Download PDF
Thromb Haemost 1989; 61(02): 197-203
DOI: 10.1055/s-0038-1646558
Original Article
Schattauer GmbH Stuttgart

Risks to the Fetus of Anticoagulant Therapy During Pregnancy

Jeffrey S Ginsberg
The Departments of Medicine and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
,
Jack Hirsh
The Departments of Medicine and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
,
D Christoper Turner
The Departments of Medicine and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
,
Mark N Levine
The Departments of Medicine and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
,
Robert Burrows
The Departments of Medicine and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Received 07 September 1988

Accepted after revision 16 November 1988

Publication Date:
30 June 2018 (online)

  PDF Download  Permissions and Reprints

Summary

The use of anticoagulants during pregnancy is problematic because of the potential adverse effects to the mother and the fetus. Heparin does not cross the placenta, and thus, it was surprising that a recent report concluded that heparin therapy during pregnancy was as risky as oral anticoagulant therapy. Therefore, we performed a literature review of fetal/infant outcomes following anticoagulant therapy during pregnancy. We examined 186 reports which described fetal/infant outcomes in 1,325 pregnancies associated with anticoagulant therapy. The rates of adverse fetal/infant outcomes including death, prematurity and congenital malformations following treatment with heparin, oral anticoagulants, or both were calculated. The previously described high rate of adverse feta/infant outcomes with heparin- treated patients, could be accounted for by the frequent use of heparin in pregnancies with comorbid conditions independently associated with adverse outcomes and by reports of uncomplicated prematurity. After excluding such pregnancies, outcomes in heparin-treated patients are similar to the normal population.

Keywords

Pregnancy - Heparin - Oral anticoagulants - Thromboembolism
 

  • References

  • 1 Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am J Obstet Gynecol 1965; 93: 570-573
    CrossrefPubMedGoogle Scholar
  • 2 Becker MH, Genieser NB, Finegold M, Miranda D, Spackman T. Chondrodysplasia Punctata. Is maternal warfarin a factor Am J Dis Child 1975; 129: 356-359
    CrossrefPubMedGoogle Scholar
  • 3 Hall JA G, Paul RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122-140
    CrossrefPubMedGoogle Scholar
  • 4 Yahr MD, Reich C, Eggers C. The treatment of thrombophlebitis. Surg Gynecol Obstet 1945; 80: 615-619
    PubMedGoogle Scholar
  • 5 Page EW. Use of heparin in pre-eclampsia. Am J Med 1948; 4: 784
    PubMedGoogle Scholar
  • 6 von Sydow G. Hypoprotrombinemi och hjarnskada hos barn till dikumarin-behandled moder. Nord Med 1947; 34: 1171-1188
    PubMedGoogle Scholar
  • 7 Maeck JV S, Zilliacus H. Heparin in the treatment of toxemia of pregnancy. Am J Obstet Gynecol 1948; 55: 326-331
    CrossrefPubMedGoogle Scholar
  • 8 Felder DA. Evaluation of the various clinical signs of thrombophlebitis and experience in therapy with anticoagulants. Surg Gynecol Obstet 1949; 88: 337-350
    PubMedGoogle Scholar
  • 9 Sachs JJ, Labate JS. Dicumarol in the treatment of antenatal thromboembolic disease. Am J Obstet Gynecol 1949; 57: 965-971
    CrossrefPubMedGoogle Scholar
  • 10 Adamson DL, Weaver RT, Jaimet CH. A new view on the use of dicumarol in the pregnant patient. Am J Obstet Gynecol 1950; 59: 498-504
    CrossrefPubMedGoogle Scholar
  • 11 Butler BC, Taylor HC, Graff S. The relationship of disorders of the blood-clotting mechanism to toxemia of pregnancy and the value of heparin in therapy. Am J Obstet Gynecol 1950; 60 (03) 564-574
    CrossrefPubMedGoogle Scholar
  • 12 Brambel CE, Fitzpatrick Vde P, Hunter RE. Protracted anticoagulant therapy during the antenatal period. Trans N Engl Obstet Gynecol Soc 1951; 5: 27-45
    PubMedGoogle Scholar
  • 13 Davis WL. Antepartum phlebothrombosis and thrombophlebitis. Am J Obstet Gynecol 1951; 62: 353-358
    CrossrefPubMedGoogle Scholar
  • 14 Thornton WN. (Quoted in [13] Davis). Antepartum phlebothrombosis and thrombophlebitis Am J Obstet Gynecol 1951; 62: 353-358
