Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.
BACKGROUND
Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use.


OBJECTIVE
The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines.


METHODS
A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article.


RESULTS
Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%-57%).


CONCLUSIONS
As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.
Martinowitz
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U
National Hemophilia Center, Chaim Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. hemophil@bezeqint.net
Michaelson
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M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000628:therapy*; D002986:Clinical Trials as Topic; D005167:Factor VII / Q000191:economics / Q000627:therapeutic use*; D015942:Factor VIIa; D006470:Hemorrhage / Q000188:drug therapy* / Q000628:therapy*; D006489:Hemostatic Techniques; D006490:Hemostatics / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome
D006490:Hemostatics; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa