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Expert Review of Hematology Volume 6, 2013 - Issue 3
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Review

Preventing thrombophilia-related complications of pregnancy: an update

Shannon M Bates Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute (TaARI), Hamilton, ON, Canada. [email protected]
Pages 287-300 | Published online: 10 Jan 2014

References

  • Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann. Intern. Med. 143(10), 697–706 (2005).
  • Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet. Gynecol. 94(5 Pt 1), 730–734 (1999).
  • Lindqvist P, Dahlbäck B, Marsál K. Thrombotic risk during pregnancy: a population study. Obstet. Gynecol. 94(4), 595–599 (1999).
  • Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 108(1), 56–60 (2001).
  • James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am. J. Obstet. Gynecol. 194(5), 1311–1315 (2006).
  • Andersen BS, Steffensen FH, Sørensen HT, Nielsen GL, Olsen J. The cumulative incidence of venous thromboembolism during pregnancy and puerperium – an 11 year Danish population-based study of 63,300 pregnancies. Acta Obstet. Gynecol. Scand. 77(2), 170–173 (1998).
  • Rodger M. Evidence base for the management of venous thromboembolism in pregnancy. Hematology Am. Soc. Hematol. Educ. Program 201, 173–180 (2010).
  • De Stefano V, Rossi E, Za T, Leone G. Prophylaxis and treatment of venous thromboembolism in individuals with inherited thrombophilia. Semin. Thromb. Hemost. 32(8), 767–780 (2006).
  • Robertson L, Wu O, Langhorne P et al.; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br. J. Haematol. 132(2), 171–196 (2006).
  • Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO; American College of Chest Physicians. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl.), e691S–e736S (2012).
  • American College of Obstetricians and Gynecologists. Practice Bulletin 124: inherited thrombophilias in pregnancy. Obstet. Gynecol. 118, 730–740 (2011).
  • American College of Obstetricians and Gynecologists. Practice Bulletin 123: thromboembolism in pregnancy. Obstetrics Gynecol. 123, 718–729 (2011).
  • Brenner B. Haemostatic changes in pregnancy. Thromb. Res. 114(5–6), 409–414 (2004).
  • Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb. Haemost. 103(4), 718–727 (2010).
  • Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case–control study. J. Thromb. Haemost. 6(6), 905–912 (2008).
  • Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet. Gynecol. Surv. 54(4), 265–271 (1999).
  • Chang J, Elam-Evans LD, Berg CJ et al. Pregnancy-related mortality surveillance – United States, 1991–1999. MMWR. Surveill. Summ. 52(2), 1–8 (2003).
  • Lewis G. Confidential Enquiry into Maternal and Child Health. Saving Mothers’ Lives – Reviewing Maternal Deaths to Make Motherhood Safer 2003–2005. CEMACH, London, UK (2007).
  • Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J. Thromb. Haemost. 6(4), 632–637 (2008).
  • Rai R, Regan L. Recurrent miscarriage. Lancet 368(9535), 601–611 (2006).
  • Brenner B. Clinical management of thrombophilia-related placental vascular complications. Blood 103(11), 4003–4009 (2004).
  • Kist WJ, Janssen NG, Kalk JJ, Hague WM, Dekker GA, de Vries JI. Thrombophilias and adverse pregnancy outcome – a confounded problem! Thromb. Haemost. 99(1), 77–85 (2008).
  • Redline RW. Thrombophilia and placental pathology. Clin. Obstet. Gynecol. 49(4), 885–894 (2006).
  • Gupta S, Agarwal A, Banerjee J, Alvarez JG. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet. Gynecol. Surv. 62(5), 335–347; quiz 353 (2007).
  • Rand JH, Wu XX, Andree HA et al. Pregnancy loss in the antiphospholipid-antibody syndrome – a possible thrombogenic mechanism. N. Engl. J. Med. 337(3), 154–160 (1997).
