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Evaluation of a standardized protocol for thrombin generation using the calibrated automated thrombogram : A Nordic study

Ljungkvist, Marcus LU ; Strandberg, Karin LU ; Berntorp, Erik LU ; Chaireti, Roza; Holme, Pål André; Larsen, Ole Halfdan; Lassila, Riitta; Jouppila, Annukka; Szanto, Timea and Zetterberg, Eva LU (2019) In Haemophilia 25(2). p.334-342
Abstract

Introduction: The thrombin generation assay-calibrated automated thrombogram (TGA-CAT) method is used to measure the overall coagulation capacity in plasma. However, the method is still considered to be a research tool, mainly because of its’ lack of standardization. Aim: Our study aimed to further raise the standardization level for the TGA-CAT method by evaluating a detailed standardization protocol and three reference plasmas’ (RP)s ability to normalize results. Methods: Six Nordic centres participated in the study, and with input from all centres a detailed laboratory standardization protocol based on the TGA-CAT manual of the manufacturer was established. Three types of plasma, hypo-,normal and hypercoagulable plasma were assessed.... (More)

Introduction: The thrombin generation assay-calibrated automated thrombogram (TGA-CAT) method is used to measure the overall coagulation capacity in plasma. However, the method is still considered to be a research tool, mainly because of its’ lack of standardization. Aim: Our study aimed to further raise the standardization level for the TGA-CAT method by evaluating a detailed standardization protocol and three reference plasmas’ (RP)s ability to normalize results. Methods: Six Nordic centres participated in the study, and with input from all centres a detailed laboratory standardization protocol based on the TGA-CAT manual of the manufacturer was established. Three types of plasma, hypo-,normal and hypercoagulable plasma were assessed. Three commercial lyophilized RPs were used for normalization of data. All samples were aliquoted at the Malmö centre and sent frozen at −20˚C to participating centres. Results: Before normalization, all results under all testing conditions showed inter-laboratory coefficient of variability of 10% or lower except for endogenous thrombin potential (12%) and peak (14%) in hypo-plasma with 1 pmol/L tissue factor as starting agent. Successful normalization, improving variability in results, was obtained with two of the three evaluated RPs (HemosIL RP and Affinity RP). Conclusion: With our standardization concept, we were able to produce TGA-CAT results as robust as standard coagulation assays used in the routine laboratories. Normalization with HemosIL RP may be considered in populations with low or unknown coagulability, while when analysing plasma samples from populations where hypercoagulability is known or suspected, normalization with Affinity RP may be preferred.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
haemophilia, normalization, reference plasma, standardization, test of agreement, thrombin generation assay
in
Haemophilia
volume
25
issue
2
pages
334 - 342
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • scopus:85061037179
ISSN
1351-8216
DOI
10.1111/hae.13640
language
English
LU publication?
yes
id
1a8834f2-08d1-4ecc-aa20-ac9655181890
date added to LUP
2019-02-12 13:07:13
date last changed
2019-06-28 10:29:02
@article{1a8834f2-08d1-4ecc-aa20-ac9655181890,
  abstract     = {<p>Introduction: The thrombin generation assay-calibrated automated thrombogram (TGA-CAT) method is used to measure the overall coagulation capacity in plasma. However, the method is still considered to be a research tool, mainly because of its’ lack of standardization. Aim: Our study aimed to further raise the standardization level for the TGA-CAT method by evaluating a detailed standardization protocol and three reference plasmas’ (RP)s ability to normalize results. Methods: Six Nordic centres participated in the study, and with input from all centres a detailed laboratory standardization protocol based on the TGA-CAT manual of the manufacturer was established. Three types of plasma, hypo-,normal and hypercoagulable plasma were assessed. Three commercial lyophilized RPs were used for normalization of data. All samples were aliquoted at the Malmö centre and sent frozen at −20˚C to participating centres. Results: Before normalization, all results under all testing conditions showed inter-laboratory coefficient of variability of 10% or lower except for endogenous thrombin potential (12%) and peak (14%) in hypo-plasma with 1 pmol/L tissue factor as starting agent. Successful normalization, improving variability in results, was obtained with two of the three evaluated RPs (HemosIL RP and Affinity RP). Conclusion: With our standardization concept, we were able to produce TGA-CAT results as robust as standard coagulation assays used in the routine laboratories. Normalization with HemosIL RP may be considered in populations with low or unknown coagulability, while when analysing plasma samples from populations where hypercoagulability is known or suspected, normalization with Affinity RP may be preferred.</p>},
  author       = {Ljungkvist, Marcus and Strandberg, Karin and Berntorp, Erik and Chaireti, Roza and Holme, Pål André and Larsen, Ole Halfdan and Lassila, Riitta and Jouppila, Annukka and Szanto, Timea and Zetterberg, Eva},
  issn         = {1351-8216},
  keyword      = {haemophilia,normalization,reference plasma,standardization,test of agreement,thrombin generation assay},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {334--342},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Evaluation of a standardized protocol for thrombin generation using the calibrated automated thrombogram : A Nordic study},
  url          = {http://dx.doi.org/10.1111/hae.13640},
  volume       = {25},
  year         = {2019},
}