Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-09T20:11:53.850Z Has data issue: false hasContentIssue false

11 - Low molecular weight heparins in pregnancy

Published online by Cambridge University Press:  01 February 2010

By
Debra A. Hoppensteadt Ph.D. ,
Jawed Fareed Ph.D. ,
Harry L. Messmore M.D. ,
Omer Iqbal M.D. ,
William Wehrmacher M.D.  and
Rodger L. Bick M.D., Ph.D.
Edited by
Rodger L. Bick ,
Eugene P. Frenkel ,
William F. Baker  and
Ravi Sarode
Debra A. Hoppensteadt Ph.D.
Affiliation:
Professor of Pathology and Pharmacology, Loyola University, Chicago Maywood, Illinois, USA
Jawed Fareed Ph.D.
Affiliation:
Professor of Pathology and Pharmacology, Loyola University, Chicago, Maywood, Illinois, USA
Harry L. Messmore M.D.
Affiliation:
Professor Emeritus Department of Medicine, Loyola University, Chicago, Maywood, Illinois, USA
Omer Iqbal M.D.
Affiliation:
Research Assistant Professor Department of Pathology, Loyola University, Chicago, Maywood, Illinois, USA
William Wehrmacher M.D.
Affiliation:
Professor Emeritus Department of Physiology, Loyola Univeristy, Chicago, Maywood, Illinois, USA
Rodger L. Bick M.D., Ph.D.
Affiliation:
Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center
Rodger L. Bick
Affiliation:
University of Texas Southwestern Medical Center, Dallas
Eugene P. Frenkel
Affiliation:
University of Texas Southwestern Medical Center, Dallas
William F. Baker
Affiliation:
University of California, Los Angeles
Ravi Sarode
Affiliation:
University of Texas Southwestern Medical Center, Dallas
Get access

Summary

The pathophysiology of the thrombotic process is multicomponent and involves blood, vascular system, humoral mediators and target sites. Furthermore, the intiating event and the site of thrombogenesis play a key role in the overall pathogenesis. The process of thrombogenesis is depicted in Figure 11.1. Initially, vascular injury results in the localized alterations of the vessels, generation of tissue factor, and subsequent activation of platelets. Activated cells mediate several direct or signal transduction induced processes resulting in the activation of platelets. Cellular activation also results in the release of various mediators which amplify vascular spasm and the coagulation process. Adhesion molecules, cytokines, oxidative stress and flow conditions signficantly contribute to the ischemic and occlusive outcome. Drugs that target various sites of the activation process have been developed to control thrombotic events. Because of the coupled pathophysiology, a drug that targets a single site may not be able to produce the desired therapeutic effects. Furthermore, many of these mediators produce localized actions at cellular and subcellular levels. Feedback amplification processes also play an important role in the pathology of these disorders and interruption of these pathways can be a therapeutic goal. This understanding has led to the concept of polytherapy in the management of thrombotic disorders.

Pregnancy and thrombosis

Pregnancy is associated with a hypercoagulable state that can lead to thrombosis and thromboembolism. The risk of venous thromboembolism (VTE) in pregnancy is approximately six times higher than in non-pregnant women.

