Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States

Abstract

Low fibrinolytic activity has been associated with pathologic thrombosis and multiple-organ failure. Low fibrinolytic activity has two commonly associated terms, hypofibrinolysis and fibrinolysis shutdown. Hypofibrinolysis is a chronic state of lack of ability to generate an appropriate fibrinolytic response when anticipated. Fibrinolysis shutdown is the shutdown of fibrinolysis after systemic activation of the fibrinolytic system. There has been interchanging of these terms to describe critically ill patients in multiple settings. This is problematic in understanding the pathophysiology of disease processes related to these conditions. There is also a lack of research on the cellular mediators of these processes. The purpose of this article is to review the on and off mechanisms of fibrinolysis in the context of low fibrinolytic states to define the importance in differentiating hypofibrinolysis from fibrinolysis shutdown. In many clinical scenarios, the etiology of a low fibrinolytic state cannot be determined due to ambiguity if a preceding fibrinolytic activation event occurred. In this scenario, the term “low fibrinolytic activity” or “fibrinolysis resistance” is a more appropriate descriptor, rather than using assumptive of hypofibrinolysis and fibrinolysis shutdown, particularly in the acute setting of infection, injury, and surgery.

Postoperative fibrinolytic resistance is associated with early allograft dysfunction in liver transplantation: A prospective observational study

“…This new inflection point was then used to define postoperative FR on POD-1 (see Results). Within the FR cohort, patients were further substratified into hypofibrinolysis versus fibrinolysis shutdown 18,19 . Hypofibrinolysis is defined as a failure to generate a fibrinolytic response when anticipated 20 .…”

“…To understand the potential differences in clinical characteristics between transplant recipients with and without FR, we compared the 2 cohorts (Table 2). Transplant recipients with FR on POD-1 had higher median MELD-Na scores than those without FR [24 (14-26) vs. 21 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), p = 0.003, Table 2]. This was driven by higher bilirubin [4.9 (2.7-11.7) mg/dL vs. 3.4 (2.1-7.3) mg/dL, p = 0.03] and higher INR [2.0 (1.6-2.5) vs. 1.7 (1.4-2.2), p = 0.06] with less significant differences in sodium and creatinine (Table 2).…”

“…Within the FR cohort, patients were further substratified into hypofibrinolysis versus fibrinolysis shutdown. [18,19] Hypofibrinolysis is defined as a failure to generate a fibrinolytic response when anticipated. [20] Fibrinolysis shutdown is defined as the systemic activation of fibrinolysis with subsequent inhibition, [21] in which a TEG LY30 > 3.0% has been previously used to define high systemic fibrinolytic activity.…”

SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock

“…The similarities between SIC and TIC are instructive and are summarized in Table 3. Whereas the hemostatic derangement characteristic of hyperfibrinolytic phenotype associated with early severe TIC in shock is transformed in late TIC into a hypofibrinolytic phenotype characteristic of SIC (Taylor Jr et al, 2001;Gando and Wada, 2019;Vulliamy et al, 2019;Moore, 2022).…”

Editorial Compilation—XIII

“…1 The second entry in this issue is fittingly a contribution from a prior (i.e., 2021) Eberhard F. Mammen Young Investigator winner, 2 Dr Hunter B. Moore, on the topic of fibrinolysis shutdown and hypofibrinolysis. 3 Low fibrinolytic activity has been associated with pathologic thrombosis and multiple organ failure but has two separate commonly associated terms, “hypofibrinolysis” and “fibrinolysis shutdown.” According to Dr. Moore, hypofibrinolysis is a chronic state of lack of ability to generate an appropriate fibrinolytic response when anticipated. Instead, fibrinolysis shutdown can be defined as shutdown after systemic activation of the fibrinolytic system.…”