    CrossrefPubMedGoogle Scholar
  • 15 Wright HP. Venous thrombosis during pregnancy treated with dicoumarin. J Obstet Gynecol Br Emp 1951; 59: 272-277
    PubMedGoogle Scholar
  • 16 Da Cunha FA. Massive haemorrhage following anticoagulant therapy in pregnancy. J Obstet Gynecol Br Emp 1952; 59: 521-522
    CrossrefPubMedGoogle Scholar
  • 17 Mansell RV. Antepartum dicumarol therapy. Am J Obstet Gynecol 1952; 64: 155-161
    CrossrefPubMedGoogle Scholar
  • 18 Flood CM. Antepartum femoral thrombosis. J Obstet Gynecol Br Emp 1953; 60: 706-709
    CrossrefPubMedGoogle Scholar
  • 19 Ullery JC. Thromboembolic disease complicating pregnancy and the puerperium. Am J Obstet Gynecol 1954; 68: 1243-1260
    PubMedGoogle Scholar
  • 20 Gordon RR, Dean T. Foetal deaths from antenatal anticoagulant therapy. Br Med J 1955; 2: 719-721
    CrossrefPubMedGoogle Scholar
  • 21 Barry GR, Olson MJ. Antepartum thrombophlebitis: a case report. Am J Obstet Gynecol 1956; 72 (04) 910-912
    CrossrefPubMedGoogle Scholar
  • 22 Blum M. Anticoagulant treatment of phlebothrombosis during pregnancy. Am J Obstet Gynecol 1957; 73 (02) 440-443
    CrossrefPubMedGoogle Scholar
  • 23 Forssell J, Brunial T. Cardiac infarction and pregnancy. Acta Med Scand 1957; 157: 387-397
    PubMedGoogle Scholar
  • 24 Lloyd TS. Dicumarol in antepartum thrombophlebitis. A case report Va Med 1957; 84: 560-562
    PubMedGoogle Scholar
  • 25 Parker RT, Anlyan WG, Mairs DA. et al. Thromboembolic complications of pregnancy. South Med J 1957; 50: 1228
    CrossrefPubMedGoogle Scholar
  • 26 Der Ohanesian O. Antepartum thrombophlebitis: Report of a case. Obstet Gynecol 1959; 13 (03) 341-342
    PubMedGoogle Scholar
  • 27 Epstein WA. Antepartum fetal death during anticoagulant therapy of thromboembolism. J Mt Sinai Hosp NY 1959; 26: 562-565
    PubMedGoogle Scholar
  • 28 McElin TW, Danforth DN, Buckingham JC. Thrombophlebitis in antepartum patients. Q Bull Northwest Univ Med Sch 1959; 33: 242-246
    PubMedGoogle Scholar
  • 29 Quenneville G, Barton B, McDevitt E, Wright IS. The use of anticoagulants for thrombophlebitis during pregnancy. Am J Obstet Gynecol 1959; 77: 1135-1149
    CrossrefPubMedGoogle Scholar
  • 30 Feldman R, Smith L. Antepartum thrombophlebitis treated by longterm use of bishydroxycoumarin. Am J Obstet Gynecol 1960; 79: 810-811
    CrossrefPubMedGoogle Scholar
  • 31 Pagliari M. Sui possibili effectti nocivi sulla madre e il feta dei preparati dicumarolici usati in gravidanza. Quad Clin Ostet Ginecol 1960; 15: 910
    PubMedGoogle Scholar
  • 32 Gopelrud CP, Anderson GS. Antepartum venous thrombosis with multiple pulmonary emboli: A case report and a discussion. J Iowa Med Soc 1961; LI (12) 771-773
    PubMedGoogle Scholar
  • 33 Joseph R, Ribierre M, Hemery G. Mizzi. Les hémorragies foetales provoquées par Tadministration d’anticoagulants à la femme enceinte. Ann Pediatr 1961; 37: 359-361
    PubMedGoogle Scholar
  • 34 Krembs MA, Kozina TJ. Antenatal pulmonary embolic disease. Am J Obstet Gynecol 1961; 81: 1233-1236
    CrossrefPubMedGoogle Scholar
  • 35 Naden RS, Johnson HF, Murray EN. Myocardial infarction during pregnancy. JAMA 1961; 178: 659-661
    CrossrefPubMedGoogle Scholar
  • 36 Finnerty JJ, MacKay BR. Antepartum thrombophlebitis and pulmonary embolism. Report of a case and review of the literature Obstet Gynecol 1962; 19: 405-410
    PubMedGoogle Scholar
  • 37 Mahairas GH, Weingold AB. Fetal hazard with anticoagulant therapy. Am J Obstet Gynecol 1963; 85: 234-237
    CrossrefPubMedGoogle Scholar
  • 38 Cegelski FC, DeWeese JA, Lund CJ. Deep iliofemoral venous thrombosis during pregnancy. Am J Obstet Gynecol 1964; 89: 510-518
    CrossrefPubMedGoogle Scholar
  • 39 Jennings JA. Hodgkinson C R Anticoagulation for pulmonary embolism in pregnancy. Obstet Gynecol 1964; 24: 85-88
    PubMedGoogle Scholar
  • 40 DeVita VT, Wiener L, Massumi R. Antepartum thrombophlebitis and pulmonary embolization. Report of a case and review of the literature Med Ann DC 1965; 34: 177-180
    PubMedGoogle Scholar
  • 41 Villasanta U. Thromboembolic disease in pregnancy. Am J Obstet Gynecol 1965; 93: 142-160
    CrossrefPubMedGoogle Scholar
