Optimal intra- and post-arrest care for out-of-hospital cardiac arrest (OHCA) requires careful management of the complex interaction between clot formation (i.e., coagulation) and its natural resolution (i.e., fibrinolysis).1

In greater than 70% of cases, OHCA is caused by a clot blocking either a coronary artery, pulmonary artery, acute coronary syndrome (ACS), or pulmonary thromboembolism (PTE).2 When OHCA occurs, lack of pulsatile blood flow facilitates rapid clot formation in larger blood vessels and structures demonstrated by abnormally high levels of clotting byproducts, such as d-dimer.3

CPR mechanically disrupts further clot formation by restoring a modest amount of laminar blood flow from the heart to systemic vasculature. Once return of spontaneous circulation (ROSC) occurs, the clot burden accumulated during pulselessness is distributed throughout the entire vasculature and vital organs.

In response, the human body experiences a brief period of systemic fibrinolysis represented by the activation of the anticoagulant protein C (aPC).4 As aPC is rapidly consumed in the two hours following arrest, the brief hypocoagulable state is replaced by a prolonged hypercoagulable state causing microcirculatory occlusion, profound lactic acidosis and progressive multiorgan failure.5 (See Figure 1.)

Although individual mechanisms of hypotensive coagulopathy have been associated with poor outcomes in other critically ill populations (e.g., trauma, sepsis), coagulopathy resulting from cardiac arrest is poorly understood.6,7 Standard of care for the most frequent precipitating pathologies of OHCA (ACS and PTE) requires treatment with systemic anticoagulation. Such therapy requires delicate titration that’s problematic without a more complete understanding of coagulation dysfunction following OHCA.8,9

Furthermore, targeted temperature management (TTM) is the only other evidence-based treatment for post-cardiac arrest. TTM is the deliberate reduction of body temperature between 33–36 degrees C to reduce organ injury.10–12 However, TTM is known to impair coagulation13 and alter the metabolism anticoagulant therapies.14 Traditional diagnostic tests (PT/PTT/INR) used to measure effectiveness of those therapies aren’t reliable during TTM.11

Based upon our current understanding of the coagulation homeostasis that follows ROSC after OHCA, strong consideration should be given to administration of drug therapies that reduce the likelihood of hypercoagulation in the first week after cardiac arrest.


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5. Böttiger BW, Motsch J, Böhrer H, et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation. 1995; 92(9):2572–2578. 

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8. O’Connor RE, Al Ali AS, Brady WJ, et al. Part 9: Acute coronary syndromes: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18 Suppl 2):S483–S500.

9. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease. Chest. 2016;149(2):315–352.

10. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–556.

11. Bernard SA1, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–563.

12. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197–2206.

13. Chun-Lin H, Jie W, Xiao-Xing L, et al. Effects of therapeutic hypothermia on coagulopathy and microcirculation after cardiopulmonary resuscitation in rabbits. Am J Emerg Med. 2011;29(9):1103–1110.

14. Wahby KA, Jhajhria S, Dalal BD, et al. Heparin dosing in critically ill patients undergoing therapeutic hypothermia following cardiac arrest. Resuscitation. 2014;85(4):533–537.