Semin Respir Crit Care Med 2017; 38(02): 135-147
DOI: 10.1055/s-0037-1602241
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pulmonary Complications of Pregnancy: Venous Thromboembolism

Leslie Skeith
1   Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2   Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Marc A. Rodger
1   Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2   Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
3   Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
22 May 2017 (online)

Abstract

Unique considerations are needed when diagnosing and treating venous thromboembolism (VTE) in women who are pregnant or postpartum. What are the risks to the fetus, such as drug exposure or the risk of radiation with diagnostic imaging? How does the physiology of pregnancy affect imaging techniques and anticoagulation management? How should anticoagulation be managed around labor and delivery? These questions highlight some of the important considerations needed when managing a pregnant patient with suspected or confirmed VTE. This review outlines what is known about the epidemiology, pathophysiology, clinical risk factors, diagnosis, and therapeutic management of VTE in pregnancy. We also review our preferred diagnostic and treatment algorithm for a pregnant patient with suspected or confirmed VTE.

 
  • References

  • 1 Simpson EL, Lawrenson RA, Nightingale AL, Farmer RDT. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001; 108 (01) 56-60
  • 2 Kuriya A, Piedimonte S, Spence AR, Czuzoj-Shulman N, Kezouh A, Abenhaim HA. Incidence and causes of maternal mortality in the USA. J Obstet Gynaecol Res 2016; 42 (06) 661-668
  • 3 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
  • 4 Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008; 6 (04) 632-637
  • 5 Liu S, Rouleau J, Joseph KS. , et al; Maternal Health Study Group of the Canadian Perinatal Surveillance System. Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada. J Obstet Gynaecol Can 2009; 31 (07) 611-620
  • 6 Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999; 94 (5, Pt 1): 730-734
  • 7 Andersen BS, Steffensen FH, Sørensen HT, Nielsen GL, Olsen J. The cumulative incidence of venous thromboembolism during pregnancy and puerperium--an 11 year Danish population-based study of 63,300 pregnancies. Acta Obstet Gynecol Scand 1998; 77 (02) 170-173
  • 8 Lindqvist P, Dahlbäck B, Marŝál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94 (04) 595-599
  • 9 Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014; 370 (14) 1307-1315
  • 10 Sultan AA, West J, Grainge MJ. , et al. Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study. BMJ 2016; 355: i6253
  • 11 Anderson Jr FA, Wheeler HB, Goldberg RJ. , et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151 (05) 933-938
  • 12 Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999; 54 (04) 265-271
  • 13 James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194 (05) 1311-1315
  • 14 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium--a register-based case-control study. Am J Obstet Gynecol 2008; 198 (02) 233.e1-233.e7
  • 15 Rodger M. Evidence base for the management of venous thromboembolism in pregnancy. Hematology (Am Soc Hematol Educ Program) 2010; 2010 (01) 173-180
  • 16 Macklon NS, Greer IA, Bowman AW. An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy. Br J Obstet Gynaecol 1997; 104 (02) 191-197
  • 17 Goulart VB, Cabral ACV, Reis ZS. , et al. Anatomical and physiological changes in the venous system of lower limbs in pregnant women and findings associated with the symptomatology. Arch Gynecol Obstet 2013; 288 (01) 73-78