  • 42 Aaro LA, Johnson TR, Juergens JL. Acute deep venous thrombosis associated with pregnancy. Obstet Gynecol 1966; 28: 553-558
    PubMedGoogle Scholar
  • 43 Johnson AS, Meyers MP, Eckhous AS, Bacher B, Limia A. Successful pregnancies in patients with prosthetic mitral valves. Mich Med 1966; 65: 718-719
    PubMedGoogle Scholar
  • 44 Harthome JW, Buckley MJ, Grover JW, Austen WG. Valve replacement during pregnancy. Ann Intern Med 1967; 67: 1032-1034
    CrossrefPubMedGoogle Scholar
  • 45 Husni EA, Pena LI, Lenhert AE. Thrombophlebitis in pregnancy. Am J Obstet Gynecol 1967; 97: 901-905
    CrossrefPubMedGoogle Scholar
  • 46 Bennett GG, Oakley CM. Pregnancy in a patient with a mitral-valve prosthesis. Lancet 1968; 1: 616-619
    PubMedGoogle Scholar
  • 47 Carty AT, Crowdes RL. Pregnancy in a patient with a mitral valve prosthesis. Lancet 1968; 2: 456-457
    PubMedGoogle Scholar
  • 48 Hedstrand H, Cullhed I. Pregnancy after aortic-valve prosthesis. Lancet 1968; 2: 916
    PubMedGoogle Scholar
  • 49 Kenmure AC F. Pregnancy in a patient with a prosthetic mitral valve. J Obstet Gynecol Br Commonw 1968; 75: 581-582
    CrossrefPubMedGoogle Scholar
  • 50 Kerber IJ, Warr OS, Richardson C. Pregnancy in a patient with a prosthetic mitral valve. JAMA 1968; 203: 223-225
    CrossrefPubMedGoogle Scholar
  • 51 Otterson WN, McGranahan G, Freeman MV R. Successful pregnancy with McGovern aortic prosthesis and long-term heparin therapy. Obstet Gynecol 1968; 31: 273-275
    CrossrefPubMedGoogle Scholar
  • 52 Turner RW D, Kitchin AH. Pregnancy after mitral-valve prosthesis. Lancet 1968; 1: 862-863
    PubMedGoogle Scholar
  • 53 Bloomfield DK, Rubinstein LI. Mitral-valve prosthesis, warfarin anticoagulation, and pregnancy. Lancet 1969; 2: 290-291
    PubMedGoogle Scholar
  • 54 Mueller MJ, Lebherz TB. Antepartum thrombophlebitis: Morbidity with long-term heparin and a proposed regimen of therapy. Obstet Gynecol 1969; 34 (06) 874-881
    PubMedGoogle Scholar
  • 55 Olwin JH, Koppel JL. Anticoagulant therapy during pregnancy: A new approach. Obstet Gynecol 1969; 34: 847-852
    PubMedGoogle Scholar
  • 56 Palacios-Macedo X, Diaz-Devis C, Escudero J. Fetal risk with the use of coumarin anticoagulant agents in pregnant patients with intracardiac ball valve prosthesis. Am J Cardiol 1969; 24: 853-856
    CrossrefPubMedGoogle Scholar
  • 57 Szekely P, Snaith L. Mitral-valve prosthesis, warfarin anticoagulation and pregnancy. Lancet 1969; 2: 598-599
    PubMedGoogle Scholar
  • 58 Bemiller CR, Forker AD, Morgan JR. Complete heart block, prosthetic aortic valve and successful pregnancy. JAMA 1970; 214: 915
    PubMedGoogle Scholar
  • 59 Fillmore SJ, McDevitt E. Effects of coumarin compounds on the fetus. Ann Intern Med 1970; 73: 731-735
    CrossrefPubMedGoogle Scholar
  • 60 Friefeld DM. Successful outcome of pulmonary embolism in the first trimester of pregnancy. J La State Med Soc 1970; 122: 177-179
    PubMedGoogle Scholar
  • 61 Hirsh J, Cade JF, O’Sullivan EF. Clinical experience with anticoagulant therapy during pregnancy. Br Med J 1970; 1: 270-273
    CrossrefPubMedGoogle Scholar
  • 62 Ikonen E, Merikallio E, Osterlund K, Seppala M. Mitral-valve prosthesis, warfarin anticoagulation and pregnancy. Lancet 1970; 2: 1252
    PubMedGoogle Scholar
  • 63 Laros RK, Hage ML, Hayashi RH. Pregnancy and heart valve prostheses. Obstet Gynecol 1970; 35: 241-247
    PubMedGoogle Scholar
  • 64 Aaro LA, Juergens JL. Thrombophlebitis associated with pregnancy. Am J Obstet Gynecol 1971; 109 (08) 1128-1136
    CrossrefPubMedGoogle Scholar
  • 65 Buxbaum A, Aygen MM, Shahin W, Levy MJ, Ekerling B. Pregnancy in patients with prosthetic heart valves. Chest 1971; 59: 639-642
    CrossrefPubMedGoogle Scholar
  • 66 Duncan ID, Coyle MG. Management and treatment of 34 cases of antepartum thromboembolism. J Obstet Gynecol Br Commonw 1971; 78: 904-911
    CrossrefPubMedGoogle Scholar
  • 67 Hill WC, Pearson JW. Outpatient intravenous heparin therapy for antepartum iliofemoral thrombophlebitis. Obstet Gynecol 1971; 37 (05) 785-789
    PubMedGoogle Scholar
  • 68 Jenkins BS, Braimbridge MV. Management of anticoagulant therapy during pregnancy in patients with prosthetic heart valves. Thorax 1971; 26: 206-211
