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

Ingunn Dybedal; Nina Iversen; Anne Flem Jacobsen; Line Bjørge; Roza Chaireti; Carola Elisabeth Henriksson; Nina Hagenrud Schultz; Anne Mette Hvas; Per Morten Sandset; Harald Weedon-Fekjær; Katarina Bremme; Ulrich Abildgaard

doi:10.1016/j.jtha.2025.03.001

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

J Thromb Haemost. 2025 Mar 12:S1538-7836(25)00138-2. doi: 10.1016/j.jtha.2025.03.001. Online ahead of print.

Affiliations

¹ Department of Haematology, Oslo University Hospital, Oslo, Norway; Department of Pharmacology, Clinical Research Unit, Oslo University Hospital, Oslo, Norway. Electronic address: idybedal@ous-hf.no.
² Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
³ Department of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Center for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway.
⁵ Department of Haematology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
⁷ Department of Haematology, Oslo University Hospital, Oslo, Norway.
⁸ Faculty of Health, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
⁹ Department of Haematology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁰ Oslo Center for Biostatistics and Epidemiology, Research Support Services, Oslo University Hospital, Oslo, Norway.
¹¹ Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; The Women's Health, Medical Unit Pregnancy and Delivery, Karolinska University Hospital, Stockholm, Sweden.

PMID: 40086756
DOI: 10.1016/j.jtha.2025.03.001

Abstract

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

Objectives: 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.

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 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.

Conclusion: 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.

Keywords: antithrombin concentrate; antithrombin deficiency; low-molecular-weight heparin; pregnancy; venous thrombosis.