  • 18 Chan WS, Spencer FA, Ginsberg JS. Anatomic distribution of deep vein thrombosis in pregnancy. CMAJ 2010; 182 (07) 657-660
  • 19 Blondon M, Casini A, Hoppe KK, Boehlen F, Righini M, Smith NL. Risks of venous thromboembolism after cesarean sections: a meta-analysis. Chest 2016; 150 (03) 572-596
  • 20 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
  • 21 Rosenkranz A, Hiden M, Leschnik B. , et al. Calibrated automated thrombin generation in normal uncomplicated pregnancy. Thromb Haemost 2008; 99 (02) 331-337
  • 22 Brenner B. Haemostatic changes in pregnancy. Thromb Res 2004; 114 (5-6): 409-414
  • 23 Murphy N, Broadhurst DI, Khashan AS, Gilligan O, Kenny LC, O'Donoghue K. Gestation-specific D-dimer reference ranges: a cross-sectional study. BJOG 2015; 122 (03) 395-400
  • 24 Grossman KB, Arya R, Peixoto AB, Akolekar R, Staboulidou I, Nicolaides KH. Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy. Am J Obstet Gynecol 2016; 215 (04) 466.e1-466.e8
  • 25 Chan WS, Ginsberg JS. A review of upper extremity deep vein thrombosis in pregnancy: unmasking the ‘ART’ behind the clot. J Thromb Haemost 2006; 4 (08) 1673-1677
  • 26 Bauersachs RM, Manolopoulos K, Hoppe I, Arin MJ, Schleussner E. More on: the ‘ART’ behind the clot: solving the mystery. J Thromb Haemost 2007; 5 (02) 438-439
  • 27 Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 92-128
  • 28 Rodger M. Pregnancy and venous thromboembolism: ‘TIPPS’ for risk stratification. Hematology (Am Soc Hematol Educ Program) 2014; 2014 (01) 387-392
  • 29 Chan WS, Rey E, Kent NE. , et al; VTE in Pregnancy Guideline Working Group; Society of Obstetricians and Gynecologists of Canada. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 2014; 36 (06) 527-553
  • 30 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos A-M, 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 2012; 141 (2, Suppl): e691S-e736S
  • 31 Gerhardt A, Scharf RE, Greer IA, Zotz RB. Hereditary risk factors of thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium. Blood 2016; 128 (19) 2343-2349
  • 32 Chan WS, Ray JG, Murray S, Coady GE, Coates G, Ginsberg JS. Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes. Arch Intern Med 2002; 162 (10) 1170-1175
  • 33 Cahill AG, Stout MJ, Macones GA, Bhalla S. Diagnosing pulmonary embolism in pregnancy using computed-tomographic angiography or ventilation-perfusion. Obstet Gynecol 2009; 114 (01) 124-129
  • 34 Shahir K, Goodman LR, Tali A, Thorsen KM, Hellman RS. Pulmonary embolism in pregnancy: CT pulmonary angiography versus perfusion scanning. AJR Am J Roentgenol 2010; 195 (03) W214-20
  • 35 Parilla BV, Fournogerakis R, Archer A. , et al. Diagnosing pulmonary embolism in pregnancy: are biomarkers and clinical predictive models useful?. AJP Rep 2016; 6 (02) e160-e164
  • 36 Wells PS, Ginsberg JS, Anderson DR. , et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129 (12) 997-1005
  • 37 Chan WS, Lee A, Spencer FA. , et al. D-dimer testing in pregnant patients: towards determining the next ‘level’ in the diagnosis of deep vein thrombosis. J Thromb Haemost 2010; 8 (05) 1004-1011
  • 38 Chan W-S, Lee A, Spencer FA. , et al. Predicting deep venous thrombosis in pregnancy: out in “LEFt” field?. Ann Intern Med 2009; 151 (02) 85-92
  • 39 Righini M, Jobic C, Boehlen F. , et al; EDVIGE Study Group. Predicting deep venous thrombosis in pregnancy: external validation of the LEFT clinical prediction rule. Haematologica 2013; 98 (04) 545-548
  • 40 Le Moigne E, Genty C, Meunier J. , et al; OPTIMEV Investigators. Validation of the LEFt score, a newly proposed diagnostic tool for deep vein thrombosis in pregnant women. Thromb Res 2014; 134 (03) 664-667