    CrossrefPubMedGoogle Scholar
  • 69 Reid JM, Barclay RS. Pregnancy and mitral valve prosthesis. Br Med J 1971; 1: 326-327
    CrossrefPubMedGoogle Scholar
  • 70 Sher MH. Management of antepartum thrombophlebitis. Am Surg 1971; 37: 587-589
    PubMedGoogle Scholar
  • 71 DeJager NS T, Boyd NF, Ginsburg AD. Attempted abortion by the use of bishydroxycoumarin. Can Med Assoc J 1972; 107: 50-51
    PubMedGoogle Scholar
  • 72 Henderson SR, Lund CJ, Creasman WT. Antepartum pulmonary embolism. Am J Obstet Gynecol 1972; 112: 476-486
    CrossrefPubMedGoogle Scholar
  • 73 Ibarra-Perez C, Bosque-Ruis M. Pregnancy in 6 patients with Starr- Edwards heart valve prostheses. Am J Cardiol 1972; 30: 565-568
    CrossrefPubMedGoogle Scholar
  • 74 Kanarek KS, Bloom KR. Successful pregnancy after aortic and mitral valve replacements. S Afr Med J 1973; 47: 1373-1374
    PubMedGoogle Scholar
  • 75 Tejani N. Anticoagulant therapy with cardiac valve prosthesis during pregnancy. Obstet Gynecol 1973; 42: 785-793
    PubMedGoogle Scholar
  • 76 Whitworth JA, Fairley KF. Heparin in the treatment of preeclamptic toxemia. Perspect Nephrol Hypert 1973; 1: 1027-1029
    PubMedGoogle Scholar
  • 77 Buyse FG C, Wormgoor BH, Bernard JT H, Koudstaal J. Anticoagulant therapy of patients with repeated placental infarction. Obstet Gynecol 1974; 43: 844-848
    PubMedGoogle Scholar
  • 78 Salas G, Wells W, Bianchi R. Maneje de una embarazada con reemplazo valvulary tramiento anticoagulante. Rev Chil Obstet Ginecol 1974; 39: 93-96
    PubMedGoogle Scholar
  • 79 Shaker K, Amr M, Sliman NA. Uterine contractions due to heparin. Br Med J 1974; 4: 408-409
    PubMedGoogle Scholar
  • 80 Biale Y, Lewenthal H, Gueron M, Ben-Adereth N. Cesarean section in a patient with a mitral valve prosthesis. Isr J Med Sci 1975; 11: 906-908
    PubMedGoogle Scholar
  • 81 Casanegra P, Aviles G, Maturana G, Dubernet J. Cariovascular management of pregnant women with a heart valve prosthesis. Am J Cardiol 1975; 36: 802-806
    CrossrefPubMedGoogle Scholar
  • 82 Cokkinos D, Papadakis N, Kaskarellis D, Voridis E. Pregnancy and successful delivery in a patient with a Bjork-Shiley aortic prosthesis. Acta Cardiol 1975; 28: 441-445
    PubMedGoogle Scholar
  • 83 Darbois PY. L’attitude de l’obstetricien face aux phlebites profondes gravidiques. Phlebologie 1975; 28 (01) 131-137
    PubMedGoogle Scholar
  • 84 Fairley KF, Adey FD, Ross IC, Kincaid Smith P. Heparin treatment in severe pre-eclampsia and glonerulonephritis in pregnancy. Perspect Nephrol Hyper 1975; 5: 103-112
    PubMedGoogle Scholar
  • 85 Fourie DT, Hay IT. Warfarin as a possible teratogen. S Afr Med J 1975; 49: 2081-2083
    PubMedGoogle Scholar
  • 86 Holswade GR, Arditi L. Pregnancy in women with prosthetic heart valves. NY State J Med 1975; 75: 2374-2377
    PubMedGoogle Scholar
  • 87 Howie PW, Prentice CR M, Forbes CD. Failure of heparin therapy to affect the clinical course of severe pre-eclampsia. Br J Obstet Gynecol 1975; 82: 711-717
    CrossrefPubMedGoogle Scholar
  • 88 Moore DS, Trelford JD. Scoliosis and pregnancy. JAMA 1975; 233: 183-184
    PubMedGoogle Scholar
  • 89 Nilsson IM, Hedner U, Astedt B. et al. Case reports: Intravascular coagulation in pregnancy - treatment with heparin. Acta Obstet Gynecol Scand 1975; 54: 491-496
    CrossrefPubMedGoogle Scholar
  • 90 Pettifor JM, Benson R. Congenital malformations associated with the administration of oral anticoagulants during pregnancy. J Pediatr 1975; 86: 459-462
    CrossrefPubMedGoogle Scholar
  • 91 Pridmore BR, Murray KH, McAllen PM. The management of anticoagulant therapy during and after pregnancy. Br J Obstet Gynecol 1975; 82: 740-744
    CrossrefPubMedGoogle Scholar
  • 92 Ramsay DM. Thromboembolism in pregnancy. Obstet Gynecol 1975; 45: 129-132
    PubMedGoogle Scholar
  • 93 Shaul WL, Emery H, Hall JG. Chondrodysplasia punctata and maternal warfarin use during pregnancy. Am J Dis Child 1975; 129: 360-362
    PubMedGoogle Scholar
  • 94 Warkany J, Bofinger M. Le rôle de la coumarine dans les malformations congénitales. Med Hyg 1975; 33: 1454-1456
    PubMedGoogle Scholar
