Venous thromboembolism in pregnancy

Clinics in Chest Medicine

Volumn 31, Issue 4, 2010, Pages 731-740

  Marik, Paul E ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

Deep venous thrombosis; Low molecular weight heparin; Pregnancy; Pulmonary embolus; Thrombophilia; Venous thromboembolism

Indexed keywords

DALTEPARIN; ENOXAPARIN; FONDAPARINUX; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; TINZAPARIN; WARFARIN;

BLOOD CLOTTING; CESAREAN SECTION; CLINICAL TRIAL; COMPRESSION GARMENT; DEEP VEIN THROMBOSIS; DELIVERY; DIAGNOSTIC PROCEDURE; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; ERYTHEMA; FIBRINOLYSIS; FIBRINOLYTIC THERAPY; HUMAN; INCIDENCE; LABOR; LUNG EMBOLISM; PREGNANCY; PREVALENCE; PRIORITY JOURNAL; PROPHYLAXIS; PRURITUS; PUERPERIUM; REVIEW; RISK FACTOR; SENSITIVITY AND SPECIFICITY; SKIN NECROSIS; THROMBOPHILIA; URTICARIA; VENOUS THROMBOEMBOLISM;

ANTICOAGULANTS; FEMALE; HEPARIN, LOW-MOLECULAR-WEIGHT; HUMANS; PREGNANCY; PREGNANCY COMPLICATIONS, HEMATOLOGIC; PULMONARY EMBOLISM; RISK FACTORS; VENOUS THROMBOEMBOLISM;

EID: 78049484166     PISSN: 02725231     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ccm.2010.06.004     Document Type: Review

References (85)