  • Greer IA. The challenge of thrombophilia in maternal-fetal medicine. N. Engl. J. Med. 342(6), 424–425 (2000).
  • Miyakis S, Lockshin MD, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 4(2), 295–306 (2006).
  • Bertina RM, Koeleman BP, Koster T et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369(6475), 64–67 (1994).
  • Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 112(1), 19–27 (2008).
  • Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3´-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88(10), 3698–3703 (1996).
  • Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia 14(6), 1229–1239 (2008).
  • Pierangeli SS, Chen PP, Raschi E et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin. Thromb. Hemost. 34(3), 236–250 (2008).
  • Bick RL. Antiphospholipid syndrome in pregnancy. Hematol. Oncol. Clin. North Am. 22(1), 107–120, vii (2008).
  • Villani M, Tiscia GL, Margaglione M et al. Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias. J. Thromb. Haemost. 10(2), 223–228 (2012).
  • Rossi E, Ciminello A, Za T, Betti S, Leone G, De Stefano V. In families with inherited thrombophilia the risk of venous thromboembolism is dependent on the clinical phenotype of the proband. Thromb. Haemost. 106(4), 646–654 (2011).
  • Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch. Intern. Med. 169(6), 610–615 (2009).
  • Lensen RP, Bertina RM, de Ronde H, Vandenbroucke JP, Rosendaal FR. Venous thrombotic risk in family members of unselected individuals with factor V Leiden. Thromb. Haemost. 83(6), 817–821 (2000).
  • Friederich PW, Sanson BJ, Simioni P et al. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann. Intern. Med. 125(12), 955–960 (1996).
  • Middeldorp S, Libourel EJ, Hamulyák K, Van der Meer J, Büller HR. The risk of pregnancy-related venous thromboembolism in women who are homozygous for factor V Leiden. Br. J. Haematol. 113(2), 553–555 (2001).
  • Martinelli I, Legnani C, Bucciarelli P, Grandone E, De Stefano V, Mannucci PM. Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia. Thromb. Haemost. 86(3), 800–803 (2001).
  • Tormene D, Simioni P, Prandoni P et al. Factor V Leiden mutation and the risk of venous thromboembolism in pregnant women. Haematologica 86(12), 1305–1309 (2001).
  • Middeldorp S, Henkens CM, Koopman MM et al. The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann. Intern. Med. 128(1), 15–20 (1998).
  • Simioni P, Sanson BJ, Prandoni P et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb. Haemost. 81(2), 198–202 (1999).
  • Middeldorp S, Meinardi JR, Koopman MM et al. A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism. Ann. Intern. Med. 135(5), 322–327 (2001).
  • Simioni P, Tormene D, Prandoni P et al. Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: a prospective cohort study. Blood 99(6), 1938–1942 (2002).
  • Couturaud F, Leroyer C, Mottier D; Groupe dEtude de la Thrombose de Bretagne Occidentale (GETBO). Risk factors and clinical presentation of venous thromboembolism according to the age of relatives of patients with factor V Leiden. Thromb. Haemost. 99(4), 793–794 (2008).
  • Bank I, Libourel EJ, Middeldorp S et al. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study. Arch. Intern. Med. 164(17), 1932–1937 (2004).
  • Coppens M, van de Poel MH, Bank I et al. A prospective cohort study on the absolute incidence of venous thromboembolism and arterial cardiovascular disease in asymptomatic carriers of the prothrombin 20210A mutation. Blood 108(8), 2604–2607 (2006).
  • Martinelli I, Battaglioli T, De Stefano V et al.; GIT (Gruppo Italiano Trombofilia). The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A. J. Thromb. Haemost. 6(3), 494–498 (2008).
  • Conard J, Horellou MH, Van Dreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women. Thromb. Haemost. 63(2), 319–320 (1990).
  • De Stefano V, Leone G, Mastrangelo S et al. Thrombosis during pregnancy and surgery in patients with congenital deficiency of antithrombin III, protein C, protein S. Thromb. Haemost. 71(6), 799–800 (1994).