  • 41 Cutts BA, Tran HA, Merriman E. , et al. The utility of the Wells clinical prediction model and ventilation-perfusion scanning for pulmonary embolism diagnosis in pregnancy. Blood Coagul Fibrinolysis 2014; 25 (04) 375-378
  • 42 O'Connor C, Moriarty J, Walsh J, Murray J, Coulter-Smith S, Boyd W. The application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy. J Matern Fetal Neonatal Med 2011; 24 (12) 1461-1464
  • 43 Damodaram M, Kaladindi M, Luckit J, Yoong W. D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use?. J Obstet Gynaecol 2009; 29 (02) 101-103
  • 44 Le Gal G, Kercret G, Ben Yahmed K. , et al; EDVIGE Study Group. Diagnostic value of single complete compression ultrasonography in pregnant and postpartum women with suspected deep vein thrombosis: prospective study. BMJ 2012; 344 (e2635): e2635
  • 45 Bulas D, Egloff A. Benefits and risks of MRI in pregnancy. Semin Perinatol 2013; 37 (05) 301-304
  • 46 Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 2016; 316 (09) 952-961
  • 47 Moody AR. Magnetic resonance direct thrombus imaging. J Thromb Haemost 2003; 1 (07) 1403-1409
  • 48 Rodger MA, Avruch LI, Howley HE, Olivier A, Walker MC. Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section. Am J Obstet Gynecol 2006; 194 (02) 436-437
  • 49 Khalil H, Avruch L, Olivier A, Walker M, Rodger M. The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery. Am J Obstet Gynecol 2012; 206 (04) 356.e1-356.e4
  • 50 PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263 (20) 2753-2759
  • 51 Righini M, Le Gal G, Aujesky D. , et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371 (9621): 1343-1352
  • 52 Brill-Edwards P, Ginsberg JS, Gent M. , et al; Recurrence of Clot in This Pregnancy Study Group. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000; 343 (20) 1439-1444
  • 53 Revel M-P, Cohen S, Sanchez O. , et al. Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography?. Radiology 2011; 258 (02) 590-598
  • 54 Balan KK, Critchley M, Vedavathy KK, Smith ML, Vinjamuri S. The value of ventilation-perfusion imaging in pregnancy. Br J Radiol 1997; 70 (832) 338-340
  • 55 Scarsbrook AF, Bradley KM, Gleeson FV. Perfusion scintigraphy: diagnostic utility in pregnant women with suspected pulmonary embolic disease. Eur Radiol 2007; 17 (10) 2554-2560
  • 56 Nijkeute M, Tan M, Middeldorp S, Kroft L, Beenen L, Huisman M. Safety of ruling out pulmonary embolism (PE) in pregnancy by computed tomography pulmonary angiography (CTPA). J Thromb Haemost 2013; 11: 130
  • 57 International Commission of Radiological Protection. Pregnancy and medical radiation: publication 84. Ann ICRP 2000; 30: 1-44
  • 58 McCollough CH, Schueler BA, Atwell TD. , et al. Radiation exposure and pregnancy: when should we be concerned?. Radiographics 2007; 27 (04) 909-917 , discussion 917–918
  • 59 Leung AN, Bull TM, Jaeschke R. , et al; ATS/STR Committee on Pulmonary Embolism in Pregnancy. An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med 2011; 184 (10) 1200-1208
  • 60 Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and Use of Sealed Radioactive Sources. Available at: https://www.gov.uk/government/publications/arsac-notes-for-guidance . Accessed April 26, 2017
  • 61 Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M. Pulmonary embolism in pregnancy. Lancet 2010; 375 (9713): 500-512
  • 62 Hurwitz LM, Yoshizumi T, Reiman RE. , et al. Radiation dose to the fetus from body MDCT during early gestation. AJR Am J Roentgenol 2006; 186 (03) 871-876
  • 63 Groves AM, Yates SJ, Win T. , et al. CT pulmonary angiography versus ventilation-perfusion scintigraphy in pregnancy: implications from a UK survey of doctors' knowledge of radiation exposure. Radiology 2006; 240 (03) 765-770
