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Thromb Haemost 1992; 68(06): 652-656
DOI: 10.1055/s-0038-1646338
Original Article
Schattauer GmbH Stuttgart

Use of Low Molecular Weight Heparin in Pregnancy

Euthemia Melissari
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Christopher J Parker
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Noel V Wilson
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Giovanni Monte
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Chryso Kanthou
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Kieran D Pemberton
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
,
Kypros H Nicolaides
1   The Harris Birthright Research Centre, King’s College School of Medicine and Dentistry, London, UK
,
John J Barrett
2   The Nuclear Medicine, King’s College School of Medicine and Dentistry, London, UK
,
Vijay V Kakkar
The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London, UK
› Author Affiliations
Further Information

Publication History

Received 08 November 1991

Accepted after revision 10 July 1992

Publication Date:
04 July 2018 (online)

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Summary

In a controlled study of 15 pregnant patients undergoing therapeutic termination of pregnancy, seven received subcutaneously 5,000 anti-FXa units of low molecular weight (LMW) heparin 15 and 3 h prior to the termination, and eight patients acted as controls. Paired maternal and fetal blood samples were taken (before or immediately after the termination) for assay of heparin activity by a chromogenic anti-FXa method sensitive to levels of 0.02 anti-FXa U/ml. LMW heparin was detected in all maternal samples of the test patients but was not detected in any of the fetal samples.

The use of LMW heparin as a thromboprophylactic agent was then evaluated in 11 patients who were known to have a severe thromboembolic tendency, had suffered recurrent miscarriages and had responded poorly to conventional anticoagulation (oral anticoagulant, conventional heparin). All patients receiving LMW heparin in thromboprophylactic doses completed uneventful pregnancies and gave birth to healthy babies (three for the first time) without complication. Bone density scans performed in all patients shortly after the delivery showed normal mineral mass. We conclude that LMW heparin does not cross the placental barrier, and in addition offers satisfactory antithrombotic protection for both maternal and placental circulation. In addition, this study provides preliminary data from 11 patients suggesting LMWH may not give rise to maternal osteoporosis, a finding that now needs further investigation.

 