  • 95 Barr M, Burdi AR. Warfarin-associated embryopathy in a 17-week-old abortus. Teratology 1976; 14: 129-134
    CrossrefPubMedGoogle Scholar
  • 96 Carson M, Reid M. Warfarin and fetal abnormality. Lancet 1976; 1: 1127
    PubMedGoogle Scholar
  • 97 Holzgreve W, Carey JC, Hall BD. Warfarin-induced fetal abnormalities. Lancet 1976; 2: 914-915
    PubMedGoogle Scholar
  • 98 Ibarra-Perez C, Arevalo-Toledo N, Alvarez-De La Cadena O, Noriega-Guerra L. The course of pregnancy in patients with artifical heart valves. Am J Med 1976; 61: 504-512
    CrossrefPubMedGoogle Scholar
  • 99 McCans JL, Wenger NK. Problems in management of the pregnant patient with rheumatic heart disease and valve prosthesis. South Med J 1976; 69: 1007-1010
    CrossrefPubMedGoogle Scholar
  • 100 Merrill LK, Verburg DJ. The choice of long-term anticoagulants for the pregnant patient. Obstet Gynecol 1976; 47 (06) 711-714
    PubMedGoogle Scholar
  • 101 Oakley C, Doherty P. Pregnancy in patients after valve replacement. Br Heart J 1976; 38: 1140-1148
    CrossrefPubMedGoogle Scholar
  • 102 Pauli RM, Madden JD, Kranzler KJ, Culpepper W, Port R. Warfarin therapy initiated during pregnancy and phenotypic chondrodysplasia punctata. J Pediatr 1976; 88: 506-508
    CrossrefPubMedGoogle Scholar
  • 103 Richman EM, Lahman JE. Fetal anomalies associated with warfarin therapy initiated shortly prior to conception. J Pediatr 1976; 88: 509-510
    CrossrefPubMedGoogle Scholar
  • 104 Saka DM, Marx GF. Management of a parturient with cardiac valve prosthesis. Anesth Analg (Cleve) 1976; 55 (02) 214-216
    PubMedGoogle Scholar
  • 105 Sherman S, Hall BD. Warfarin and fetal abnormality. Lancet 1976; 1: 692
    CrossrefPubMedGoogle Scholar
  • 106 Zucker ML, Gomperts ED, Marcus RG. Prophylactic and therapeutic use of anticoagulants in inherited antithrombin III deficiency. S Afr Med J 1976; 50: 1743-1748
    PubMedGoogle Scholar
  • 107 Abbott A, Sibert JR, Weaver JB. Chondrodysplasia punctata and maternal warfarin treatment. Br Med J 1977; 1: 1639-1640
    CrossrefPubMedGoogle Scholar
  • 108 Baskin HF, Murray JM, Harris RE. Low-dose heparin for prevention of thromboembolic disease in pregnancy. Am J Obstet Gynecol 1977; 129 (05) 590-591
    CrossrefPubMedGoogle Scholar
  • 109 Collins ML, Leal J, Thompson NJ. Tricuspid atresia and pregnancy. Obstet Gynecol 1977; 50 (02) Suppl 72S-73S
    PubMedGoogle Scholar
  • 110 Cox DR, Martin L, Hall BD. Asplenia syndrome after fetal exposure to warfarin. Lancet 1977; 2: 1134
    PubMedGoogle Scholar
  • 111 Gamerre M, Brajon R. Anticoagulants et grossesse. J Gyn Obstet Biol Reprod 1977; 6: 829-837
    PubMedGoogle Scholar
  • 112 Limet R, Grondin CM. Cardiac valve prostheses, anticoagulation and pregnancy. Ann Thorac Surg 1977; 23: 337-341
    CrossrefPubMedGoogle Scholar
  • 113 Raivio KO, Ikonen E, Saarikoski S. Fetal risks due to warfarin therapy during pregnancy. Acta Pediatr Scand 1977; 66: 735-739
    CrossrefPubMedGoogle Scholar
  • 114 Valentine BH, Baker JL. Treatment of recurrent pregnancy hypertension by prophylactic anticoagulation. Br J Obstet Gynecol 1977; 84: 309-311
    CrossrefPubMedGoogle Scholar
  • 115 Vanlaeys R, Deroubaix P, Deroubaix G, Lelong M. Les antivita–mines K sont-elles teratogènes. Nouv Presse Méd 1977; 6: 756
    PubMedGoogle Scholar
  • 116 Lutz DJ, Noller KL, Spittell JA, Danielson GK, Fish CR. Pregnancy and its complications following cardiac valve prostheses. Am J Obstet Gynecol 1978; 131 (04) 460-468
    CrossrefPubMedGoogle Scholar
  • 117 McLeod AA, Jennings KP, Townsend ER. Near fatal puerperal thrombosis on Bjork-Shiley mitral valve prosthesis. Br Heart J 1978; 40: 934-937
    CrossrefPubMedGoogle Scholar
  • 118 Meltzer DB V. Outpatient management of placental insufficiency with heparin. J Perinat Med 1978; 6: 141-148
    CrossrefPubMedGoogle Scholar
  • 119 Robinson MJ, Pash J, Grimwade J, Campbell J. Fetal warfarin syndrome. Med J Aust 1978; 1: 157
    PubMedGoogle Scholar
  • 120 Spearing G, Fraser I, Turner G, Dixon G. Long-term self-administered subcutaneous heparin in pregnancy. Br Med J 1978; 3: 1457-1458
    PubMedGoogle Scholar
  • 121 Brandt P, Stenbjerg S. Subcutaneous heparin for thrombosis in pregnant women with hereditary antithrombin deficiency. Lancet 1979; 100-101
