SeveN BleeP Registry – 5 Years Later: An Update.

SeveN Bleep (Seven A in Nonhemophilia Bleeding in Pediatrics) is a web-based registry for collecting data on the use of rFVIIa in the treatment of severe and/or life threatening bleeding in children without hemophilia. The registry was endorsed by the Paediatric/Perinatal SSC subcommittee of ISTH.

The registry was established in 2005. During the five years of its existence, 191 cases were recorded, of which 164 (86%) records fulfilled the validation criteria and were eligible for further analyses. For the purpose of analysis, the patients were stratified into two groups: neonates and infants <1 year, and children >1 yr old. Statistical methods were used as appropriate.

Fifty nine (36%) valid records described the treatment with rFVIIa in neonates and infants, and 105 (64%) in older children. Of these, 27(16%) were for the prevention of severe bleeding. In the rest (84%) of cases, rFVIIa was used to treat severe bleeding. Those 137 cases (42 neonates+infants and 95 older children) were further analysed for the purpose of this report. The median weight in the <1 year old was 2.4 kg. The reasons for administration of rFVIIa included: bleeding during “non-trauma” surgery (17%), cardiac surgery (12%), trauma (12%) and intracranial haemorrhage (12%). Overall survival rate was 50%. Only one neonate experienced a thrombembolic event as a possible SAE from the treatment with rFVIIa. There were no deaths related to rFVIIa treatment.

In those older than 1 year, the median age was 10 years and median weight 30 kg. The reasons for administration of rFVIIa included trauma (45%), “non-trauma” surgery (14%) and bleeding related to malignancy and/or its treatment (11%). Survival rate in this group was 72%. 17% of deaths were related to the underlying hemorrhage treated. There were no thrombotic event or death related to rFVIIa treatment recorded in this group. There was a trend towards using a higher total dose (median 160ug/kg) in patients that died compared to a lower dose (median 120 ug/kg) in those who survived (p=0.078). In addition, those who survived needed lesser number of doses as compared to the deceased patients (median number of doses 1 and 2, respectively; p=0.052). Use of rFVIIa led to a significant decrease in the consumption of blood products in the 24 hour period after rFVIIa administration compared to the 24 hours prior to the use of rFVIIa - packed red cells (280 ml vs. 560 ml; p=0.001), FFP (250 ml vs. 500 ml; p=0.003). There were also significant changes in certain laboratory parameters related to rFVIIa administration also. Estimated blood loss decreased from 30 ml/kg prior to rFVIIa administration to 3 ml/kg after the use of rFVIIa (p=0.002).

SevNBleep registry has proven to be a useful international tool for collection of relevant clinical data on the use of rFVIIa. rFVIIa appears to be beneficial in the management of bleeding in the pediatric population. The prevalence of adverse events related to use of rFVIIa was very low, though not absent. To minimize the potential bias related to reporting of SAEs, all major contributing centers has been contacted for further information with regards to consecutive reporting of patients treated with rFVIIa.

Off Label Use: rFVIIa use in life threatening bleeding in children.