitus, is a risk factor for venous thromboembolism in pregnancy.
        Korean Circ J. 2011; 41: 23-27
        • Lindqvist P.
        • Dahlback B.
        • Marsal K.
        Thrombotic risk during pregnancy: a population study.
        Obstet Gynecol. 1999; 94: 595-599
        • Liu S.
        • Rouleau J.
        • Joseph K.S.
        • et al.
        Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada.
        J Obstet Gynaecol Can. 2009; 31: 611-620
        • Ghaji N.
        • Boulet S.L.
        • Tepper N.
        • Hooper W.C.
        Trends in venous thromboembolism among pregnancy-related hospitalizations, United States, 1994-2009.
        Am J Obstet Gynecol. 2013; 209: 433.e1-433.e8
        • Kane E.V.
        • Calderwood C.
        • Dobbie R.
        • Morris C.
        • Roman E.
        • Greer I.A.
        A population-based study of venous thrombosis in pregnancy in Scotland 1980-2005.
        Eur J Obstet Gynecol Reprod Biol. 2013; 169: 223-229
        • Morris J.M.
        • Algert C.S.
        • Roberts C.L.
        Incidence and risk factors for pulmonary embolism in the postpartum period.
        J Thromb Haemost. 2010; 8: 998-1003
        • Pallasmaa N.
        • Ekblad U.
        • Gissler M.
        Severe maternal morbidity and the mode of delivery.
        Acta Obstet Gynecol Scand. 2008; 87: 662-668
        • Chauleur C.
        • Quenet S.
        • Varlet M.N.
        • et al.
        Feasibility of an easy-to-use risk score in the prevention of venous thromboembolism and placental vascular complications in pregnant women: a prospective cohort of 2736 women.
        Thromb Res. 2008; 122: 478-484
        • Silver R.M.
        • Landon M.B.
        • Rouse D.J.
        • et al.
        Maternal morbidity associated with multiple repeat cesarean deliveries.
        Obstet Gynecol. 2006; 107: 1226-1232
        • Burrows R.F.
        • Gan E.T.
        • Gallus A.S.
        • Wallace E.M.
        • Burrows E.A.
        A randomised double-blind placebo controlled trial of low molecular weight heparin as prophylaxis in preventing venous thrombolic events after caesarean section: a pilot study.
        BJOG. 2001; 108: 835-839
        • Cavazza S.
        • Rainaldi M.P.
        • Adduci A.
        • Palareti G.
        Thromboprophylaxis following cesarean delivery: one site prospective pilot study to evaluate the application of a risk score model.
        Thromb Res. 2012; 129: 28-31
        • Gates S.
        • Brocklehurst P.
        • Ayers S.
        • Bowler U.
        Thromboprophylaxis and pregnancy: two randomized controlled pilot trials that used low-molecular-weight heparin.
        Am J Obstet Gynecol. 2004; 191: 1296-1303
        • Gizzo S.
        • Noventa M.
        • Anis O.
        • et al.
        Pharmacological anti-thrombotic prophylaxis after elective caesarean delivery in thrombophilia unscreened women: should maternal age have a role in decision making?.
        J Perinatal Med. 2014; 42: 339-347
        • Kalro B.N.
        • Davidson R.A.
        • Owen P.
        Low incidence of asymptomatic deep venous thrombosis following caesarean section: a colour Doppler study.
        Health Bull. 1999; 57: 418-421
        • Larsson C.
        • Saltvedt S.
        • Wiklund I.
        • Andolf E.
        Planned vaginal delivery versus planned caesarean section: short-term medical outcome analyzed according to intended mode of delivery.
        JOGC. 2011; 33: 796-802
        • Lindqvist P.G.
        • Svensson P.J.
        • Marsal K.
        • Grennert L.
        • Luterkort M.
        • Dahlback B.
        Activated protein C resistance (FV: Q506) and pregnancy.
        Thromb Haemost. 1999; 81: 532-537
        • Salomon O.
        • Seligsohn U.
        • Steinberg D.M.
        • et al.