Type
Chapter
Information
Hematological Complications in Obstetrics, Pregnancy, and Gynecology , pp. 341 - 360
Publisher: Cambridge University Press
Print publication year: 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Toglia, M. R., Weg, J. G.Current concepts. VTE during pregnancy. N. Engl. J. Med., 1996; 335: 108–14.CrossRefGoogle Scholar
Greer, I. A.Exploring the role of low-molecular-weight heparins in pregnancy. Semin. Thromb. Hemost., 2002; 28(Suppl. 3): 25–31S.CrossRefGoogle ScholarPubMed
Eldor, A. Management of thrombophilia and antiphospholipid syndrome during pregnancy In Consultative Hemostasis and Thrombosis, ed. Kitchens, C., Alving, B., Kessler, C.Philadelphia, PA: W. B. Saunders Co. Elsevier Science, 2002, pp. 449–60.Google Scholar
Howard, P. A.Low molecular weight heparin in special populations. J. Infus. Nurs., 2003; 26(5): 304–10.CrossRefGoogle ScholarPubMed
Bonnar, J., Prentice, C. R., McNicol, G. P., et al. Haemostatic mechanisms in the uterine circulation during placental seperation. Br. Med. J., 1970; 1: 564–70.CrossRefGoogle Scholar
Greer, I. A. In Haemostasis and Thrombosis in Pregnancy, ed. Bloom, A. L., Forbes, C. D., Thomas, D. P., et al. Edinburgh: Churchill Livingstone, 1994, p. 987.Google Scholar
Greer, I. A.Thrombosis in pregnancy: maternal and fetal issues. Lancet, 1999; 353: 1258–65.CrossRefGoogle ScholarPubMed
Leduc, L., Wheeler, J. M., Kirshon, B., et al. Coagulation profile in severe preeclampsia. Obstet. Gynecol., 1992; 79: 14.Google ScholarPubMed
Astedt, B., Lecander, I., Ny, T.Placental type plasminogen activator inhibitor: PAI-2. Fibrinolysis, 1987; 1: 203–9.CrossRefGoogle Scholar
Redman, C. W.Platelets and the beginning of preeclampsia. N. Engl. J. Med., 1990; 323: 478.CrossRefGoogle Scholar
Burrows, R. F., Hunter, D. J., Andrew, M., et al. A prospective study investigating the mechanism of thrombocytopenia in preeclampsia. Obstet. Gynecol., 1987; 70: 334.Google ScholarPubMed
Greer, I. A.Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology. Baillieres Clin. Obstet. Gynaecol., 1997; 11: 403–30.CrossRefGoogle ScholarPubMed
Macklon, N. S., 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. Gynaecol., 1997; 104: 191–7.CrossRefGoogle ScholarPubMed
Rutherford, S. E., Phelan, J. P.Thromboembolic disease in pregnancy. Clin. Perinatol., 1986; 13: 719.CrossRefGoogle ScholarPubMed
Brown, T. K., Munsick, R. A.Puerperal ovarian vein thrombophlebitis: A syndrome. Am. J. Obstet. Gynecol., 1971; 109: 263–73.CrossRefGoogle ScholarPubMed
Lockshin, M. D.Pregnancy loss in the antiphospholipid syndrome. Thromb. Haemost., 1999; 82: 641–8.Google ScholarPubMed
Greaves, M.Antiphospholipid antibodies and thrombosis (Letter; Comment). Lancet, 1999; 354: 1031.CrossRefGoogle Scholar
Long, A. A., Ginsberg, J. S., Brill-Edwards, P., et al. The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb. Haemost., 1991; 66: 520–4.Google ScholarPubMed
Ginsberg, J. S., Brill-Edwards, P., Johnston, M., et al. Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study. Blood, 1992; 80: 975–80.Google ScholarPubMed
Ginsberg, J. S., Greer, I., Hirsh, J.Use of antithrombotic agents during pregnancy. Chest, 2001; 119: 1225–315.CrossRefGoogle ScholarPubMed
Fareed, J., Walenga, J. M., Kumar, A., et al. A modified stasis thrombosis model to study the antithrombotic actions of heparin and its fractions. Semin. Thromb. Hemost., 1985; 11: 155.CrossRefGoogle Scholar
Fareed, J., Hoppensteadt, D., Huan, X., et al. Comparative study on the in vitro and in vivo activities of seven low molecular weight heparins. Hemostasis, 1989; 18(Suppl. 3): 3.Google Scholar
Abildgaard, U., Sandset, P., Lindahl, A. Tissue factor pathway inhibitor. In Recent Advances in Blood Coagulation, 6th edn, ed. Poller, L.Edinburgh: Churchill Livingstone, 1993, pp. 105–24.Google Scholar
