Does plasmin have anticoagulant activity?

Abstract

The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.

Physiological and regulatory underpinnings of geographic variation in reptilian cold tolerance across a latitudinal cline

“…As a major blood anticoagulant, GO enrichment of heparin binding among modules negatively associated with lactate concentration suggests that regulation of blood coagulation and clotting pathways may reduce cellular oxygen limitation by maintaining some degree of oxygen delivery during cold exposure. This hypothesis is further supported by the GO enrichment of regulatory networks responsible for activation of plasminogen, which plays a role in anticoagulation (Hoover‐Plow, ) and dissolving blood clots (fibrinolysis) as well as activation of platelets, which provide surfaces for coagulation to occur (Markiewski, Nilsson, Ekdahl, Mollnes, & Lambris, ). Negative regulation of platelet activation may act to diminish the magnitude of clot formation.…”

Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions

“…On the other hand, AAS19 inhibition of plasmin can, at a glance, be viewed as contradictory since plasmin is mostly known for its role in digesting blood clots (fibrinolysis) (Angles-Cano, 1994; Angles-Cano et al, 1994), an activity that seems beneficial to tick feeding. Similarly, plasmin degrades and inactivates blood-clotting factors V, VIII, IX and X in vitro, suggesting plasmin has anti-coagulant functions (Hoover-Plow, 2010) and is thus beneficial to tick feeding. On the other hand, plasmin has been reported to participate in several processes such as pro-inflammatory cytokine release (Syrovets et al, 2001), inducing monocyte and dendritic cell chemotaxis (Li et al, 2010), modifying IL-8 and producing a potent attractant of neutrophils (Mortier et al, 2011), tissue remodeling and wound healing (Shen et al, 2012), all of which can negatively impact tick-feeding success.…”

Coagulation and the surgical neonate

“…While the fibrinolytic system in neonates has lower activity, large rises in d ‐Dimer concentration (indicating fibrinolysis) can be demonstrated in situations such as cardiopulmonary bypass. Plasmin may increase bleeding by other mechanisms: breakdown of fibrinogen, cleavage of platelet receptors , interaction with inflammation , and possibly by breakdown of other procoagulant proteins . The products of fibrin breakdown may also exert anticoagulant effects, principally by interfering with polymerization of fibrinogen.…”