Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature

Abstract

Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern country with a high rate of consanguineous marriages, there are approximately 473 patients afflicted with FXIIID. An approximately 12-fold higher prevalence of FXIIID is estimated in Iran in comparison with overall worldwide frequency. In this study, we have undertaken a comprehensive review on different aspects of FXIIID in the Iranian population. The distribution of this disease in different regions of Iran reveals that Sistan and Baluchestan Province has not only the highest number of patients with FXIIID in Iran but the highest global incidence of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and prolonged wound bleeding are the most frequent clinical manifestations. There are several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg being the most common mutation in FXIIID in Iran. Traditionally, the management of FXIIID in Iran was only based on administration of fresh frozen plasma or cryoprecipitate, until 2009 when FXIII concentrate became available for patient management. Various studies have evaluated the efficacy and safety of prophylactic regimens in different situations with valuable findings. Although the focus of this study is on Iran, it offers considerable insight into FXIIID, which can be applied more extensively to improve the management and quality of life in all affected patients.

Factor XIII Deficiency, Review of the Literature and Report of a Case

“…Although fibrogammin-P is the product of choice, due to its unavailability, cryoprecipitate (containing F I, F VIII, F XIII and Von Willebrand Factor) was infused to control bleeding. In order to control bleeding before the dental procedure Factor XIII 10 -20 U/Kg concentrate was used as prophylactic therapy every four to six weeks in order to have adequate plasma level (19)(20)(21)(22). As routine, it is recommended for all F XIII-deficient patients to receive prophylactic treatment immediately after confirmation of the diagnosis due to high risk of intracranial hemorrhage.…”

Establishment of a prenatal diagnosis schedule as part of a prophylaxis program of factor XIII deficiency in the southeast of Iran

“…The disorder is mostly prevalent in regions with a high rate of parental consanguinity [1]. FXIIID is associated with different clinical manifestations varying from mild bleeding tendency to lifethreatening features.…”

Challenges in implementation of ISTH diagnostic algorithm for diagnosis and classification of factor XIII deficiency in Iran

“…J Thromb Haemost 2015; 13: 1735-6.Factor XIII (FXIII) deficiency is an extremely rare hemorrhagic disorder with an~12-fold higher incidence in Iran compared with the overall prevalence of the disorder [1]. Consanguineous marriage is a major reason for the high incidence of this disorder in the Iranian population [1,2].…”

“…Therefore, the clot solubility test has remained the first-line screening test for the detection of FXIII deficiency in all coagulation laboratories in Iran [1,4]. The procedures for detection of FXIII activity and inhibitors have been recently set up in a coagulation laboratory as a part of a research study [5].Although the clot solubility test alone is not suitable for FXIII deficiency screening, it has been performed for the confirmation of FXIII deficiency as a screening test in Iran in combination with family history and clinical presentation [1].FXIII antigen assays, including FXIII-A2B2 heterotetramers, FXIII-A2 and FXIII-B2 homodimers in plasma, or FXIII-A2 homodimer in platelets, have not been conducted in Iranian patients up to now even as part of research studies. Although molecular studies were performed in a large number of patients, almost all of these studies were limited to the southeast of Iran with the highest global prevalence of the disorder.…”

“…Consanguineous marriage is a major reason for the high incidence of this disorder in the Iranian population [1,2]. The high prevalence of FXIII deficiency in Iran requires more profound and extensive studies for the detection of other patients with mild bleeding disorders.…”