    PubMedGoogle Scholar
  • 122 Guillot M, Toubas P-L, Mselati J-C, Gamarra E, Moriette G, Relier JP. Embryo-foetopathie coumarinique et maladie des epiphyses ponctuées. Arch Fr Pediatr 1979; 36: 63-66
    PubMedGoogle Scholar
  • 123 Russo R, Bortolotti U, Schivazappa L, Girolami A. Warfarin treatment during pregnancy: A clinical note. Haemostasis 1979; 8: 96-98
    PubMedGoogle Scholar
  • 124 Schramm M. Prophylactic anticoagulation in the management of recurrent pre-eclampsia and fetal death. Aust NZ J Obstet Gynecol 1979; 19: 230-232
    CrossrefPubMedGoogle Scholar
  • 125 Smith MF, Cameron MD. Warfarin as teratogen. Lancet 1979; 1: 727
    PubMedGoogle Scholar
  • 126 Baillie M, Allen D, Elkington AR. The congenital warfarin syndrome: A case report. Br J Ophthalmol 1980; 64: 633-635
    CrossrefPubMedGoogle Scholar
  • 127 Robinson MJ, Cameron MD, Smith MF, Ayers AB. Fetal subdural haemorrhages presenting as hydrocephalus. Br Med J 1980; 5: 35
    PubMedGoogle Scholar
  • 128 Shuck JW, Walder JS, Kam TH, Thomas HM. Chronic persistent pulmonary embolism. Report of three cases Am J Med 1980; 69: 790-794
    CrossrefPubMedGoogle Scholar
  • 129 Stevenson RE, Burton M, Ferlauto GJ, Taylor HA. Hazards of oral anticoagulants during pregnancy. JAMA 1980; 243 (15) 1549-1551
    CrossrefPubMedGoogle Scholar
  • 130 Whitfield MF. Chondrodysplasia punctata after warfarin in early pregnancy. Arch Dis Child 1980; 55: 139-142
    CrossrefPubMedGoogle Scholar
  • 131 Brandt P. Observations during the treatment of antithrombin III deficient women with heparin and antithrombin concentrate during pregnancy, parturition and abortion. Thromb Res 1981; 22: 15-24
    CrossrefPubMedGoogle Scholar
  • 132 Dean H, Berliner S, Shoenfeld Y, Pinkhas J. Warfarin treatment during pregnancy in patients with prosthetic mitral valves. Acta Haematol 1981; 66: 65-66
    CrossrefPubMedGoogle Scholar
  • 133 Harrod MJ E, Sherrod PS. Warfarin embryopathy in siblings. Obstet Gynecol 1981; 57 (05) 673-676
    PubMedGoogle Scholar
  • 134 Kort HI, Cassel GA. An appraisal of warfarin therapy during pregnancy. S Afr Med J 1981; 60: 578-579
    PubMedGoogle Scholar
  • 135 Knuppel RA, Petrucha RA. The anticoagulated patient in labor: An obstetric dilemma. S Med J 1981; 74 (09) 1084-1087
    CrossrefPubMedGoogle Scholar
  • 136 Babul J, Bianchi C, Duran G. et al. Materno-neonatal management and complications in patients with cardiac valve prosthesis and in anticoagulant treatment. Rev Chil Obstet Gynecol 1982; 47 (06) 415-26
    PubMedGoogle Scholar
  • 137 Chen WW C, Chan CS, Lee PK, Wang RY C, Wong VC W. Pregnancy in patients with prosthetic heart valves: An experience with 45 pregnancies. Quart J Med 1982; 203: 358-365
    PubMedGoogle Scholar
  • 138 Hellgren M, Nygards E-B. Long-term therapy with subcutaneous heparin during pregnancy. Gynecol Obstet Invest 1982; 13: 76-89
    CrossrefPubMedGoogle Scholar
  • 139 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
    CrossrefPubMedGoogle Scholar
  • 140 Kaplan LC, Anderson GG, Ring BA. Congenital hydrocephalus and Dandy-Walker malformation associated with warfarin use during pregnancy. Birth Defects 1982; 18 (03) a 79-83
    PubMedGoogle Scholar
  • 141 O’Neill H, Blake S, Sugrue D, MacDonald D. Problems in the management of patients with artifical valves during pregnancy. Br J Obstet Gynecol 1982; 89: 940-943
    CrossrefPubMedGoogle Scholar
  • 142 Tawes RL, Kennedy PA, Harris EJ. Management of deep venous thrombosis and pulmonary embolism during pregnancy. Am J Surg 1982; 144: 141-145
    CrossrefPubMedGoogle Scholar
  • 143 Wozniak AJ, Kitchens CS. Prospective hemostatic studies in a patient having paroxysmal nocturnal hemoglobinuria, pregnancy, and cerebral venous thrombosis. Am J Obstet Gynecol 1982; 142 (05) 591-593
    CrossrefPubMedGoogle Scholar
  • 144 Bergqvist A, Bergqvist D, Hallbook T. Deep vein thrombosis during pregnancy. Acta Obstet Gynecol Scand 1983; 62: 443-448
    CrossrefPubMedGoogle Scholar
  • 145 Cohen AW, Gabbe SG, Mennuti MT. Adjusted-dose heparin therapy by continuous intravenous infusion for recurrent pulmonary embolism during pregnancy. Am J Obstet Gynecol 1983; 15: 463-464
