Abstract
Normal pregnancy is accompanied by an increase in clotting factors. The resulting
hypercoagulable state has likely evolved to protect women from hemorrhage at the time
of miscarriage and childbirth. During pregnancy, women are 4 times more likely to
suffer from venous thromboembolism (VTE) compared with when they are not pregnant.
Relative to pregnancy, the risk postpartum is even higher. The incidence of VTE is
approximately 2 per 1,000 births, and VTE accounts for 1 death per 100,000 births,
or approximately 10% of all maternal deaths. The most important risk factors during
pregnancy are thrombophilia and a history of thrombosis. A history of thrombosis increases
the risk for VTE to 2% to 12%. Thrombophilia increases not only the risk for maternal
thrombosis but also the risk of poor pregnancy outcome. Despite the increased risk
for thrombosis during pregnancy and the postpartum period, most women do not require
anticoagulation. Those who do require anticoagulation include women with current VTE,
women on lifelong anticoagulation, and many women with thrombophilia or a history
of thrombosis. Recommended options for anticoagulation in pregnancy are limited to
heparins, which do not cross the placenta. Low-molecular-weight heparin (LMWH) is
preferred over unfractionated heparin because LMWH has a longer half-life and is presumed
to have fewer side effects. The longer half-life is a disadvantage around the time
of delivery, when unfractionated heparin, with its shorter half-life, is easier to
manage. For women who develop or are at high risk for heparin-induced thrombocytopenia
or severe cutaneous reactions, fondaparinux is probably the agent of choice. Women
who do not require lifelong anticoagulation, but require anticoagulation during pregnancy,
will still require anticoagulation for the first 6 weeks postpartum.
Keywords
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References
- Venous thrombosis: on the history of Virchow’s Triad.University of Toronto Medical Journal. 2004; 81: 166-171
- Maternal physiology in pregnancy.in: Gabbe S. Niebyl J. Simpson J. Normal and Problem Pregnancies. 4th ed. Churchill Livingstone, New York2002: 63-92
- An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy.Br J Obstet Gynaecol. 1997; 104: 191-197
- Respiratory diseases in pregnancy.in: Gabbe S. Niebyl J. Simpson J. Normal and Problem Pregnancies. 4th ed. Churchill Livingstone, New York2002: 1033-1064
- Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a population-based, case-control study.Am J Obstet Gynecol. 2001; 184: 104-110
- Prolonged bedrest during pregnancy: does the risk of deep vein thrombosis warrant the use of routine heparin prophylaxis?.J Matern Fetal Med. 1997; 6: 264-267
- The prevalence of thromboembolic events among women with extended bed rest prescribed as part of the treatment for premature labor or preterm premature rupture of membranes.Am J Obstet Gynecol. 2000; 182: 1089-1092
- Leiden mutation, bed rest and infection: simultaneous triggers for maternal deep-vein thrombosis and neonatal intracranial hemorrhage?.Fetal Diagn Ther. 2004; 19: 275-277
- Haemostatic changes in pregnancy.Best Pract Res Clin Haematol. 2003; 16: 153-168
- The undecided serpin: the ins and outs of plasminogen activator inhibitor type 2.FEBS J. 2005; 272: 4858-4867
- Thrombosis during pregnancy and the postpartum period.Am J Obstet Gynecol. 2005; 193: 216-219
- Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation.Obstet Gynecol Surv. 1999; 54: 265-271
Postpartum Hemorrhage: Postpartum Hemorrhage Initiative, Office of Health, Infectious Diseases and Nutrition, Bureau for Global Health, US Agency for International Development. http://www.pphprevention.org/pph.php. Accessed September 3, 2007.
