Hereditary antithrombin deficiency and venous thrombosis in pregnancy-results of a retrospective multicenter study

The optimal anticoagulant regimen to prevent pregnancy-related venous thrombosis (VT) in women with antithrombin (AT) deficiency is unknown.

This study aims to identify optimal doses of low-molecular-weight heparin (LMWH) to prevent pregnancy-related VT and to investigate if AT concentrate peripartum could reduce postpartum VT in women with AT deficiency.

This retrospective study includes 115 pregnancies in 57 women with subclassified AT deficiency treated with LMWH in Denmark, Norway, and Sweden (1991-2017).

In pregnancies with high-risk AT deficiency, LMWH doses of <5000 IU/24 h, 5000 to 12 500 IU/24 h, and >12 500 IU/24 h revealed different VT risks (P = .02). The hazard ratios for VT were 1.0 (reference), 0.5 (95% CI [0.1, 2.3]), and 0 (95% CI [0, ∞]), correspondingly. Of the additional risk factors, only previous VT reached statistical significance. In 100 pregnancies with high-risk AT deficiency, 15 VTs occurred in contrast to none in the 15 pregnancies with low-/intermediate-risk AT deficiency. Six of the 12 antepartum VTs occurred before week 9. All had a prior VT, and 5 were hormone-associated. Of these 5, 1 had received a LMWH dose of 7500 IU/24 h and 3 had received a LMWH dose of 10 000 IU/24 h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in 1 VT (1.5%). Without AT concentrate (8 pregnancies), 2 VTs occurred (25%; 95% CI [2, 61]). Peripartum hemorrhage (>1000 mL) occurred in 8 (11%) term pregnancies. Six had received therapeutic LMWH doses.

In high-risk AT deficiency pregnancies with previous VT, our results support prophylaxis with high prophylactic doses of LMWH from confirmed pregnancy. Hence, AT concentrate should be given peri-/postpartum.