Abstract
Thromboelastography is increasingly utilized in the management of bleeding and thrombotic complications where heparin management remains a cornerstone. This study assessed the feasibility of the cartridge-based TEG ® 6s system (Haemonetics Corp., Braintree, Massachusetts, United States) to monitor and quantify the effect of unfractionated and low-molecular-weight heparin (UFH and LMWH). Blood samples from healthy donors were spiked with UFH ( n = 23; 0–1.0 IU/mL) or LMWH (enoxaparin; n = 22; 0–1.5 IU/mL). Functional fibrinogen maximum amplitude (CFF.MA), RapidTEG activated clotting time (CRT.ACT), and kaolin and kaolin with heparinase reaction time (CK.R and CKH.R) were evaluated for their correlation with heparin concentrations, as well as the combination parameters ΔCK.R − CKH.R, ratio CK.R/CKH.R, and ratio CKH.R/CK.R. Nonlinear mixed-effect modelling was used to study the relationship between concentrations and parameters, and Bayesian classification modelling for the prediction of therapeutic ranges. CK.R and CRT.ACT strongly correlated with the activity of LMWH and UFH ( p < 0.001). Using combination parameters, heparin activity could be accurately quantified in the range of 0.05 to 0.8 IU/mL for UFH and 0.1 to 1.5 IU/mL for LMWH. CRT.ACT was able to quantify heparin activity at higher concentrations but was only different from the reference range ( p < 0.05) at >0.5 IU/mL for UFH and >1.5 IU/mL for LMWH. Combination parameters classified blood samples into subtherapeutic, therapeutic, and supratherapeutic heparin ranges, with an accuracy of >90% for UFH, and >78% for LMWH. This study suggests that TEG 6s can effectively monitor and quantify heparin activity for LMWH and UFH. Additionally, combination parameters can be used to classify blood samples into therapeutic ranges based on heparin activity.
Highlights
Readings for the CK assay were within reference range limits for therapeutic levels of heparin, and higher Unfractionated heparin (UFH) concentrations were associated with higher CK.R results as shown by a positive Spearman correlation of ρ 1⁄4 0.929 (p < 0.001)
This study suggests that the TEG 6s system can be used effectively to monitor anticoagulation and hemostasis within therapeutic ranges for both UFH and low-molecular-weight heparin (LMWH), and can accurately classify 78 to 92% of blood samples according to clinically relevant levels of heparin
A higher concentration of heparin tended to be associated with a larger CK.R value, and was significantly associated with an increase in CRT.activated clotting time (ACT) readings
Summary
Heparin is a mainstay of antithrombotic therapy used primarily for systemic anticoagulation and for the treatment or. Prevention of conditions such as thromboembolism.[1,2] The anticoagulant effect of heparin is a result of binding to antithrombin, resulting in a conformational change which increases antithrombin activity and inhibition of coagulation factors, including factor (F) Xa and IIa received March 23, 2019 accepted after revision July 25, 2019. E296 TEG Can Evaluate Anticoagulation with Heparin Dias et al. The heterogeneity of the heparin molecules present in UFH allows it to promote the inhibition of more proteases than any single heparin molecule; it results in variable bioactivity and patient response.[1,3,4] An alternative is low-molecularweight heparins (LMWHs), which are produced by fractionating heparin through chemical or enzymatic cleavage.[1,4] This process results in a more homogenous preparation consisting of fragments with a lower molecular weight and more predictable action than UFH
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