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Semin Vasc Med 2001; 01(1): 097-104
DOI: 10.1055/s-2001-14546
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Pregnancy and Deep Vein Thrombosis

Shannon M. Bates, Jeffrey S. Ginsberg
  • Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Publication History

Publication Date:
31 December 2001 (online)

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ABSTRACT

The diagnosis, treatment, and prevention of deep vein thrombosis (DVT) during pregnancy remain problematic. This article reviews the pathophysiology of pregnancy-related DVT and suggests diagnostic strategies, highlighting the pitfalls specific to this patient population. The treatment of DVT in pregnant patients is difficult because unfractionated heparin and low-molecular-weight heparins, the cornerstones of initial therapy, may have significant maternal side effects and warfarin can cause embryopathy and other adverse fetal effects. As well, there are limited data regarding the efficacy of anticoagulant therapy in the treatment and prophylaxis of DVT during pregnancy. This article briefly reviews the areas of controversy and provides recommendations for the treatment of acute DVT and thromboprophylaxis in pregnant patients.

KEYWORD

Pregnancy - thrombosis - treatment - diagnosis - prophylaxis

REFERENCES

  • 1 Sachs B P, Brown D A, Driscoll S G. Maternal mortality in Massachusetts. Trends and prevention.  N Engl J Med . 1987;  316 667-672
    PubMedGoogle Scholar
  • 2 Atrash H K, Koonin L M, Lawson H W. Maternal morbidity in the United States 1979-1986.  Obstet Gynecol . 1990;  76 1055-1060
    PubMedGoogle Scholar
  • 3 Hogberg U, Innala E, Sandstrom A. <~>Maternal Mortality in Sweden.  Obstet Gynecol . 1994;  84 240-244
    PubMedGoogle Scholar
  • 4 Rutherford S E, Phelan J P. Thromboembolic disease in pregnancy.  Clin Perinatol . 1986;  13 719-739
    PubMedGoogle Scholar
  • 5 Anderson B S, Steffensen F H, Sorensen H T, Nielson G L, 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;  77 110-113
    CrossrefPubMedGoogle Scholar
  • 6 Nordstom M, Lindblad B. A prospective study of the incidence of deep-vein thrombosis within a defined urban population.  J Intern Med . 1992;  232 155-160
    PubMedGoogle Scholar
  • 7 Aaro L A, Juergens J L. Thrombophlebitis associated with pregnancy.  Am J Obstet Gynecol . 1971;  109 1128-1133
    PubMedGoogle Scholar
  • 8 Hiilsmaa V. Occurrence and anticoagulant treatment of thromboembolism in gravidas, parturients and gynecologic patients: a study of 678 cases treated in the Women's Clinic of the University of Helsinki in 1953-1957.  Acta Obstet Gynecol Scand . 1960;  5-12 (5-12)
    PubMedGoogle Scholar
  • 9 Jeffcoaate T NA, Miller J, Roos R F, Tindall V R. Puerperal thromboembolism in relation to inhibition of lactation by estrogen therapy.  Br Med J . 1968;  3 19-25
    PubMedGoogle Scholar
  • 10 Tengborn L, Bergqvist D, Matzsch T, Bergqvist A, Hedner U. Recurrent thromboembolism in pregnancy and puerperium.  Am J Obstet Gynecol . 1985;  28 107-118
    PubMedGoogle Scholar
  • 11 Ginsberg J S, Brill-Edwards P, Burrows R F. Venous thrombosis during pregnancy: leg and trimester of presentation.  Thromb Haemost . 1992;  67 519-520
    PubMedGoogle Scholar
  • 12 Ikard R W, Ueland K, Folse R. Lower limb venous dynamics in pregnant women.  Surg Gynecol Obstet . 1971;  132 483-488
    PubMedGoogle Scholar
  • 13 Macklon N C, 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 Gynecol . 1997;  104 191-197
