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Plasma levels of enoxaparin oligosaccharides, antifactor-Xa and thrombin generation in patients undergoing haemodialysis

Citation

Batt, TJ and Lincz, LF and Prasad, R and Patel, RP and Shastri, M and Lioufas, N and Smith, AG and Jose, MD, Plasma levels of enoxaparin oligosaccharides, antifactor-Xa and thrombin generation in patients undergoing haemodialysis, Blood Coagulation and Fibrinolysis, 31, (2) pp. 152-159. ISSN 0957-5235 (2020) [Refereed Article]

Copyright Statement

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

DOI: doi:10.1097/MBC.0000000000000892

Abstract

Lowmolecular weight heparins are used during haemodialysis for thromboprophylaxis of the dialysis circuit, with plasma antifactor-Xa (anti-Xa) activity used as a surrogate measure for effective anticoagulation. However, this pharmacokinetic parameter does not always correlate with pharmacodynamic effects in patients. The aim of this study was to investigate the relationship between actual plasma levels of the lowmolecular weight heparins enoxaparin, anti-Xa activity, and global coagulation measurement of thrombin generation during haemodialysis. Blood was analysed from 16 adult patients with end-stage kidney disease at 0, 2, 4 h, and at completion of 31 dialysis sessions where single fixed doses of 20 (n U 3), 40 (n U 16), 60 (n U 6), or 80 (n U 6)mg of enoxaparin (equating to 0.23–1.07mg/kg) were used as thromboprophylaxis. Plasma enoxaparin oligosaccharides [degree of polymerization (dp)6–dp16] were measured by high-performance size exclusion chromatography, anti-Xa activity by colourimetric assay, and thrombin generation by calibrated automated thrombogram. Plasma enoxaparin fragments were undetectable at the beginning of each dialysis, peaked at 2 h to levels that correlated with dose (r U 0.68, P< 0.001) then remained relatively stable. In contrast, therapeutic anti-Xa levels achieved at 2 h in 18 cases (58%) quickly dropped to only six cases (19%) at the end of dialysis, by which time thrombin generation had also recovered in 81% of patients. Statistical modelling revealed a threshold value of anti-Xa at 0.53 IU/ml that supressed thrombin generation to 15.28% of baseline (P< 0.001). Despite loss of anticoagulant activity in themajority of patients, plasma levels of enoxaparin oligosaccharides remained detectable and relatively unchanged throughout dialysis.

Item Details

Item Type:Refereed Article
Keywords:anticoagulation, antifactor-Xa, enoxaparin, enoxaparin fragments, haemodialysis, thrombin generation
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Clinical pharmacology and therapeutics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Patel, RP (Dr Rahul Patel)
UTAS Author:Shastri, M (Mr Madhur Shastri)
UTAS Author:Jose, MD (Professor Matthew Jose)
ID Code:139812
Year Published:2020
Deposited By:Pharmacy
Deposited On:2020-07-07
Last Modified:2020-08-11
Downloads:0

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