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Thrombin generation abnormalities in commonly encountered platelet function disorders
INTRODUCTION: Studies of thrombin generation (TG) with platelet‐rich plasma (PRP) and platelet‐poor plasma (PPP) have provided insights on bleeding disorders. We studied TG for a cohort with commonly encountered platelet function disorders (PFD). METHODS: Participants included 40 controls and 31 wit...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599625/ https://www.ncbi.nlm.nih.gov/pubmed/34185390 http://dx.doi.org/10.1111/ijlh.13638 |
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author | Sharma, Tanmya Brunet, Justin G. Tasneem, Subia Smith, Stephanie A. Morrissey, James H. Hayward, Catherine P.M. |
author_facet | Sharma, Tanmya Brunet, Justin G. Tasneem, Subia Smith, Stephanie A. Morrissey, James H. Hayward, Catherine P.M. |
author_sort | Sharma, Tanmya |
collection | PubMed |
description | INTRODUCTION: Studies of thrombin generation (TG) with platelet‐rich plasma (PRP) and platelet‐poor plasma (PPP) have provided insights on bleeding disorders. We studied TG for a cohort with commonly encountered platelet function disorders (PFD). METHODS: Participants included 40 controls and 31 with PFD due to: nonsyndromic dense granule (DG) deficiency (PFD‐DGD, n = 9), RUNX1 haploinsufficiency (n = 6) and aggregation defects from other, uncharacterized causes (n = 16). TG was tested with PRP and PPP samples. As DG store ADP and polyphosphate that enhance platelet‐dependent TG, PFD‐DGD PRP TG was tested for correction with ADP, polyphosphate and combined additives. Tissue factor pathway inhibitor (TFPI), platelet factor V (FV), and platelet TFPI and ANO6 transcript levels were also evaluated. Findings were tested for associations with TG endpoints and bleeding. RESULTS: PFD samples had impaired PRP TG, but also impaired PPP TG, with strong associations between their PRP and PPP TG endpoints (P ≤ .005). PFD‐DGD PRP TG endpoints showed associations to PPP TG endpoints but not to DG counts, and were improved, but not fully corrected, by adding polyphosphate and agonists. PFD participants had increased plasma TFPI and reduced platelet TFPI (P ≤ .02) but normal levels of platelet FV, and platelet TFPI and ANO6 transcripts levels. PFD plasma TFPI levels showed significant association to several PPP TG endpoints (P ≤ .04). Several PFD PRP TG endpoints showed significant associations to bleeding symptoms, including wound healing problems and prolonged bleeding from minor cuts (P ≤ .04). CONCLUSION: TG is impaired in commonly encountered PFD, with their PRP TG findings showing interesting associations to symptoms. |
format | Online Article Text |
id | pubmed-8599625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85996252022-10-14 Thrombin generation abnormalities in commonly encountered platelet function disorders Sharma, Tanmya Brunet, Justin G. Tasneem, Subia Smith, Stephanie A. Morrissey, James H. Hayward, Catherine P.M. Int J Lab Hematol ORIGINAL ARTICLES INTRODUCTION: Studies of thrombin generation (TG) with platelet‐rich plasma (PRP) and platelet‐poor plasma (PPP) have provided insights on bleeding disorders. We studied TG for a cohort with commonly encountered platelet function disorders (PFD). METHODS: Participants included 40 controls and 31 with PFD due to: nonsyndromic dense granule (DG) deficiency (PFD‐DGD, n = 9), RUNX1 haploinsufficiency (n = 6) and aggregation defects from other, uncharacterized causes (n = 16). TG was tested with PRP and PPP samples. As DG store ADP and polyphosphate that enhance platelet‐dependent TG, PFD‐DGD PRP TG was tested for correction with ADP, polyphosphate and combined additives. Tissue factor pathway inhibitor (TFPI), platelet factor V (FV), and platelet TFPI and ANO6 transcript levels were also evaluated. Findings were tested for associations with TG endpoints and bleeding. RESULTS: PFD samples had impaired PRP TG, but also impaired PPP TG, with strong associations between their PRP and PPP TG endpoints (P ≤ .005). PFD‐DGD PRP TG endpoints showed associations to PPP TG endpoints but not to DG counts, and were improved, but not fully corrected, by adding polyphosphate and agonists. PFD participants had increased plasma TFPI and reduced platelet TFPI (P ≤ .02) but normal levels of platelet FV, and platelet TFPI and ANO6 transcripts levels. PFD plasma TFPI levels showed significant association to several PPP TG endpoints (P ≤ .04). Several PFD PRP TG endpoints showed significant associations to bleeding symptoms, including wound healing problems and prolonged bleeding from minor cuts (P ≤ .04). CONCLUSION: TG is impaired in commonly encountered PFD, with their PRP TG findings showing interesting associations to symptoms. John Wiley and Sons Inc. 2021-06-29 2021-12 /pmc/articles/PMC8599625/ /pubmed/34185390 http://dx.doi.org/10.1111/ijlh.13638 Text en © 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | ORIGINAL ARTICLES Sharma, Tanmya Brunet, Justin G. Tasneem, Subia Smith, Stephanie A. Morrissey, James H. Hayward, Catherine P.M. Thrombin generation abnormalities in commonly encountered platelet function disorders |
title | Thrombin generation abnormalities in commonly encountered platelet function disorders |
title_full | Thrombin generation abnormalities in commonly encountered platelet function disorders |
title_fullStr | Thrombin generation abnormalities in commonly encountered platelet function disorders |
title_full_unstemmed | Thrombin generation abnormalities in commonly encountered platelet function disorders |
title_short | Thrombin generation abnormalities in commonly encountered platelet function disorders |
title_sort | thrombin generation abnormalities in commonly encountered platelet function disorders |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599625/ https://www.ncbi.nlm.nih.gov/pubmed/34185390 http://dx.doi.org/10.1111/ijlh.13638 |
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