GTC Biotherapeutics (fka GTCB)

[DB9]

Reversal of coagulopathy in critically ill patients with traumatic brain injury: recombinant factor VIIa is more cost-effective than plasma.
http://www.ncbi.nlm.nih.gov/pubmed/19131807?dopt=Abstract

Stein DM, Dutton RP, Kramer ME, Scalea TM.
J Trauma. 2009 Jan.

R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [e-mail]

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability after trauma. Coagulopathy is common in this patient population and requires rapid reversal to allow for safe neurosurgical intervention and prevent worsening of the primary injury. Typically reversal of coagulopathy is accomplished with the use of plasma. Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has become increasingly used "off-label" in patients with neurosurgical emergencies to rapidly reverse coagulopathy. We hypothesized that the use of rFVIIa in this patient population would prove to be cost-effective as well as demonstrate clinical benefit.
METHODS: The trauma registry at the R Adams Cowley Shock Trauma Center was used to identify all coagulopatic trauma patients admitted between January 2002 and December 2007 with relatively isolated TBI (head Abbreviated Injury Scale score of >or=4). The medical records of patients were reviewed and demographics, injury-specific data, medications administered, laboratory values, blood product utilization, neurosurgical procedures, length of stay (LOS), discharge disposition, and outcome data were abstracted. Patients who received rFVIIa for reversal of coagulopathy were compared against those who did not receive rFVIIa. t Tests were used to compare differences between continuous variables, and chi2 analysis was used to compare categorical variables. A p value of <0.05 was considered significant for all statistical tests.
RESULTS: During a 6-year period, there were 179 patients who met inclusion criteria. One hundred eleven patients (62.0%) were treated with conventional therapy alone whereas 68 (38.0%) received rFVIIa. Baseline characteristics between the two groups were similar except that Injury Severity Score and admission International normalized ratio were higher in the rFVIIa group and the rFVIIa group had a higher percentage of patients with head Abbreviated Injury Scale score of 5 injuries, patients who underwent neurosurgical procedures and patients with preinjury warfarin use. There was no difference in total charges between these groups (mean US $63,403 in the conventionally treated group vs. $66,086). When patients who required admission to the intensive care unit were analyzed (n = 110, 50% received rFVIIa), total mean charges and costs were significantly lower in the group that received rFVIIa (mean US $108,900 vs. $77,907). Hospital LOS, days of mechanical ventilation, and plasma utilization were lower in the rFVIIa group. Mortality and thromboembolic complication rates were not different between the two groups.
CONCLUSION: In this study, we were able to demonstrate a significant economic benefit of the use of rFVIIa for reversal of coagulopathy in severely injured patients with TBI. Not all patients with coagulopathy and an anatomic brain injury benefit, but in patients who are neurologically or physiologically compromised, using rFVIIa decreases total charges and costs of hospitalization. This decrease in overall cost is directly attributable to the significant decrease in LOS and decrease in the need for mechanical ventilation. This study demonstrates that in coagulopathic patients with TBI who require intensive care unit admission, rFVIIa is cost-effective and safe. Prospective studies are needed to confirm these findings and establish clinical effectiveness.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 19131807 [PubMed - in process]






Use of albumin fusion technology to prolong the half-life of recombinant factor VIIa.
http://www.ncbi.nlm.nih.gov/pubmed/18929521?dopt=Abstract

Schulte S.
Thromb Res. 2008

CSL Behring GmbH, Emil-von-Behring Strasse 76, Marburg, Germany. [e-mail]

A significant proportion of patients with haemophilia A develop inhibitors to administered factor VIII (FVIII) and require therapy with bypassing agents such as activated factor VII (FVIIa) or activated prothrombin complex concentrates. NovoSeven is a commercially available recombinant FVIIa (rFVIIa) with a very short half-life of approximately 2.4 hours. As a result, patients generally require multiple, frequent infusions for the management of bleeding episodes. Thus, there is growing interest in extending the circulating half-life of coagulation factors through the use of innovative drug delivery and formulation technologies. One such approach uses albumin fusion technology in which human albumin is genetically fused to the C-terminus of rFVIIa via a flexible glycine serine linker. The properties of this rFVIIa fusion protein (rVIIa-FP) have recently been examined in pre-clinical studies. Results from these investigations demonstrate the feasibility of this approach, which successfully extended the half-life and biological activity of rFVIIa without compromising haemostatic efficacy. These data suggest that rVIIa-FP may be a promising therapy for the treatment of haemophilia patients with inhibitors and warrants further investigation in clinical trials.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 18929521 [PubMed - indexed for MEDLINE]