Adherence to Transfusion Protocols and the Use of Recombinant Activated Factor VII.

Most hospitals have clinical guidelines for the off-label use of recombinant activated Factor VII (rFVIIa, Novoseven), primarily as part of a massive transfusion protocol. Over the past years rFVIIa has increasingly been used outside the approved indications in haemophilia with inhibitors and Glanzmann's Thrombasthenia, particularly in trauma, cardiac surgery and other critical bleeding episodes. Use in these areas remains controversial.

Monash University established the Haemostasis Registry in 2005 (with an educational grant from NovoNordisk Pharmaceuticals) to monitor the use of rFVIIa throughout Australia and New Zealand. More than 95 hospitals are contributing data to the Registry including all major users of rFVIIa in Australia and New Zealand. As part of the process of joining the Registry project, participating hospitals are asked to supply copies of their protocols for use of rFVIIa.

Approximately 3000 cases of rFVIIa use have been reported to the Register. Major areas of use are cardiac surgery (∼ 41%), other surgery (∼17%) and trauma (∼15%). The majority(77.3%) of hospitals have documented protocols for rFVIIa use. Many of these are similar and are centred around situations of massive transfusion. However, 64.5% of cases of rFVIIa use submitted to the Haemostasis Registry, from hospitals where protocols exist, do not conform with the numerical components of these protocols.

This is the largest dataset of rFVIIa cases published to date and can now provide greater insight into the actual rather than theoretical use of rFVIIa in Australia and New Zealand. Lack of compliance with hospital protocols for rFVIIa use indicates either that the protocols do not reflect actual and appropriate use or that clinicians need to be further educated regarding what is currently considered appropriate use. In the absence of sound clinical trial evidence, consensus regarding appropriate use has not been achieved. In these circumstances, data from the Haemostasis Registry continues to be important in elucidating the safety and efficacy of rFVIIa and providing important feedback to doctors and hospitals.

The Haemostasis Registry is funded through an unrestricted Educational Grant from NovoNordisk Pharmaceuticals Pty Ltd. None of the authors have a financial interest in the outcomes of the study.

Off Label Use: Recombinant activated Factor VII (rFVIIa, Novoseven). FVIIa is a naturally occurring initiator of haemostasis. Its recombinant form, rFVIIa, is approved for the treatment of spontaneous & surgical bleeding in patients with haemophilia A or B and with antibodies to either factor VIII or factor IX. It has been extensively used amongst haemophiliacs and appears to enhance clotting at the site of bleeding without systemic activation of the coagulation cascade At high doses rFVIIa binds to the surface of activated platelets and initiates the coagulation cascade at these sites Recently various case series and case reports have reported the efficacy of rFVIIa in patients with life-threatening bleeding in patients with coagulation disturbances but without coagulation inhibitors.