Development and application of global assays of hyper- and hypofibrinolysis.

euglobulin clot lysis time fibrinolysis hemophilia plasminogen plasminogen activator inhibitor 1

Journal

Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775

Informations de publication

Date de publication:
Jan 2020
Historique:
received: 13 04 2019
revised: 03 09 2019
accepted: 10 09 2019
entrez: 29 1 2020
pubmed: 29 1 2020
medline: 29 1 2020
Statut: epublish

Résumé

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 α

Identifiants

pubmed: 31989084
doi: 10.1002/rth2.12275
pii: S2475-0379(22)01949-5
pmc: PMC6971323
doi:

Types de publication

Journal Article

Langues

eng

Pagination

46-53

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL146226
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007149
Pays : United States

Informations de copyright

© 2019 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.

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Auteurs

Anton Ilich (A)

Department of Medicine University of North Carolina Chapel Hill North Carolina.

Denis F Noubouossie (DF)

Department of Medicine University of North Carolina Chapel Hill North Carolina.

Michael Henderson (M)

Department of Medicine University of North Carolina Chapel Hill North Carolina.

Patrick Ellsworth (P)

Department of Medicine University of North Carolina Chapel Hill North Carolina.

Kathleen F Betbadal (KF)

Indiana Hemophilia and Thrombosis Center Indianapolis Indiana.

Elena Campello (E)

Thrombotic and Hemorrhagic Diseases Unit Department of Medicine University of Padova Padova Italy.

Shannon Meeks (S)

Department of Pediatrics Emory University Aflac Cancer and Blood Disorders Center Children's Healthcare of Atlanta Atlanta Georgia.

Amy Dunn (A)

Nationwide Children's Hospital Columbus Ohio.

Myung S Park (MS)

Trauma, Critical Care and General Surgery Mayo Clinic Rochester Minnesota.

Rafal Pawlinski (R)

Department of Medicine University of North Carolina Chapel Hill North Carolina.

Paolo Simioni (P)

Thrombotic and Hemorrhagic Diseases Unit Department of Medicine University of Padova Padova Italy.

Amy Shapiro (A)

Indiana Hemophilia and Thrombosis Center Indianapolis Indiana.

Nigel S Key (NS)

Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill North Carolina.

Classifications MeSH