        The common prothrombotic factors in nulliparous women do not compromise blood flow in the feto-maternal circulation and are not associated with preeclampsia or intrauterine growth restriction.
        Am J Obstet Gynecol. 2004; 191: 2002-2009
        • Häger R.M.
        • Daltveit A.K.
        • Hofoss D.
        • et al.
        Complications of cesarean deliveries: rates and risk factors.
        Am J Obstet Gynecol. 2004; 190: 428-434
        • Pallasmaa N.
        • Ekblad U.
        • Aitokallio-Tallberg A.
        • et al.
        Cesarean delivery in Finland: maternal complications and obstetric risk factors.
        Acta Obstet Gynecol Scand. 2010; 89: 896-902
        • Chan L.Y.
        • Lam K.Y.
        • Metreweli C.
        • Lau T.K.
        Duplex ultrasound screening for deep vein thrombosis in Chinese after cesarean section.
        Acta Obstet Gynecol Scand. 2005; 84: 368-370
        • Goto M.
        • Yoshizato T.
        • Tatsumura M.
        • et al.
        Safety and efficacy of thromboprophylaxis using enoxaparin sodium after cesarean section: a multi-center study in Japan.
        Taiwan J Obstet Gynecol. 2015; 54: 248-252
        • Jacobsen A.F.
        • Drolsum A.
        • Klow N.E.
        • Dahl G.F.
        • Qvigstad E.
        • Sandset P.M.
        Deep vein thrombosis after elective cesarean section.
        Thromb Res. 2004; 113: 283-288
        • Macklon N.S.
        • Barry J.
        • Greer I.A.
        Duplex ultrasound screening for deep venous thrombosis in the puerperium.
        Br J Obstet Gynaecol. 1995; 102: 255-256
        • Rodger M.A.
        • Avruch L.I.
        • Howley H.E.
        • Olivier A.
        • Walker M.C.
        Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section.
        Am J Obstet Gynecol. 2006; 194: 436-437
        • Sia W.W.
        • Powrie R.O.
        • Cooper A.B.
        • et al.
        The incidence of deep vein thrombosis in women undergoing cesarean delivery.
        Thromb Res. 2009; 123: 550-555
        • Clark P.
        • Walker I.D.
        • Govan L.
        • Wu O.
        • Greer I.A.
        The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes.
        Br J Haematol. 2008; 140: 236-240
        • Hannah M.E.
        • Hannah W.J.
        • Hewson S.A.
        • Hodnett E.D.
        • Saigal S.
        • Willan A.R.
        Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group.
        Lancet. 2000; 356: 1375-1383
        • Raees M.
        • Yasmeen S.
        • Jabeen S.
        • Utman N.
        • Karim R.
        Maternal morbidity associated with emergency versus elective caesarean section.
        J Postgrad Med Instit. 2013; 27: 55-62
        • Said J.M.
        • Higgins J.R.
        • Moses E.K.
        • et al.
        Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women.
        Obstet Gynecol. 2010; 115: 5-13
        • Sharma R.
        • Atkin H.
        • Mackillop L.
        • Paterson-Brown S.
        Assessment of the mobility of mothers postpartum to identify those at greatest risk of venous thromboembolism.
        J Obstet Gynaecol. 2012; 32: 461-463
        • Hill N.C.
        • Hill J.G.
        • Sargent J.M.
        • Taylor C.G.
        • Bush P.V.
        Effect of low dose heparin on blood loss at caesarean section.
        Br Med J (Clin Res Ed). 1988; 296: 1505-1506
        • Masliah-Planchon R.
        • Lavigne F.
        • Claquin C.
        • Papiernik E.
        Systematic prevention of deep vein thrombosis with subcutaneous heparin therapy following cesarean section. Advantages and disadvantages [in French].
        J Gynecol Obstet Biol Reprod (Paris). 1983; 12: 95-100
        • Jackson E.
        • Curtis K.M.
        • Gaffield M.E.
        Risk of venous thromboembolism during the postpartum period: a systematic review.
        Obstet Gynecol. 2011; 117: 691-703
        • Abdul Sultan A.
        • Tata L.J.
        • Grainge M.J.
        • West J.
