Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

[1]  W. Schobersberger,et al.  The Effect of Fibrinogen Substitution on Reversal of Dilutional Coagulopathy: An In Vitro Model , 2006, Anesthesia and analgesia.

[2]  C. Kolbitsch,et al.  Normal values for thrombelastography (ROTEM) and selected coagulation parameters in porcine blood. , 2006, Thrombosis research.

[3]  D. Chinkes,et al.  Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs. , 2005, American journal of physiology. Endocrinology and metabolism.

[4]  T. Haas,et al.  Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model. , 2005, British journal of anaesthesia.

[5]  D. Spahn,et al.  Molecular weight of hydroxyethyl starch: is there an effect on blood coagulation and pharmacokinetics? , 2005, British journal of anaesthesia.

[6]  J. Ingerslev,et al.  Thrombelastographic whole blood clot formation after ex vivo addition of plasma substitutes: improvements of the induced coagulopathy with fibrinogen concentrate. , 2005, British journal of anaesthesia.

[7]  B. M. Cohen,et al.  Effects of coagulation factor deficiency on plasma coagulation kinetics determined via thrombelastography®: critical roles of fibrinogen and factors II, VII, X and XII , 2005, Acta anaesthesiologica Scandinavica.

[8]  K. Lindner,et al.  Gerinnungsmanagement beim Polytrauma , 2005, Der Anaesthesist.

[9]  J. Holcomb,et al.  RECOMBINANT FACTOR VIIa INCREASES THE PRESSURE AT WHICH REBLEEDING OCCURS IN PORCINE UNCONTROLLED AORTIC HEMORRHAGE MODEL , 2004, Shock.

[10]  S. Brunskill,et al.  Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials , 2004, British journal of haematology.

[11]  J. Duguid,et al.  Guidelines for the use of fresh‐frozen plasma, cryoprecipitate and cryosupernatant , 2004, British journal of haematology.

[12]  G. Findlay,et al.  Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients , 2004, British journal of haematology.

[13]  D. Tweardy,et al.  The effect of recombinant factor VIIa on noncoagulopathic pigs with grade V liver injuries. , 2003, Journal of the American College of Surgeons.

[14]  W. Schobersberger,et al.  The Effects of Perioperatively Administered Colloids and Crystalloids on Primary Platelet-Mediated Hemostasis and Clot Formation , 2002, Anesthesia and analgesia.

[15]  J. Holcomb,et al.  The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. , 2002, The Journal of trauma.

[16]  W. Schobersberger,et al.  The Effect of the Combined Administration of Colloids and Lactated Ringer’s Solution on the Coagulation System: An In Vitro Study Using Thrombelastograph® Coagulation Analysis (ROTEG®) , 2002, Anesthesia and analgesia.

[17]  S. Cohn,et al.  Early use of recombinant factor VIIa improves mean arterial pressure and may potentially decrease mortality in experimental hemorrhagic shock: a pilot study. , 2002, The Journal of trauma.

[18]  W. van Oeveren,et al.  A novel hydroxyethyl starch (Voluven®) for effective perioperative plasma volume substitution in cardiac surgery , 2000, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[19]  J. Feyh,et al.  Coagulation effects of a recently developed hydroxyethyl starch (HES 130/0.4) compared to hydroxyethyl starches with higher molecular weight , 2000, Acta anaesthesiologica Scandinavica.

[20]  K. Laczika,et al.  Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients , 1999, Intensive Care Medicine.

[21]  R. Strauss,et al.  An international view of hydroxyethyl starches , 1999, Intensive Care Medicine.

[22]  S. Hiippala Replacement of Massive Blood Loss , 1998, Vox sanguinis.

[23]  G. Schierhout,et al.  Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials , 1998, BMJ.

[24]  R. Ibbotson,et al.  Reduced quality of clot formation with gelatin-based plasma substitutes. , 1998, British journal of anaesthesia.

[25]  K. Lindner,et al.  Large-Dose Administration of 6% Hydroxyethyl Starch 200/0.5 for Total Hip Arthroplasty: Plasma Homeostasis, Hemostasis, and Renal Function Compared to Use of 5% Human Albumin , 1996, Anesthesia and analgesia.

[26]  E. Vahtera,et al.  Hemostatic Factors and Replacement of Major Blood Loss with Plasma-Poor Red Cell Concentrates , 1995, Anesthesia and analgesia.

[27]  P. Toy,et al.  Laboratory hemostatic abnormalities in massively transfused patients given red blood cells and crystalloid. , 1991, American journal of clinical pathology.

[28]  J. Tinker,et al.  Coagulation Changes during Packed Red Cell Replacement of Major Blood Loss , 1988, Anesthesiology.

[29]  D. Ménaché PROTHROMBIN COMPLEX CONCENTRATES: CLINICAL USE * , 1981, Annals of the New York Academy of Sciences.

[30]  T. Simon,et al.  Hemostasis in Massively Transfused Trauma Patients , 1979, Annals of surgery.

[31]  E. Engvall,et al.  Affinity of fibronectin to collagens of different genetic types and to fibrinogen , 1978, The Journal of experimental medicine.