Prophylaxis in Hemophilia A Patients with Inhibitors

The development of antibodies to factor VIII is one of the most serious complications of haemophilia treatment. Approximately 30% of patients with severe haemophilia develop neutralizing inhibitors to replacement FVIII. Although most patients with inhibitors do not bleed more frequently than patients without inhibitors, bleeding is more difficult to control and this patients suffer more severe bleeding and have greater morbidity and mortality. Patients with persistent high-titer inhibitor who are not candidates or fail ITI, pose a great challenge to haemophilia management. The efficacy and safety of prophylaxis with bypassing agents in reducing bleeding tendency, has been described in numerous studies. Patients and methods: We report tree adult severe haemophilia A patients, two with persistent high-titre inhibitors and one who failed ITI, on prophylactic treatment after several significant musculoskeletal and life-threatening haemorrhagic episodes (intrabdominal/intramuscular) and pseudotumor haemorrhage. Treatment regimens consisted of APCC (Feiba®) in doses of 60-70UKg-1, 2-3 times per week, according underlying bleeding phenotype. Breakthrough bleeds were treated with either APCC (Feiba®) or rFVIIa (NovoSeven®). Results and Conclusion: There was reduction in total bleeding episodes in two patients (43% to 80%) and one patient remained stable, while receiving prophylaxis. Absence of severe and life threatening bleeding episodes, as well as inpatient stays, contributing to a better quality of life in those patients, was observed. APCC (Feiba®) was well tolerated and no thrombotic events were observed.

Incidentes de Segurança do Doente. Porquê Relatar?

Na última década, verificou-se uma preocupação crescente dos profissionais e instituições de saúde, pelas questões associadas à segurança dos doentes e vários estudos revelaram ao mundo que nos hospitais os incidentes associados aos cuidados de saúde são frequentes. O relatório “To Err is Human” reforçou a evidência de que ocorriam cerca de dez eventos adversos, em cada 100 episódios de internamento e que 50% destes, poderiam ter sido evitados. Em Portugal um estudo epidemiológico sobre eventos adversos em contexto hospitalar levado a cabo pela Escola Nacional de Saúde Pública, evidenciou em 2010 uma taxa de incidência de 11,1%. Torna-se evidente a necessidade de uma intervenção global nas questões da segurança do doente, pelo que, a organização Mundial de Saúde lançou vários desafios, sendo um deles a criação e implementação de Sistemas de Relatos de Incidentes nas organizações de saúde. A principal finalidade destes sistemas é a partilha e aprendizagem com os erros de forma a encontrar soluções para a sua prevenção. Este artigo tem como objetivo apresentar a experiência do Centro Hospitalar de Lisboa Central na implementação de um sistema de relato de incidentes de segurança do doente ao longo de treze anos.

Urinary Tract Effects of HPSE2 Mutations

Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.