Abstract
The Acute Respiratory Distress Syndrome (ARDS) has caused innumerable deaths worldwide since its initial description over five decades ago. Population-based estimates of ARDS vary from 1 to 86 cases per 100,000, with the highest rates reported in Australia and the United States. This syndrome is characterised by a breakdown of the pulmonary alveolo-epithelial barrier with subsequent severe hypoxaemia and disturbances in pulmonary mechanics. The underlying pathophysiology of this syndrome is a severe inflammatory reaction and associated local and systemic coagulation dysfunction that leads to pulmonary and systemic damage, ultimately causing death in up to 40% of patients. Since inflammation and coagulation are inextricably linked throughout evolution, it is biological folly to assess the two systems in isolation when investigating the underlying molecular mechanisms of coagulation dysfunction in ARDS. Although the body possesses potent endogenous systems to regulate coagulation, these become dysregulated and no longer optimally functional during the acute phase of ARDS, further perpetuating coagulation, inflammation and cell damage. The inflammatory ARDS subphenotypes address inflammatory differences but neglect the equally important coagulation pathway. A holistic understanding of this syndrome and its subphenotypes will improve our understanding of underlying mechanisms that then drive translation into diagnostic testing, treatments, and improve patient outcomes.
Highlights
Acute Respiratory Distress Syndrome (ARDS) is a critical respiratory syndrome plagued by severe hypoxaemia and loss of pulmonary function [1]
ARDS pathophysiology is characterised by dysregulated inflammation and associated coagulation dysfunction which can result in multisystem organ failure
The impact of reduced levels of circulating endogenous anticoagulants (i.e., Activated Protein C (APC), TM, AT) in ARDS patients appears to have a significant impact in the pathophysiology of this syndrome [34, 42, 67, 68]
Summary
Acute Respiratory Distress Syndrome (ARDS) is a critical respiratory syndrome plagued by severe hypoxaemia and loss of pulmonary function [1] Five decades after it was first described [2] ARDS still represents over 10% of all Intensive Care Unit (ICU) admissions and is the cause of almost one quarter of patients requiring mechanical ventilation. Coagulation dysfunction in ARDS is a wellrecognised phenomenon, largely due to exposure of tissue factor (TF) [6] with subsequent activation of the coagulation pathways, and loss of endogenous anticoagulant function This leads to unregulated intravascular coagulation, microvascular and endothelial damage, and the dysfunction of essential organs such as the lungs, heart and kidneys [3, 4]. The variability in severity of dysregulation and inconsistency in response to treatment suggest that a single underlying mechanism is very unlikely [6]
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