ETRO Working Party on Factor XIII Questionnaire on Congenital Factor XIII Deficiency in Europe: Status and Perspectives

Abstract

A questionnaire was sent out in 1993 to more than 350 European institutions caring for patients with hemorrhagic disorders with the request to provide data of patients with congenital factor XIII deficiency, to pursue the following aims: (1) establish a registry of congenital factor XIII deficiency patients, (2) promote exchange between clinicians and basic researchers, (3) improve diagnostic and therapeutic approaches, and (4) stimulate research on gene defects and their impact on factor XIII function. So far, 72 patient questionnaires from 60 families have been collected. Their bleeding pattern is typical, with frequent involvement of the umbilical cord and the central nervous system. Forty-nine patients receive regular factor XIII replacement, but obviously some patients with mild symptoms do not require prophylactic substitution, despite low factor XIII levels. On the other hand, 18 patients had factor XIII activities of > or = 5% of normal, but only 3 of those patients were reported to have no bleeding symptoms. Furthermore, 17 symptomatic, apparently heterozygous relatives in eight families were observed. Seven out of 30 females aged over 18 years had experienced spontaneous abortions; wound healing problems were seen in 26 patients. Currently, a second questionnaire is being distributed to obtain more detailed information on bleeding and other symptoms, diagnostic approaches, and exclusion of concurrent other bleeding diatheses. Future activities will be validation and standardization of assays, and study of gene defects and their impact on the structure of factor XIII and symptoms of patients. We intend to expand the survey to countries outside Europe.

Possible role for cellular FXIII in monocyte-derived dendritic cell motility

“…Monocytes lacking FXIII-A showed impaired receptor-mediated phagocytic activities (Sarvary et al, 2004). In spite of this, increased susceptibility to infectious diseases has not been reported in patients with FXIII-A deficiency (Seitz et al, 1996). Taken together, the herein reported data suggest that up-regulation of FXIII-A during DC differentiation may be crucially involved in migration of mature DCs.…”

Impaired dimer assembly and decreased stability of naturally recurring R260C mutant A subunit for coagulation factor XIII

“…In the final stage of the blood coagulation cascade, FXIII is activated by thrombin and promotes clot stability by forming covalent bonds between fibrin molecules; it also cross-links fibrin with other proteins including fibronectin and a 2 -plasmin inhibitor. Accordingly, FXIII deficiency results in defective crosslinking reactions, leading to a life-long bleeding tendency and abnormal wound healing in affected patients, and recurrent miscarriage in affected females (1,4).…”

Unusual Prevalence of c559T > C Mutation in Patients with Factor XIII deficiency in Southeast of Iran

“…Sistan and Balouchestan province with 2,700,000 population had about 200 FXIII deficient known cases (1 per 13,500 population), which is 70 times higher than the global average. The number of FXIII deficient cases were few in the other parts of the world, for example, in UK it was 26 cases (7) and 72 cases were recognized in a vast study carried out in European Coagulation Disorders Research Center (1996) (17). Frequency ratio of factor XIII deficiency to blood coagulation disorders was reported in 62% Caucasians, 6% in African-America, 19% in Latinos, 3% in Asian (7) whereas Factor XIII deficiency is the second most common blood coagulation disorders in southeast of Iran (10).…”