Hematologic Aspects of Pregnancy
Epidemiology and Pathogenesis: Hypercoaguable States in Pregnancy, Fetal Loss, Venous Thromboembolism, and Thrombocytopenia
Antiphospholipid antibodies in predicting adverse pregnancy outcome. A prospective study.
Lynch A, Marlar R, Murphy J, et al.
Ann Intern Med. 1994;120:470-475.
Description: This was a prospective study demonstrating that the presence of antiphospholipid antibodies (most notably anticardiolipin IgG) in unselected pregnant women was associated with a higher risk of fetal loss (absolute risk of 15.8% versus 6.5%). However, given that a high proportion of women with antiphospholipid antibodies had successful pregnancies, and that studies have not been conducted evaluating the role of intervention in this clinical scenario, routine screening of all pregnant women has not been recommended. PubMed citation number: 8093135
Pregnancy loss in the antiphospholipid antibody syndrome – a possible thrombogenic mechanism.
Rand JH, Wu XX, Andree HA, et al.
N Engl J Med. 1997;337:154-160.
Description: This study implicates annexin V, a potent anticoagulant, in the pathogenesis of fetal loss in the antiphospholipid antibody syndrome by showing that incubation of trophoblast and endothelial cells with antiphospholipid antibodies leads to the reduced surface expression of annexin V and the acceleration of coagulation.
PubMed citation number: 9219701
Increased fetal loss in women with heritable thrombophilia.
Preston FE, Rosendaal FR, Walker ID, et al.
Lancet. 1996;348:913-916.
Description: This was the first study demonstrating an increased risk of late fetal loss (after 28 weeks of gestation) in women with inherited thrombophilia, particularly in those with more than 1 heritable thrombophilia or antithrombin deficiency.
PubMed citation number: 8843809
Increased frequency of genetic thrombophilia in women with complications of pregnancy.
Kupferminc MJ, Eldor A, Steinman N, et al.
N Engl J Med. 1999;340:9-13.
Description: This was a retrospective study that showed an increased risk of an inherited thrombophilia in pregnant women who had fetal loss, preeclampsia, abruptio placentae, or fetal growth restriction compared with women who had uneventful pregnancies.
PubMed citation number: 9878639
The above studies are collectively important because they: (1) provide a biologically-relevant rationale for vascular complications of pregnancy in select cases; (2) raise important questions about screening women with recurrent and nonrecurrent pregnancy complications; and (3) provide the basis for evaluating the effectiveness of prophylactic anticoagulation for women with a history of pregnancy complications and heritable thrombophilia in a prospective, randomized fashion.
Thrombophilic disorders and fetal loss: a meta-analysis.
Rey, E, Kahn, SR, David, M, Shrier, I.
Lancet. 2003;361:901-908.
Description: This is a meta-analysis of 31 studies evaluating the risk of early versus late and recurrent versus nonrecurrent fetal loss for women carrying individual heritable thrombophilias.
PubMed citation number: 12648968
Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.
Gerhardt A, Scharf RE, Beckmann MW, et al.
N Engl J Med. 2000;342:374-379.
Description: This was a retrospective study that showed an increased risk of venous thromboembolism (VTE) during pregnancy and the puerperium for women carrying the factor V Leiden mutation (relative risk 9.3, absolute risk 0.2%) or the prothrombin gene mutation (relative risk 15.2, absolute risk 0.5%) and a disproportionately higher risk of VTE for women carrying both mutations (estimated odds ratio 107, absolute risk 4.6%).
PubMed citation number: 10666427
Frequency of pregnancy related venous thromboembolism in anticoagulant factor deficient women: Implications for prophylaxis.
Friederich PW, Sanson BJ, Simioni P, et al.
Ann Intern Med. 1996;125:955-960.
Description: This was a retrospective study of female family members of patients with a history of VTE and established protein C, protein S, or antithrombin deficiency demonstrating an increased risk of VTE during pregnancy in women with an anticoagulant factor deficiency compared with women without a deficiency (hazard ratio 8.0; absolute risk 4.1% versus 0.5%).
PubMed citation number: 8967705
Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism.
Pabinger I, Grafenhofer H, Kyrle P, et al.
Blood. 2002;100:1060-1062.
Description: This was a retrospective study of women with a prior history of VTE that demonstrated an increased risk of recurrent VTE during pregnancy compared with recurrence outside of pregnancy (10.9% per 100 patient-years compared with 3.7% per 100 patient-years, respectively; relative risk 3.5).
PubMed citation number: 12130523
The above 3 studies collectively provide a framework on which to make decisions regarding VTE prophylaxis in pregnant women with heritable thrombophilias and provide a basis for future randomized prospective studies addressing VTE prophylaxis in pregnant women with thrombophilia and no history of prior VTE.
Fetal thrombocytopenia and its relationship to maternal thrombocytopenia.
Burrows RF, Kelton JG.
N Engl J Med. 1993;329:1463-1466.
