Prothrombin Complex Concentrate Versus Recombinant Factor VIIa for Reversal of Hemodilutional Coagulopathy in a Porcine Trauma Model

被引:71
作者
Dickneite, Gerhard [1 ]
Doerr, Baerbel [1 ]
Kaspereit, Franz [1 ]
Tanaka, Kenichi A. [2 ]
机构
[1] CSL Behring GmbH, Dept Pharmacol & Toxicol, D-35041 Marburg, Germany
[2] Emory Univ, Sch Med, Dept Anesthesiol, Atlanta, GA 30322 USA
来源
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE | 2010年 / 68卷 / 05期
关键词
Prothrombin complex concentrates; Recombinant factor VIIa; Hemodilution; Blood coagulation disorders; Thrombin generation; Models; Animal; ACTIVATED FACTOR-VII; FRESH-FROZEN PLASMA; COAGULATION-FACTOR VIIA; DECREASES BLOOD-LOSS; V LIVER INJURIES; DILUTIONAL COAGULOPATHY; MASSIVE TRANSFUSION; THROMBIN GENERATION; BLUNT TRAUMA; HEMORRHAGE;
D O I
10.1097/TA.0b013e3181b06364
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Fluid resuscitation after traumatic injury may necessitate coagulation factor replacement to prevent bleeding complications of dilutional coagulopathy. Recombinant activated factor VII (rFVIIa) is being widely investigated as a hemostatic agent in trauma. Multicomponent therapy with prothrombin complex concentrate (PCC) containing coagulation factors II, VII, IX, and X might offer potential advantages. Methods: Anesthetized mildly hypothermic normotensive pigs were hemodiluted by substituting 65% to 70% of total blood volume in phases with hydroxyethyl starch and red cells. Thereafter, animals received 12.5 mL . kg(-1) isotonic saline placebo, 35 IU . kg(-1) PCC, or 180 mu g . kg(-1) rFVIIa. Immediately afterward, a standardized spleen injury was inflicted, and prothrombin time (PT) and hemostasis were assessed. Thrombin generation was also determined. Results: Hemodilution depleted levels of factors II, VII, IX, and X markedly, prolonged PT and decreased thrombin formation. PCC and rFVIIa both fully normalized the hemodilution-induced lengthening of PT. In PCC recipients, peak thrombin generation was greater by a median of 60.7 nM (confidence interval 56.4-64.9 nM) compared with the rFVIIa group (p = 0.008). After spleen trauma, time to hemostasis was shortened to a median of 35 minutes in animals treated with PCC versus 94 minutes with rFVIIa (p = 0.016). Conclusions: In a pilot study involving an in vivo large-animal model of spleen trauma, PCC accelerated hemostasis and augmented thrombin generation compared with rFVIIa. Further investigations are warranted on PCC as a hemostatic agent in trauma.
引用
收藏
页码:1151 / 1157
页数:7
相关论文
共 38 条
[1]   Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: Two parallel randomized, placebo-controlled, double-blind clinical trials [J].
Boffard, KD ;
Riou, B ;
Warren, B ;
Choong, PIT ;
Rizoli, S ;
Rossaint, R ;
Axelsen, M ;
Kluger, Y .
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 2005, 59 (01) :8-16
[2]   Effectiveness of alternative treatments for reducing potential viral contaminants from plasma-derived products [J].
Chandra, S ;
Groener, A ;
Feldman, F .
THROMBOSIS RESEARCH, 2002, 105 (05) :391-400
[3]   Prothrombin complex concentrate vs fresh frozen plasma for reversal of dilutional coagulopathy in a porcine trauma model [J].
Dickneite, G. ;
Pragst, I. .
BRITISH JOURNAL OF ANAESTHESIA, 2009, 102 (03) :345-354
[4]   Characterization of the coagulation deficit in porcine dilutional coagulopathy and substitution with a prothrombin complex concentrate [J].
Dickneite, Gerhard ;
Doerr, Baerbel ;
Kaspereit, Franz .
ANESTHESIA AND ANALGESIA, 2008, 106 (04) :1070-1077
[5]   Prothrombin complex concentrate versus recombinant factor VIIa for reversal of coumarin anticoagulation [J].
Dickneite, Gerhard .
THROMBOSIS RESEARCH, 2007, 119 (05) :643-651
[6]   The use of recombinant activated factor VII in obstetric and gynaecological haemorrhage [J].
Franchini, M. ;
Lippi, G. ;
Franchi, M. .
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2007, 114 (01) :8-15
[7]   Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy - a porcine model [J].
Fries, D. ;
Haas, T. ;
Klingler, A. ;
Streif, W. ;
Klima, G. ;
Martini, J. ;
Wagner-Berger, H. ;
Innerhofer, P. .
BRITISH JOURNAL OF ANAESTHESIA, 2006, 97 (04) :460-467
[8]   Fresh frozen plasma should be given earlier to patients requiring massive transfusion [J].
Gonzalez, Ernest A. ;
Moore, Frederick A. ;
Holcomb, John B. ;
Miller, Charles C. ;
Kozar, Rosemary A. ;
Todd, S. Rob ;
Cocanour, Christine S. ;
Balldin, Bjorn C. ;
McKinley, Bruce A. .
JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, 2007, 62 (01) :112-119
[9]   Thrombin generation, a function test of the haemostatic-thrombotic system [J].
Hemker, H. Coenraad ;
Al Dieri, Raed ;
De Smedt, Erik ;
Beguin, Suzette .
THROMBOSIS AND HAEMOSTASIS, 2006, 96 (05) :553-561
[10]   Calibrated automated thrombin generation measurement in clotting plasma [J].
Hemker, HC ;
Giesen, P ;
Al Dieri, R ;
Regnault, V ;
de Smedt, E ;
Wagenvoord, R ;
Lecompte, T ;
Béguin, S .
PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS, 2003, 33 (01) :4-15