Hemorrhagic blood failure

Abstract

Our understanding of the events taking place within the blood following severe injury with hemorrhagic shock is quickly evolving. Traditional concepts have given way to a detailed and nuanced understanding of coagulopathy, bleeding, and shock at the cellular and biochemical levels. In doing so, the tremendous complexity of events taking place within the blood have been illuminated and present an additional challenge. In this review, we seek to understand shock, endotheliopathy, and coagulopathy not as isolated events, but rather as the result of changes taking place within a single dynamic organ system. This review will highlight the key linkages existing between blood and endothelium and how these processes are perturbed by hemorrhagic shock to produce a syndrome that we call “hemorrhagic blood failure.” From this perspective, it may be regarded that the blood organ system fails in providing its vital functions predictably after injury. We review how accumulation of oxygen debt during shock leads to endotheliopathy and coagulopathy, and how current transfusion strategies may impact the syndrome of hemorrhagic blood failure.

Innate immune responses to trauma

“…In addition, the abundance of the bioactive lipid S1P, a preserver of endothelial integrity, is diminished in the plasma of patients who have suffered polytrauma; this unleashes metalloproteinase activity that contributes to damage to protective GAGs 66 . The resultant increasingly leaky endothelial barrier defines trauma-induced endotheliopathy 50,61,64 , which promotes the development of edema that hinders oxygen transport and aggravates hypoxic conditions 67 . The shed GAGs, such as syndecan-1 and heparan sulfate, can temporarily stabilize hemodynamics after trauma (‘autotransfusion’) 61 , exhibit heparinlike anti-coagulatory effects (‘autoheparinization’) 64,68 and inhibit the antibacterial activity of plasma and thereby promote infection 69 .…”

A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants

“…Anticoagulants interfere with the normal hemostatic process and lead to excessive bleeding and hematoma expansion after a disruption in the vessel wall integrity and alteration in vascular endothelium. This could happen from mechanical causes (trauma, tumor invasion, thrombosis, hypertension, invasive vascular procedures) or from an alteration in the endothelial cell barrier function (sepsis, hypoxia, ischemia, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapeutic agents, infections, etc.,) [48]. Microbleeds are common in the brain and can also occur in other organs like the mucosal lining of the gastrointestinal tract.…”

“…Risk factors for spontaneous hemorrhage in patients receiving direct oral anticoagulants[7,48,49,62,66].…”

Optimizing transfusion strategies in damage control resuscitation: current insights

“…A systemic hypoxia may also contribute to endothelial injury causing destabilization of homeostasis and barrier disruption by promoting release of angiopoietins, TF, PAI-1, soluble TM, vWF, and tPA. 84 In severely injured patients, high levels of a marker of significant glycocalyx disruption, syndecan-1, can be detected in ~5% of patients with ACOT. 85 After adjusting for ISS, syndecan-1 independently predicts increased mortality.…”