  • Galli M, Barbui T. Antiphospholipid syndrome: clinical and diagnostic utility of laboratory tests. Semin. Thromb. Hemost. 31(1), 17–24 (2005).
  • Bergrem A, Jacobsen EM, Skjeldestad FE, Jacobsen AF, Skogstad M, Sandset PM. The association of antiphospholipid antibodies with pregnancy-related first time venous thrombosis – a population-based case–control study. Thromb. Res. 125(5), e222–e227 (2010).
  • Quenby S, Farquharson RG, Dawood F, Hughes AM, Topping J. Recurrent miscarriage and long-term thrombosis risk: a case–control study. Hum. Reprod. 20(6), 1729–1732 (2005).
  • Clark CA, Spitzer KA, Crowther MA et al. Incidence of postpartum thrombosis and preterm delivery in women with antiphospholipid antibodies and recurrent pregnancy loss. J. Rheumatol. 34(5), 992–996 (2007).
  • Bauersachs RM, Dudenhausen J, Faridi A et al.; EThIG Investigators. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb. Haemost. 98(6), 1237–1245 (2007).
  • Kearon C, Akl EA, Comerota AJ et al.; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis (9th Edition): American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl.), e419S–e494S (2012).
  • Pabinger I, Grafenhofer H, Kyrle PA et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 100(3), 1060–1062 (2002).
  • Brill-Edwards P, Ginsberg JS, Gent M et al.; Recurrence of Clot in This Pregnancy Study Group. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N. Engl. J. Med. 343(20), 1439–1444 (2000).
  • Pabinger I, Grafenhofer H, Kaider A et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J. Thromb. Haemost. 3(5), 949–954 (2005).
  • De Stefano V, Martinelli I, Rossi E et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br. J. Haematol. 135(3), 386–391 (2006).
  • White RH, Chan WS, Zhou H, Ginsberg JS. Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism. Thromb. Haemost. 100(2), 246–252 (2008).
  • Stirrat GM. Recurrent miscarriage. Lancet 336(8716), 673–675 (1990).
  • Sibai BM, Mercer B, Sarinoglu C. Severe preeclampsia in the second trimester: recurrence risk and long-term prognosis. Am. J. Obstet. Gynecol. 165(5 Pt 1), 1408–1412 (1991).
  • Sinha P, Kuruba N. Ante-partum haemorrhage: an update. J. Obstet. Gynaecol. 28(4), 377–381 (2008).
  • Ananth CV, Berkowitz GS, Savitz DA, Lapinski RH. Placental abruption and adverse perinatal outcomes. JAMA 282(17), 1646–1651 (1999).
  • Hille ET, den Ouden AL, Bauer L, van den Oudenrijn C, Brand R, Verloove-Vanhorick SP. School performance at nine years of age in very premature and very low birth weight infants: perinatal risk factors and predictors at five years of age. Collaborative Project on Preterm and Small for Gestational Age (POPS) Infants in The Netherlands. J. Pediatr. 125(3), 426–434 (1994).
  • Ginsberg JS, 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 80(4), 975–980 (1992).
  • Laskin CA, Bombardier C, Hannah ME et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N. Engl. J. Med. 337(3), 148–153 (1997).
  • Rai RS, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum. Reprod. 10(12), 3301–3304 (1995).
  • Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst. Rev. 2, CD002859 (2005).
  • Opatrny L, David M, Kahn SR, Shrier I, Rey E. Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J. Rheumatol. 33(11), 2214–2221 (2006).
  • Abou-Nassar K, Carrier M, Ramsay T, Rodger MA. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb. Res. 128(1), 77–85 (2011).
  • Rodger MA, Betancourt MT, Clark P et al. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med. 7(6), e1000292 (2010).
  • Flessa HC, Kapstrom AB, Glueck HI, Will JJ. Placental transport of heparin. Am. J. Obstet. Gynecol. 93(4), 570–573 (1965).
