Publication

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.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Croles, F. N., Lukens, M. V., Mulder, R., de Maat, M. P. M., Mulder, A. B., & Meijer, K. (2019). Monitoring of heparins in antithrombin-deficient patients. Thrombosis Research, 175, 8-12. https://doi.org/10.1016/j.thromres.2019.01.007

Author

Croles, Frederik Nanne ; Lukens, Michael V. ; Mulder, Rene ; de Maat, Moniek P. M. ; Mulder, Andre B. ; Meijer, Karina. / Monitoring of heparins in antithrombin-deficient patients. In: Thrombosis Research. 2019 ; Vol. 175. pp. 8-12.

Harvard

Croles, FN, Lukens, MV, Mulder, R, de Maat, MPM, Mulder, AB & Meijer, K 2019, 'Monitoring of heparins in antithrombin-deficient patients', Thrombosis Research, vol. 175, pp. 8-12. https://doi.org/10.1016/j.thromres.2019.01.007

Standard

Monitoring of heparins in antithrombin-deficient patients. / Croles, Frederik Nanne; Lukens, Michael V.; Mulder, Rene; de Maat, Moniek P. M.; Mulder, Andre B.; Meijer, Karina.

In: Thrombosis Research, Vol. 175, 03.2019, p. 8-12.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Croles FN, Lukens MV, Mulder R, de Maat MPM, Mulder AB, Meijer K. Monitoring of heparins in antithrombin-deficient patients. Thrombosis Research. 2019 Mar;175:8-12. https://doi.org/10.1016/j.thromres.2019.01.007


BibTeX

@article{2adee44ed6304d10a300cd7df8690d03,
title = "Monitoring of heparins in antithrombin-deficient patients",
abstract = "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.",
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",
author = "Croles, {Frederik Nanne} and Lukens, {Michael V.} and Rene Mulder and {de Maat}, {Moniek P. M.} and Mulder, {Andre B.} and Karina Meijer",
year = "2019",
month = "3",
doi = "10.1016/j.thromres.2019.01.007",
language = "English",
volume = "175",
pages = "8--12",
journal = "Thrombosis Research",
issn = "0049-3848",
publisher = "PERGAMON-ELSEVIER SCIENCE LTD",

}

RIS

TY - JOUR

T1 - Monitoring of heparins in antithrombin-deficient patients

AU - Croles, Frederik Nanne

AU - Lukens, Michael V.

AU - Mulder, Rene

AU - de Maat, Moniek P. M.

AU - Mulder, Andre B.

AU - Meijer, Karina

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - Antithrombin III deficiency

KW - Heparin

KW - Low-molecular-weight heparin

KW - SERPINC1 gene

KW - Anti-Xa measurements

KW - BETA-ANTITHROMBIN

KW - VENOUS THROMBOEMBOLISM

KW - UNFRACTIONATED HEPARIN

KW - RISK

KW - HEREDITARY

KW - THROMBOSIS

KW - PREGNANCY

KW - AFFINITY

KW - GLYCOSYLATION

KW - MANAGEMENT

U2 - 10.1016/j.thromres.2019.01.007

DO - 10.1016/j.thromres.2019.01.007

M3 - Article

VL - 175

SP - 8

EP - 12

JO - Thrombosis Research

JF - Thrombosis Research

SN - 0049-3848

ER -

ID: 77240679