Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 3/2009

01-04-2009

A descriptive evaluation of unfractionated heparin use during pregnancy

Authors: Nathan P. Clark, Thomas Delate, Daniel M. Witt, Suzanne Parker, Robert McDuffie

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2009

Login to get access

Abstract

Background The mainstay of oral anticoagulant therapy, warfarin sodium, crosses the placenta during pregnancy and may cause fetal complications. Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) do not cross the placenta and have demonstrated utility in the prevention and treatment of thrombosis during pregnancy. Objectives The purpose of this study was to review treatment strategy, indication, and maternal and fetal outcomes in anticoagulated pregnancies at Kaiser Permanente Colorado. Patients/Methods We identified 103 pregnancies in 93 mothers prescribed an anticoagulant during a pregnancy occurring between January 1, 1998 and March 31, 2005. Results The majority of patients were treated with UFH (89.3%). Indications for anticoagulation included venous thromboembolism (VTE) prophylaxis (53.4%), history of pregnancy loss (29.1%), acute VTE (16.5%), and history of cerebral vascular accident (CVA) (1.0%). There were no maternal deaths. Fetal demise occurred in 8 pregnancies (7.8%) at a median 14 weeks gestation (range 7–22 weeks). No fetal demise occurred in pregnancies treated for acute VTE or history of CVA. There were two occurrences of pulmonary embolism (1.9%) and two hemorrhagic events requiring transfusion (1.9%). Conclusions Maternal and fetal adverse events were infrequent in our population of anticoagulated pregnancies. UFH remains a viable option among more expensive LMWH products.
Literature
1.
go back to reference Rey E, Kahn S, David M, Shrier I (2003) Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 361:901–908PubMedCrossRef Rey E, Kahn S, David M, Shrier I (2003) Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 361:901–908PubMedCrossRef
2.
3.
go back to reference Ginsberg J, Hirsh J, Turner C, Levine MN, Burrows R (1989) Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 61:197–203PubMed Ginsberg J, Hirsh J, Turner C, Levine MN, Burrows R (1989) Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 61:197–203PubMed
4.
go back to reference Hall J, Paul R, Wilson K (1980) Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 68:122–140PubMedCrossRef Hall J, Paul R, Wilson K (1980) Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 68:122–140PubMedCrossRef
5.
go back to reference Wesseling J, Van Driel D, Heymans H, Rosendaal FR, Geven-Boere LM, Smrkovsky M, Touwen BC, Sauer PJ, Van der Veer E (2001) Coumarins during pregnancy: long term effects on growth and development in school age children. Thromb Haemost 85:609–613PubMed Wesseling J, Van Driel D, Heymans H, Rosendaal FR, Geven-Boere LM, Smrkovsky M, Touwen BC, Sauer PJ, Van der Veer E (2001) Coumarins during pregnancy: long term effects on growth and development in school age children. Thromb Haemost 85:609–613PubMed
6.
go back to reference Jacobsen A, Qvigstad E, Sandset P (2003) Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy. BJOG 110:139–144PubMedCrossRef Jacobsen A, Qvigstad E, Sandset P (2003) Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy. BJOG 110:139–144PubMedCrossRef
7.
go back to reference Hunt B, Gatten M, Khamashta M, Nelson-Piercy C, Almeida A (2003) Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event. Blood Coagul Fibrinolysis 14:735–739PubMedCrossRef Hunt B, Gatten M, Khamashta M, Nelson-Piercy C, Almeida A (2003) Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event. Blood Coagul Fibrinolysis 14:735–739PubMedCrossRef
8.
go back to reference Ulander V, Lehtola A, Kaaja R (2003) Long-term outcome of deep venous thrombosis during pregnancy treated with unfractionated heparin or low molecular weight heparin. Thromb Res 111:239–242PubMedCrossRef Ulander V, Lehtola A, Kaaja R (2003) Long-term outcome of deep venous thrombosis during pregnancy treated with unfractionated heparin or low molecular weight heparin. Thromb Res 111:239–242PubMedCrossRef
