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CARDIOVASCULAR ANESTHESIOLOGY

Improved Clot Formation by Combined Administration of Activated Factor VII (NovoSeven®) and Fibrinogen (Haemocomplettan® P)

Kenichi A. Tanaka, MD, MSc^*, Taro Taketomi, MD^*, Fania Szlam, MMSc^*, Andreas Calatzis, MD, and Jerrold H. Levy, MD^*

From the *Department of Anesthesiology, Division of Cardiothoracic Anesthesia, Emory University School of Medicine, Atlanta, Georgia; and Haemostasis and Transfusion Medicine, Munich University Clinic, Munich, Germany.

Address correspondence and reprint requests to Jerrold H. Levy, MD, Professor of Anesthesiology, Department of Anesthesiology, Division of Cardiothoracic Anesthesia, Emory University School of Medicine, 1364 Clifton Rd., NE, Atlanta, GA 30322. Address e-mail to jerrold.levy{at}emoryhealthcare.org.

Abstract

BACKGROUND: Recombinant activated factor VII (rFVIIa) is increasingly used for treating refractory bleeding after cardiac surgery. However, hemostasis also depends on coagulation factors, including fibrinogen, which stabilizes platelet plugs at sites of vascular injury. We compared the hemostatic effects of rFVIIa, fibrinogen, or their combination.

METHODS: Blood samples were obtained from 12 volunteers and from 7 patients after cardiopulmonary bypass (CPB). The in vitro effects of rFVIIa (1.5 µg/mL), fibrinogen (100 mg/dL), and the combination were evaluated under simulated coagulopathy in volunteer plasma using heparin (0.1 U/mL) or tissue plasminogen activator (0.1 µg/mL). Hemostatic interventions were compared using thromboelastometry, which measures clotting time (CT, s), angle of thrombus formation, and maximal clot firmness (MCF, mm). The Thrombinoscope^TM was used to quantitate thrombin generation after addition of fibrinogen and/or rFVIIa.

RESULTS: In heparinized volunteer plasma, rFVIIa shortened CT (1st and 3rd quartiles) from 663 (522–736) to 435 (397–531) s, but it did not affect MCF. Fibrinogen increased MCF from 26.0 (24.4–26.7) to 30.5 (26.3–31.5) mm without affecting CT. The combination of rFVIIa and fibrinogen in heparinized samples was most effective in improving CT to 359 (324–522) s and MCF to 29 (27.8–31.0) mm. In tissue plasminogen activator-treated volunteer plasma, fibrinolysis increased by more than 45% by the addition of rFVIIa. After CPB, both CT and MCF were most improved with coadministration of rFVIIa and fibrinogen. Thrombinoscope evaluation demonstrated that rFVIIa decreased the lag time and increased peak thrombin generation, whereas fibrinogen had no effect.

CONCLUSION: The onset of fibrin formation and thrombin generation were shortened after rFVIIa addition, but fibrin clot strength was only increased after fibrinogen supplementation. In vitro clot formation was most improved by using both rFVIIa and fibrinogen in whole blood after CPB.

This article has been cited by other articles:

				T. Lang, K. Johanning, H. Metzler, S. Piepenbrock, C. Solomon, N. Rahe-Meyer, and K. A. Tanaka The Effects of Fibrinogen Levels on Thromboelastometric Variables in the Presence of Thrombocytopenia Anesth. Analg., March 1, 2009; 108(3): 751 - 758. [Abstract] [Full Text] [PDF]

				R. Sniecinski, F. Szlam, E. P. Chen, S. O. Bader, J. H. Levy, and K. A. Tanaka Antithrombin Deficiency Increases Thrombin Activity After Prolonged Cardiopulmonary Bypass Anesth. Analg., March 1, 2008; 106(3): 713 - 718. [Abstract] [Full Text] [PDF]

				F. Szlam, T. Taketomi, C. A. Sheppard, C. L. Kempton, J. H. Levy, and K. A. Tanaka Antithrombin Affects Hemostatic Response to Recombinant Activated Factor VII in Factor VIII Deficient Plasma Anesth. Analg., March 1, 2008; 106(3): 719 - 724. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999