Description: This was a cross-sectional study demonstrating that the absolute risk of clinically significant thrombocytopenia in neonates born to mothers with incidental thrombocytopenia or idiopathic thrombocytopenic purpura is low, whereas neonates of mothers with platelet alloantibodies are at high risk of severe thrombocytopenia and bleeding events.
PubMed citation number: 8413457
Incidentally detected thrombocytopenia in healthy mothers and their infants.
Burrows RF, Kelton JG.
N Engl J Med. 1988;319:142-145.
Description: This was a prospective study demonstrating that mild incidental thrombocytopenia is a common finding during pregnancy (8.3% of all pregnancies) and confers no risk of significant thrombocytopenia to the fetus.
PubMed citation number: 3386694
The above 2 studies are important, because they form the basis for the argument that special obstetrical interventions such as cesarean section or funipuncture are unnecessary in women with incidental thrombocytopenia and idiopathic thrombocytopenic purpura.
Treatment
Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies).
Rai R, Cohen H, Dave M, and Regan L.
BMJ. 1997;314:253-257.
Description: This was a randomized, controlled trial that established aspirin and unfractionated heparin as the standard of care in preventing fetal loss in pregnant women with a history of recurrent miscarriages associated with antiphospholipid antibodies.
PubMed citation number: 9022487
Safety of withholding heparin in pregnant women with a history of venous thromboembolism: Recurrence of Clot in This Pregnancy Study Group.
Brill-Edwards P, Ginsberg JS, Gent M, et al.
N Engl J Med. 2000;343:1439-1444.
Description: This was a prospective study of pregnant women with a prior history of VTE demonstrating that the absolute risk of antepartum VTE was low despite no prophylactic heparin during this time (2.4% of the entire group). However, the risk was higher for women with a prior history of idiopathic VTE and/or VTE associated with a known heritable thrombophilia (5.9%) compared with women without a known heritable thrombophilia and a prior VTE that occurred in association with a temporary risk factor (0%). All patients received postpartum prophylaxis for 4 to 6 weeks.
PubMed citation number: 11078768
Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin.
Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS.
Thromb Haemost. 2000;83:693-697.
Description: Although not randomized, this study provides compelling evidence that low-molecular-weight heparin prophylaxis of women with a history of recurrent pregnancy loss and an inherited thrombophilia leads to a significantly increased percentage of live births.
PubMed citation number: 10823264
Low molecular weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder.
Gris JC, Mercier E, Quere I, et al.
Blood. 2004;103:3695-3699.
Description: This randomized trial demonstrates that low-molecular-weight heparin (enoxaparin) is significantly superior to aspirin for preventing fetal loss in women with a history of 1 fetal loss beyond 10 weeks gestation and documented heritable thrombophilia (factor V Leiden mutation, prothrombin gene mutation, protein S deficiency).
PubMed citation number: 14739212
Anticoagulation of pregnant women with mechanical heart valves.
Ginsberg JS, Chan WS, Bates SM, Kaatz S.
Arch Intern Med. 2003;163:694-698.
Description: This study: (1) challenges the warning issued by Aventis that enoxaparin is not recommended for pregnant women with prothetic heart valves due to a risk of valve thrombosis; (2) challenges the precaution that pregnant women who have received enoxaparin (an agent that does not cross the placenta) have delivered infants with congenital anomalies; and (3) highlights the need for properly designed clinical trials for this group of patients.
PubMed citation number: 12639202
Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study.
Koshy M, Burd L, Wallace D, Moawad A, Baron J.
N Engl J Med. 1988;319:1447-1452.
Description: This study demonstrated that perinatal fetal outcomes were no different between women assigned to prophylactic red blood cell transfusion and those who were not, dispelling the long-regarded belief that prophylactic transfusions are essential in pregnant women with sickle cell disease.
PubMed citation number: 3054555
Review
Management of venous thromboembolism during pregnancy.
Ginsberg JS, Bates SM.
J Thromb Haemost. 2003;1:1435-1442.
PubMed citation number: 12871278
Use of antithrombotic agents during pregnancy.
Ginsberg JS, Greer I, Hirsh J.
Chest. 2001;119:122S-131S.
PubMed citation number: 11157646
Clinical management of thrombophilia related placental vascular complications.
Brenner B.
Blood. 2004;103:4003-4009.
PubMed citation number: 14962907
Thrombotic microangiopathy during pregnancy.
McCrae KR, Cines DB.
Semin Hematol. 1997;34:148-158.
PubMed citation number: 9109217
Antiphospholipid syndrome: obstetric diagnosis, management, and controversies.
Branch DW, Khamashta MA.
Obstet Gynecol. 2003;101:1333-1344.
PubMed citation number: 12798544
How we manage venous thromboembolism during pregnancy.
Bates SM, Ginsberg JS.
Blood. 2002;100:3470-3478.
PubMed citation number: 12393666
Anticoagulation of pregnant women with mechanical heart valves.
Chan WS, Anand S, Ginsberg JS.
Arch Intern Med. 2000;160:191-196.
Description: This study provides a thorough review of the effectiveness and hazards of several anticoagulation strategies for pregnant women with prosthetic heart valves.
PubMed citation number: 10647757