Abstract

Pregnant women with primary hypercoagulable states have an increased risk of recurrent fetal loss, fetal growth retardation, preclampsia, and placental abruption, as well as thromboembolism in both the antepartum and postpartum periods. Conditions that have been associated with adverse pregnancy outcomes include inherited gene mutation disorders such as Factor V Leiden G1691A (FVL); prothrombin gene mutation G20210A (PGM); hyperhomocysteinemia with C677T mutation (MTHFR); deficiencies of protein S (PS), protein C (PC), antithrombin III (ATIII); and anticardiolipin antibodies/lupus anticoagulants (LA). Screening by obstetricians for these disorders has led to an increase in diagnosis yet there are no established guidelines and therapeutic interventions are variable. A retrospective chart review was conducted on 59 women and 197 pregnancies (1–12 per pt) in whom primary hypercoagulable state was diagnosed: FVL (n=7), PGM (n=11), MTHFR (n=3), ATIII (n=2), PC (n=1), PS (n=8), LA (n=10), and those with more than one thrombophilic risk (TR) (n=12) or lupus (n=2). Of the 197 pregnancies, only 106 (54%) were carried to term in 50 pts (85%). Of the remaining 91 pregnancies, there were 16 terminations, 5 ectopic pregnancies and 4 preterm live births. 66 fetal losses occurred: 45 in the first trimester (26 with single TR/19 with >1 TR), 19 in the 2nd–3rd trimester (14 with single TR/5 with > 1 TR) and 2 unknown. See Table for risk of fetal loss by class of hypercoagulable state. Venous thromboembolism occurred in 8/106 (8%) of term pregnancies, including 5 postpartum. Of women with previous fetal losses, management with anticoagulation (A/C) subsequently was utilized in 20 pregnancies: 9 low molecular weight heparin (LMWH), 6 LMWH+aspirin (ASA), 3 heparin (H), 1 ASA, and 1 H+ASA. 18/20(90%) of these pregnancies resulted in live term births; 1 loss due to intracranial hemorrhage at 27 weeks in a patient on L+ASA. Compared to 146 pregnancies untreated with A/C, successful completion of pregnancy was significantly greater on A/C, 90% vs. 58% (p=0.006).

Conclusions: Fetal losses secondary to TR occurred in both the first and late trimesters in high proportion of pregnancies in women with hypercoagulable states. Outcomes may be improved with the use of A/C therapy.

Table -

Risk of Fetal Loss by Class of Hypercoagulable State

LAPGMMTHFRPSFVLATIIIFVL/other
Trimester1 9/38 (24%) 7/44 (16%) 3/9 (33%) 3/27 (11%) 1/27 (4%) 2/5 (40%) 17/42 (40%) 
Trimester 2–3 5/38 (13%) 1/36 (3%) 0% 5/16 (31%) 2/27 (7%) 1/5 (20%) 4/44 (9%) 
LAPGMMTHFRPSFVLATIIIFVL/other
Trimester1 9/38 (24%) 7/44 (16%) 3/9 (33%) 3/27 (11%) 1/27 (4%) 2/5 (40%) 17/42 (40%) 
Trimester 2–3 5/38 (13%) 1/36 (3%) 0% 5/16 (31%) 2/27 (7%) 1/5 (20%) 4/44 (9%) 

Disclosures: Use of LMWH in pregnancy.; Alice J. Cohen M.D.: speaker - Sanofi Aventis.

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