Procoagulant and fibrinolytic activity after polytrauma in rat

Abstract

Wu X, Darlington DN, Cap AP. Procoagulant and fibrinolytic activity after polytrauma in rat. Am J Physiol Regul Integr Comp Physiol 310: R323-R329, 2016. First published December 2, 2015; doi:10.1152/ajpregu.00401.2015.-The purpose of this study was to determine whether trauma-induced coagulopathy is due to changes in 1) thrombin activity, 2) plasmin activity, and/or 3) factors that stimulate or inhibit thrombin or plasmin. Sprague-Dawley rats were anesthetized with 1-2% isoflurane/100% oxygen, and their left femoral artery and vein were cannulated. Polytrauma included right femur fracture, and damage to the small intestines, the left and medial liver lobes, and right leg skeletal muscle. Rats were then bled 40% of blood volume. Plasma samples were taken before trauma, and at 30, 60, 120, and 240 min. Polytrauma and hemorrhage led to a significant fall in prothrombin levels. However, circulating thrombin activity did not change significantly over time. Antithrombin III and ␣ 2 macroglobulin fell significantly by 2 h, then rose by 4 h. Soluble thrombomodulin was significantly elevated over the 4 h. Circulating plasmin activity, plasminogen, and D-dimers were elevated for the entire 4 h. Tissue plasminogen activator (tPA) was elevated at 30 min, then decreased below baseline levels after 1 h. Plasminogen activator inhibitor-1 was significantly elevated at 2-4 h. Neither tissue factor pathway inhibitor nor thrombin activatable fibrinolysis inhibitor changed significantly over time. The levels of prothrombin and plasminogen were 30 -100 times higher than their respective active enzymes. Polytrauma and hemorrhage in rats lead to a fibrinolytic coagulopathy, as demonstrated by an elevation in plasmin activity, D-dimers, and tPA. These results are consistent with the observed clinical benefit of tranexamic acid in trauma patients.

Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity

“…At present, the mechanism by which severe trauma results in decreased ADAMTS13 activity is incompletely understood; however, there is likely a component of consumption in these severely injured patients, many of whom are bleeding, which is reflected in our data with decreased antigen levels of ADAMTS13, while potential microthrombotic complications arise due to elevated levels of UL‐VWF . Potential contributors to this consumptive process include thrombin and plasmin, which have both been shown to cleave ADAMTS13 and would intermittently increase in the period after injury . Furthermore, ADAMTS13 activity has been associated with bleeding events both in patients with sepsis and in pediatric patients with congenital heart disease undergoing surgery .…”

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

“…Early activation of fibrinolysis is common after trauma and is associated with increased mortality 11 . Trauma triggers the release of tissue plasminogen activator, the enzyme that converts plasminogen to the fibrinolytic enzyme plasmin 12, 13…”

Evaluation of thrombomodulin and pentraxin-3 as diagnostic biomarkers in calves with sepsis

“…Numerous studies have been conducted so far on the role of biomarkers such as TM and PTX3 in human patients with sepsis but there is no report on livestock. The studies conducted on humans and laboratory animals have identified elevated TM concentrations in conjunction with disease processes that cause haemostatic disorders and endothelial damage (Ohdama et al 1994;Wu et al 2016;Lin et al 2017). TM binds to highmobility group box 1 protein and thereby prevents activation of leucocytes under in vitro conditions and lipopolysaccharide-induced lethality under in vivo conditions (Abeyama et al 2005).…”