Abstract Consensus evidence-based guidelines regarding prophylactic treatment for circumcision in patients with haemophilia are lacking. In this study, we retrospectively examined the results of circumcision of 40 consecutive neonates with haemophilia, diagnosed after delivery. Our protocol included application of a single dose of factor replacement prior to the procedure and 3 days’ oral treatment with tranexamic acid. Only 3/40 neonates with haemophilia experienced mild postcircumcision bleeding. No major or any life-threatening bleeds were encountered. As the therapy administered was minimal and the procedure simple and feasible, we concluded that circumcision in neonates with haemophilia should be performed according to family’s and physician’s discretion. Avoidance of circumcising male babies with haemophilia due to fear of bleeding complications is not supported by the results shown within our patient cohort.

SummaryOur goal in this research was to evaluate potential and targeted therapy, correlated with haemophilia severity and dental procedural risk, to reduce postoperative bleeding risk. Patients with haemophilia who were treated at the Oral and Maxillofacial Surgery Clinic at Sheba Medical Center between 1996 and 2012 comprised the study cohort. Data collected included disease history and severity, perioperative factor concentrate therapy, local haemostatic agent application, systemic tranexamic acid use and outcome. Bleeding was defined as excessive bleeding during or within 20 days following procedure. Dental procedures (n = 1968) of 125 patients were studied. Patients’ bleeding risk score was evaluated according to the severity of haemophilia with or without the presence of an inhibitor, presence of comorbid coagulopathy and the type of dental procedure. Thirty‐four patients undergoing a total of 880 high‐risk and 1088 low‐risk procedures suffered 40 postoperative bleeding events that necessitated further dental and/or haematological intervention. Among risk factors for delayed bleeding, the use of fibrin glue was significantly (P = 0.027) associated with the risk of postprocedural bleed probably as it was applied to high‐risk patients and procedures. Earlier treatment period (P = 0.055), postprocedure hospitalization (P = 0.039) and dental “high‐risk” procedures (P < 0.0001) also increased bleeding risk. Patients with haemophilia may be safely treated if meticulous haemostasis is applied, along with fibrin glue and systemic therapy as required. Factor transfusions are not mandatory and should be applied considering the procedure‐related risk and the patient's calculated haematological risk for bleeding.

Single-nucleotide polymorphisms (SNPs) near the IL28B gene were identified as major predictors of treatment response (sustained virologic response--SVR) and spontaneous clearance of HCV. Haemophilia patients have the highest prevalence of HCV, and are a unique target for genetic studies. The Israeli population is ethnically heterogeneous; therefore, genetic variability is anticipated. To determine the IL28B haplotypes in HCV-infected haemophilia patients and association with SVR and spontaneous viral clearance. IL28B polymorphism at SNPs rs12979860 and rs8099917 was determined in sera obtained from 130 HCV-infected haemophilia patients. The frequency of the various haplotypes was analysed according to treatment response, spontaneous HCV clearance, viral load and degree of fibrosis. The CC haplotype at SNP rs12979860 was found in 31% of patients, whereas the TT genotype at SNP rs8099917 was detected in 57% of cases. SVR was achieved in 70% of patients carrying the CC haplotype (P = 0.0196 vs. CT/TT), and 50% of the TT genotype at SNP rs8099917 (P = 0.0227 vs. TG/GG). Thirty-five percent of patients carrying the CC haplotype and 26% with the TT genotype at SNP rs8099917 showed spontaneous clearance of HCV infection (P = 0.00262 vs. CT/TT; and P = 0.00371 vs. TG/GG respectively). The C-allele frequency was exceptionally high (71%) in immigrants from the Asian republics of Russia. In HCV-infected haemophilia patients, SVR was more commonly achieved among patients who had the CC (rs12979860) or TT (rs8099917) genotype. Likewise, patients who possess harbour the CC or TT genotypes were more likely to clear HCV infection spontaneously. A unique distribution of the CC genotype was observed in some ethnic groups.

Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety-two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min-max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or 'continuous infusion' and the family history of inhibitor development were investigated. During the follow-up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36-8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies.

POSTERSat Week 8 and were eligible for shorter therapy.These patients attained similarly high SVR rates in both arms (86% [64/74] BOC RGT and 88% [74/84] BOC/PR48).As seen in treatment-naive patients, comparable lower SVR rates were reported in previous-treatmentfailure patients with detectable HCV-RNA results at Week 8 in the BOC RGT and BOC/PR48 arms (40% and 43%, respectively).Conclusions: BOC RGT reduced treatment duration in patients with early HCV-RNA negativity at Week 8 in both treatment-naive and previous-treatment-failure patients.Many patients will only require 24 or 32 weeks of BOC therapy.SVR by Week 8 HCV-RNA Week 8 HCV-RNA SVR, n/N (%) Treatment Naive Previous Treatment Failures BOC RGT BOC/PR48 BOC RGT BOC/