β-Antithrombin, subtype of antithrombin deficiency and the risk of venous thromboembolism in hereditary antithrombin deficiency
A family cohort study
Hereditary antithrombin deficiency is associated with a high incidence of venous thromboembolism (VTE), but VTE risk differs between families. Beta-antithrombin is reported to be the most active isoform of antithrombin in vivo. Whether β-antithrombin activity and subtypes in antithrombin deficiency have impact on VTE risk has not been investigated outside the proband setting. We performed a retrospective family cohort study to investigate whether subtypes of antithrombin deficiency or β-antithrombin levels are associated with the risk of first or recurrent VTE. Eighty-one subjects from 21 families were included, of which 52 were antithrombin deficient. Βeta-antithrombin levels were decreased in most type I and type IIPE subjects, but normal levels were found in all subtypes of antithrombin deficiency. The annual incidence of VTE in antithrombin-deficient family members was 1.24%, 95%CI: 0.72–1.99%, in low β-antithrombin 1.36% (95%CI: 0.76–2.25%) and in normal β-antithrombin 0.79% (95%CI: 0.10–2.77). The annual incidence of recurrence in family members was 3.1% (95%CI: 0.9–7.1%). Duration of anticoagulation had an impact on recurrence risk: In family members annual recurrence with fixed duration was 10% (95%CI: 2.1–29.2%), with indefinite duration 1.5% (95%CI: 0.2–5.4%), p < 0.05. Beta-antithrombin levels were not associated with the risk for first or recurrent VTE in antithrombin deficient subjects. Conclusions: In this high-risk antithrombin-deficient population, both subjects with low and normal plasma β-antithrombin activity had high risks of first and recurrent VTE. This puts the importance of β-antithrombin into question. Long-term anticoagulation is warranted in antithrombin-deficient VTE patients.
|Keywords||Antithrombin deficiency, Natural anticoagulants, Pregnancy, Venous thrombosis, β-Antithrombin|
|Persistent URL||dx.doi.org/10.1016/j.thromres.2018.06.004, hdl.handle.net/1765/108930|
|Journal||Thrombosis Research: vascular obstruction, hemorrhage and hemostasis|
Croles, F.N, Mulder, R. (René), Mulder, A.B, Lukens, M.V, & Meijer, K. (Karina). (2018). β-Antithrombin, subtype of antithrombin deficiency and the risk of venous thromboembolism in hereditary antithrombin deficiency. Thrombosis Research: vascular obstruction, hemorrhage and hemostasis, 168, 47–52. doi:10.1016/j.thromres.2018.06.004