Thrombophilias During Pregnancy

Contributor: John V. Dacus, MD  
Last Update: 1/28/2015

Thromboembolism is the leading cause of maternal death in Western Countries(1).  The presence of inherited and acquired thrombophilias (antiphospholipid antibodies) are risk factors for thromboembolic events.  Acquired thrombophilias have been demonstrated to be associated with adverse pregnancy outcomes: severe early onset preeclampsia (less than 34 weeks gestation), stillbirth, and recurrent abortion.  The obstetric literature is less clear in demonstrating an association of inherited thrombophilias and complications of pregnancy (recent literature suggests no correlation)(2).

In individuals with a prior thromboembolic event and found to be positive for anti-thrombin III deficiency, homozygous factor V Leiden, homozygous prothrombin 20210 mutation,   compound heterozygote for factor V Leiden and prothrombin 20210 mutation or acquired thrombophilia, therapeutic heparinization is recommended during pregnancy with therapeutic heparin or Coumadin postpartum for 6 to 18 weeks(3).  Referral postpartum to a hematologist is suggested.  In minor inherited thrombophilias, prophylactic antepartum  and postpartum anticoagulation is warranted following a prior thromboembolism(4).

In patients with an inherited minor thrombophilia and no prior personal or 1st degree family history of a thromboembolic event, no antepartum anticoagulation is warranted.  Postpartum prophylactic anticoagulation is offered for 6 weeks.  If there is a 1st degree relative with a history of thromboembolism, the patient with an inherited lesser thrombophilia should receive prophylactic antepartum and prophylactic postpartum anticoagulation for 6 weeks.

There is a convincing body of evidence that the antiphospholipid antibody syndrome is associated with arterial and venous thromboembolism, and adverse pregnancy outcome.  The antiphospholipid antibody syndrome requires the presence of lupus anticoagulant and/or anticardiolipin antibodies of the IgG or IgM variety with moderate or high titers, or B2 glycoprotein-1 antibodies with medium to high titers confirmed by appropriate testing on at least two occasions 12 weeks apart in association with a thromboembolic event or adverse pregnancy outcome.  Several studies have shown that the use of prophylactic heparin plus low dose aspirin decreases fetal loss rate (5).

In patients with a history of a thromboembolic event and a negative thrombophilia work-up, three scenarios are possible.  If the thrombotic event was associated with a non-recurring risk factor (i.e. bed rest following orthopedic surgery), anticoagulation may be withheld during pregnancy and given in the postpartum period(3).  However, if the thrombotic event was not associated with any possible precipitating cause or the cause is recurrent (i.e. prior event occurred while patient was pregnant), prophylactic heparin and postpartum anticoagulation are reasonable options(3).

Conclusions:

1. Pregnant patients with a history of a thromboembolic event and a major inherited thrombophilia or acquired thrombophilia should receive therapeutic anticoagulation  during pregnancy and the puerperium for 6 weeks and referral to hematologist for  possible life-long anticoagulation.
2. Pregnant patients with a history of a thromboembolic event and a lesser inherited thrombophilia should receive prophylactic anticoagulation during pregnancy and  postpartum for six weeks.
3. Patients with adverse pregnancy outcomes and acquired thrombophilia will benefit from anticoagulation during pregnancy (probably prophylactic) and low  dose aspirin.  Postpartum prophylactic anticoagulation is reasonable for 6 weeks.
4. Patients with adverse pregnancy outcomes and inherited lesser thrombophilia  (no history of thromboembolic event) have not been shown in prospective studies to  benefit from heparinization during pregnancy.  Further studies are needed before  this can be considered the standard of care.  Consider postpartum prophylactic  anticoagulation following delivery.
5.  Patients with inherited minor thrombophilias and 1st degree relatives, under 50 years of age, with a prior thromboembolic event should receive prophylactic antepartum and prophylactic postpartum anticoagulation for 6 weeks.
6.  Patients with a prior thrombotic event without a precipitating cause and a negative  thrombophilia work-up, should receive prophylactic heparinization during pregnancy and prophylactic anticoagulation postpartum for 6 weeks.
7. In patients with a prior thrombotic event with a possible recurrent cause (i.e. patient on OCP’s when event occurred) and a negative thrombophilia work-up, prophylactic heparinization during pregnancy and prophylactic anticoagulation postpartum should be considered.
8. In patients with a prior thrombotic event with a non-recurring precipitating cause  (i.e., prior bed rest with orthopedic surgery) and a negative thrombophilia work-up,  only anticoagulation in the postpartum period seems appropriate.

References

1. Dizon-Townson D, Shak SS, Phelan JP. Thromboembolic disease. Crit Care  Obstet  2004; Blackwell Pub Co: 275-97.
2. Branch D.W.  The truth about inherited thrombophilias and pregnancy.  Obstet Gynecol 2010; 115: 2-4.
3. Lockwood CJ. Inherited thrombophilias in pregnant patients: detection and  treatment paradigm.  Obstet Gynecol 2002; 99: 333-41.
4. Lindqvist PG, Svensson PJ, Marsal K, et l.  Activated protein C resistance  (FV:Q506) and pregnancy.  Thromb Haemost 1999; 81:532 – 37.
5. Pabinger I, Grafenhofer H. Anticoagulation during pregnancy.  Semin Thromb  Hemost 2003; 29: 633-38.
6. Chandramouli NB, Rodger GM. Management of thrombosis in women with  antiphospholipid syndrome.  Clin Obstet Gynecol 2001; 44: 36-47.
7. Practice bulletin. Thromboembolism in pregnancy. Obstet Gynecol 2011; 118:718-728.
8. Practice bulletin. Inherited Thrombophilias in pregnancy. Obstet Gynecol 2011; 118:730-740.