1. Heit J.A., Kobbervig C.E., James A.H., 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.
2. James A.H., Jamison M.G., Brancazio L.R., et al. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006, 194:1311-1315.
3. Pomp E.R., Lenselink A.M., Rosendaal F.R., et al. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008, 6:632-637.
4. Brenner B. Haemostatic changes in pregnancy. Thromb Res 2004, 114:409-414.
5. Eichinger S., Weltermann A., Philipp K., et al. Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden. Thromb Haemost 1999, 82:1232-1236.
6. Bremme K.A. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003, 16:153-168.
7. Macklon N.S., Greer I.A., Bowman A.W. An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy. Br J Obstet Gynaecol 1997, 104:191-197.
8. Macklon N.S., Greer I.A. The deep venous system in the puerperium: an ultrasound study. Br J Obstet Gynaecol 1997, 104:198-200.
9. Haemostasis and Thrombosis Task Force British Committee for Standards in Haematology, Investigation, and Management of Heritable Thrombophilia. Br J Haematol 2001, 114:512-528.
10. Robertson L., Wu O., Langhorne P., et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006, 132:171-196.
11. Nelson S.M., Greer I.A. Thrombophilia and the risk for venous thromboembolism during pregnancy, delivery, and puerperium. Obstet Gynecol Clin North Am 2006, 33:413-427.
12. Greer I.A. Thrombosis in pregnancy: maternal and fetal issues. Lancet 1999, 353:1258-1265.
13. Rosendaal F.R. Venous thrombosis: a multicausal disease. Lancet 1999, 353:1167-1173.
14. Clark P., Twaddle S., Walker I.D., et al. Cost-effectiveness of screening for the factor V Leiden mutation in pregnant women. Lancet 2002, 359:1919-1920.
15. Wu O., Robertson L., Twaddle S., et al. Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis. Br J Haematol 2005, 131:80-90.
16. Ginsberg J.S., Brill-Edwards P., Burrows R.F., et al. Venous thrombosis during pregnancy: leg and trimester of presentation. Thromb Haemost 1992, 67:519-520.
17. Merhi Z., Awonuga A. Acute abdominal pain as the presenting symptom of isolated iliac vein thrombosis in pregnancy. Obstet Gynecol 2006, 107:468-470.
18. Rodger M.A., Avruch L.I., Howley H.E., et al. Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section. Am J Obstet Gynecol 2006, 194:436-437.
19. Wells P.S., Anderson D.R., Bormanis J., et al. Value of assessment of pretest probability of deep vein thrombosis in clinical management. Lancet 1997, 350:1795-1798.
20. Chan W.S., Lee A., Spencer F.A., et al. Predicting deep venous thrombosis in pregnancy: out in ″ LEFt″ field?. Ann Intern Med 2009, 151:85-92.
21. Bates S.M., Greer I.A., Pabinger I., et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:844S-886S.
22. Royal College of Obstetricians and Gynaecologists Thromboprophylaxis during pregnancy, labour, and after vaginal delivery. Green Top Guideline No. 37 Available at:, Accessed November 16, 2009. http://www.rcog.org.uk/resources/Public/pdf/Thromboprophylaxis_no037.pdf.
23. Kearon C., Julian J.A., Newman T.E., et al. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 1998, 128:663-677.
24. Chan W.S., Chunilal S., Lee A., et al. A red blood cell agglutination D-dimer test to exclude deep venous thrombosis in pregnancy. Ann Intern Med 2007, 147:165-170.
25. Chunilal S.D., Bates S.M. Venous thromboembolism in pregnancy: diagnosis, management and prevention. Thromb Haemost 2009, 101:428-438.
26. Eskandari M.K., Sugimoto H., Richardson T., et al. Is color-flow duplex a good diagnostic test for detection of isolated calf vein thrombosis in high-risk patients?. Angiology 2000, 51:705-710.
27. Fraser D.G., Moody A.R., Morgan P.S., et al. Diagnosis of lower-limb deep venous thrombosis: a prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002, 136:89-98.
28. Frede T.E., Ruthberg B.N., Frede T.E., et al. Sonographic demonstration of iliac venous thrombosis in the maternity patient. J Ultrasound Med 1988, 7:33-37.
29. Zerhouni E.A., Barth K.H., Siegelman S.S. Demonstration of venous thrombosis by computed tomography. AJR Am J Roentgenol 1980, 134:753-758.
30. Nolan T.E., Smith R.P., Devoe L.D. Maternal plasma D-dimer levels in normal and uncomplicated pregnancies. Obstet Gynecol 1993, 81:235-238.
31. Nijkeuter M., Huisman M.V. Diagnosing pulmonary embolism in pregnancy: Is there a role for D-dimer as a stand-alone test?. Crit Care Med 2006, 34:2701-2702.
32. King-Im J.M., Freeman S.J., Boylan T., et al. Quality of CT pulmonary angiography for suspected pulmonary embolus in pregnancy. Eur Radiol 2008, 18:2709-2715.
33. Schaefer-Prokop C., Prokop M. CTPA for the diagnosis of acute pulmonary embolism during pregnancy. Eur Radiol 2008, 18:2705-2708.
34. Cook J.V., Kyriou J. Radiation from CT and perfusion scanning in pregnancy. BMJ 2005, 331:350.
35. International Commission on Radiological Protection Publication 84. Annals of the International Commission on Radiological Protection 2000, 30:1-43.
36. Nijkeuter M., Geleijns J., De R.A., et al. Diagnosing pulmonary embolism in pregnancy: rationalizing fetal radiation exposure in radiological procedures. J Thromb Haemost 2004, 2:1857-1858.
37. Duhl A.J., Paidas M.J., Ural S.H., et al. Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 2007, 197:457. e1-21.
38. Wesseling J., van Driel D., Heymans H.S., et al. Coumarins during pregnancy: long-term effects on growth and development of school-age children. Thromb Haemost 2001, 85:609-613.
39. Lee H.C., Cho S.Y., Lee H.J., et al. Warfarin-associated fetal intracranial hemorrhage: a case report. J Korean Med Sci 2003, 18:764-767.
40. Pati S., Helmbrecht G.D. Congenital schizencephaly associated with in utero warfarin exposure. Reprod Toxicol 1994, 8:115-120.
41. Forestier F., Daffos F., Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy study by direct fetal blood sampling under ultrasound. Thromb Res 1984, 34:557-560.
42. Greer I.A., Nelson-Piercy C. Low molecularweight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005, 106:401-407.
43. Warkentin T.E., Greinacher A., Koster A., et al. Treatment and prevention of heparin-induced thrombocytopenia. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:340S-380S.
44. Pettila V., Leinonen P., Markkola A., et al. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 2002, 87:182-186.
