Development and application of global assays of hyper‐ and hypofibrinolysis

Abstract Numerous methods for evaluation of global fibrinolytic activity in whole blood or plasma have been proposed, with the majority based on tissue‐type plasminogen activator (t‐PA) addition to initiate fibrinolysis. We propose that such an approach is useful to reveal hypofibrinolysis, but t‐PA...

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Autores principales:	Anton Ilich, Denis F. Noubouossie, Michael Henderson, Patrick Ellsworth, Kathleen F. Molitor, Elena Campello, Shannon Meeks, Amy Dunn, Myung S. Park, Rafal Pawlinski, Paolo Simioni, Amy Shapiro, Nigel S. Key
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2020
Materias:	euglobulin clot lysis time fibrinolysis hemophilia plasminogen plasminogen activator inhibitor 1 Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/900e4ab51d71429d996a029b893c09f7
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spelling	oai:doaj.org-article:900e4ab51d71429d996a029b893c09f72021-11-15T06:10:44ZDevelopment and application of global assays of hyper‐ and hypofibrinolysis2475-037910.1002/rth2.12275https://doaj.org/article/900e4ab51d71429d996a029b893c09f72020-01-01T00:00:00Zhttps://doi.org/10.1002/rth2.12275https://doaj.org/toc/2475-0379Abstract Numerous methods for evaluation of global fibrinolytic activity in whole blood or plasma have been proposed, with the majority based on tissue‐type plasminogen activator (t‐PA) addition to initiate fibrinolysis. We propose that such an approach is useful to reveal hypofibrinolysis, but t‐PA concentrations should be kept to a minimum. In this paper, we describe a low‐concentration t‐PA plasma turbidity assay to evaluate several congenital factor deficiencies, including plasminogen activator inhibitor‐1 (PAI‐1) and plasminogen deficiency, as well as hemophilia A and B. In addition, we demonstrate a threshold dependency on endogenous PAI‐1 levels. To assess endogenous hyperfibrinolysis, we suggest that assays that avoid t‐PA addition are preferable, with assays based on euglobulin fractionation remaining a viable choice. We describe a euglobulin fraction clot lysis time (ECLT) assay with spectrophotometric readout and other modifications, and evaluate it as a tool to measure hyperfibrinolysis in inherited clotting factor deficiency states. We demonstrate that the ECLT is predominantly driven by residual amounts of PAI‐1, t‐PA, and α2‐antiplasmin. These assays should be further evaluated for the detection of hypo‐ or hyperfibrinolysis in acquired thrombotic or hemorrhagic disorders.Anton IlichDenis F. NoubouossieMichael HendersonPatrick EllsworthKathleen F. MolitorElena CampelloShannon MeeksAmy DunnMyung S. ParkRafal PawlinskiPaolo SimioniAmy ShapiroNigel S. KeyWileyarticleeuglobulin clot lysis timefibrinolysishemophiliaplasminogenplasminogen activator inhibitor 1Diseases of the blood and blood-forming organsRC633-647.5ENResearch and Practice in Thrombosis and Haemostasis, Vol 4, Iss 1, Pp 46-53 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	euglobulin clot lysis time fibrinolysis hemophilia plasminogen plasminogen activator inhibitor 1 Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	euglobulin clot lysis time fibrinolysis hemophilia plasminogen plasminogen activator inhibitor 1 Diseases of the blood and blood-forming organs RC633-647.5 Anton Ilich Denis F. Noubouossie Michael Henderson Patrick Ellsworth Kathleen F. Molitor Elena Campello Shannon Meeks Amy Dunn Myung S. Park Rafal Pawlinski Paolo Simioni Amy Shapiro Nigel S. Key Development and application of global assays of hyper‐ and hypofibrinolysis
description	Abstract Numerous methods for evaluation of global fibrinolytic activity in whole blood or plasma have been proposed, with the majority based on tissue‐type plasminogen activator (t‐PA) addition to initiate fibrinolysis. We propose that such an approach is useful to reveal hypofibrinolysis, but t‐PA concentrations should be kept to a minimum. In this paper, we describe a low‐concentration t‐PA plasma turbidity assay to evaluate several congenital factor deficiencies, including plasminogen activator inhibitor‐1 (PAI‐1) and plasminogen deficiency, as well as hemophilia A and B. In addition, we demonstrate a threshold dependency on endogenous PAI‐1 levels. To assess endogenous hyperfibrinolysis, we suggest that assays that avoid t‐PA addition are preferable, with assays based on euglobulin fractionation remaining a viable choice. We describe a euglobulin fraction clot lysis time (ECLT) assay with spectrophotometric readout and other modifications, and evaluate it as a tool to measure hyperfibrinolysis in inherited clotting factor deficiency states. We demonstrate that the ECLT is predominantly driven by residual amounts of PAI‐1, t‐PA, and α2‐antiplasmin. These assays should be further evaluated for the detection of hypo‐ or hyperfibrinolysis in acquired thrombotic or hemorrhagic disorders.
format	article
author	Anton Ilich Denis F. Noubouossie Michael Henderson Patrick Ellsworth Kathleen F. Molitor Elena Campello Shannon Meeks Amy Dunn Myung S. Park Rafal Pawlinski Paolo Simioni Amy Shapiro Nigel S. Key
author_facet	Anton Ilich Denis F. Noubouossie Michael Henderson Patrick Ellsworth Kathleen F. Molitor Elena Campello Shannon Meeks Amy Dunn Myung S. Park Rafal Pawlinski Paolo Simioni Amy Shapiro Nigel S. Key
author_sort	Anton Ilich
title	Development and application of global assays of hyper‐ and hypofibrinolysis
title_short	Development and application of global assays of hyper‐ and hypofibrinolysis
title_full	Development and application of global assays of hyper‐ and hypofibrinolysis
title_fullStr	Development and application of global assays of hyper‐ and hypofibrinolysis
title_full_unstemmed	Development and application of global assays of hyper‐ and hypofibrinolysis
title_sort	development and application of global assays of hyper‐ and hypofibrinolysis
publisher	Wiley
publishDate	2020
url	https://doaj.org/article/900e4ab51d71429d996a029b893c09f7
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Development and application of global assays of hyper‐ and hypofibrinolysis

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