- Pregnancy-related mortality surveillance—United States, 1991–1999.MMWR Surveill Summ. 2003; 52: 1-8
- Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study.Ann Intern Med. 2005; 143: 697-706
- Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality.Am J Obstet Gynecol. 2006; 194: 1311-1315
- Late symptoms after pregnancy-related deep vein thrombosis.Br J Obstet Gynaecol. 1990; 97: 338-341
- Long-term outcome of deep venous thrombosis during pregnancy treated with unfractionated heparin or low molecular weight heparin.Thrombosis Research. 2003; 111: 239-242
- A 16-year haemodynamic follow-up of women with pregnancy-related medically treated iliofemoral deep venous thrombosis.Eur J Vasc Endovasc Surg. 2001; 22: 448-455
- Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations.Am J Obstet Gynecol. 1998; 179: 1324-1328
- Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.N Engl J Med. 2000; 342: 374-380
- Prothrombin 20210 G-- >A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.BJOG. 2000; 107: 565-569
- Genetic factors associated with thrombosis in pregnancy in a United States population.Am J Obstet Gynecol. 2000; 183: 1271-1277
- Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium.Thromb Haemost. 2002; 87: 791-795
- High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance).Blood. 1995; 85: 1504-1508
- Thrombophilia in pregnancy: a systematic review.Br J Haematol. 2006; 132: 171-196
- Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency: a cooperative, retrospective study.Arterioscler Thromb Vasc Biol. 1996; 16: 742-748
- Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women.Thromb Haemost. 1990; 63: 319-320
- Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin.Gynecol Obstet Invest. 1982; 14: 127-141
- Inherited thrombophilia and pregnancy.Curr Opin Obstet Gynecol. 1998; 10: 135-144
- A retrospective review of 61 patients with antiphospholipid syndrome: analysis of factors influencing recurrent thrombosis.Arch Intern Med. 1997; 157: 2101-2108
- High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin.Arthritis Rheum. 2001; 44: 1466-1467
- Heparin therapy during pregnancy: risks to the fetus and mother.Arch Intern Med. 1989; 149: 2233-2236
- Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.BJOG. 2001; 108: 1134-1140
- Clotting and hemorrhage in the placenta—a delicate balance.N Engl J Med. 2002; 347: 57-59
- Safety of withholding heparin in pregnant women with a history of venous thromboembolism.N Engl J Med. 2000; 343: 1439-1444
- Safety of low-molecular-weight heparin in pregnancy: a systematic review.Thromb Haemost. 1999; 81: 668-672
- Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis.J Thromb Haemost. 2005; 3: 949-954
- The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis.Br J Haematol. 2006; 135: 386-391
- Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism.Blood. 2002; 100: 1060-1062
- Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 627S-644S
- Thrombosis, thrombophilia, and thromboprophylaxis in pregnancy.Clin Adv Hematol Oncol. 2005; 3: 187-197
- Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.Obstet Gynecol. 2003; 101: 1333-1344
- Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.Blood. 2004; 103: 3695-3699
- Thromboembolism in pregnancy. ACOG, Washington, DC2000
- Inherited thrombophilias in pregnant patients: detection and treatment paradigm.Obstet Gynecol. 2002; 99: 333-341
- Organogenetic period: The fourth to eighth weeks.in: The Developing Human: Clinically Oriented Embryology. 6th ed. WB Saunders Company, Philadelphia1998: 83-106
- Binge drinking in the preconception period and the risk of unintended pregnancy: implications for women and their children.Pediatrics. 2003; 111: 1136-1141
- Risks of anticoagulant therapy in pregnant women with artificial heart valves.N Engl J Med. 1986; 315: 1390-1393
- Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves.BJOG. 2000; 107: 245-253
- Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature.Arch Intern Med. 2000; 160: 191-196
- Pregnancy outcome in women with prosthetic heart valves.Am J Obstet Gynecol. 2004; 191: 1009-1013
- The risk of fetal loss associated with warfarin anticoagulation.Int J Gynaecol Obstet. 2002; 78: 221-225
- Effect of oral anticoagulant during pregnancy with prosthetic heart valve.Asian Cardiovasc Thorac Ann. 2002; 10: 306-309
- Anticoagulation in pregnant women with mechanical heart valve prostheses.Heart. 1999; 82: 23-26
- Pregnancy in patients with prosthetic heart valves: an experience with 45 pregnancies.Q J Med. 1982; 51: 358-365
- Risk of warfarin during pregnancy with mechanical valve prostheses.Obstet Gynecol. 2002; 99: 35-40
- Coumarins during pregnancy: long-term effects on growth and development of school-age children.Thromb Haemost. 2001; 85: 609-613
- Lack of anti-factor Xa activity in umbilical cord vein samples after subcutaneous administration of heparin or low molecular mass heparin in pregnant women.Haemostasis. 1993; 23: 314-320
- Placental transfer of low-molecular weight heparin.Geburtshilfe Frauenheilkd. 1995; 55 ([in German]): 93-98
- Bone mineral density during long-term prophylaxis with heparin in pregnancy.Am J Obstet Gynecol. 1994; 170: 1315-1320
- A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry.Am J Obstet Gynecol. 1994; 170: 862-869
- Bone density changes in women who receive thromboprophylaxis in pregnancy.Am J Obstet Gynecol. 2006; 195: 1109-1113
- 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
- Heparin-induced thrombocytopenia is rare in pregnancy.Am J Obstet Gynecol. 2001; 185: 148-152
- Prospective observational study of bone mineral density during pregnancy: low molecular weight heparin versus control.Hum Reprod. 2004; 19: 1211-1214
