Perceived challenges and attitudes to regimen and product selection from Italian haemophilia treaters: the 2013 AICE survey.

Despite great advances in haemophilia care in the last 20 years, a number of questions on haemophilia therapy remain unanswered. These debated issues primarily involve the choice of the product type (plasma-derived vs. recombinant) for patients with different characteristics: specifically, if they were infected by blood-borne virus infections, and if they bear high or low risk of inhibitor development. In addition, the most appropriate treatment regimen in non-inhibitor and inhibitor patients compel physicians operating at the haemophilia treatment centres (HTCs) to take important therapeutic decisions, which are often based on their personal clinical experience rather than on evidence-based recommendations from published literature data. To know the opinion on the most controversial aspects in haemophilia care of Italian expert physicians, who are responsible for common clinical practice and therapeutic decisions, we have conducted a survey among the Directors of HTCs affiliated to the Italian Association of Haemophilia Centres (AICE). A questionnaire, consisting of 19 questions covering the most important topics related to haemophilia treatment, was sent to the Directors of all 52 Italian HTCs. Forty Directors out of 52 (76.9%) responded, accounting for the large majority of HTCs affiliated to the AICE throughout Italy. The results of this survey provide for the first time a picture of the attitudes towards clotting factor concentrate use and product selection of clinicians working at Italian HTCs.

Identification of a novel and recurrent mutation in the SERPING1 gene in patients with hereditary angioedema.

Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is an autosomal dominant disorder caused by mutations in SERPING1 gene. More than 200 different mutations are known, with high genetic heterogeneity and high frequency of private familial mutations. We analyzed for genetic mutations the C1-INH locus in 11 Sardinian families, revealing in seven subjects from four unrelated families the novel nonsense mutation S318X. This mutation, detected with unexpected high frequency, accounts for over a third of the here reported Sardinian families affected by HAE. The recurrence of a pathogenic mutation within the same geographical area is a unique finding, previously unreported in HAE due to C1-INH deficiency.

Prophylaxis of venous thromboembolism in bariatric surgery.

Patients with morbid obesity who undergo bariatric surgery are usually considered at high risk of developing venous thromboembolism. Considering that deep vein thrombosis is often asymptomatic, primary prevention is the key to reducing morbidity and mortality. Between 1995 and 2003, 151 patients underwent surgery for morbid obesity at the Obesity Surgery Centre-University of Sassari. At the beginning of our experience in this field, in the first 65 cases, prophylaxis of thromboembolism consisted in a single intravenous injection of heparin sodium at the time of induction of anaesthesia. The dose of heparin ranged from 2500 to 5000 IU according to weight and any diseases associated with obesity. In a later stage of our experience (86 cases) we modified the drug therapy and used low doses of calcic heparin: the dose was obtained by daily monitoring of Pt, TT and aPTT in order to obtain good anticoagulation. This treatment was usually begun 4-5 days before the operation and continued until the patient was discharged (8-9 days). In the first group of patients we had 2 cases (3%) of fatal acute pulmonary embolism. In the second group 1 (1.16%) case of non-fatal pulmonary embolism developed on postoperative day 20. No clear consensus emerges from the literature as to the best approach to reduce the risk of thromboembolism in bariatric surgery to a minimum. Our experience suggests that "personalized heparin prophylaxis" before, during and after bariatric surgery could be the key to reducing morbidity and mortality.

Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen AO-chain gene are not associated with the decay of the mutant mRNAs

Congenital afibrinogenemia is a rare coagulation disorder with autosomal recessive inheritance, characterized by the complete absence or extremely reduced levels of fibrinogen in patients, plasma and platlets. Eight afibrinogemic probands, with very low plasma levels of immunoreactive fibriogen were studied. Sequencing of the fibrinogen gene cluster of each proband disclosed 4 novel point mutations (1914C>G, 1193G> T, 1215delT, and 3075C> T) and 1 already reported (3192C>T). All mutations, localized within the first 4 exons of the AO-chain gene, were null mutations predicted to produce severely truncated AO-chains because of the presence of premature termination codons. Since premature termination codons are frequently known to affect the metabolism of the corresponding messenger RNAs (mRNAs), the degree of stability of each mutant mRNA was investigated. Contransfection experiments with plasmids expressing the wild type and each of the mutant AO-chains, followed by RNA extraction and semiquantative reversetranscriptase-polymerase chain reaction analysis, demonstrated that all the identified null mutations escaped nonsense-mediated mRNA decay. Moreover, ex vivo analysis at the protein level demonstrated that the presence of each mutation was sufficient to abolish fibrinogen sectretion. (AU)