45. Baglin T.P., Brush J., Streff B.M. Guidelines on the use of vena cava filters. British Committee for Standards in Haematology. Br J Haematol 2006, 134:590-595.
46. Kocher M., Krcova V., Cerna M., et al. Retrievable Gunther Tulip Vena Cava Filter in the prevention of pulmonary embolism in patients with acute deep venous thrombosis in perinatal period. Eur J Radiol 2009, 70:165-169.
47. Casele H.L., Laifer S.A., Woelkers D.A., et al. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol 1999, 181:1113-1117.
48. Sephton V., Farquharson R.G., Topping J., et al. A longitudinal study of maternal dose response to low molecular weight heparin in pregnancy. Obstet Gynecol 2003, 101:1307-1311.
49. Greer I.A. Anticoagulants in pregnancy. J Thromb Thrombolysis 2006, 21:57-65.
50. Voke J., Keidan J., Pavord S., et al. The management of antenatal venous thromboembolism in the UK and Ireland: a prospective multicentre observational survey. Br J Haematol 2007, 139:545-558.
51. Narin C., Reyhanoglu H., Tulek B., et al. Comparison of different dose regimens of enoxaparin in deep vein thrombosis therapy in pregnancy. Adv Ther 2008, 25:585-594.
52. Rodie V.A., Thomson A.J., Stewart F.M., et al. Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series. BJOG 2002, 109:1020-1024.
53. Bank I., Libourel E.J., Middeldorp S., et al. High rate of skin complications due to low-molecular-weight heparins in pregnant women. J Throm Haemo 2003, 1:859-861.
54. Verdonkschot A.E., Vasmel W.L., Middeldorp S., et al. Skin reactions due to low molecular weight heparin in pregnancy: a strategic dilemma. Arch Gynecol Obstet 2005, 271:163-165.
55. Gerhardt A., Zotz R.B., Stockschlaeder M., et al. Fondaparinux is an effective alternative anticoagulant in pregnant women with high risk of venous thromboembolism and intolerance to low-molecular-weight heparins and heparinoids. Thromb Haemost 2007, 97:496-497.
56. Lagrange F., Vergnes C., Brun J.L., et al. Absence of placental transfer of pentasaccharide (Fondaparinux, Arixtra) in the dually perfused human cotyledon in vitro. Thromb Haemost 2002, 87:831-835.
57. Kopp S.L., Horlocker T.T. Anticoagulation in pregnancy and neuraxial blocks. Anesthesiol Clin 2008, 26:1-22.
58. Brancazio L.R., Roperti K.A., Stierer R., et al. Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy. Am J Obstet Gynecol 1995, 173:1240-1245.
59. Morris T.A., Jacobson A., Marsh J.J., et al. Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thromb Res 2005, 115:45-51.
60. Horlocker T.T., Wedel D.J., Benzon H., et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 2003, 28:172-197.
61. Ginsberg J.S., Hirsh J., Turner D.C., et al. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989, 61:197-203.
62. McColl M.D., Ellison J., Greer I.A., et al. Prevalence of the post-thrombotic syndrome in young women with previous venous thromboembolism. Br J Haematol 2000, 108:272-274.
63. Brandjes D.P., Buller H.R., Heijboer H., et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997, 349:759-762.
64. Leonhardt G., Gaul C., Nietsch H.H., et al. Thrombolytic therapy in pregnancy. J Throm Haemo 2006, 21:271-276.
65. Stefanovic B.S., Vasiljevic Z., Mitrovic P., et al. Thrombolytic therapy for massive pulmonary embolism 12 hours after cesarean delivery despite contraindication?. Am J Emerg Med 2006, 24:502-504.
66. Richards S.R., Barrows H., O'Shaughnessy R. Intrapartum pulmonary embolus. A case report. J Reprod Med 1985, 30:64-66.
67. Fagher B., Ahlgren M., Astedt B. Acute massive pulmonary embolism treated with streptokinase during labor and the early puerperium. Acta Obstet Gynecol Scand 1990, 69:659-661.
68. Hall R.J., Young C., Sutton G.C., et al. Treatment of acute massive pulmonary embolism by streptokinase during labour and delivery. Br Med J 1972, 4:647-649.
69. Woodward D.K., Birks R.J., Granger K.A. Massive pulmonary embolism in late pregnancy. Can J Anaesth 1998, 45:888-892.
70. Splinter W.M., Dwane P.D., Wigle R.D., et al. Anaesthetic management of emergency caesarian section followed by pulmonary embolectomy. Can J Anaesth 1989, 36:689-692.
71. Bechtel J.J., Mountford M.C., Ellinwood W.E. Massive pulmonary embolism in pregnancy treated with catheter fragmentation and local thrombolysis. Obstet Gynecol 2005, 106:1158-1160.
72. Lepercq J., Conard J., Borel-Derlon A., et al. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. BJOG 2001, 108:1134-1140.
73. De Stefano V., Martinelli I., Rossi E., et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br J Haematol 2006, 135:386-391.
74. Pabinger I., Grafenhofer H., Kaider A., et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Throm Haemo 2005, 3:949-954.
75. Brill-Edwards P., Ginsberg J.S., Gent M., et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med 2000, 343:1439-1444.
76. Martinelli I., Battaglioli T., De S., et al. The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A. J Thromb Haemost 2008, 6:494-498.
77. Simioni P., Tormene D., Prandoni P., et al. Pregnancy-related recurrent events in thrombophilic women with previous venous thromboembolism. Thromb Haemost 2001, 86:929.
78. Royal College of Obstetricians and Gynaecologists Thromboembolic disease in pregnancy and the puerperium: acute management. Green-Top Guideline No. 28 Available at:, Accessed November 16, 2009. http://www.rcog.org.uk/resources/public/pdf/green_top_28_thromboembolic_minorrevision.pdf.
79. McColl M.D., Ramsay J.E., Tait R.C., et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997, 78:1183-1188.
80. Geerts W.H., Bergqvist D., Pineo G.F., et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133:381S-453S.
81. Bonnar J. Can more be done in obstetric and gynecologic practice to reduce morbidity and mortality associated with venous thromboembolism?. Am J Obstet Gynecol 1999, 180:784-791.
82. Greer I.A. Epidemiology, risk factors and prophylaxis of venous thromboembolism in obstetrics and gynaecology. Baillieres Clin Obstet Gynaecol 1997, 11:403-430.
83. 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.
84. Royal College of Obstetrics and Gynaecology Report of the RCOG working party on prophylaxis against thromboembolism in gynaecology and obstetrics 1995, Royal College of Obstetrics and Gynaecology, London.
85. Jacobsen A.F., Skjeldestad F.E., Sandset P.M. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Throm Haemost 2008, 6:905-912.