C-terminal RUNX1 mutation in familial platelet disorder with predisposition to myeloid malignancies.

Here we report a C-terminal RUNX1 mutation in a family with platelet disorder and predisposition to myeloid malignancies. We identified the mutation c.866delG:p.Gly289Aspfs*22 (NM_001754) (RUNX1 b-isoform NM_001001890; c.785delG:p.Gly262Aspfs*22) using exome sequencing of samples obtained from eight members of a single family. The mutation found in our pedigree is within exon eight and the transactivation domain of RUNX1. One of the affected individuals developed myelodysplastic syndrome (MDS), which progressed to acute myelogenous leukemia (AML). A search for the second hit which led to the development of MDS and later AML in this individual revealed the PHF6 gene variant (exon9:c.872G > A:p.G291E; NM_001015877), BCORL1 (exon3:c.1111A > C:p.T371P; NM_001184772) and BCOR gene variant (exon4:c.2076dupT:p.P693fs; NM_001123383), which appear to be very likely second hits participating in the progression to myeloid malignancy.

Safety and efficacy of recombinant activated factor VII in nonhemophilia children with severe or life-threatening bleeding: a report from the SeveNBleeP registry.

We evaluated efficacy and safety of recombinant activated factor VII (rFVIIa) in nonhemophilia children with life-threatening or severe bleeding. Using data from the SeveNBleeP registry, we analyzed demographic, clinical, laboratory, and treatment data for children who received rFVIIa to treat severe hemorrhage. The SeveNBleeP registry was international registry formed in 2005, to collect information on the use of rFVIIa in the off-label setting of severe bleeding in nonhemophilia patients. There were 191 patient records entered into this registry, of which 164 were validated. Of the 164 records, in 137 patient records, rFVIIa was used for treatment of bleeding episodes. Of these 137 treatment episodes, 42 were in neonates and infants under 1 year of age. Use of rFVIIa significantly improved laboratory parameters (prothrombin time, international normalized ratio, activated partial thromboplastin time, hematocrit), reduced estimated blood loss, and reduced requirements for blood products (packed red blood cells and fresh frozen plasma) in those more than 1 year of age. There was no significant reduction in requirements for blood products after rFVIIa administration in the neonates and infants, but there was a trend to lower frequency of FFP use after rFVIIa administration. There was one thromboembolic event in an infant that was related to administration of rFVIIa. No other serious adverse events were reported that were related to administration of rFVIIa. In nonhemophilia-associated bleeding in children, rFVIIa appears to be safe and efficacious in reducing estimated blood loss in children over 1 year of age, although its effectiveness in infants below 1 year of age was less clear.

Treatment of Deep Vein Thrombosis with Continuous IV Infusion of LMWH: A Retrospective Study in 32 Children.

Thirty-two consecutive children aged 0-18 years with VTE treated with LMWH administered as a continuous infusion (CI) were identified at the Children's University Hospital Brno. The treatment led to at least partial resolution of the thrombus within two weeks in 85% of patients. There were no adverse events or increased bleeding reported in any patients. No recurrences were observed during a followup period of 6 months. Although continuous infusion should not replace subcutaneous (SC) administration of LMWH, CI appeared to be safe and efficient and may provide an alternate method of administering LMWH in a subset of the paediatric population where SC administration may not be feasible. Further prospective studies are needed to support the promising findings of our pilot clinical observation.