Consumptive coagulopathy is associated with organ dysfunction during PICS

Abstract

Patients who survive the acute phase of sepsis can progress to persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Although sepsis is characterized by early hypercoagulability and delayed hypocoagulability, coagulopathy during chronic critical illness is not fully understood. The objective of this study was to determine whether sepsis-induced PICS is associated with coagulation abnormalities. Using our previously described murine PICS model, outbred mice underwent cecal ligation and puncture, and coagulability was characterized after 8 days. We found that during PICS the spleen became markedly enlarged with increased splenocytes and splenic megakaryocytes without a concomitant increase in circulating platelets. Microscopy revealed a nearly sevenfold increase in pulmonary microvascular thrombi in PICS mice, along with significantly decreased pulmonary tidal volumes and inspiratory times and with significantly increased respiratory rates. Thromboelastometry showed that PICS mice had significantly delayed clot initiation time but increased clot firmness. Finally, PICS mice displayed delayed thrombin production and decreased overall thrombin concentrations. All together, these data demonstrate a general dysregulation of coagulation resulting in microthrombus formation and compromised lung function. On the basis of these findings, we propose that consumptive coagulopathy constitutes another cardinal feature of PICS and may contribute to the ongoing tissue damage and multiple organ failure that can occur in chronic critical illness.

Disseminated Intravascular Coagulopathy Is Associated with the Outcome of Persistent Inflammation, Immunosuppression and Catabolism Syndrome

“…Although the activation of coagulation is protective to counteract pathogens through fibrin deposition [ 20 ], excessive coagulopathy can be expected to accelerate inflammation [ 8 ] and to worsen microcirculation, possibly leading to multiple organ failure [ 7 ]. Reportedly, extreme coagulopathy has been observed in the blood and organs in PIICS model mice [ 21 ]. Based on results of the present study, decreased antithrombin activity was identified as a risk factor for PIICS.…”

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

“…"Persistent Inflammation, Immunosuppression, and Catabolism Syndrome" (PICS) has been postulated as the underlying pathophysiology of chronic critical illness (CCI) (18,47). About 50% of sepsis patients have a debilitating condition characterized by a self-perpetuating cycle of persistent low-grade systemic inflammation mimicking chronic stress (elevated cortisol) (44,48,49), glucocorticoid resistance, altered hemostasis (50,51), mitochondrial dysfunction (52,53), and accelerated inflamm-aging (9,54), with increased risk for chronic inflammatory systemic diseases (7,55). The evolutionary trade-off between acutely beneficial and chronically harmful homeostatic corrections was the subject of a recent review (7).…”

Distinct Neutrophil Populations in the Spleen During PICS

“…Cecal ligation and puncture was performed on 6 to 8-weekold male CD-1 mice from the Charles River Laboratories (Wilmington, MA, USA) as described previously (15). The animal protocol was approved under the Institutional Animal Care and Use Committee of the University of Cincinnati (Protocol No.…”