Bronze, G. J.Tissue factor pathway inhibitor and the current concept of blood coagulation. Blood Coag. Fibrinolysis, 1995; 6(1): 7–12S.CrossRefGoogle Scholar
Fareed, J., Hoppensteadt, D., Jeske, W., et al. Low molecular weight heparins: pharmacologic profile and product differentiation. Am. J. Cardiol., 1995; 82(5B): 3–10L.CrossRefGoogle Scholar
Fareed, J., Hoppensteadt, D., Jeske, W., et al. Low molecular weight heparins: are they different?. Can. J. Cardiol., 1998; 14(28): 28–34E.Google ScholarPubMed
Brieger, D., Dawes, J.Production method affects the pharmacokinetic and ex vivo biologic properties of low molecular weight heparins. Thromb. Haemost., 1997; 77(2): 317–22.Google Scholar
Fareed, J., Hoppensteadt, D., Jeske, W., et al. Low molecular weight heparins: a developmental perspective. Exp. Opin. Invest. Drugs., 1997; 6(6): 705–20.CrossRefGoogle ScholarPubMed
Wolzt, M., Eder, M., Welterman, A., et al. Comparison of the effects of different low molecular weight heparins on the hemostatic system activation in vivo in man. Thromb. Haemost., 1997; 78(2): 876–9.Google ScholarPubMed
Hoppensteadt, D., Jeske, W., Fareed, J., et al. The role of tissue factor pathway inhibitor in the mediation of the antithrombotic actions of heparin and low molecular weight heparin. Blood Coag. Fibrinolysis, 1995; 6: S57.CrossRefGoogle ScholarPubMed
Bognacki, J., Hammelburger, J.Functional and immunologic methods for the measurement of human tissue factor pathway inhibitor. Blood Coag. Fibrinolysis, 1995; 6: S65.CrossRefGoogle ScholarPubMed
Hoppensteadt, D., Walenga, J. M., Fasanella, A., et al. TFPI antigen levels in normal human volunteers after intravenous and subcutaneous administration of unfractionated heparin and low molecular weight heparin. Thromb. Res., 1995; 77(2): 175.CrossRefGoogle ScholarPubMed
Fareed, J.Basic and applied pharmacology of low molecular weight heparins. Pharmacy and Therapeutics, 1995; 46: 16–24S.Google Scholar
Fareed, J., Callas, D., Hoppensteadt, D., et al. Recent developments in antithrombotic agents. Invest. Exp. Opin. Drugs, 1995; 4: 389–412.CrossRefGoogle Scholar
Fareed, J., Walenga, J. M., Pifarre, R.Newer approaches to the pharmacologic management of acute myocardial infarction. Cardiac Surgery: State of the Art Reviews, 1992; 6: 101.Google Scholar
Hirsh, J., Guyatt, G., Albers, G., et al. The seventh ACCP conference on antithrombotic and thrombolytic therapy: evidence based medicine. Chest, 2004: 126: 167–696S.CrossRefGoogle Scholar
Hunt, B. J., Doughty, H. A., Majumdar, G., et al. Thromboprophylaxis with low-molecular-weight heparin in high risk pregnancies. Thromb. Hemost., 1997; 77: 39.Google ScholarPubMed
Kobayashi, T. K., Terao, T., Ikenoue, T., et al. Treatment of severe preeclampsia with antithrombin concentrate: results of a prospective feasibility study. Semin. Ped. Thromb. Hemost., 2003; 29(6): 645–53.Google ScholarPubMed
Ohta, K., Kobashi, G., Hata, A., et al. Association between a variant of the glutathione s-transferase p1 gene (GSTP1) and hypertension in pregnancy in Japanese: interaction with parity, age, and genetic factors. Semin. Thromb. Hemost., 2003; 29(6): 653–8.Google ScholarPubMed
Eldor, A.Thrombophilia, thrombosis and pregnancy. Thromb. Haemost., 2001; 86(1): 104–11.Google Scholar
Sanson, B. J., Lensing, A. W., Prins, M. H., et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb. Haemost., 1999; 81: 668–72.CrossRefGoogle ScholarPubMed
Casele, H. L., Laifer, S. A., Woelkers, D. A., et al. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am. J. Obstet. Gynecol., 1999; 181: 1113–17.CrossRefGoogle ScholarPubMed
Gibson, J. L., Ekevall, K., Walker, I., et al. Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin. Br. J. Obstet. Gynaecol., 1998; 105: 795–7.CrossRefGoogle ScholarPubMed
