Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis

J Thromb Haemost. 2023 Apr;21(4):1043-1054. doi: 10.1016/j.jtha.2023.01.008. Epub 2023 Jan 14.

Abstract

Fibrinolysis is a series of enzymatic reactions that degrade insoluble fibrin. Plasminogen activators convert the zymogen plasminogen to the active serine protease plasmin, which cleaves and solubilizes crosslinked fibrin clots into fibrin degradation products. The quantity and quality of fibrinolytic enzymes, their respective inhibitors, and clot structure determine overall fibrinolysis. The quantity of protein can be measured by antigen-based assays, and both quantity and quality can be assessed using functional assays. Furthermore, variations of commonly used assays have been reported, which are tailored to address the role(s) of specific fibrinolytic factors and cellular elements (eg, platelets, neutrophils, and red blood cells). Although the concentration and/or activity of a protein can be quantified, how these individual components contribute to the overall fibrinolysis outcome can be challenging to determine. This difficulty is due to temporal changes within and around the thrombi during the clot breakdown, particularly the fibrin matrix structure, and composition. Furthermore, terms such as "fibrinolytic activity/potential," "plasminogen activation," and "plasmin activity" are often used interchangeably despite having different definitions. The purpose of this review is to 1) summarize the assays measuring fibrinolysis activity and potential, 2) facilitate the interpretation of data generated by these assays, and 3) summarize the strengths and limitations of these assays.

Keywords: ELISA; enzyme assays; fibrinolysis; plasminogen; plasminogen activators.

Publication types

  • Review
  • Practice Guideline
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Communication
  • Fibrin / metabolism
  • Fibrinolysin / metabolism
  • Fibrinolysis* / physiology
  • Humans
  • Plasminogen / metabolism
  • Serine Proteases
  • Thrombosis*

Substances

  • Fibrinolysin
  • Plasminogen
  • Fibrin
  • Serine Proteases