  • Forestier F, Daffos F, Capella-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. 34(6), 557–560 (1984).
  • 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. Haemost. 57(2), 234 (1987).
  • Ginsberg JS, Hirsh J, Turner DC, Levine MN, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb. Haemost. 61(2), 197–203 (1989).
  • Ginsberg JS, Kowalchuk G, Hirsh J, Brill-Edwards P, Burrows R. Heparin therapy during pregnancy. Risks to the fetus and mother. Arch. Intern. Med. 149(10), 2233–2236 (1989).
  • Clark NP, Delate T, Witt DM, Parker S, McDuffie R. A descriptive evaluation of unfractionated heparin use during pregnancy. J. Thromb. Thrombolysis 27(3), 267–273 (2009).
  • Lepercq J, Conard J, Borel-Derlon A et al. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. BJOG 108(11), 1134–1140 (2001).
  • Hall JAG, Paul RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am. J. Med. 68, 122–140 (1980).
  • Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch. Intern. Med. 160(2), 191–196 (2000).
  • Hassouna A, Allam H. Anticoagulation of pregnant women with mechanical heart valve prosthesis: a systematic review of the literature (2000–2009). J. Coagul. Disorders 2, 81–88 (2010).
  • Pauli RM, Haun J. Intrauterine effects of coumarin derivatives. Dev. Brain Dysfunct. 6, 229–247 (1993).
  • Schaefer C, Hannemann D, Meister R et al. Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study. Thromb. Haemost. 95(6), 949–957 (2006).
  • Hirsh J, Cade JF, O’Sullivan EF. Clinical experience with anticoagulant therapy during pregnancy. Br. Med. J. 1(5691), 270–273 (1970).
  • Lagrange F, Vergnes C, Brun JL et al. Absence of placental transfer of pentasaccharide (fondaparinux, Arixtra) in the dually perfused human cotyledon in vitro. Thromb. Haemost. 87(5), 831–835 (2002).
  • Dempfle CE. Minor transplacental passage of fondaparinux in vivo. N. Engl. J. Med. 350(18), 1914–1915 (2004).
  • Harenberg J. Treatment of a woman with lupus and thromboembolism and cutaneous intolerance to heparins using fondaparinux during pregnancy. Thromb. Res. 119(3), 385–388 (2007).
  • Mazzolai L, Hohlfeld P, Spertini F, Hayoz D, Schapira M, Duchosal MA. Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy. Blood 108(5), 1569–1570 (2006).
  • Wijesiriwardana A, Lees DA, Lush C. Fondaparinux as anticoagulant in a pregnant woman with heparin allergy. Blood Coagul. Fibrinolysis 17(2), 147–149 (2006).
  • Gerhardt A, Zotz RB, Stockschlaeder M, Scharf RE. Fondaparinux is an effective alternative anticoagulant in pregnant women with high risk of venous thromboembolism and intolerance to low-molecular-weight heparins and heparinoids. Thromb. Haemost. 97(3), 496–497 (2007).
  • Schapkaitz E, Jacobson BF. Delayed hypersensitivity to low-molecular-weight heparin (LMWH) in pregnancy. S. Afr. Med. J. 97(12), 1255–1257 (2007).
  • Winger EE, Reed JL. A retrospective analysis of fondaparinux versus enoxaparin treatment in women with infertility or pregnancy loss. Am. J. Reprod. Immunol. 62(4), 253–260 (2009).
  • Knol HM, Schultinge L, Erwich JJ, Meijer K. Fondaparinux as an alternative anticoagulant therapy during pregnancy. J. Thromb. Haemost. 8(8), 1876–1879 (2010).
  • Dabigatran etexilate, summary of product characteristics. Boehringer Ingelheim GmbH, Ingelheim, Germany (2009).
  • Rivaroxaban, summary of product characteristics. Bayer Schering Pharma AG, Leverkusen, Germany (2009).
  • Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 106(2), 401–407 (2005).
  • Weitz JI. Low-molecular-weight heparins. N. Engl. J. Med. 337(10), 688–698 (1997).
  • Sanson BJ, Lensing AW, Prins MH et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb. Haemost. 81(5), 668–672 (1999).
  • Warkentin TE, Levine MN, Hirsh J et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N. Engl. J. Med. 332(20), 1330–1335 (1995).
  • Garcia DA, Baglin TP, Weitz JI, Samama MM; American College of Chest Physicians. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis (9th Edition): American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl.), e24S–e43S (2012).
  • Pettilä V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb. Haemost. 87(2), 182–186 (2002).
  • Carlin AJ, Farquharson RG, Quenby SM, Topping J, Fraser WD. Prospective observational study of bone mineral density during pregnancy: low molecular weight heparin versus control. Hum. Reprod. 19(5), 1211–1214 (2004).
  • Rodger MA, Kahn SR, Cranney A et al.; TIPPS investigators. Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: substudy of a randomized controlled trial. J. Thromb. Haemost. 5(8), 1600–1606 (2007).
  • Bank I, Libourel EJ, Middeldorp S, Van Der Meer J, Büller HR. High rate of skin complications due to low-molecular-weight heparins in pregnant women. J. Thromb. Haemost. 1(4), 859–861 (2003).
  • Wütschert R, Piletta P, Bounameaux H. Adverse skin reactions to low molecular weight heparins: frequency, management and prevention. Drug Saf. 20(6), 515–525 (1999).
  • Douketis JD, Spyropoulos AC, Spencer FA et al.; American College of Chest Physicians. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis (9th Edition): American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl.), e326S–e350S (2012).
  • Horlocker TT, Wedel DJ, Rowlingson JC et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (3rd Edition). Reg. Anesth. Pain Med. 35(1), 64–101 (2010).
  • Orme ML, Lewis PJ, de Swiet M et al. May mothers given warfarin breast-feed their infants? Br. Med. J. 1(6076), 1564–1565 (1977).
  • McKenna R, Cole ER, Vasan U. Is warfarin sodium contraindicated in the lactating mother? J. Pediatr. 103(2), 325–327 (1983).
  • Richter C, Sitzmann J, Lang P, Weitzel H, Huch A, Huch R. Excretion of low molecular weight heparin in human milk. Br. J. Clin. Pharmacol. 52(6), 708–710 (2001).
  • Askie LM, Duley L, Henderson-Smart DJ, Stewart LA; PARIS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. Lancet 369(9575), 1791–1798 (2007).
  • Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. Am. J. Obstet. Gynecol. 187(6), 1623–1630 (2002).
  • Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 327(7411), 368 (2003).
  • James AH, Brancazio LR, Price T. Aspirin and reproductive outcomes. Obstet. Gynecol. Surv. 63(1), 49–57 (2008).
  • Blombäck M, Bremme K, Hellgren M, Siegbahn A, Lindberg H. Thromboprophylaxis with low molecular mass heparin, ‘Fragmin’ (dalteparin), during pregnancy – a longitudinal safety study. Blood Coagul. Fibrinolysis 9(1), 1–9 (1998).
  • Casele HL, Laifer SA, Woelkers DA, Venkataramanan R. Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy. Am. J. Obstet. Gynecol. 181(5 Pt 1), 1113–1117 (1999).
  • Kovacs MJ, Keeney M, MacKinnon K, Boyle E. Three different chromogenic methods do not give equivalent anti-Xa levels for patients on therapeutic low molecular weight heparin (dalteparin) or unfractionated heparin. Clin. Lab. Haematol. 21(1), 55–60 (1999).
  • Kitchen S, Iampietro R, Woolley AM, Preston FE. Anti Xa monitoring during treatment with low molecular weight heparin or danaparoid: inter-assay variability. Thromb. Haemost. 82(4), 1289–1293 (1999).