Forestier, F., Daffos, F., Capella-Pavlovsky, M.Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: studied by direct fetal blood sampling ultrasound. Thromb. Res., 1984; 34: 557–60.CrossRefGoogle ScholarPubMed
Pettila, V., Kaaja, R., Leinonem, P., et al. Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy. Thromb. Res., 1999; 96: 275–82.CrossRefGoogle ScholarPubMed
Nelson-Piercy, C., Letsky, E. A., Swiet, M.Low molecular weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at high risk. Am. J. Obstet. Gynecol., 1997; 176: 1062–8.CrossRefGoogle ScholarPubMed
Ellison, J., Walker, I. D., Greer, I. A.Antenatal use of enoxaparin for the prevention and treatment of thromboembolism in pregnancy. Br. J. Obstet. Gynaecol., 2000; 107: 1116–21.CrossRefGoogle ScholarPubMed
Lepercq, J., Conard, J., Borel Derlon, A., et al. Venous thromboembolism during pregnancy: a systematic review. Thromb. Haemost., 1999; 81: 668–72.Google Scholar
Sanson, B. J., Lensing, A. W. A., Prins, M. H., et al. Safety of low-molecular weight heparin in pregnancy: a systematic review. Thromb. Haemost., 1999; 81: 668–72.CrossRefGoogle ScholarPubMed
Enson, M. H. H., Stephenson, M. D.Low-molecular-weight heparins in pregnancy. Pharmacotherapy, 1999; 19: 1013–25.CrossRefGoogle Scholar
Ginsberg, J. S., Greer, I., Hirsh, J. Use of antithrombotic agents during pregnancy. In Dalen J. E., Hirsh, J., Guyatt G. H., eds. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest, 2001; 119(Suppl. 1): 122–31S.
Rai, R., Cohen, H., Dave, M., et al. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). Br. Med. J., 1997; 314: 253–7.CrossRefGoogle Scholar
Kutteh, W. H.Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low dose aspirin is superior to low-dose aspirin alone. Am. J. Obstet. Gynecol., 1996; 174: 1584–89.CrossRefGoogle ScholarPubMed
Yamada, H., Kato, E. H., Morikawa, M., et al. Anticardiolipin B2-glycoprotein I antibody: is a high titer related to unfavorable pregnancy outcome? Semin. Thromb. Hemost., 2003; 29(6): 639–43.Google Scholar
AGOC Committee Opinion: safety of Lovenox in pregnancy. Obstet. Gynecol., 2002; 100(4): 845–6.CrossRef
Aggarwal, M.Use of low-molecular-weight heparin in pregnant women with mechanical heart valves. Mayo Clin. Proc., 2002; 77: 1133–4.CrossRefGoogle Scholar
Wu, C. L.Regional anesthesia and anticoagulationJ. Clin. Anesth., 2001; 13: 49–58.CrossRefGoogle ScholarPubMed
Montalescot, G., Polle, V., Collet, J. P., et al. Low molecular weight heparin after mechanical heart valve replacement. Circulation, 2000, 20: 1083–6.CrossRefGoogle Scholar
Messmore, H. L., Kundur, R., Wehrmacher, W., et al. Anticoagulant therapy of pregnant patients with prosthetic heart valves: rationale for a clinical trial of low molecular weight heparin. Clin. Appl. Thrombosis/Hemostasis, 1999; 5(2): 73–7.CrossRefGoogle ScholarPubMed
Chan, W. S., Anand, S., Ginsberg, J. S.Anticoagulation of pregnant women with mechanical heart valves. Arch. Intern. Med., 2000; 160: 191–6.CrossRefGoogle ScholarPubMed
Vitale, N., Feo, M., Santo, L. S., et al. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J. Am. Coll. Cardiol., 1999; 33: 1637–41.CrossRefGoogle ScholarPubMed
Chong, B., Magnani, H. Danaparoid for the treatment of heparin induced thrombocytopenia. In Heparin Induced Thrombocytopenia, 2nd edn, ed. Warkentin, T. E., Greinacher, A.Basel, Switzerland: Marcel Dekker Inc., NY, 2001, pp. 323–47.Google ScholarPubMed
Magnani, H. N.Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with orgaran (org 10172). Thromb. Hemost., 1993; 70(4), 554–61.Google Scholar
Hoppensteadt, D., Walenga, J. M., Fareed, J.Heparin, low-molecular-weight heparins, and heparin pentasaccharide. Basic and clinical differentiation. Hematol. Oncol. Clin. N. Am., 2003; 17: 313–41.CrossRefGoogle ScholarPubMed