    PubMedGoogle Scholar
  • 146 Hatjis CG, Gibson M, Capeless EL, Auletta FJ, Anderson GG. Pregnancy in patients with tricuspid atresia. Am J Obstet Gynecol 1983; 145: 114-115
    CrossrefPubMedGoogle Scholar
  • 147 Howell R, Fidler J, Letsky E. The risks of antenatal subcutaneous heparin prophylaxis: A controlled trial. Br J Obstet Gynecol 1983; 90: 1124-1128
    CrossrefPubMedGoogle Scholar
  • 148 Larrea JL, Nunez L, Reque JA, Aquado MG, Matarros R, Minguez JA. Pregnancy and mechanical valve prostheses: A high risk situation for the mother and the fetus. Ann Thorac Surg 1983; 36 (04) 459-463
    CrossrefPubMedGoogle Scholar
  • 149 McKenna R, Cole ER, Vasan U. Is warfarin sodium contraindicated in the lactating mother. Pediatrics 1983; 103 (02) 325-327
    CrossrefPubMedGoogle Scholar
  • 150 van Wersch JW J, Sandvoort JA, van Dieijen-Visser MP. Heparin- dipyridamole (persantin) treatment in pregnancy: Effect on blood coagulation parameters. Haemostasis 1983; 13: 335-340
    PubMedGoogle Scholar
  • 151 Vellenga E, Van Imhoff GW, Arnoudse JG. Effective prophylaxis with oral anticoagulants and low-dose heparin during pregnancy in an antithrombin III dieficient woman. Lancet 1983; 2: 224
    PubMedGoogle Scholar
  • 152 Wang RY C, Lee PK, Chow JS F, Chen WW C. Efficacy of low- dose subcutaneously administered heparin in treatment of pregnant women with artificial heart valves. Med J Aust 1983; 6: 126-128
    PubMedGoogle Scholar
  • 153 Aarskog D, Aksnes L, Markestad T, Ulstein M, Sager N. Heparin- induced inhibition of 1,25-dihydroxy vitamin D formation. Am J Obstet Gynecol 1984; 148 (08) 1141-2
    CrossrefPubMedGoogle Scholar
  • 154 Chong MK B, Harvey D, De Swiet M. Follow-up study of children whose mothers were treated with warfarin during pregnancy. Br J Obstet Gynecol 1984; 91: 1070-1073
    CrossrefPubMedGoogle Scholar
  • 155 Griffiths HT, Liu DT Y. Severe heparin osteoporosis in pregnancy. Postgrad Med 1984; 60: 424-425
    CrossrefPubMedGoogle Scholar
  • 156 Guidozzi F. Pregnancy in patients with prosthetic cardiac valves. S Afr Med J 1984; 65: 961-963
    PubMedGoogle Scholar
  • 157 Hatjis Cg. Heparin-induced thrombocytopenia in pregnancy: A case report. J Reprod Med 1984; 29 (05) 337-338
    PubMedGoogle Scholar
  • 158 Javares T, Coto EO, Maiques V, Rincom A, Such M, Caffarena JM. Pregnancy after heart valve replacement. Int J Cardiol 1984; 5: 731-739
    CrossrefPubMedGoogle Scholar
  • 159 Lamontagne JM, Leclerc JE, Carrier C, Bureau M. Warfarin embryopathy: A case report. J Otolaryngol 1984; 13 (02) 127-129
    PubMedGoogle Scholar
  • 160 Letsky EA, De Swiet M. Thromboembolism in pregnancy and its management. Br J Haematol 1984; 57: 543-552
    CrossrefPubMedGoogle Scholar
  • 161 Michiels JJ, Stibbe J, Velleuge E, Van Vliet HH D M. Prophylaxis of thrombosis in antithrombin III-deficient women during pregnancy and delivery. Eur J Obstet Gynecol Reprod Biol 1984; 18: 149-153
    CrossrefPubMedGoogle Scholar
  • 162 Nelson DM, Stempel LE, Fabri PJ, Talbert M. Hickman catheter use in a pregnant patient requiring therapeutic heparin anticoagulation. Am J Obstet Gynecol 1984; 15: 461-462
    PubMedGoogle Scholar
  • 163 Romero R, Duffy TP, Berkowitz RL, Chang E, Hobbins JC. Prolongation of a preterm pregnancy complicated by death of a single twin in utero and disseminated intravascular coagulation. N Engl J Med 1984; 310: 772-774
    CrossrefPubMedGoogle Scholar
  • 164 Samson D, Stirling Y, Woolf L, Howarth D, Seghatchian MJ, Chazai Rde. Management of planned pregnancy in a patient with congenital antithrombin III deficiency. Br J Haematol 1984; 56: 243-249
    CrossrefPubMedGoogle Scholar
  • 165 Barss VA, Schwartz PA, Greene MF, Phillippe M, Saltzman D, Frigoletto FD. Use of the subcutaneous heparin pump during pregnancy. J Reprod Med 1985; 30 (12) 899-901
    PubMedGoogle Scholar
  • 166 Cola LM, Lavin JP. Pregnancy complicated by Marfan’s syndrome with aortic arch dissection, subsequent aortic arch replacement and triple coronary artery bypass grafts. J Reprod Med 1985; 30 (09) 685-688
    PubMedGoogle Scholar
