Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway.

Abstract

We investigated coagulation abnormalities in out-of-hospital cardiac arrest (OHCA) patients, with special attention to the protein C anticoagulant pathway. Successfully resuscitated cardiac arrest is followed by a systemic inflammatory response and by activation of coagulation, both of which may contribute to organ failure and neurological dysfunction. Coagulation parameters were measured in all patients admitted after successfully resuscitated OHCA. At admission, 67 patients had a systemic inflammatory response with increased interleukin-6 and coagulation activity (thrombin-antithrombin complex), reduced anticoagulation (antithrombin, protein C, and protein S), activated fibrinolysis (plasmin-antiplasmin complex), and, in some cases, inhibited fibrinolysis (increased plasminogen activator inhibitor-1 with a peak on day 1). These abnormalities were more severe in patients who died within two days (50 of 67, 75%) and were most severe in patients dying from early refractory shock. Protein C and S levels were low compared to healthy volunteers and discriminated OHCA survivors from nonsurvivors. Furthermore, a subgroup of patients had a transient increase in plasma-activated protein C at admission followed by undetectable levels. This, along with an increase in soluble thrombomodulin over time, suggests secondary endothelial injury and dysfunction of the protein C anticoagulant pathway similar to that observed in severe sepsis. Major coagulation abnormalities were found after successful resuscitation of cardiac arrest. These abnormalities are consistent with secondary down-regulation of the thrombomodulin-endothelial protein C receptor pathway.