9.
go back to reference Nelson-Piercy C, Letsky E, de Swiet M (1997) Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at risk. Am J Obstet Gynecol 176:1062–1068PubMedCrossRef Nelson-Piercy C, Letsky E, de Swiet M (1997) Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at risk. Am J Obstet Gynecol 176:1062–1068PubMedCrossRef
10.
go back to reference Blanco-Molina A, Trujillo-Santos J, Criado J (2007) Venous thromboembolism during pregnancy or postpartum: findings from the RIETE registry. Thromb Haemost 97:186–190PubMed Blanco-Molina A, Trujillo-Santos J, Criado J (2007) Venous thromboembolism during pregnancy or postpartum: findings from the RIETE registry. Thromb Haemost 97:186–190PubMed
11.
go back to reference Bates S, Greer I, Hirsh J, Ginsberg J (2004) Use of antithrombotic agents during pregnancy. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. CHEST 126:627S–644SPubMedCrossRef Bates S, Greer I, Hirsh J, Ginsberg J (2004) Use of antithrombotic agents during pregnancy. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. CHEST 126:627S–644SPubMedCrossRef
12.
go back to reference Copplestone J, Pavord S, Hunt B (2004) Anticoagulation in pregnancy: a survey of current practice. Br J Haemotol 124:123–125CrossRef Copplestone J, Pavord S, Hunt B (2004) Anticoagulation in pregnancy: a survey of current practice. Br J Haemotol 124:123–125CrossRef
13.
go back to reference Kearon C, Ginsberg J, Julian J, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, Mackinnon B, Hirsh J, Gent M (2006) Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 296:935–942PubMedCrossRef Kearon C, Ginsberg J, Julian J, Douketis J, Solymoss S, Ockelford P, Jackson S, Turpie AG, Mackinnon B, Hirsh J, Gent M (2006) Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 296:935–942PubMedCrossRef
14.
go back to reference Lockwood C (2002) Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol 99:333–341PubMedCrossRef Lockwood C (2002) Inherited thrombophilias in pregnant patients: detection and treatment paradigm. Obstet Gynecol 99:333–341PubMedCrossRef
15.
go back to reference Brill-Edwards P, Ginsberg J, Gent M, Hirsh J, Burrows R, Kearon C, Geerts W, Kovacs M, Weitz J, Robinson KS, Whittom R, Couture G (2000) Safety of withholding heparin in pregnant women with a history of venous thromboembolism. NEJM 343:1439–1444PubMedCrossRef Brill-Edwards P, Ginsberg J, Gent M, Hirsh J, Burrows R, Kearon C, Geerts W, Kovacs M, Weitz J, Robinson KS, Whittom R, Couture G (2000) Safety of withholding heparin in pregnant women with a history of venous thromboembolism. NEJM 343:1439–1444PubMedCrossRef
16.
go back to reference Barbour L, Oja J, Schultz L (2004) A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol 191:1024–1029PubMedCrossRef Barbour L, Oja J, Schultz L (2004) A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation. Am J Obstet Gynecol 191:1024–1029PubMedCrossRef
17.
go back to reference De Carolis S, Ferrazzani S, De Stefano V, Garofalo S, Fatigante G, Rossi E, Leone G, Caruso A (2006) Inherited thrombophilia: treatment during pregnancy. Fetal Diagn Ther 21:281–286PubMedCrossRef De Carolis S, Ferrazzani S, De Stefano V, Garofalo S, Fatigante G, Rossi E, Leone G, Caruso A (2006) Inherited thrombophilia: treatment during pregnancy. Fetal Diagn Ther 21:281–286PubMedCrossRef
18.
go back to reference Kupferminc M, Fait G, Many A, Lessing JB, Yair D, Bar-Am A, Eldor A (2001) Low-molecular weight heparin for the prevention of obstetric complications in women with thrombophilia. Hypertens Pregnancy 20:34–44 Kupferminc M, Fait G, Many A, Lessing JB, Yair D, Bar-Am A, Eldor A (2001) Low-molecular weight heparin for the prevention of obstetric complications in women with thrombophilia. Hypertens Pregnancy 20:34–44
19.
go back to reference Triolo G, Ferrante A, Ciccia F, Accardo-Palumbo A, Perino A, Castelli A, Giarratano A, Licata G (2003) Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum 48:728–731PubMedCrossRef Triolo G, Ferrante A, Ciccia F, Accardo-Palumbo A, Perino A, Castelli A, Giarratano A, Licata G (2003) Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum 48:728–731PubMedCrossRef
20.
go back to reference Gris J, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, Ripart-Niveu S, Tailland M, Dauzat M, Mares P (2004) Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 103:3695–3699PubMedCrossRef Gris J, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, Ripart-Niveu S, Tailland M, Dauzat M, Mares P (2004) Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 103:3695–3699PubMedCrossRef
21.
go back to reference Rai R, Cohen H, Dave M, Regan L (1997) Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 314:253–257PubMed Rai R, Cohen H, Dave M, Regan L (1997) Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 314:253–257PubMed
22.
go back to reference Grandone E, Brancaccio V, Colaizzo D, Scianname N, Pavone G, Di Minno G, Margaglione M (2002) Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril 78:371–375PubMedCrossRef Grandone E, Brancaccio V, Colaizzo D, Scianname N, Pavone G, Di Minno G, Margaglione M (2002) Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril 78:371–375PubMedCrossRef
23.
go back to reference Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis J (2000) Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 83:693–697PubMed Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis J (2000) Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost 83:693–697PubMed
24.
go back to reference Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L (1999) Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 106:102–107PubMed Backos M, Rai R, Baxter N, Chilcott IT, Cohen H, Regan L (1999) Pregnancy complications in women with recurrent miscarriage associated with antiphospholipid antibodies treated with low dose aspirin and heparin. Br J Obstet Gynaecol 106:102–107PubMed
25.
go back to reference Farquharson R, Quenby S, Greaves M (2002) Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 100:408–413PubMedCrossRef Farquharson R, Quenby S, Greaves M (2002) Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol 100:408–413PubMedCrossRef
26.
go back to reference Folkeringa N, Brouwer JL, Kortweg F, Veeger NJ, Erwich JJ, Holm JP, van der Meer J (2007) Reduction of high fetal loss rate by anticoagulant treatment in antithrombin, protein C or protein S deficient women. Br J Heamatol 136:656–661CrossRef Folkeringa N, Brouwer JL, Kortweg F, Veeger NJ, Erwich JJ, Holm JP, van der Meer J (2007) Reduction of high fetal loss rate by anticoagulant treatment in antithrombin, protein C or protein S deficient women. Br J Heamatol 136:656–661CrossRef
27.
go back to reference Matziolis G, Perka C, Disch A, Zippel H (2003) Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int 73:370–379PubMedCrossRef Matziolis G, Perka C, Disch A, Zippel H (2003) Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts. Calcif Tissue Int 73:370–379PubMedCrossRef
28.
go back to reference Douketis J, Ginsberg J, Burrows R, Duku EK, Webber CE, Brill-Edwards P (1996) The effects of long-term heparin therapy during pregnancy on bone density. Thromb Haemost 75:254–257PubMed Douketis J, Ginsberg J, Burrows R, Duku EK, Webber CE, Brill-Edwards P (1996) The effects of long-term heparin therapy during pregnancy on bone density. Thromb Haemost 75:254–257PubMed
29.
go back to reference Backos M, Rai R, Thomas E, Murphy M, Dore C, Regan L (1999) Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study. Hum Reprod 14:2876–2880PubMedCrossRef Backos M, Rai R, Thomas E, Murphy M, Dore C, Regan L (1999) Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study. Hum Reprod 14:2876–2880PubMedCrossRef
30.
go back to reference Casele H, Haney E, James A, Rosene-Montella K, Carson M (2006) Bone density changes in women who receive thromboprophylaxis in pregnancy. Am J Obstet Gynecol 195:1109–1113PubMedCrossRef Casele H, Haney E, James A, Rosene-Montella K, Carson M (2006) Bone density changes in women who receive thromboprophylaxis in pregnancy. Am J Obstet Gynecol 195:1109–1113PubMedCrossRef
31.