    PubMedGoogle Scholar
  • 14 Metcalfe J, Ueland K. Maternal cardiovascular adjustments to pregnancy.  Prog Cardiovasc Dis . 1974;  16 363-374
    CrossrefPubMedGoogle Scholar
  • 15 Kerr M G, Scott D B, Samuel E. Studies of the inferior vena cava in late pregnancy.  Br Med J . 1964;  1 532-533
    PubMedGoogle Scholar
  • 16 Cockett F B, Thomas M L. The iliac compression syndrome.  Br J Surg . 1965;  52 816-821
    CrossrefPubMedGoogle Scholar
  • 17 Hull R D, Raskob G E, Carter C J. Serial impedance plethysmography in pregnant patients with clinically suspected deep vein thrombosis.  Ann Intern Med . 1990;  112 663-667
    PubMedGoogle Scholar
  • 18 Stirling Y, Woolf L, North W RS. Haemostasis in normal pregnancy.  Thromb Haemost . 1984;  52 176-182
    PubMedGoogle Scholar
  • 19 Woodhams B J, Candotti G, Shaw R, Kernoff P B. Changes in coagulation and fibrinolysis during pregnancy: evidence of activation of coagulation preceding spontaneous abortion.  Thromb Res . 1989;  55 99-107
    CrossrefPubMedGoogle Scholar
  • 20 Bonnar J. Blood coagulation and fibrinolysis in obstetrics.  Clin Hematol . 1973;  12 58-63
    PubMedGoogle Scholar
  • 21 Comp P C, Thurnau G R, Welsh J. Functional and immunologic protein S levels are decreased during pregnancy.  Blood . 1986;  68 881-885
    PubMedGoogle Scholar
  • 22 Clark P, Brennand J, Conkie J A. Activated protein C sensitivity, protein C, protein S, and coagulation in normal pregnancy.  Thromb Haemost . 1998;  79 1166-1170
    PubMedGoogle Scholar
  • 23 Wright J G, Cooper P, Astedt B. Fibrinolysis during normal human pregnancy: complex interrelationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time.  Br J Haematol . 1988;  69 253-258
    CrossrefPubMedGoogle Scholar
  • 24 Bremme K, Ostlund E, Almqvist I, Heinonen K, Blomback M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium.  Obstet Gynecol . 1992;  80 132-137
    PubMedGoogle Scholar
  • 25 Kruithof E KO, Tran-Thang C, Gudinchet A. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.  Blood . 1987;  69 460-466
    PubMedGoogle Scholar
  • 26 Lindqvist P G, Svensson P J, Marsaal K. Activated protein C resistance (FV:Q506) and pregnancy.  Thromb Hemost . 1999;  81 532-537
    PubMedGoogle Scholar
  • 27 Martinelli I, Sacchi I, Landi G. High risk of cerebral vein thrombosis in carriers of a prothrombin gene mutation and in users of oral contraceptives.  N Engl J Med . 1998;  338 1793-1797
    CrossrefPubMedGoogle Scholar
  • 28 Conrad J, Horellou M H, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women (letter).  Thromb Haemost . 1990;  63 319-320
    PubMedGoogle Scholar
  • 29 Friederich P W, Sanson B J, Simioni P. Frequency of pregnancy related venous thromboembolism in anticoagulant deficient women: implications for prophylaxis.  Ann Intern Med . 1996;  125 955-960
    CrossrefPubMedGoogle Scholar
  • 30 Hellgren M, Tengborn L, Abildgaard U. Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin.  Gynecol Obstet Invest . 1982;  14 127-141
    PubMedGoogle Scholar
  • 31 De Stefano V, Leone G, Mastrangelo S. Thrombosis during pregnancy and surgery in patients with congenital deficiency of antithrombin III, protein C, protein S (letter).  Thromb Haemost . 1994;  71 799-800
    PubMedGoogle Scholar
  • 32 Barnes R W, Wu K K, Hoak J C. Fallibility of clinical diagnosis of venous thrombosis.  JAMA . 1975;  234 605-607
    CrossrefPubMedGoogle Scholar
  • 33 Rabinov K, Paulen S. Roentgen diagnosis of venous thrombosis in the leg.  Arch Surg . 1972;  104 134-144