  • 64 Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B. EANM guidelines for ventilation/perfusion scintigraphy: Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V/P(SPECT) and MDCT. Eur J Nucl Med Mol Imaging 2009; 36 (09) 1528-1538
  • 65 Bourjeily G, Chalhoub M, Phornphutkul C, Alleyne TC, Woodfield CA, Chen KK. Neonatal thyroid function: effect of a single exposure to iodinated contrast medium in utero. Radiology 2010; 256 (03) 744-750
  • 66 Worsley DF, Alavi A. ; Prospective Investigation of Pulmonary Embolism Diagnosis Study. Comprehensive analysis of the results of the PIOPED Study. J Nucl Med 1995; 36 (12) 2380-2387
  • 67 Andreou AK, Curtin JJ, Wilde S, Clark A. Does pregnancy affect vascular enhancement in patients undergoing CT pulmonary angiography?. Eur Radiol 2008; 18 (12) 2716-2722
  • 68 Parker A, Alotaibi G, Wu C, Lapner S. The proportion of nondiagnostic computed tomographic pulmonary angiography and ventilation/perfusion lung scans in pregnant women with suspected pulmonary embolism: a systematic review. J Thromb Haemost 2015 ;13(Suppl 2): 9 . Abstract AS023
  • 69 McLintock C, Brighton T, Chunilal S. , et al; Councils of the Society of Obstetric Medicine of Australia and New Zealand; Australasian Society of Thrombosis and Haemostasis. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Aust N Z J Obstet Gynaecol 2012; 52 (01) 14-22
  • 70 Linnemann B, Scholz U, Rott H. , et al; Working Group in Women's Health of the Society of Thrombosis and Hemostasis. Treatment of pregnancy-associated venous thromboembolism - position paper from the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH). Vasa 2016; 45 (02) 103-118
  • 71 Royal College of Obstetricians and Gynaecologists. Thromboembolic disease in pregnancy and the puerperium: acute management. 2015 ;37b. Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37b.pdf . Accessed April 26, 2017
  • 72 Cooper M, Matthews S. Imaging pulmonary embolism in pregnancy: what is the value of routine bilateral leg Doppler ultrasound in women without symptoms of deep venous thrombosis?. J Thorac Imaging 2012; 27 (05) W155
  • 73 Leonhardt G, Gaul C, Nietsch HH, Buerke M, Schleussner E. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis 2006; 21 (03) 271-276
  • 74 Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv 1995; 50 (07) 534-541
  • 75 te Raa GD, Ribbert LS, Snijder RJ, Biesma DH. Treatment options in massive pulmonary embolism during pregnancy; a case-report and review of literature. Thromb Res 2009; 124 (01) 1-5
  • 76 Holden EL, Ranu H, Sheth A, Shannon MS, Madden BP. Thrombolysis for massive pulmonary embolism in pregnancy--a report of three cases and follow up over a two year period. Thromb Res 2011; 127 (01) 58-59
  • 77 Meyer G, Vicaut E, Danays T. , et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014; 370 (15) 1402-1411
  • 78 Spectre G, Bloom A, Roth B. , et al. Pharmacomechanical catheter directed thrombolysis for pregnancy related proximal lower extremity deep venous thrombosis: effectiveness in the prevention of post thrombotic syndrome. Blood 2016 ;128(22): 1488
  • 79 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 (06) 557-560
  • 80 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 (11) 1134-1140
  • 81 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 (02) 401-407
  • 82 Bank I, Libourel EJ, Middeldorp S, Van Der Meer J, Büller HR. High rate of skin complications due to low-molecular-weight heparins in pregnant women. J Thromb Haemost 2003; 1 (04) 859-861
  • 83 Linkins L-A, Dans AL, Moores LK. , et al; American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e495S-e530S