        The incidence of first venous thromboembolism in and around pregnancy using linked primary and secondary care data: a population based cohort study from England and comparative meta-analysis.
        PloS One. 2013; 8: e70310
        • Epiney M.
        • Boehlen F.
        • Boulvain M.
        • et al.
        D-dimer levels during delivery and the postpartum.
        J Thromb Haemost. 2005; 3: 268-271
        • Friedman A.M.
        • Ananth C.V.
        • Lu Y.S.
        • D'Alton M.E.
        • Wright J.D.
        Underuse of postcesarean thromboembolism prophylaxis.
        Obstet Gynecol. 2013; 122: 1197-1204
        • Alalaf S.K.
        • Jawad R.K.
        • Muhammad P.R.
        • Ali M.S.
        • Al Tawil N.G.
        Bemiparin versus enoxaparin as thromboprophylaxis following vaginal and abdominal deliveries: a prospective clinical trial.
        BMC Pregnancy Childbirth. 2015; 15: 72
        • James A.
        • Committee on Practice Bulletins–Obstetrics
        Practice bulletin no. 123: thromboembolism in pregnancy.
        Obstet Gynecol. 2011; 118: 718-729
        • Bates S.M.
        • Greer I.A.
        • Middeldorp S.
        • et al.
        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. 2012; 141: e691S-e736S
      2. Royal College of Obstetricians and Gynecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-top Guideline No. 37a. 2015. https://www.rcog.uk/globalassets/documents/guidelines/gtg_37a.pdf. Accessed August 2, 2016.

        • Blondon M.
        • Perrier A.
        • Nendaz M.
        • et al.
        Thromboprophylaxis with low-molecular-weight heparin after cesarean delivery.
        Thromb Haemost. 2010; 103: 129-137
        • Waldman M.
        • Sheiner E.
        • Sergienko R.
        • Shoham-Vardi I.
        Can we identify risk factors during pregnancy for thrombo-embolic events during the puerperium and later in life?.
        J Matern Fetal Neonatal Med. 2015; 28: 1005-1009
        • O'Connor D.J.
        • Scher L.A.
        • Gargiulo 3rd, N.J.
        • Jang J.
        • Suggs W.D.
        • Lipsitz E.C.
        Incidence and characteristics of venous thromboembolic disease during pregnancy and the postnatal period: a contemporary series.
        Ann Vasc Surg. 2011; 25: 9-14
        • Barrett J.F.
        • Hannah M.E.
        • Hutton E.K.
        • et al.
        A randomized trial of planned cesarean or vaginal delivery for twin pregnancy.
        N Engl J Med. 2013; 369: 1295-1305
        • Hutton E.K.
        • Hannah M.E.
        • Ross S.J.
        • et al.
        The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.
        BJOG. 2011; 118: 564-577
        • Hauth J.C.
        • Macpherson C.
        • Carey J.C.
        • et al.
        Early pregnancy threshold vaginal pH and Gram stain scores predictive of subsequent preterm birth in asymptomatic women.
        Am J Obstet Gynecol. 2003; 188: 831-835
        • Murphy D.J.
        • Liebling R.E.
        • Verity L.
        • Swingler R.
        • Patel R.
        Early maternal and neonatal morbidity associated with operative delivery in second stage of labour: a cohort study.
        Lancet. 2001; 358: 1203-1207
        • Ellison J.
        • Thomson A.J.
        • Conkie J.A.
        • McCall F.
        • Walker I.D.
        • Greer I.A.
        Thromboprophylaxis following caesarean section—a comparison of the antithrombotic properties of three low molecular weight heparins—dalteparin, enoxaparin and tinzaparin.
        Thromb Haemost. 2001; 86: 1374-1378
        • Rageth J.C.
        • Juzi C.
        • Grossenbacher H.
        Delivery after previous cesarean: a risk evaluation.
        Obstet Gynecol. 1999; 93: 332-337
        • Nielsen T.F.
        • Hokegard K.H.
        Postoperative cesarean section morbidity: a prospective study.
        Am J Obstet Gynecol. 1983; 146: 911-916