    PubMedGoogle Scholar
  • 34 Hull R D, Hirsh J, Sackett D L. Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis.  Circulation . 1981;  64 622-625
    CrossrefPubMedGoogle Scholar
  • 35 Ginsberg J S, Hirsh J, Rainbow A J, Coates G. Risks to the fetus of radiologic procedures used in the diagnosis of maternal venous thromboembolic disease.  Thromb Haemost . 1989;  61 189-196
    PubMedGoogle Scholar
  • 36 Doll R, Wakefield R. Risk of childhood cancer from fetal radiation.  Br J Radiol . 1997;  70 130-139
    CrossrefPubMedGoogle Scholar
  • 37 Hull R, Hirsh J, Carter C J. Diagnostic efficacy of impedance plethysmography for clinically suspected deep vein thrombosis.  Ann Intern Med . 1985;  102 21-28
    PubMedGoogle Scholar
  • 38 Huisman M V, Buller H R, ten Cate W J, Vreeken J. Serial impedance plethysmography for suspected deep venous thrombosis in outpatients: the Amsterdam General Practioner Study.  N Engl J Med . 1986;  314 823-828
    PubMedGoogle Scholar
  • 39 Clarke-Pearson D L, Jelovsek F R. Alterations of occlusive cuff impedance plethysmography results in the obstetric patient.  Surgery . 1981;  89 594-598
    PubMedGoogle Scholar
  • 40 Kearon C, Julian J A, Ginsberg J S. Noninvasive diagnosis of deep venous thrombosis.  Ann Intern Med . 1998;  128 663-677
    Google Scholar
  • 41 Lensing A WA, Prandoni P, Brandjes D. Detection of deep vein thrombosis by real time B mode ultrasonography.  N Engl J Med . 1989;  320 342-345
    Google Scholar
  • 42 Heijboer H, Buller H R, Lensing A WA. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients.  N Engl J Med . 1993;  329 1365-1369
    Google Scholar
  • 43 Frede T E, Ruthberg B N. Sonographic demonstration of iliac venous thrombosis in the maternity patient.  J Ultrasound Med . 1988;  7 33-37
    PubMedGoogle Scholar
  • 44 Polak J F, O'Leary D H. Deep venous thrombosis in pregnancy: noninvasive diagnosis.  Radiol . 1988;  166 377-379
    PubMedGoogle Scholar
  • 45 Bounameaux H, de Moerloose P, Perrier A, Raber G. Plasma measurement of D-dimer as a diagnostic aid in suspected venous thromboembolism: an overview.  Thromb Haemost . 1994;  71 1-6
    PubMedGoogle Scholar
  • 46 Nolan T E, Smith R P, Devoe L D. Maternal plasma D-dimer levels in normal and complicated pregnancies.  Obstet Gynecol . 1993;  81 235-238
    PubMedGoogle Scholar
  • 47 Proietti A B, Johnson M J, Proietti F A. Assessment of fibrin(ogen) degradation products in preeclampsia using immunoblot enzyme-linked immunosorbent assay and latex-bead agglutination.  Obstet Gynecol . 1991;  77 696-700
    PubMedGoogle Scholar
  • 48 Francalanci I, Comeglio P, Alessandrello A. D-dimer concentrations during normal pregnancy, as measured by ELISA.  Thromb Res . 1995;  78 399-405
    CrossrefPubMedGoogle Scholar
  • 49 Quick A J. Experimentally induced changes in the prothrombin level of the blood. III. Prothrombin concentration of newborn pups of a mother given Dicoumarol before parturition.  J Biol Chem . 1946;  164 371-376
    PubMedGoogle Scholar
  • 50 Hall J G, Pauli R M, Wilson K M. Maternal and fetal sequelae of anticoagulants during pregnancy.  Am J Med . 1980;  68 122-140
    CrossrefPubMedGoogle Scholar
  • 51 Ginsberg J S, Hirsh J, Turner C, Levine M N, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy.  Thromb Haemost . 1989;  61 197-203
    PubMedGoogle Scholar
  • 52 Iturbe-Alessio I, del Carmen Fonesca M, Mutchinik O. Risks of anticoagulant therapy in pregnant women with artificial heart valves.  N Engl J Med . 1986;  315 1390-1393