  • 84 Rodger MA, Kahn SR, Cranney A. , et al; TIPPS investigators. Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: substudy of a randomized controlled trial. J Thromb Haemost 2007; 5 (08) 1600-1606
  • 85 Pettilä V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 2002; 87 (02) 182-186
  • 86 Barbour LA, Oja JL, Schultz LK. A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol 2004; 191 (03) 1024-1029
  • 87 Galambosi P, Hiilesmaa V, Ulander VM, Laitinen L, Tiitinen A, Kaaja R. Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density. Thromb Res 2016; 143: 122-126
  • 88 Herbstreit F, Kienbaum P, Merguet P, Peters J. Conservative treatment of paraplegia after removal of an epidural catheter during low-molecular-weight heparin treatment. Anesthesiology 2002; 97 (03) 733-734
  • 89 Wysowski DK, Talarico L, Bacsanyi J, Botstein P. Spinal and epidural hematoma and low-molecular-weight heparin. N Engl J Med 1998; 338 (24) 1774-1775
  • 90 Howell R, Fidler J, Letsky E, de Swiet M. The risks of antenatal subcutaneous heparin prophylaxis: a controlled trial. Br J Obstet Gynaecol 1983; 90 (12) 1124-1128
  • 91 Schaefer C, Hannemann D, Meister R. , et al. Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study. Thromb Haemost 2006; 95 (06) 949-957
  • 92 Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med 2000; 160 (02) 191-196
  • 93 Bapat P, Kedar R, Lubetsky A. , et al. Transfer of dabigatran and dabigatran etexilate mesylate across the dually perfused human placenta. Obstet Gynecol 2014; 123 (06) 1256-1261
  • 94 Bapat P, Pinto LS, Lubetsky A. , et al. Examining the transplacental passage of apixaban using the dually perfused human placenta. J Thromb Haemost 2016; 14 (07) 1436-1441
  • 95 Beyer-Westendorf J, Michalski F, Tittl L. , et al. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost 2016; 116 (04) 651-658
  • 96 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (08) 1673-1676
  • 97 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH: reply. J Thromb Haemost 2016; 15 (01) 195-197
  • 98 Gándara E, Carrier M, Rodger MA. Management of pregnancy associated venous-thromboembolism: a survey of practices. Thromb J 2014; 12 (12) 12
  • 99 Bhutia S, Wong PF. Once versus twice daily low molecular weight heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev 2013; (07) CD003074
  • 100 Voke J, Keidan J, Pavord S, Spencer NH, Hunt BJ. ; British Society for Haematology Obstetric Haematology Group. The management of antenatal venous thromboembolism in the UK and Ireland: a prospective multicentre observational survey. Br J Haematol 2007; 139 (04) 545-558
  • 101 Jacobsen AF, Qvigstad E, Sandset PM. Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series. Br J Obstet Gynaecol 2003; 110: 139-144
  • 102 Lebaudy C, Hulot JS, Amoura Z. , et al. Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy. Clin Pharmacol Ther 2008; 84 (03) 370-377
  • 103 Lee AY, Levine MN, Baker RI. , et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153
  • 104 Das SK, Cohen AT, Edmondson RA, Melissari E, Kakkar VV. Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: a randomized trial. World J Surg 1996; 20 (05) 521-526 , discussion 526–527
  • 105 Kahn SR, Shapiro S, Wells PS. , et al; SOX Trial Investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014; 383 (9920): 880-888
  • 106 Harris SA, Velineni R, Davies AH. Inferior vena cava filters in pregnancy: a systematic review. J Vasc Interv Radiol 2016; 27 (03) 354-60.e8
  • 107 Orme ML, Lewis PJ, de Swiet M. , et al. May mothers given warfarin breast-feed their infants?. BMJ 1977; 1 (6076): 1564-1565
  • 108 Richter C, Sitzmann J, Lang P, Weitzel H, Huch A, Huch R. Excretion of low molecular weight heparin in human milk. Br J Clin Pharmacol 2001; 52 (06) 708-710