  • Holbrook A, Schulman S, Witt DM et al.; American College of Chest Physicians. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis (9th Edition): American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(2 Suppl.), e152S–e184S (2012).
  • Tooher R, Gates S, Dowswell T, Davis LJ. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst. Rev. 5, CD001689 (2010).
  • Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst. Rev. 2, CD002859 (2005).
  • Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am. J. Obstet. Gynecol. 174(5), 1584–1589 (1996).
  • Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 314(7076), 253–257 (1997).
  • Goel N, Tuli A, Choudhry R. The role of aspirin versus aspirin and heparin in cases of recurrent abortions with raised anticardiolipin antibodies. Med. Sci. Monit. 12(3), CR132–CR136 (2006).
  • Kutteh WH, Ermel LD. A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin. Am. J. Reprod. Immunol. 35(4), 402–407 (1996).
  • Cowchock S, Reece EA. Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial. Am. J. Obstet. Gynecol. 176(5), 1099–1100 (1997).
  • Pattison NS, Chamley LW, Birdsall M, Zanderigo AM, Liddell HS, McDougall J. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am. J. Obstet. Gynecol. 183(4), 1008–1012 (2000).
  • Tulppala M, Marttunen M, Söderstrom-Anttila V et al. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production. Hum. Reprod. 12(7), 1567–1572 (1997).
  • Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet. Gynecol. 100(3), 408–413 (2002).
  • Mak A, Cheung MW, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology 49(2), 281–288 (2010).
  • Laskin CA, Spitzer KA, Clark CA et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA trial. J. Rheumatol. 36(2), 279–287 (2009).
  • Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil. Steril. 83(3), 684–690 (2005).
  • Stephenson MD, Ballem PJ, Tsang P et al. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin. J. Obstet. Gynaecol. Can. 26(8), 729–734 (2004).
  • Gris JC, Mercier E, Quéré I et al. Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 103(10), 3695–3699 (2004).
  • Middeldorp S. Thrombophilia and pregnancy complications: cause or association? J. Thromb. Haemost. 5(Suppl. 1), 276–282 (2007).
  • Rodger M. Important publication missing key information. Blood 104(10), 3413; author reply 3413–3414 (2004).
  • Rodger MA, Paidas M, McLintock C et al. Inherited thrombophilia and pregnancy complications revisited. Obstet. Gynecol. 112(2 Pt 1), 320–324 (2008).
  • Middeldorp S. Low-molecular-weight heparins have no place in recurrent miscarriage: debate–for the motion. Thromb. Res. 127(Suppl. 3), S105–S109 (2011).
  • Coppens M, Folkeringa N, Teune MJ et al. Outcome of the subsequent pregnancy after a first loss in women with the factor V Leiden or prothrombin 20210A mutations. J. Thromb. Haemost. 5(7), 1444–1448 (2007).
  • Kaandorp SP, Goddijn M, van der Post JA et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N. Engl. J. Med. 362(17), 1586–1596 (2010).
  • Visser J, Ulander VM, Helmerhorst FM et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial. Thromb. Haemost. 105(2), 295–301 (2011).
  • DeVries JIP, VanPampus MG, Hague WM, Bezemer PD, Joosten JH; on behalf of FRUIT Investigators. Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT. J. Thromb. Haemost. 10, 64–72 (2012).
  • Cohn DM, Vansenne F, Kaptein AA, De Borgie CA, Middeldorp S. The psychological impact of testing for thrombophilia: a systematic review. J. Thromb. Haemost. 6(7), 1099–1104 (2008).
  • Wu O, Robertson L, Twaddle S et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol. Assess. 10(11), 1–110 (2006).
  • Cohn D, Vansenne F, de Borgie C, Middeldorp S. Thrombophilia testing for prevention of recurrent venous thromboembolism. Cochrane Database Syst. Rev. 1, CD007069 (2009).

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