Plasminogen-deficient mice survive embryonic development but develop spontaneous fibrin deposition due to impaired thrombolysis and suffer retarded growth and reduced fertility and survival. The Plg-/- phenotype is reminiscent of the combined tPA-/-:uPA-/- phenotype, which suggests that there is no significant additional pathway for physiological plasminogen activation in mice.

Background To determine the prevalence of platelet dysfunction, using an end-point of assembly into a stable thrombus, following severe injury. Background: Although the current debate on acute traumatic coagulopathy (ATC) has focused on the consumption or inhibition of coagulation factors, the question of early platelet dysfunction in this setting remains unclear. Study Design Prospective platelet function in assembly and stability of the thrombus was determined within 30 minutes of injury using whole blood samples from trauma patients at the point of care employing thrombelastography (TEG)-based platelet functional analysis. Results There were 51 patients in the study. There were significant differences in the platelet response between trauma patients and healthy volunteers such that there was impaired aggregation to these agonists. In trauma patients, the median ADP inhibition of platelet function was 86.1% (IQR: 38.6–97.7%), compared to 4.2 % (IQR 0–18.2%) in healthy volunteers. Following trauma, the impairment of platelet function in response to AA was 44.9% (IQR 26.6–59.3%), compared to 0.5% (IQR 0–3.02%) in volunteers (Wilcoxon non parametric test p<0.0001 for both tests). Conclusions In this study, we show that platelet dysfunction is manifest following major trauma, before significant fluid or blood administration. These data suggest a potential role for early platelet transfusion in severely injured patients at risk for postinjury coagulopathy.

The plasminogen/plasmin system has the potential to affect the outcome of inflammatory diseases by regulating accumulation of fibrin and other matrix proteins. In human and experimental crescentic glomerulonephritis (GN), fibrin is an important mediator of glomerular injury and renal impairment. Glomerular deposition of matrix proteins is a feature of progressive disease. To study the role of plasminogen and plasminogen activators in the development of inflammatory glomerular injury, GN was induced in mice in which the genes for these proteins had been disrupted by homologous recombination. Deficiency of plasminogen or combined deficiency of tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA) was associated with severe functional and histological exacerbation of glomerular injury. Deficiency of tPA, the predominant plasminogen activator expressed in glomeruli, also exacerbated disease. uPA deficiency reduced glomerular macrophage infiltration and did not significantly exacerbate disease. uPA receptor deficiency did not effect the expression of GN. These studies demonstrate that plasminogen plays an important role in protecting the glomerulus from acute inflammatory injury and that tPA is the major protective plasminogen activator.