go back to reference Pettila V, Leinonen P, Markkola A, Hillesmaa V, Kaaja R (2002) Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 87:182–186PubMed Pettila V, Leinonen P, Markkola A, Hillesmaa V, Kaaja R (2002) Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost 87:182–186PubMed
32.
go back to reference Dahlman T, Sjoberg H, Ringertz H (1994) Bone mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol 170:1315–1320PubMed Dahlman T, Sjoberg H, Ringertz H (1994) Bone mineral density during long-term prophylaxis with heparin in pregnancy. Am J Obstet Gynecol 170:1315–1320PubMed
33.
go back to reference Barbour L, Kick S, Steiner J, LoVerde M, Heddleston L, Lear J, Baron A, Barton P (1994) A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 170:862–869PubMed Barbour L, Kick S, Steiner J, LoVerde M, Heddleston L, Lear J, Baron A, Barton P (1994) A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 170:862–869PubMed
34.
go back to reference Morris T, Castrejon S, Devendra G, Gamst A (2007) No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous throbosis with either low-molecular-weight heparin or unfractionated heparin. A meta-analysis. CHEST 132:1131–1139PubMedCrossRef Morris T, Castrejon S, Devendra G, Gamst A (2007) No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous throbosis with either low-molecular-weight heparin or unfractionated heparin. A meta-analysis. CHEST 132:1131–1139PubMedCrossRef
35.
go back to reference Handeland GF, Abidgaard GF, Holm U, Arneses KE (1990) Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 39:107–112PubMedCrossRef Handeland GF, Abidgaard GF, Holm U, Arneses KE (1990) Dose adjusted heparin treatment of deep venous thrombosis: a comparison of unfractionated and low molecular weight heparin. Eur J Clin Pharmacol 39:107–112PubMedCrossRef
36.
go back to reference Wolzt M, Weltermann A, Nieszpauer-Los M, Schneider B, Fassolt A, Lechner K, Eichler HG, Kyrle P (1995) Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man. Thromb Haemost 73:439–443PubMed Wolzt M, Weltermann A, Nieszpauer-Los M, Schneider B, Fassolt A, Lechner K, Eichler HG, Kyrle P (1995) Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man. Thromb Haemost 73:439–443PubMed
37.
go back to reference Beng CJ. Berstad A. Talstad I (1991) Incomplete reversal of enoxaparin-induced bleeding by protamine sulfate. Haemostasis 21:155–160 Beng CJ. Berstad A. Talstad I (1991) Incomplete reversal of enoxaparin-induced bleeding by protamine sulfate. Haemostasis 21:155–160
38.
go back to reference Shojania A (2004) More one: is laboratory monitoring of low-molecular-weight heparin necessary? Thromb Haemost 2:2276–2277CrossRef Shojania A (2004) More one: is laboratory monitoring of low-molecular-weight heparin necessary? Thromb Haemost 2:2276–2277CrossRef
39.
go back to reference Buller H, Agnelli G, Hull R, Hyers TM, Prins H, Raskob GE (2004) Antithrombotic therapy for venous thromboembolic disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. CHEST 126:401S–428SPubMedCrossRef Buller H, Agnelli G, Hull R, Hyers TM, Prins H, Raskob GE (2004) Antithrombotic therapy for venous thromboembolic disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. CHEST 126:401S–428SPubMedCrossRef
40.
go back to reference Kitchen S, Iampietro R, Woolley A, Preston F (1999) Anti Xa monitoring during treatment with low-molecular-weight heparin or danaparoid: inter-assay variability. Thromb Haemost 82:1289–1293PubMed Kitchen S, Iampietro R, Woolley A, Preston F (1999) Anti Xa monitoring during treatment with low-molecular-weight heparin or danaparoid: inter-assay variability. Thromb Haemost 82:1289–1293PubMed
Metadata
Title
A descriptive evaluation of unfractionated heparin use during pregnancy
Authors
Nathan P. Clark
Thomas Delate
Daniel M. Witt
Suzanne Parker
Robert McDuffie
Publication date
01-04-2009
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2009
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-008-0207-0

Other articles of this Issue 3/2009

Journal of Thrombosis and Thrombolysis 3/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.