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Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?

Salvagno, G. L.; Astermark, Jan LU ; Lippi, G.; Ekman, Maj LU ; Franchini, M.; Guidi, G. C. and Berntorp, Erik LU (2009) In Haemophilia 15(1). p.290-296
Abstract
Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50... (More)
Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P < 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C < 5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
thrombin generation assay, FVIII, haemophilia
in
Haemophilia
volume
15
issue
1
pages
290 - 296
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000262470600038
  • scopus:63049137583
ISSN
1351-8216
DOI
10.1111/j.1365-2516.2008.01877.x
language
English
LU publication?
yes
id
45aef9d8-e5f2-4697-a8b5-8e1c5862e70f (old id 1312814)
date added to LUP
2009-03-18 09:03:43
date last changed
2017-08-27 04:15:02
@article{45aef9d8-e5f2-4697-a8b5-8e1c5862e70f,
  abstract     = {Severity assessment of patients with haemophilia A (HA) is traditionally based on FVIII activity (FVIII:C). Clinical phenotype of HA patients often differs between individuals with the same FVIII:C determined with clotting and chromogenic assays. The aim of this study was to assess the influence of the FVIII:C on thrombin generation (TG) assay parameters both in vitro and ex-vivo postinfusion plasma. For in-vitro approach, influence of FVIII:C was evaluated on TG parameters in several dilutions of a normal plasma pool with commercial FVIII-depleted-plasma (FVIIIDP) and in others experiments, adding increasing amounts of different commercial FVIII concentrates (Fanhdi, Haemate-P, Hemofil-M and Kogenate Bayer) to FVIIIDP. In a series of 50 postinfusion samples, from HA patients of different severity, we assayed TG and FVIII:C (chromogenic and clotting). In vitro experiments, the 50% of maximum TG peak (TGMP) was achieved using only 5% FVIII:C and the TGMP was obtained with 40% of normal VIII:C. Impaired response compared with normal plasma was found in FVIIIDP using addition of increasing amounts of different commercial FVIII concentrates. An overall good correlation between the two FVIII assays was observed (y = 0.9115x - 0.273, r = 0.975, P &lt; 0.001); TGMP and the Lag-Phase-Time (LPT) provided some discrepant results when compared with the total range of FVIII:C measurements. In contrast, correlations for TGMP, LPT and endogenous thrombin potential were improved in samples restricted to FVIII:C &lt; 5%. We conclude that TG parameters tentatively could be a tool to tailor the global haemostatic capacity in haemophilic patients.},
  author       = {Salvagno, G. L. and Astermark, Jan and Lippi, G. and Ekman, Maj and Franchini, M. and Guidi, G. C. and Berntorp, Erik},
  issn         = {1351-8216},
  keyword      = {thrombin generation assay,FVIII,haemophilia},
  language     = {eng},
  number       = {1},
  pages        = {290--296},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Thrombin generation assay: a useful routine check-up tool in the management of patients with haemophilia?},
  url          = {http://dx.doi.org/10.1111/j.1365-2516.2008.01877.x},
  volume       = {15},
  year         = {2009},
}