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

Abstract

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

Objectives: 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.

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

Results: In pregnancies with high-risk AT deficiency, LMWH doses<5000 IU/24h, 5000-12500 IU/24h and>12500 IU/24h revealed different VT risks (p=0.02). The hazard ratio for VT was 1.0 (reference), 0.5 (95% confidence interval; CI [0.1, 2.3] and 0 (95% CI [0,∞]), correspondingly. Of additional risk factors, only previous VT reached statistical significance. In the 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, five were hormone-associated. Of these five, one had received LMWH 7500- and three 10000 IU/24h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in one VT (1.5%). Without AT concentrate (8 pregnancies) two VTs occurred (25%, CI [2, 61]). Peripartum haemorrhage (>1000 mL) occurred in 8 (11%) term pregnancies. Six had received therapeutic LMWH doses.

Conclusion: In high-risk AT deficiency pregnancies with previous VT, our results support prophylaxis with high prophylactic doses of LMWH from confirmed pregnancy.