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

Abstract

Objectives: We investigated coagulation abnormalities in out-of-hospital cardiac arrest (OHCA) patients, with special attention to the protein C anticoagulant pathway.

Background: 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.

Methods: Coagulation parameters were measured in all patients admitted after successfully resuscitated OHCA.

Results: 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.

Conclusions: 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.