Thromb Haemost 2010; 103(01): 129-137
DOI: 10.1160/TH09-06-0349
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Thromboprophylaxis with low-molecular-weight heparin after cesarean delivery

A decision analysis
Marc Blondon
1   Division of General Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Arnaud Perrier
1   Division of General Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Mathieu Nendaz
1   Division of General Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Marc Righini
2   Division of Angiology and Hemostasis, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Francoise Boehlen
2   Division of Angiology and Hemostasis, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Michel Boulvain
3   Department of Gynaecology and Obstetrics, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Philippe De Moerloose
2   Division of Angiology and Hemostasis, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

Received: 04 June 2009

Accepted after major revision: 07 September 2009

Publication Date:
22 November 2017 (online)

Summary

Although venous thromboembolism (VTE) is the leading cause of maternal mortality in developed countries, the usefulness of preventive low-molecular-weight heparin (LMWH) after cesarean delivery remains a matter of controversy. It was the objective of this study to evaluate the usefulness of thromboprophylaxis with LMWH after cesarean delivery. A decision model was constructed to evaluate the risks and benefits associated with a seven-day LMWH prophylaxis, compared with none. All probabilities were obtained from literature according to the highest level of evidence. We performed our analysis on two different sets of outcomes (utilities and disutilities), to calculate the quality-adjusted life expectancy at three months. Finally, we calculated the outcomes for four hypothetical cases with different risk. Prophylaxis with LMWH yielded the highest quality-adjusted life expectancy, with a net gain of 1.5–2.8 quality-adjusted days. Sensitivity analyses showed the incidence of VTE after cesarean delivery and the haemorrhagic risk related to LMWH to be critical, at threshold values of 0.15–0.22% and 0.23–0.35%, respectively. In the hypothetical cases, LMWH was safe but only marginally more effective in women with no risk factors. In case of an emergency procedure, a body-mass index >25kg/m2, tobacco smoking, or any combination of these, reductions in VTE greatly outnumbered the increase in major haemorrhages, with a modest benefit on mortality. Our decision analysis suggests that the benefits of LMWH after cesarean delivery exceed the risks. This benefit is, however, very low in women with no risk factors.