- Bruising in women undergoing thromboprophylaxis in pregnancy.Am J Obstet Gynecol. 2006; 193 ([abstract]): S81
- Effects of fondaparinux compared with dalteparin, enoxaparin and unfractionated heparin on human osteoblasts.Calcif Tissue Int. 2003; 73: 370-379
- Fondaparinux sodium does not cross the placental barrier: study using the in-vitro human dually perfused cotyledon model.Clin Pharmacokinet. 2002; 41: 47-49
- Minor transplacental passage of fondaparinux in vivo.N Engl J Med. 2004; 350: 1914-1915
- Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation.Nat Med. 2004; 10: 1222-1226
- Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy.Blood. 2006; 108: 1569-1570
- The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.Chest. 2004; 126: 204S-233S
- Thromboembolic disease associated with ovarian stimulation and assisted conception techniques.Hum Reprod. 1997; 12: 2167-2173
- Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.N Engl J Med. 1995; 332: 1330-1335
- Platelets: an update on diagnosis and management of thrombocytopenic disorders.Hematology (Am Soc Hematol Educ Program). 2001; 282: 305
- Thromboembolic prophylaxis with danaparoid (Orgaran) in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal’s disease.Clin Appl Thromb Hemost. 2000; 6: 187-189
- Danaparoid thromboprophylaxis in pregnant women with heparin-induced thrombocytopenia.BJOG. 2002; 109: 466-468
- Heparin-induced thrombocytopenia-alternative anticoagulation in pregnancy and lactation.Semin Thromb Hemost. 2002; 28: 439-446
- Successful use of danaparoid in treatment of heparin-induced thrombocytopenia during twin pregnancy.Obstet Gynecol. 1997; 90: 648-650
- Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin.Gynecol Obstet Invest. 2000; 49: 67-69
- Management of heparin allergy in pregnancy.Am J Hematol. 2001; 67: 268-269
- Fondaparinux as anticoagulant in a pregnant woman with heparin allergy.Blood Coagul Fibrinolysis. 2006; 17: 147-149
- Pregnancy after mechanical mitral valve replacement.J Heart Valve Dis. 2003; 12: 370-376
- May mothers given warfarin breast-feed their infants?.BMJ. 1977; 1: 1564-1565
- Transfer of drugs and other chemicals into human milk.Pediatrics. 2001; 108: 776-789
- Placental transport of heparin.Am J Obstet Gynecol. 1965; 93: 570-573
- Absence of transplacental passage of the low molecular weight heparin enoxaparin.Haemostasis. 2000; 30: 243-248
- Use of low molecular weight heparin in pregnancy.Thromb Haemost. 1992; 68: 652-656
- Successful use of heparinoids in a pregnancy complicated by allergy to heparin.BJOG. 2001; 108: 1011-1012
- Treatment with danaparoid during pregnancy for a woman with a cutenous allergy to low-molecular-weight heparin.Ann Fr Anesth Reanim. 2000; 19 ([in French]): 751-754
- Prophylactic use of danaparoid in high-risk pregnancy with heparin-induced thrombocytopaenia-positive skin reaction.Blood Coagul Fibrinolysis. 2003; 14: 485-487
- Treatment of heparin-induced thrombocytopenia.Ann Pharmacother. 2002; 36: 489-503
- Pharmacological survey of recombinant hirudin.Pharmazie. 1988; 43: 202-207
- Hirudin treatment in a breastfeeding woman.Lancet. 2000; 355: 467-468
- Fondaparinux (ARIXTRA) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins.Haematologica. 2003; 88: 147-148
- Absence of placental transfer of pentasaccharide (Fondaparinux, Arixtra) in the dually perfused human cotyledon in vitro.Thromb Haemost. 2002; 87: 831-835
- Enoxaparin treatment in women with mechanical heart valves during pregnancy.Am J Obstet Gynecol. 2001; 185: 633-637
- Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review.BMJ. 2001; 322: 329-333
- Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review.Obstet Gynecol. 2003; 101: 1319-1332
- A study of salicylate and caffeine excretion in the breast milk of two nursing mothers.J Anal Toxicol. 1982; 6: 64-68
- Analgesic drugs in breast milk and plasma.Clin Pharmacol Ther. 1981; 29: 625-633
- Side and site of deep vein thrombosis in women using oral contraceptives.Acta Obstet Gynecol Scand. 1985; 64: 399-402
- Deep vein thrombosis and the oestrogen content in oral contraceptives: an epidemiological analysis.Contraception. 1985; 31: 29-41
- The iliac compression syndrome.Br J Surg. 1965; 52: 816-821
- Venous thrombosis during pregnancy: leg and trimester of presentation.Thromb Haemost. 1992; 67: 519-520
- A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.Am J Cardiol. 2004; 93: 259-262
- How we manage venous thromboembolism during pregnancy.Blood. 2002; 100: 3470-3478
- Thrombotic disorders: diagnosis and treatment.Hematology (Am Soc Hematol Educ Program). 2003; X: 520-539
- A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation.Am J Obstet Gynecol. 2004; 191: 1024-1029
- Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy.Am J Obstet Gynecol. 1999; 181: 1113-1117
- A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy.Blood Coagul Fibrinolysis. 1998; 9: 343-350
- Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy.Am J Obstet Gynecol. 1995; 173: 1240-1245
- Low molecular weight heparin (dalteparin) for the treatment of venous thromboembolism in pregnancy.BJOG. 2003; 110: 139-144
- A longitudinal study of maternal dose response to low molecular weight heparin in pregnancy.Obstet Gynecol. 2003; 101: 1307-1311
- Tinzaparin sodium for thrombosis treatment and prevention during pregnancy.Am J Obstet Gynecol. 2004; 190: 495-501
- Use of thrombolytics for the treatment of thromboembolic disease during pregnancy.Obstet Gynecol Surv. 1995; 50: 534-541
- Low molecular weight heparin and neuraxial anesthesia.Thromb Res. 2001; 101: 141-154
- Pneumatic compression devices for prophylaxis of deep venous thrombosis (DVT).Am Surg. 1986; 52: 371-373
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