Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency.

BACKGROUND: Congenital fibrinogen deficiency (CFD) is a rare, inherited disorder affecting normal blood clotting function, where patients can experience severe and/or frequent bleeding episodes (BEs). Treatment with human fibrinogen concentrate (HFC) can prevent/arrest bleeding. There is a need for more data on the efficacy, pharmacokinetics (PK) and safety of HFC treatment in paediatric patients with CFD. METHODS: Haemostatic efficacy of HFC (Fibryga® , Octapharma AG) for on-demand treatment of bleeding and surgical prophylaxis in patients <12 years old was assessed by investigators and an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) based on an objective 4-point efficacy scale. Maximum clot firmness (MCF; surrogate marker of haemostatic efficacy), single-dose PK and safety were also assessed. RESULTS: Of 14 patients receiving HFC (median [range] age 6.0 years [1.0-10.0]), eight received HFC for 10 BEs, three for surgical prophylaxis and 13 for PK. The IDMEAC rated haemostatic efficacy as 100% successful for on-demand BE treatment (95% CI 69.15-100.00) and surgical prophylaxis (95% CI 29.24-100.00). After a mean first dose of 70.78 mg/kg for BEs, mean (±SD) MCF significantly increased from pre-treatment to 1-hour post-infusion (3.3 mm [±1.77]; P = 0.0002), coinciding with haemostatic efficacy. PK parameters were favourable. Two possibly related adverse events occurred, including one serious (portal vein thrombosis). No allergic/hypersensitivity reactions or deaths were observed. CONCLUSION: HFC treatment for on-demand treatment of BEs and surgical prophylaxis was efficacious for this ultra-rare paediatric population with congenital afibrinogenaemia and showed a favourable PK and safety profile.

Psychosocial Issues in Children With Thalassemia: From Identification to a Model for Management in a Developing Country.

INTRODUCTION: Children with chronic disorders like ß thalassemia major (TM) and their care givers are known to face various psychosocial problems. This study used screening tests to detect these psychosocial issues so that prompt referral for counseling is possible. METHODS: A semistructured demographic questionnaire, Pediatric Symptom Checklist (PSC-17) and the Strengths and Difficulties Questionnaire (SDQ) were administered to 30 children with TM, on regular treatment at a tertiary care hospital. The same questionnaires were administered to age-matched and sex-matched controls. Parents were administered the General Health Questionnaire (GHQ). Children with TM scored higher on both PSC-17 (9.93 vs. 4.87; P<0.001) and SDQ (14.9 vs. 10.9; P=0.008). The parents of children with TM scored higher on the GHQ (10.3 vs. 8.0; P=0.027). RESULTS: Psychosocial morbidity was higher in children with TM and their care-givers. Screening tools help detect children and care givers in need of formal counseling. CONCLUSIONS: The study makes a case for management of these issues by the pediatrician in tandem with mental health professionals. Some strategies that can be used in managing these children and their families are presented. In addition, issues in management with particular focus on a developing country context are highlighted and discussed.

Glanzmann Thrombasthenia in Children: Experience From a Tertiary Care Center in Southern India.

BACKGROUND: Glanzmann thrombasthenia (GT) is a globally rare inherited disorder of hemostasis. OBJECTIVES: To describe the clinical profile of GT in a tertiary care center in Southern India. METHODS: A retrospective chart review of all children with GT was performed between January 2005 and August 2017 in the Department of Paediatrics. RESULTS: A total of 48 patients (representing 43 families) were included. Median age at diagnosis was 2.75 years (interquartile range: 1.5 to 6.75). Two thirds had an onset of bleeding within the first 2 years of life. Sixty-seven percent were born out of consanguineous marriage. The common symptoms were epistaxis, gingival bleeding, and ecchymoses. Neonatal onset of bleeding manifested as purpura, epistaxis, and intracranial hemorrhage. Postsurgical bleeding and menorrhagia were unique presentations in adolescence. About 25% had life-threatening hemorrhage while 50% had growth retardation due to chronic anemia. CONCLUSIONS: GT is relatively more common in areas of Southern India due to the higher prevalence of consanguinity. Chronic anemia can contribute to growth stunting in these patients.

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule.

BACKGROUND: Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age. METHODS: 299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age. RESULTS: One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 µg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group. CONCLUSIONS: The DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00473668.

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients.

BACKGROUND: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. METHODS: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. RESULTS: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. CONCLUSIONS: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.

Fanconi's anemia in monozygotic twins.

Fanconi's anemia is one of the inherited causes of bone marrow failure. It is inherited in autosomal recessive fashion. It presents as aplastic anemia usually at the age of 7-8 yr. Leukemias and solid tumours are complications in those who manage to survive beyond two decades. Though it has been seen in siblings, reports in monozygotic twins have been very few.

Spinal intramedullary neuroepithelial (ependymal) cyst. A rare cause of treatable acute para paresis.

An 8-yr-old female child presented with acute onset of severe pain in the lower limbs and difficulty in walking. Spine MRI showed hyperintense signals on T2 weighted images at T2-T3 level, which was intramedullary in location. The patient was operated and histopathology reported as neuroepithelial cyst. Spinal intramedullary neuroepithelial cysts are rare. Spinal cord compression due to the cyst is very uncommon and because of its rarity the present case is being reported. The clinical features, embryogenesis and literature were reviewed briefly.