 
  • References

  • 1 Alexander S. et al. Maternal health outcomes in Europe. Eur J Obstet Gynecol Re-prod Biol 2003; 111 (Suppl. 01) S78-87.
  • 2 Chang J. et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ 2003; 52: 1-8.
  • 3 Chunilal SD, Bates SM. Venous thromboembolism in pregnancy: diagnosis, management and prevention. Thromb Haemost 2009; 101: 428-438.
  • 4 Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999; 353: 1258-1265.
  • 5 Heit JA. et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143: 697-706.
  • 6 Kobayashi T. 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.
  • 7 Macklon NS, Greer IA. Venous thromboembolic disease in obstetrics and gynaecology: the Scottish experience. Scott Med J 1996; 41: 83-86.
  • 8 Menacker F. et al. Cesarean delivery: background, trends, and epidemiology. Semin Perinatol 2006; 30: 235-241.
  • 9 Gates S. et al. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Rev 2002; 02: CD001689.
  • 10 Burrows RF. et al. 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. Br J Obstet Gynecol 2001; 108: 835-839.
  • 11 Gates S. et al. Thromboprophylaxis and pregnancy: two randomized controlled pilot trials that used low-molecular-weight heparin. Am J Obstet Gynecol 2004; 191: 1296-1303.
  • 12 Wuillemin WA. et al. Prophylaxie des événements thromboemboliques veineux. Swiss Med Wkly 2007; 07: 198-204.
  • 13 Bates SM. et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Ed.). Chest 2008; 133 (Suppl. 06) 844S-86S.
  • 14 Quinones JN. et al. Thromboprophylaxis after cesarean delivery: a decision analysis. Obstet Gynecol 2005; 106: 733-740.
  • 15 Wein L. et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167: 1476-1486.
  • 16 Simpson EL. et al. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. Br J Obstet Gynecol 2001; 108: 56-60.
  • 17 Sia WW. et al. The incidence of deep vein thrombosis in women undergoing cesarean delivery. Thromb Res 2009; 123: 550-555.
  • 18 Lindqvist P. et al. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94: 595-599.
  • 19 Kalro BN. et al. Low incidence of asymptomatic deep venous thrombosis following caesarean section: a colour Doppler study. Health Bull (Edinb) 1999; 57: 418-421.
  • 20 Jacobsen AF. et al. Deep vein thrombosis after elective cesarean section. Thromb Res 2004; 113: 283-288.
  • 21 Gherman RB. et al. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999; 94: 730-734.
  • 22 Chan LY. et al. Duplex ultrasound screening for deep vein thrombosis in Chinese after cesarean section. Acta Obstet Gynecol Scand 2005; 84: 368-370.
  • 23 Bergqvist A. et al. Acute deep vein thrombosis (DVT) after cesarean section. Acta Obstet Gynecol Scand 1979; 58: 473-476.
  • 24 Douketis JD. et al. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. J Am Med Assoc 1998; 279: 458-462.
  • 25 White RH. et al. Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism. Thromb Haemost 2008; 100: 246-252.
  • 26 Mismetti P. et al. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 2001; 88: 913-930.
  • 27 Kominiarek MA. et al. Low-molecular-weight heparin in pregnancy: peripartum bleeding complications. J Perinatol 2007; 27: 329-334.
  • 28 Lepercq J. et al. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. Br J Obstet Gynecol 2001; 108: 1134-1140.
  • 29 Maslovitz S. et al. The safety of low molecular weight heparin therapy during labor. J Matern Fetal Neonatal Med 2005; 17: 39-43.
  • 30 Sanson BJ. et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999; 81: 668-672.
  • 31 Camporese G. et al. Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial. Ann Intern Med 2008; 149: 73-82.
  • 32 Fausett MB. et al. Heparin-induced thrombocytopenia is rare in pregnancy. Am J Obstet Gynecol 2001; 185: 148-152.
  • 33 Eby CS, McBride LR. Postpartum coronary artery dissection complicated by heparin-induced thrombocytopenia and thrombosis. Ann Thorac Surg 2001; 71: 1025-1027.
  • 34 Greinacher A. et al. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. Thromb Haemost 2005; 94: 132-135.
  • 35 Lewis BE. et al. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003; 163: 1849-1856.
  • 36 Magnani HN, Gallus A. Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004. Thromb Haemost 2006; 95: 967-981.
  • 37 Tardy B. et al. Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood 2006; 108: 1492-1496.
  • 38 Linkins LA. et al. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139: 893-900.
  • 39 Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc 1997; 04: 49-56.
  • 40 O’Meara JJ. 3rd, et al. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. N Engl J Med 1994; 330: 1864-1869.
  • 41 Prandoni P. et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997; 82: 423-428.
  • 42 Tick LW. et al. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost 2008; 06: 2075-2081.
  • 43 Chau Q. et al. Cost-effectiveness of the bird’s nest filter for preventing pulmonary embolism among patients with malignant brain tumors and deep venous thrombosis of the lower extremities. Support Care Cancer 2003; 11: 795-799.
  • 44 Goodacre S. et al. Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis. Health Technol Assess 2006; 10: 1-168. iii-iv.
  • 45 Aledort JE. et al. The cost effectiveness of gonorrhea screening in urban emergency departments. Sex Transm Dis 2005; 32: 425-436.
  • 46 Aujesky D. et al. Cost-effectiveness of low-molecular-weight heparin for treatment of pulmonary embolism. Chest 2005; 128: 1601-1610.
  • 47 Jacobsen AF. et al. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 06: 905-912.
  • 48 Kominiarek MA, Kilpatrick SJ. Postpartum hemorrhage: a recurring pregnancy complication. Semin Perinatol 2007; 31: 159-166.
  • 49 Douketis JD. Prognosis in pulmonary embolism. Curr Opin Pulm Med 2001; 07: 354-359.
  • 50 Leonardi MJ. et al. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg 2006; 141: 790-799.
  • 51 Rodger MA. et al. Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section. Am J Obstet Gynecol 2006; 194: 436-437.
  • 52 Combs CA. et al. Factors associated with hemorrhage in cesarean deliveries. Obstet Gynecol 1991; 77: 77-82.
  • 53 Magann EF. et al. Postpartum hemorrhage after cesarean delivery: an analysis of risk factors. South Med J 2005; 98: 681-685.
  • 54 Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106: 401-407.
  • 55 Haddad FS. et al. Unanticipated variations between expected and delivered pneumatic compression therapy after elective hip surgery: a possible source of variation in reported patient outcomes. J Arthroplasty 2001; 16: 37-46.
  • 56 Silverstein MD. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158: 585-593.
  • 57 Jansen AJ. et al. Postpartum hemorrhage and transfusion of blood and blood components. Obstet Gynecol Surv 2005; 60: 663-671.
  • 58 Rouse DJ. et al. Blood transfusion and cesarean delivery. Obstet Gynecol 2006; 108: 891-897.
  • 59 Subtil D. et al. [Postpartum hemorrhage: frequency, consequences in terms of health status, and risk factors before delivery]. J Gynecol Obstet Biol Reprod (Paris) 2004; 33 (Suppl. 08) 4S9-4S16.
  • 60 Knight M. et al. Cesarean Delivery and Peripartum Hysterectomy. Obstet Gynecol 2008; 111: 97-105.
  • 61 Martel N. et al. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 2005; 106: 2710-2715.
  • 62 Bauersachs RM. et al. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost 2007; 98: 1237-1245.