Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study

Abstract Background Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to...

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Main Authors: Tomoyo Saito, Mineji Hayakawa, Osamu Kumano, Yoshinori Honma, Mone Murashita, Jun Kato, Syouki Fukui, Masaki Takahashi, Yuki Takahashi, Takumi Tsuchida, Asumi Mizugaki, Shuhei Takauji, Mariko Hayamizu, Tomonao Yoshida, Kenichi Katabami, Takeshi Wada, Kunihiko Maekawa
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Journal of Intensive Care
Subjects:
Online Access:https://doi.org/10.1186/s40560-023-00701-3
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author Tomoyo Saito
Mineji Hayakawa
Osamu Kumano
Yoshinori Honma
Mone Murashita
Jun Kato
Syouki Fukui
Masaki Takahashi
Yuki Takahashi
Takumi Tsuchida
Asumi Mizugaki
Shuhei Takauji
Mariko Hayamizu
Tomonao Yoshida
Kenichi Katabami
Takeshi Wada
Kunihiko Maekawa
author_facet Tomoyo Saito
Mineji Hayakawa
Osamu Kumano
Yoshinori Honma
Mone Murashita
Jun Kato
Syouki Fukui
Masaki Takahashi
Yuki Takahashi
Takumi Tsuchida
Asumi Mizugaki
Shuhei Takauji
Mariko Hayamizu
Tomonao Yoshida
Kenichi Katabami
Takeshi Wada
Kunihiko Maekawa
author_sort Tomoyo Saito
collection DOAJ
description Abstract Background Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes. Methods This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80–120%), and the upper group (> 120%). Results The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups. Conclusions Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients. Trial registration: Not applicable.
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spelling doaj.art-b45e57931d5e4a6ab8bbed1dc409f9262023-11-19T12:30:27ZengBMCJournal of Intensive Care2052-04922023-11-011111910.1186/s40560-023-00701-3Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational studyTomoyo Saito0Mineji Hayakawa1Osamu Kumano2Yoshinori Honma3Mone Murashita4Jun Kato5Syouki Fukui6Masaki Takahashi7Yuki Takahashi8Takumi Tsuchida9Asumi Mizugaki10Shuhei Takauji11Mariko Hayamizu12Tomonao Yoshida13Kenichi Katabami14Takeshi Wada15Kunihiko Maekawa16Emergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalHealth and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)Emergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalEmergency and Critical Care Center, Hokkaido University HospitalAbstract Background Unfractionated heparin (UFH) is primarily monitored using activated partial thromboplastin time (APTT). However, the recent introduction of anti-activated factor X (anti-Xa) activity testing has provided a direct evaluation of Xa inhibition by anticoagulants. This study aimed to investigate discrepancies between APTT and anti-Xa activity during UFH monitoring in critically ill patients and explore their underlying causes. Methods This study analyzed 271 pairs of laboratory test results from blood samples of 99 critically ill patients receiving continuous intravenous UFH. Theoretical APTT values were calculated using fitted curve equations from spiked sample measurements with anti-Xa activity. Samples were categorized into three groups based on the measurement of the APTT/theoretical APTT ratio: the lower group (< 80%), the concordant group (80–120%), and the upper group (> 120%). Results The overall concordance rate between APTT and anti-Xa activity was 45%, with a 55% discrepancy rate. The lower group frequently showed apparent heparin overdoses, while coagulation factor activities in the lower and upper groups were higher and lower, respectively, than those in the concordant group. Particularly, the lower group exhibited higher factor VIII activity levels than the upper and concordant groups. Conclusions Discrepancies between APTT and anti-Xa activity were frequently observed, influenced by changes in coagulation factors activity levels. The lower and upper groups were classified as pseudo-heparin-resistant and coagulopathy types, respectively. Accurate monitoring of heparin in critically ill patients is crucial, especially in cases of pseudo-heparin resistance, where APTT values may wrongly indicate inadequate heparin dosing despite sufficient anti-Xa activity. Understanding these discrepancies is important for managing heparin therapy in critically ill patients. Trial registration: Not applicable.https://doi.org/10.1186/s40560-023-00701-3Critical illnessFactor VIIIFactor XaHeparinPartial thromboplastin timePseudo-heparin resistance
spellingShingle Tomoyo Saito
Mineji Hayakawa
Osamu Kumano
Yoshinori Honma
Mone Murashita
Jun Kato
Syouki Fukui
Masaki Takahashi
Yuki Takahashi
Takumi Tsuchida
Asumi Mizugaki
Shuhei Takauji
Mariko Hayamizu
Tomonao Yoshida
Kenichi Katabami
Takeshi Wada
Kunihiko Maekawa
Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
Journal of Intensive Care
Critical illness
Factor VIII
Factor Xa
Heparin
Partial thromboplastin time
Pseudo-heparin resistance
title Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
title_full Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
title_fullStr Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
title_full_unstemmed Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
title_short Variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti-Xa activity for heparin monitoring: a retrospective observational study
title_sort variation in coagulation factor activity levels cause discrepancies between activated partial thromboplastin time and anti xa activity for heparin monitoring a retrospective observational study
topic Critical illness
Factor VIII
Factor Xa
Heparin
Partial thromboplastin time
Pseudo-heparin resistance
url https://doi.org/10.1186/s40560-023-00701-3
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