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Editorial Comment: “Coronary Artery Bypass Grafting in 2 Thrombophilic Patients with Protein S Deficiency” and “Fulminant Intraoperative Right Heart and Pulmonary Artery Thrombosis Following Prothrombin Complex Concentrate Infusion after Complex Open Heart Surgery with Cardiopulmonary Bypass”

Levy, Jerrold H. MD, FAHA, FCCM

doi: 10.1213/XAA.0000000000000004
Case Reports: Case Report

Department of Anesthesiology, Duke University School of Medicine, Durham, North Carolina. Address e-mail to

Accepted for publication September 27, 2013.

The author declares no conflicts of interest.

Hypercoagulability is a condition associated with an abnormally increased tendency toward blood clotting, leading to either venous or arterial thrombosis.1 Hypercoagulability is usually a preexisting (inherited) condition but may occur due to acquired conditions that include an abnormal response to various prothrombotic management strategies used to treat severe hemorrhage.1 Drug or factor-induced hypercoagulability includes heparin-induced thrombocytopenia or a response to therapeutic drugs used to treat life-threatening bleeding. As previously discussed in our review article, there is a complex balance between procoagulant and anticoagulant forces.1 The coagulation system ensures that bleeding does not continue indefinitely after vascular injury. At the same time, this system is balanced by thromboresistant forces that use anticoagulant proteins to regulate clot formation and fibrinolytic proteins to remove clots once vascular injury has been repaired.1 The proper balance between these systems must be maintained to ensure blood fluidity. Clinicians in the perioperative setting are usually concerned about the risk of bleeding in patients; however, hypercoagulability is also a potential cause of adverse outcomes that is often overlooked.

In this issue of the journal, 2 important cases illustrating these important perspectives are discussed. Hsu and Despotis2 report the management of coronary artery bypass grafting in 2 thrombophilic patients with protein S deficiency. Protein S, like protein C, is a critical anticoagulant protein providing regulatory mechanisms for anticoagulation. Patients deficient in these proteins have a hypercoagulable state and can present problems in a perioperative setting. The authors used fresh frozen plasma to prime the cardiopulmonary bypass circuit to replete protein S, did not use an antifibrinolytic, and patients did well. The second case by Koster et al.3 describes an acquired hypercoagulable state of intraoperative right heart and pulmonary artery thrombosis after a 4-component prothrombin complex concentrate (PCC) infusion after complex open heart surgery with cardiopulmonary bypass. PCCs are either 4 factor (II, VII, IX, X) or 3 factor (II, IX, X). A 4-factor PCC has been recently approved for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (e.g., warfarin) therapy in adult patients with acute major bleeding or need for an urgent surgery or invasive procedure. The 3-component PCCs are approved for the prevention and control of bleeding in patients with Factor IX deficiency due to hemophilia B. However, in patients with life-threatening hemorrhage, clinicians will do what they can to stop bleeding, and often, multimodal approaches are required that may include off-label use of drugs to save a patient’s life.4 Any procoagulant can cause clot formation and potentially adverse events.5 However, risk versus benefit should be considered. Finally, as Koster et al comment, additional studies are needed to further evaluate the off-label use of PCCs with life-threatening bleeding.

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1. Sniecinski RM, Hursting MJ, Paidas MJ, Levy JH. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg. 2011;112:46–58
2. Hsu Y-M, Despotis GJ. Coronary artery bypass grafting in two thrombophilic patients with protein s deficiency. Anesth Analg. 2013
3. Koster A, Meyer-Jark T, Schirmer U, Sandica E. Fulminant intraoperative right heart and pulmonary artery thrombosis following prothrombin complex concentrate infusion after complex open heart surgery with cardiopulmonary bypass. Anesth Analg. 2013
4. Karkouti K, Levy JH. Commentary: recombinant activated factor VII: the controversial conundrum regarding its off-label use. Anesth Analg. 2011;113:711–2
5. Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363:1791–800
© 2014 International Anesthesia Research Society