  • REFERENCES

  • 1 Bonnar J. Haemostasis and coagulation disorders in pregnancy. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. (eds) Churchill: London: 1987. 34 570-584
    Google Scholar
  • 2 Royal College of General Practitioners Oral contraception and thromboembolic disease. J Coll Gen Pract 1967; 13: 267-279
    PubMedGoogle Scholar
  • 3 Badaracco MA, Vessey M. Recurrence of venous thromboembolism disease and use of oral contraceptives. Br Med J 1974; 2: 215-217
    PubMedGoogle Scholar
  • 4 Wilcox AJ, Weinberg CR, O’Connor JF, Baird DD, Schlatterer JP, Canfield RE, Armstrong EG, Nisula BC. Incidence of early loss of pregnancy. N Engl J Med 1988; 319: 189-194
    CrossrefPubMedGoogle Scholar
  • 5 Hall RG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68: 122-140
    CrossrefPubMedGoogle Scholar
  • 6 Flessa HC, Kopstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am J Obstet Gynecol 1965; 93: 570-573
    CrossrefPubMedGoogle Scholar
  • 7 Kapch D, Silver D. Heparin-induced thrombocytopenia, thrombosis and haemorrhage. Arch Surg 1981; 116: 1423-1429
    CrossrefPubMedGoogle Scholar
  • 8 Ginsberg JS, Hirsh J. Anticoagulants during pregnancy. Annu Rev Med 1989; 40: 79-86
    CrossrefPubMedGoogle Scholar
  • 9 Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R, Coates G, Webber C. Heparin effect on bone density. Thromb Haemostas 1990; 64: 286-289
    PubMedGoogle Scholar
  • 10 Bergqvist D, Hedner U, Sjorin E, Holmer E. Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously. Thromb Res 1983; 32: 381-391
    CrossrefPubMedGoogle Scholar
  • 11 Johnson A, Kirkwood TBI, Stirling Y, Perez-Requejo JI, Ingram GIC, Bangham DR, Brozovic M. Four heparin preparations: Anti-Xa potentiating effect of heparin after subcutaneous injection. Thromb Haemostas 1976; 35: 586-591
    PubMedGoogle Scholar
  • 12 Murray WJG. Low molecular weight heparin in surgical practice. MS Thesis 1985; 4: 124-149
    PubMedGoogle Scholar
  • 13 Melissari E, Parker CJ, Kakkar VV. Use of low molecular weight heparin in pregnancy. Thromb Haemostas 1989; 62: 451
    PubMedGoogle Scholar
  • 14 Bang J. Ultrasound-guided fetal blood sampling. In: Progress in Perinatal Medicine. Albertini A, Crosignani PG. (eds) Excerpta Medica: Amsterdam: 1983. pp 223-225
    Google Scholar
  • 15 Melissari E, Scully MF, Paes T, Kakkar VV. The influence of LMW heparin on the coagulation and fibrinolytic response to surgery. Thromb Res 1985; 37: 115-126
    CrossrefPubMedGoogle Scholar
  • 16 Melissari E, Nicolaides KH, Scully MF, Kakkar VV. Protein S and C4b-binding protein in fetal and neonatal blood. Br J Haematol 1988; 70: 199-203
    CrossrefPubMedGoogle Scholar
  • 17 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv Kemi 1956; 10: 415-417
    PubMedGoogle Scholar
  • 18 Thiagarajan P, Pengo V, Shapiro SS. The use of dilute Russell’s viper venom for the diagnosis of lupus anticoagulants. Blood 1986; 68: 859-864
    PubMedGoogle Scholar
  • 19 Lane DA, McGregor IR, Michalski R, Kakkar VV. Anticoagulant activities of four unfractionated and fractionated heparins. Thromb Res 1978; 12: 257-271
    CrossrefPubMedGoogle Scholar
  • 20 Carter CJ, Kelton JG, Hirsh J, Cersksus A, Santos AV, Gent M. The relationship between the haemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
    PubMedGoogle Scholar
  • 21 Nicolaides KH, Rodeck CH, Mibashan RS. Obstetric and diagnosis of haematological disease in the fetus. Clin Haematol 1985; 14: 775-805
    PubMedGoogle Scholar
  • 22 Forestier F, Daffos F, Capell-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
    CrossrefPubMedGoogle Scholar
  • 23 Omri A, Delaloye JF, Andersen H, Bachmann F. Low molecular weight heparin novo (LHN-1). Does not cross the placenta during the second trimester of pregnancy. Thromb Haemostas 1989; 61: 55-56
    PubMedGoogle Scholar
  • 24 Forestier F, Daffos F, Rainaut M, Toulemonde F. Low molecular weight heparin (CY 216) does not cross the placenta during the third trimester of pregnancy. Thromb Haemostas 1987; 57: 234 (Letter)
    PubMedGoogle Scholar
  • 25 Andrew M, Boneu B, Cade J, Cerskus AL, Hirsh J, Jeffries A, Towell ME, Buchanan MR. Placental transport of low molecular weight heparin in the pregnant sheep. Br J Haematol 1985; 59: 103-108
    CrossrefPubMedGoogle Scholar
  • 26 Dansis J. Neonatology, pathophysiology and Management of the Newborn. Avery GB. (ed) 2nd edn. Lippincott: Philadelphia, PA: 1981. pp 099-106
    Google Scholar
  • 27 Priollet P, Roncaato M, Aiach M, Housset E, Poissonier MH, Chavinie J. Low molecular weight heparin in venous thrombosis during pregnancy. Br J Haematol 1986; 63: 605-606
    CrossrefPubMedGoogle Scholar
  • 28 De Boer K, Heyboer H, ten Cate JW, Borm JJJ, van Ginkel CJW. Low molecular weight heparin treatment in a pregnant woman with allergy to standard heparins and heparinoid. Thromb Haemostas 1989; 61: 148 (Letter)
    PubMedGoogle Scholar
  • 29 Lubbe WF, Butler WS, Palmer SJ, Liggins GC. Fetal survival after prednisone suppression of maternal lujpus anticoagulant. Lancet 1983; i: 1361-1363
    PubMedGoogle Scholar
  • 30 Hughes GRV. Systemic lupus erythematosus. Lacjmann PJ, Peters DK. Blackwell Scientific Publications, Clin Aspects Immunol: 1977. 2 1196-1216
    Google Scholar
  • 31 Department of Health Late deaths. In: Report on Confidential Enquiries into Maternal Deaths in England and Wales 1982–1984. 1989. 16 121-125
    Google Scholar
  • 32 Dun WL, Wahner HW, Riggs BL. Measurements of bone mineral content in human vertebrae and hip by dual photon absorptiometry. Radiology 1980; 136: 485-487
    CrossrefPubMedGoogle Scholar
  • 33 Riggs BL, Wahner HW. Bone densitometry and clinical decision making in osteoporosis. Ann Intern Med 1988; 108: 293-295
    CrossrefPubMedGoogle Scholar
  • 34 Riggs BL, Melton LJ. Involutional osteoporosis. N Engl J Med 1986; 314: 1676-1686
    CrossrefPubMedGoogle Scholar