    PubMedGoogle Scholar
  • 53 Hirsh J, Cade J F, Gallus A S. Fetal effects of Coumadin administered during pregnancy.  Blood . 1970;  36 623-627
    PubMedGoogle Scholar
  • 54 L'E Orme M, Lewis P J, de Swiet M. May mothers given warfarin breastfeed their infants?.  Br Med J . 1977;  1 1564-1565
    PubMedGoogle Scholar
  • 55 McKenna R, Cole E R, Vasan U. Is warfarin sodium contraindicated in the lactating mothers?.  J Pediatr . 1983;  103 325-327
    CrossrefPubMedGoogle Scholar
  • 56 Flessa H C, Kapstrom A B, Glueck H I, Will J. Placental transport of heparin.  Am J Obstet Gynecol . 1965;  93 570-573
    CrossrefPubMedGoogle Scholar
  • 57 Ginsberg J S, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R. Heparin therapy during pregnancy: risks to the fetus and mother.  Arch Intern Med . 1989;  149 2233-2236
    CrossrefPubMedGoogle Scholar
  • 58 Hull R, Delmore T, Carter C. Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis.  N Engl J Med . 1982;  306 189-194
    PubMedGoogle Scholar
  • 59 Hull R, Hirsh J, Jay R. Different intensities of oral anticoagulant therapy in the treatment of proximal vein thrombosis.  N Engl J Med . 1982;  307 1676-1681
    PubMedGoogle Scholar
  • 60 Warkentin T E, Levine M N, Hirsh J. Heparin-induced thrombocytopenia in patients treated with low molecular weight heparin or unfractionated heparin.  N Engl J Med . 1995;  332 1330-1335
    CrossrefPubMedGoogle Scholar
  • 61 Griffith G C, Nichols G, Asher J D, Flahagan B. Heparin osteoporosis.  J Am Med Assoc . 1965;  193 85-94
    PubMedGoogle Scholar
  • 62 Ginsberg J S, Kowalchuk G, Hirsh J. Heparin effect on bone density.  Thromb Haemost . 1990;  64 286-289
    PubMedGoogle Scholar
  • 63 Douketis J D, Ginsberg J S, Burrows R F. The effects of long-term heparin therapy during pregnancy on bone density: a prospective matched cohort study.  Thromb Haemost . 1996;  75 254-257
    PubMedGoogle Scholar
  • 64 Dahlman T C. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin.  Am J Obstet Gynecol . 1993;  168 1265-1270
    CrossrefPubMedGoogle Scholar
  • 65 Dahlman T C, Lindvall N, Hellgren M. Osteopenia in pregnancy during long-term heparin treatment: a radiological study post-partum.  Br J Obstet Gynecol . 1990;  97 221-228
    PubMedGoogle Scholar
  • 66 Zimran A, Shilo S, Fisher D, Bab I. Histomorphic evaluation of reversible heparin-induced osteoporosis in pregnancy.  Arch Intern Med . 1986;  146 386-388
    CrossrefPubMedGoogle Scholar
  • 67 Anderson D R, Ginsberg J S, Brill-Edwards P. Teflon catheter use for subcutaneous heparin administration during pregnancy: a randomized cross-over study.  Thromb Haemost . 1991;  65 924a
    PubMedGoogle Scholar
  • 68 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism: a statement for healthcare professionals.  Circulation . 1996;  93 2212-2245
    CrossrefPubMedGoogle Scholar
  • 69 Forestier F, Daffos F, Copella-Paulovsky 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
    CrossrefPubMedGoogle Scholar
  • 70 Hull R D, Raskob G E, Pineo G F. Subcutaneous low molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal vein thrombosis.  N Engl J Med . 1992;  326 975-982
    CrossrefPubMedGoogle Scholar
  • 71 Weitz J I. Low-molecular-weight heparins.  N Engl J Med . 1997;  337 688-698
    CrossrefPubMedGoogle Scholar
  • 72 Monreal M, Lafoz E, Olive A, del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin.  Thromb Haemost . 1994;  71 7-11
    PubMedGoogle Scholar
