ALBERT

Description: Background Factor XIII deficiency (FXIIID) is a rare bleeding disorder (RBD) with high bleeding tendency. A wide spectrum of bleeding episodes was reported in patients with severe FXIIID. These bleeding diathesis include delay wound bleeding, intracranial hemorrhage, epistaxis and gum bleeding. A plasma level 3% to 10% of factor XIII is sufficient to prevent occurrence of bleeding in these patients. Here we design a study with two groups including heterozygote of FXIIID and normal population as a control group to assessed present of bleeding episodes in heterozygote patients. Method This prospective study was carried out on 53 (50 females and 3 males) heterozygote patients of FXIIID as well as the same number of normal population in duration of 3 months. All heterozygote individuals were selected from homozygote patients’ family. Healthy individuals were selected randomly from different parts of provinces. Both groups were age and sex matched (p=0.3). All individuals were assessed for factor XIII deficiency by FXIII activity assay and molecular analysis for Trp187Arg; the only previously reported polymorphism of factor XIII-A subunit in southeast Iran. Initially the clinical manifestations of all cases were assessed retrospectively and recorded. Then we assessed and compared the bleeding tendency in both groups by using the adult bleeding questionnaire and in one-month intervals. Results The mean ages of study populations were 34.8±8.4 (Ranges from 20 to 48 years) and 33.9±9.1 (Ranges from 21 to 49.5 years) in case and control groups, respectively. FXIII activity of the patient group was between 50-70 % and molecular analysis revealed that all the patients were heterozygote for Trp187Arg mutation. By regards to ethnicity, most of individuals in case group were Baluch (Number: 50 (94.3%)) and remained minority was Zaboli (Number: 3 (5.7%)). Distribution of ethnicity among case group was completely matched with control group (p=0.3). None of study individuals had a history of liver or kidney diseases or other bleeding susceptibility disorders. Clinical investigations indicated that 3 patients had a history of umbilical cord bleeding and delayed separation of the umbilical cord which led to administration of FXIII concentrate. All the 3 patients later presented with delayed post-circumcision bleeding. The mean age of menorrhagia in 50 females was 13.9±1.1 (Ranges from 12 to 16 years). Menstrual intervals range from 20 to 60 days with a mean of 29±5.2 days, but half of the patients had a normal interval of 30 days. Twenty three females had experienced menstruations with the need for a new pad every 2 hours. Among affected females 15 had an abnormal menstruation with duration of more than 7 days. Eight females were complicated by menorrhagia. This phenomenon observed in only one female of control group and therefore a significant difference was found between cases and controls (p

Description: Background: factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with an estimated incidence of 1 per 1 to 3 million that transmitted in an autosomal recessive manner. The disorder is characterized by severe bleeding diathesis, impaired wound healing and recurrent spontaneous miscarriage. Sistan and Baluchistan Province in south east of Iran with high rate of consanguineous marriages has the highest incidence of FXIIID around the world. The aim of this study was to evaluate clinical manifestations and prophylaxis therapy in FXIII deficient patients with life threatening complications and to assess the risk of FXIII inhibitor development in patients with long term prophylaxis. We also investigated prophylaxis treatment in neonates with FXIIID. Methods: This study was conducted on 190 patients with FXIIID from southeast of Iran. Diagnosis of FXIIID was based on factor activity and molecular investigation of Trp187Arg which is the only reported mutation of FXIII in this region. We also selected some cases for sequencing to confirm the molecular results.Patients underwent regular prophylaxis and the efficacy of prophylaxis was assessed by prospective follow-up in duration of 4 years. The frequency of bleeding episodes as described by Tosetto et al. was recorded before and after prophylaxis each month. Patients with Intracranial hemorrhage (ICH) received Fibrogammin P® in a dose of 30 IU/Kg every 4 day as prophylaxis and in a dose of 10-26 IU/kg when ICH occurred. Patients with miscarriage underwent regular prophylaxis with FXIII concentrate with a dose of 10 IU/Kg every 2 weeks during pregnancy and also received the same dose as prophylaxis before gestation in 4 week intervals.In cases that had a history of prophylaxis for more than 4 years or had more than 50 injections, development of FXIII inhibitor was investigated by Bethesda assay. We evaluated plasma FXIII activity and FXIII inhibitor in day 28 after the last prophylaxis administration by Cobas Mira device. This assay was performed on a large amount of population for the first time. If the result of inhibitor was negative the test was replicated with 3 dilutions.We also enrolled 34 neonates with FXIIID to the study and divided them into two groups. Group 1 (17 neonates) received a standard dose of Fibrogammin (10-26 IU/Kg) while group 2 (17 neonates) received a dose of 60-80 IU/Kg. We followed both groups for 36 months and the frequency of bleeding episodes was recorded for each group and compared using independent t-test. Neonates in group 2 were assessed for thrombotic events promptly after administration of Fibrogammin P®, the following day and one week later. Results: Plasma FXIII activity in all patients was undetectable which is suggestive of severe deficiency. Genetic analysis revealed a homozygous Trp187Arg mutation in all patients and it was in agreement with the sequencing results of selected cases. Clinical manifestation of patients and the bleeding score of different diathesis before and after prophylaxis are indicated in table 1. Forty nine patients had the defined criteria for investigation of FXIII inhibitor development. Among them 14 had experienced ICH. Despite long term prophylaxis in these patients none of them was detected to develop FXIII inhibitors. No patient with ICH experienced this phenomenon after prophylaxis treatment. The majority of patients with miscarriage only experienced this diathesis once (62.5%). The prophylaxis program was successful in management of pregnancy in all 8 patients. Comparison of two neonate groups revealed that bleeding episodes in group 2 were significantly lower than group 1 (p