The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment

Abstract

The fibrinolytic system is a key player in keeping the haemostatic balance, and changes in fibrinolytic capacity can lead to both bleeding-related and thrombosis-related disorders. Our knowledge of the fibrinolytic system has expanded immensely during the last 75 years. From the first successful use of thrombolysis in myocardial infarction in the 1960s, thrombolytic therapy is now widely implemented and has reformed treatment in vascular medicine, especially ischemic stroke, while antifibrinolytic agents are used routinely in the prevention and treatment of major bleeding worldwide. Despite this, this research field still holds unanswered questions. Accurate and timely laboratory diagnosis of disturbed fibrinolysis in the clinical setting remains a challenge. Furthermore, despite growing evidence that hypofibrinolysis plays a central role in, e.g., sepsis-related coagulopathy, coronary artery disease, and venous thromboembolism, there is currently no approved treatment of hypofibrinolysis in these settings. The present review provides an overview of the fibrinolytic system and history of its discovery; measurement methods; clinical relevance of the fibrinolytic system in diagnosis and treatment; and points to future directions for research.

Tackling a deadly global phenomenon: sepsis induced coagulopathy: a narrative review

“…18 Moreover, in addition to impaired synthesis, the rapid consumption and degradation of protein C by neutrophil elastase further lowers its plasma concentration. 19 Likewise, thrombin formation induces the synthesis of thrombin-activable fibrinolysis inhibitor (TAFI). 20 Moreover, endothelial cells normally synthesise tissue-type plasminogen activator (PA) and plasminogen activator inhibitor-1 (PAI-1), the cumulative effect of which again favours a pro-coagulative state in sepsis, stabilising the clot and making it resistant to fibrinolysis.…”

Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator

“…The urokinase-type plasminogen receptor (uPAR), also termed CD87 and encoded by the PLAUR gene, is now recognized as a central immune regulating receptor. uPAR is a 50–60 kDa glycosylated protein involved in multiple physiological and pathological processes [ 7 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. uPAR is part of the Ly6 (lymphocyte antigen-6)/uPAR family of receptors.…”

“…For uPAR to effectively bind its ligand with the highest affinity, full involvement of all three D domains of uPAR is needed. Cleavage of the D1–D2 linker domains by other proteases irreversibly blocks uPAR’s interaction with other proteins [ 27 , 28 ]. In alternative pathways, uPAR is converted into a soluble form that is shed from the cell surface.…”

“…In alternative pathways, uPAR is converted into a soluble form that is shed from the cell surface. This soluble uPAR (suPAR) consists of all three domains which still maintain the full capacity to bind uPA and cannot be cleaved by uPA [ 27 , 29 ].…”