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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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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. |
format | Online Article Text |
id | pubmed-6899449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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