According to a study published in Thrombosis Research, reduced antithrombin activity in individuals with antithrombin deficiency may cause significantly reduced antifactor Xa levels, which may lead in turn to insufficient prophylactic treatment of thromboembolism with standard heparin doses.

The cross-sectional, retrospective family cohort study investigated the relationship between antithrombin deficiency and anti-Xa activity measurements from plasma samples spiked with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The activities of antithrombin and beta-antithrombin were also measured.

Plasma samples from 34 individuals with antithrombin deficiency and 17 family controls were spiked with UFH and LMWH that targeted an anti-Xa activity of 0.8 IU/mL. Anti-Xa median activity (0.57 IU/mL [range, 0.30-0.74] vs 0.81 IU/mL [range, 0.71-0.89]; P <.001) and mean recovery (69% [38%-93%] vs 103% [range, 89%-111%]) with LWMH were lower in samples from antithrombin-deficient patients compared with control samples. Expected anti-Xa measurements after LMWH spiking were found in all control samples but in only 8 of 34 antithrombin-deficient samples.

Median anti-Xa activity was also lower in samples from individuals with antithrombin deficiency compared with control samples after addition of UFH (0.51 IU/mL [range, 0.32-0.63] vs 0.79 IU/mL [range, 0.64-0.93], P <.001). Expected anti-Xa measurements after UFH spiking were found in all control samples but in only 1 of 22 antithrombin-deficient samples.

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Antithrombin and beta-antithrombin activity were correlated with anti-Xa activity of UFH (Spearman’s rho [R] = 0.77, P <.001; R = 0.59, P <.001) and of LMWH (R = 0.66, P <.001; R = 0.56, P <.001).

The authors concluded that “knowledge of inherited antithrombin deficiency causing a reduced anticoagulant effect of heparins as measured by anti-Xa assays, in combination with the clear prothrombotic phenotype of antithrombin deficiency,” supports measuring anti-Xa activity in patients with antithrombin deficiency receiving treatment with heparins. Additionally, they suggested that “doses of LMWH should be adjusted to achieve the target range in order to achieve a sufficient antithrombotic effect.”

Reference

1. Croles FN, Lukens MV, Mulder R, de Maat MPM, Mulder AB, Meijer K. Monitoring of heparins in antithrombin-deficient patients [published online January 15, 2019]. Thromb Res. doi: 10.1016/j.thromres.2019.01.007