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Monitoring of heparins in antithrombin-deficient patients

Croles, F. N., Lukens, M. V., Mulder, R., de Maat, M. P. M., Mulder, A. B. & Meijer, K., Mar-2019, In : Thrombosis Research. 175, p. 8-12 5 p.

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  • Monitoring of heparins in antithrombin-deficient patients

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DOI

Introduction: Heparins exert their anticoagulant effect through activation of antithrombin. Whether antithrombin deficiency leads to clinically relevantly reduced anti-Xa activity of heparins is unknown. We investigated the relation between antithrombin deficiency and anti-Xa activity measurements of plasma samples spiked with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).

Materials and methods: Plasma samples from 34 antithrombin-deficient subjects and 17 family controls were spiked with UFH and LMWH (nadroparin) aimed to correspond with an anti-Xa activity of 0.8 IU/mL. Antithrombin, beta-antithrombin and anti-Xa activities were measured.

Results: Mean anti-Xa activity with LWMH was 0.55 IU/mL (0.30-0.74) (recovery 69%, 38-93%) in antithrombin-deficient subjects and 0.82 (0.71-0.89) IU/mL in controls (recovery 103%, 89-111%). Expected anti-Xa measurements after LMWH spiking were found in 17/17 non-deficient subjects and in 8/34 antithrombin-deficient subjects. Anti-Xa measurements in the expected range (0.6-1.0 IU/mL) after UFH spiking were found in 17/17 non-deficient subjects and in 1/22 antithrombin-deficient subjects. Antithrombin activity correlated with anti-Xa activity of UFH (R= 0.77) and LMWH (R= 0.66). Mixing studies of pooled normal plasma and antithrombin-deficient plasma showed that anti-Xa recovery was linearly reduced with antithrombin activity decreasing below 100%.

Conclusions: Reduced antithrombin activity causes significantly reduced anti-Xa levels. Standard LWMH- or UFH-doses are likely to lead to under treatment in antithrombin-deficient individuals.

Original languageEnglish
Pages (from-to)8-12
Number of pages5
JournalThrombosis Research
Volume175
Publication statusPublished - Mar-2019

    Keywords

  • Antithrombin III deficiency, Heparin, Low-molecular-weight heparin, SERPINC1 gene, Anti-Xa measurements, BETA-ANTITHROMBIN, VENOUS THROMBOEMBOLISM, UNFRACTIONATED HEPARIN, RISK, HEREDITARY, THROMBOSIS, PREGNANCY, AFFINITY, GLYCOSYLATION, MANAGEMENT

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