Fareed, J., Hoppensteadt, D. A., Bick, R. L.Management of thrombotic and cardiovascular disorders in the new millennium. Clin. Appl. Thrombosis/Hemostasis, 2003; 9(2): 101–8.CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Low molecular weight heparins in pregnancy
    • By Debra A. Hoppensteadt, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago Maywood, Illinois, USA, Jawed Fareed, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago, Maywood, Illinois, USA, Harry L. Messmore, M.D., Professor Emeritus Department of Medicine, Loyola University, Chicago, Maywood, Illinois, USA, Omer Iqbal, M.D., Research Assistant Professor Department of Pathology, Loyola University, Chicago, Maywood, Illinois, USA, William Wehrmacher, M.D., Professor Emeritus Department of Physiology, Loyola Univeristy, Chicago, Maywood, Illinois, USA, Rodger L. Bick, M.D., Ph.D., Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center
  • Edited by Rodger L. Bick, University of Texas Southwestern Medical Center, Dallas, Eugene P. Frenkel, University of Texas Southwestern Medical Center, Dallas, William F. Baker, University of California, Los Angeles, Ravi Sarode, University of Texas Southwestern Medical Center, Dallas
  • Book: Hematological Complications in Obstetrics, Pregnancy, and Gynecology
  • Online publication: 01 February 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511526978.012
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Low molecular weight heparins in pregnancy
    • By Debra A. Hoppensteadt, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago Maywood, Illinois, USA, Jawed Fareed, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago, Maywood, Illinois, USA, Harry L. Messmore, M.D., Professor Emeritus Department of Medicine, Loyola University, Chicago, Maywood, Illinois, USA, Omer Iqbal, M.D., Research Assistant Professor Department of Pathology, Loyola University, Chicago, Maywood, Illinois, USA, William Wehrmacher, M.D., Professor Emeritus Department of Physiology, Loyola Univeristy, Chicago, Maywood, Illinois, USA, Rodger L. Bick, M.D., Ph.D., Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center
  • Edited by Rodger L. Bick, University of Texas Southwestern Medical Center, Dallas, Eugene P. Frenkel, University of Texas Southwestern Medical Center, Dallas, William F. Baker, University of California, Los Angeles, Ravi Sarode, University of Texas Southwestern Medical Center, Dallas
  • Book: Hematological Complications in Obstetrics, Pregnancy, and Gynecology
  • Online publication: 01 February 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511526978.012
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Low molecular weight heparins in pregnancy
    • By Debra A. Hoppensteadt, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago Maywood, Illinois, USA, Jawed Fareed, Ph.D., Professor of Pathology and Pharmacology, Loyola University, Chicago, Maywood, Illinois, USA, Harry L. Messmore, M.D., Professor Emeritus Department of Medicine, Loyola University, Chicago, Maywood, Illinois, USA, Omer Iqbal, M.D., Research Assistant Professor Department of Pathology, Loyola University, Chicago, Maywood, Illinois, USA, William Wehrmacher, M.D., Professor Emeritus Department of Physiology, Loyola Univeristy, Chicago, Maywood, Illinois, USA, Rodger L. Bick, M.D., Ph.D., Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center
  • Edited by Rodger L. Bick, University of Texas Southwestern Medical Center, Dallas, Eugene P. Frenkel, University of Texas Southwestern Medical Center, Dallas, William F. Baker, University of California, Los Angeles, Ravi Sarode, University of Texas Southwestern Medical Center, Dallas
  • Book: Hematological Complications in Obstetrics, Pregnancy, and Gynecology
  • Online publication: 01 February 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511526978.012
Available formats
×