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Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency

INTRODUCTION: Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI‐1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI‐1 do not provide an accurate correlation with clinical phenotype. METHODS: The Nijmegen Hemostasi...

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Autores principales: Saes, Joline L., Schols, Saskia E. M., Betbadal, Kathleen F., van Geffen, Mark, Verbeek‐Knobbe, Kitty, Gupta, Sweta, Hardesty, Brandon M., Shapiro, Amy D., van Heerde, Waander L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899449/
https://www.ncbi.nlm.nih.gov/pubmed/31469483
http://dx.doi.org/10.1111/hae.13842
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author Saes, Joline L.
Schols, Saskia E. M.
Betbadal, Kathleen F.
van Geffen, Mark
Verbeek‐Knobbe, Kitty
Gupta, Sweta
Hardesty, Brandon M.
Shapiro, Amy D.
van Heerde, Waander L.
author_facet Saes, Joline L.
Schols, Saskia E. M.
Betbadal, Kathleen F.
van Geffen, Mark
Verbeek‐Knobbe, Kitty
Gupta, Sweta
Hardesty, Brandon M.
Shapiro, Amy D.
van Heerde, Waander L.
author_sort Saes, Joline L.
collection PubMed
description INTRODUCTION: Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI‐1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI‐1 do not provide an accurate correlation with clinical phenotype. METHODS: The Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI‐1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls. RESULTS: Patients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI‐1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect. CONCLUSION: Patients with either PLGD or PAI‐1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome.
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spelling pubmed-68994492019-12-19 Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency Saes, Joline L. Schols, Saskia E. M. Betbadal, Kathleen F. van Geffen, Mark Verbeek‐Knobbe, Kitty Gupta, Sweta Hardesty, Brandon M. Shapiro, Amy D. van Heerde, Waander L. Haemophilia Original Articles INTRODUCTION: Deficiencies of plasminogen and plasminogen activator inhibitor type 1 (PAI‐1) are rare disorders of fibrinolysis. Current laboratory assays for analysis of activity of plasminogen and PAI‐1 do not provide an accurate correlation with clinical phenotype. METHODS: The Nijmegen Hemostasis Assay (NHA) was used to simultaneously measure thrombin and plasmin generation in 5 patients with plasminogen deficiency (PLGD) and 10 patients with complete PAI‐1 deficiency. Parameters analysed included: lag time ratio, thrombin peak time ratio, thrombin peak height, thrombin potential (AUC), fibrin lysis time, plasmin peak height and plasmin potential. Parameters were expressed as a percentage compared to a reference value of 53 healthy normal controls. RESULTS: Patients with PLGD demonstrated a short lag time and thrombin peak time, with normal thrombin peak height but an increased AUC. Plasmin generation was able to be detected in only one (23% plasminogen activity) of the five PLGD patients. All ten PAI‐1 deficient patients demonstrated a short lag and thrombin peak time, low thrombin peak height with normal AUC. Plasmin generation revealed an increased plasmin peak and plasmin potential; interestingly, there was a large variation between individual patients despite all patients having the same homozygous defect. CONCLUSION: Patients with either PLGD or PAI‐1 deficiency show distinct abnormalities in plasmin and thrombin generation in the NHA. The differences observed in the propagation phase of thrombin generation may be explained by plasmin generation. These results suggest that disorders of fibrinolysis also influence coagulation and a global assay measuring both activities may better correlate with clinical outcome. John Wiley and Sons Inc. 2019-08-30 2019-11 /pmc/articles/PMC6899449/ /pubmed/31469483 http://dx.doi.org/10.1111/hae.13842 Text en © 2019 The Authors. Haemophilia published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Saes, Joline L.
Schols, Saskia E. M.
Betbadal, Kathleen F.
van Geffen, Mark
Verbeek‐Knobbe, Kitty
Gupta, Sweta
Hardesty, Brandon M.
Shapiro, Amy D.
van Heerde, Waander L.
Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title_full Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title_fullStr Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title_full_unstemmed Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title_short Thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
title_sort thrombin and plasmin generation in patients with plasminogen or plasminogen activator inhibitor type 1 deficiency
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899449/
https://www.ncbi.nlm.nih.gov/pubmed/31469483
http://dx.doi.org/10.1111/hae.13842
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