  • 167 Deiter RW. Thromboembolic disease in pregnancy: A prospective trial of intermittent heparin therapy during the antepartum period. J Am Osteopath Assoc 1985; 85 (04) 247-251
    PubMedGoogle Scholar
  • 168 Hahn L. Heparin treatment during pregnancy. Am J Obstet Gynecol 1985; 153: 342-348
    PubMedGoogle Scholar
  • 169 Kaplan LC. Congenital Dandy-Walker malformation associated with first trimester warfarin: A case report and literature review. Teratology 1985; 32: 333-337
    CrossrefPubMedGoogle Scholar
  • 170 Nelson DM, Stempel LE, Brandt JT. Hereditary antithrombin III deficiency and pregnancy. Obstet Gynecol 1985; 65 (06) 848-853
    PubMedGoogle Scholar
  • 171 Hurwitz A, Milwidsky A, Medina A, Yagel S. Failure of continuous intravenous heparinization to prevent stroke in a pregnant woman with a prosthetic valve and atrial fibrillation. J Reprod Med 1985; 30 (08) 618-620
    PubMedGoogle Scholar
  • 172 Tawes Jr RL, Mehigan JT, Olcott C. et al. The treatment of the expectant mother with deep venous thrombosis. J Cardiovasc Surg 1985; 26: 303-306
    PubMedGoogle Scholar
  • 173 Toit Du DF, McCormich M, Laker L. Deep-vein thrombosis in pregnancy. S Afr Med J 1985; 67: 781-782
    PubMedGoogle Scholar
  • 174 Capetta P, Airoldi ML, Tasca A, Bertulessi C, Rossi E, Polvani F. Prevention of pre-eclampsia and placental insufficiency. Lancet 1986; 1: 919
    PubMedGoogle Scholar
  • 175 Henny CH P, ten Cate H, ten Cate JW, Prummel MF, Peters M, Büller HR. Thrombosis prophylaxis in an AT III deficient pregnant woman: Application of a low molecular weight heparinoid. Thromb Haemostas 1986; 55: 301
    PubMedGoogle Scholar
  • 176 Ismail MB, Abid F, Trabelsi S, Taktak M, Fekih M. Cardiac valve prostheses, anticoagulation and pregnancy. Br Heart J 1986; 55: 101-105
    CrossrefPubMedGoogle Scholar
  • 177 Iturbe-Alessio I, Del Carmen Fonseca M, Mutchinik O, Santos MA, Zajarias A, Salazar E. Risks of anticoagulant therapy in pregnant women with artifical heart valves. N Engl J Med 1986; 315 (22) 1390-1393
    CrossrefPubMedGoogle Scholar
  • 178 Lapiedra OJ, Bernal JM, Ninot S, Gonzalez I, Pastor E, Miralles PJ. Open heart surgery for thrombosis of a prosthetic mitral valve during pregnancy: Fetal Hydrocephalus. J Cardiovasc Surg 1986; 27: 217-220
    PubMedGoogle Scholar
  • 179 Leclerc JR, Geerts W, Panju A, Nguyen P, Hirsh J. Management of antithrombin III deficiency during pregnancy without administration of antithrombin III. Thromb Res 1986; 41: 567-573
    CrossrefPubMedGoogle Scholar
  • 180 Lee PK, Wang RY C, Chow JS F, Cheung KL, Wong VC W, Chan TK. Combined use of warfarin and adjusted subcutaneous heparin during pregnancy in patients with an artificial heart valve. J Am Coll Cardiol 1986; 8: 221-224
    CrossrefPubMedGoogle Scholar
  • 181 Lennart C, Hahn A. Pulsatile heparin administration in pregnancy: A new approach. Am J Obstet Gynecol 1986; 155: 283-287
    CrossrefPubMedGoogle Scholar
  • 182 Priollet P, Roncato M, Aiach M, Housset E, Poissonnier MH, Chavine J. Low-molecular-weight heparin in venous trombosis during pregnancy. Br J Haematol 1986; 63 (03) 605-606
    CrossrefPubMedGoogle Scholar
  • 183 Rose PG, Essig GF, Vaccavo PS, Brandt JT. Protein S deficiency in pregnancy. Am J Obstet Gynecol 1986; 155: 140-141
    CrossrefPubMedGoogle Scholar
  • 184 Vitali E, Donatelli F, Quaini E, Groppelli G, Pellegrini A. Pregnancy in patients with mechanical prosthetic heart valves. J Cardiovasc Surg 1986; 27: 221-227
    PubMedGoogle Scholar
  • 185 Zakzouk MS. The congenital warfarin syndrome. J Laryngol Otol 1986; 100: 215-219
    CrossrefPubMedGoogle Scholar
  • 186 Zirmran A, Shilo S, Fisher D, Bab I. Histomorphometric evaluation of reversible heparin-induced osteoporosis in pregnancy. Arch Intern Med 1986; 146: 386-388
    CrossrefPubMedGoogle Scholar
  • 187 Mah PK, Vengadasalam D, Chow KK. Successful outcome in antepartum pulmonary embolism. Ann Acad Med 1980; 9 (01) 122-128
    PubMedGoogle Scholar
  • 188 Ginsberg J, Kowalchuk G, Brill-Edwards P, Burrows R, Hirsh J. Heparin therapy in pregnancy. Clin Res. 1988 (in press)
    PubMedGoogle Scholar
  • 189 Schaffer AJ, Avery ME. The undersized infant. In: Diseases of the Newborn. 4. Edition WB Saundersd; 1977. pp 56-71
    Google Scholar