  • 73 Melissari E, Parker C J, Wilson N V. Use of low molecular weight heparin in pregnancy.  Thromb Haemost . 1992;  68 652-656
    PubMedGoogle Scholar
  • 74 Sefras J, Farquharson R G. Bone density studies in pregnant women receiving heparin.  Eur J Obstet Gynecol Reprod Biol . 1996;  65 171-174
    CrossrefPubMedGoogle Scholar
  • 75 Dolovich L R, Ginsberg J S, Douketis J D, Holbrook A M, Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Examining some unanswered questions regarding location of treatment, product type, and dosing frequency.  Arch Intern Med . 2000;  160 181-188
    CrossrefPubMedGoogle Scholar
  • 76 Nurmohamed M T, Rosendaal F R, Buller H R. Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis.  Lancet . 1992;  340 152-156
    CrossrefPubMedGoogle Scholar
  • 77 Leizorovicz A, Haugh M C, Chapuis F R, Samama M M, Boissel J P. Low-molecular-weight heparins in the prevention of perioperative thrombosis.  Br Med J . 1992;  305 913-920
    PubMedGoogle Scholar
  • 78 Sanson B, Lensing A WA, Prins M H. The use of low-molecular-weight heparin in pregnancy: a systematic review.  Thromb Haemost . 1999;  81 668-672
    PubMedGoogle Scholar
  • 79 Villasanta U. Thromboembolic disease in pregnancy.  Am J Obstet Gynecol . 1965;  93 142-160
    PubMedGoogle Scholar
  • 80 Hull R D, Raskob G E, Rosenbloom D. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis.  N Engl J Med . 1990;  332 1260-1264
    PubMedGoogle Scholar
  • 81 Ginsberg J S, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest . 1998;  524S-530S (524S-530S)
    PubMedGoogle Scholar
  • 82 Raschke R A, Reilly B M, Guidry J R, Fontana J R, Srinivas S. The weight-based heparin dosing nomogram compared with a ``standard care nomogram''.  Ann Intern Med . 1993;  119 874-881
    CrossrefPubMedGoogle Scholar
  • 83 Badaracco M A, Vessey M. Recurrent venous thromboembolic disease and the use of oral contraceptives.  Br Med J . 1974;  1 215-217
    PubMedGoogle Scholar
  • 84 Tengborn L. Recurrent thromboembolism in pregnancy and the puerperium: is there a need for thromboprophylaxis?.  Am J Obstet Gynecol . 1989;  160 90-94
    CrossrefPubMedGoogle Scholar
  • 85 Maternal and Neonatal Haemostasis Working Party of the Haemostasis and Thrombosis Task. Guidelines on the presentation, investigation, and management of thrombosis associated with pregnancy.  J Clin Pathol . 1993;  46 489-496
    PubMedGoogle Scholar
  • 86 Colvin B T, Barrowcliff T W. The British Society for Haematology guidelines on the use and monitoring of heparin 1992; second revision.  J Clin Pathol . 1993;  45 97-103
    PubMedGoogle Scholar
  • 87 de Swiet M, Floyd E, Letsky E. Low risk of recurrent thromboembolism in pregnancy (letter).  Br J Hosp Med . 1987;  38 264
    PubMedGoogle Scholar
  • 88 Howell R, Fidler J, Letsky E. The risk of antenatal subcutaneous heparin prophylaxis: a controlled trial.  Br J Obstet Gynecol . 1983;  90 1124-1128
    PubMedGoogle Scholar
  • 89 Brill-Edwards P, Ginsberg J S, Gent M. Safety of withholding heparin in pregnant women with a history of venous thromboembolism.  N Engl J Med . 2000;  343 1439-1444
    CrossrefPubMedGoogle Scholar
  • 90 Demers C, Ginsberg J S. Deep vein thrombosis and pulmonary embolism in pregnancy.  Clin Chest Med . 1992;  13 645-656
    PubMedGoogle Scholar
  • 91 Anderson D R, Ginsberg J S, Burrows R, Brill-Edwards P. Subcutaneous heparin therapy during pregnancy: a need for concern at the time of delivery.  Thromb Haemost . 1991;  65 248-250
    PubMedGoogle Scholar
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