The disorder is rather frequent in Ashkenazi Jews, in whom around 98% of the abnormal alleles is represented by Glu117X and Phe283Leu mutations. A wide heterogeneity of causative mutations has been previously reported in a few FXI deficient patients from Italy. In this article, we enlarge the knowledge on the genetic background of FXI deficiency in Italy. Over 4 years, 22 index cases, eight with severe deficiency and 14 with partial deficiency, have been evaluated. find more A total of 21 different mutations in 30 disease-associated alleles were identified, 10 of which were novel. Among them, a novel Asp556Gly dysfunctional mutation was also identified.

Glu117X was also detected, as previously reported from other patients in Italy, while again Phe283Leu was not identified. A total of 34 heterozygous relatives were also identified. Bleeding tendency was present in very few cases, being inconsistently related to the severity of FXI deficiency in plasma.

In conclusion, at variance with other populations, no single major founder effect is present in Italian patients with FXI deficiency. “
“Summary.  Despite major advances in diagnosis and treatment, the management of patients with mild haemophilia (MH) remains a major challenge. Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU mL−1. The bleeding Selleck Panobinostat associated with mild haemophilia is most frequently episodic, occurring during surgery or following trauma. Spontaneous bleeding is rare. Diagnosis is sometimes delayed because of insensitivity of screening clotting assays or discrepancies in factor VIII activity as measured by different assays. The treatment of choice medchemexpress in mild haemophilia A is desmopressin, which typically induces a 2–6-fold increase of factor VIII over baseline. However, desmopressin has its limitations in this setting such as the occurrence of tachyphylaxis and failure to respond in an undetermined proportion of patients. Factors underlying poor biological response

or magnitude of response to desmopressin are incompletely understood. Inhibitor development in mild haemophilia is particularly distressing. This complication arises at an older age in this patient group because of infrequent need for factor VIII replacement. Inhibitors in mild haemophilia patients often cross-react with endogenous factor VIII resulting in severe spontaneous bleeding frequently in a postoperative setting. Intensive perioperative use of factor VIII and some specific mutations induce a particularly high risk for inhibitor development, but risk factors are incompletely understood. For reasons of the older age of the patients, treatment of bleeding with bypassing agents may cause major thrombotic complications. Data on therapeutic options for inhibitor eradication in patients with mild haemophilia are particularly scarce.