The Australian and New Zealand Haemostasis Registry: ten years of data on off-licence use of recombinant activated factor VII.

BACKGROUND: Recombinant activated factor VII (rFVIIa) has been widely used as an off-licence pan-haemostatic agent in patients with critical bleeding. However, outside the trauma setting, there is relatively little high quality evidence on the risks and benefits of this agent. The Haemostasis Registry was established to investigate the extent of use, dosing, safety and outcomes of patients after off-licence rFVIIa treatment of critical bleeding. MATERIALS AND METHODS: The Registry recruited non-haemophiliac patients treated with rFVIIa from 2000-2009 (inclusive) in Australia and New Zealand. Detailed information was gathered on patients' demographics, context of bleeding, rFVIIa administration, laboratory results, blood component and other therapies, and outcomes. Outcome measures included subjectively assessed effect of rFVIIa on bleeding (response), adverse events (thromboembolic and other) and 28-day mortality. RESULTS: The registry included 3,446 cases in 3,322 patients (median [IQR] age 56 [33-70] years, 65% (n=2,147) male). Clinical indications included cardiac surgery (45%), other surgery (18%), trauma (13%), medical bleeding (6%), liver disease (6%), and obstetric haemorrhage (5%). The median [IQR] dose was 91 [72-103] µg/kg and 77% received a single dose. Reduction or cessation of bleeding was reported in 74% and 28-day survival was 71% but outcomes varied depending on clinical context. pH strongly correlated with outcome measures; 81% of patients with pH <7.1 died. Approximately 11% of patients had thromboembolic adverse events. In multivariate analysis, pH prior to administration and bleeding context were independently associated with reported response to rFVIIa and 28-day mortality. DISCUSSION: The Haemostasis Registry is the largest dataset of its kind and provides observational data on the off-licence use of rFVIIa over a 10-year period. It has been an invaluable resource for rigorously tracking adverse events and helping to inform clinical practice.

Long-term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia: a prospective study.

Infectious and thrombotic complications limit the long-term use of subcutaneous ports as venous accesses for children with haemophilia. This study has evaluated for the first time the safety and feasibility of internal arteriovenous fistulae (AVF) as alternative accesses. During the 3-year study period, 27 severe haemophiliacs, 14 with factor VIII inhibitors (52%), underwent the creation of 31 proximal AVF in the forearm. Mild forearm haematomas were observed after five procedures (16%) in five patients who had or developed inhibitors after surgery. Inadequate AVF maturation was observed after five of 31 procedures (16%) in four children. AVF were first accessed after a median of 42 d and regularly used at home by 26 patients (96%) for a median follow-up period of 29 months. Thrombosis of a venous branch occurred in one AVF (3%) after 9 months of uncomplicated use in a child with inhibitor who spontaneously recovered from the symptoms and still used AVF for nine additional months. Mild symptoms, referable to distal ischaemia, were transiently reported by two children (7%) who needed no remedial intervention. This study demonstrates that the use of AVF in haemophiliacs enabled long-term treatment at home in all patients but one.