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

Abstract

To cite this article: Dorgalaleh A, Farshi Y, Alizadeh SH, Naderi M, Tabibian SH, Kazemi A, Hosseini S. 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]. The high prevalence of FXIII deficiency in Iran requires more profound and extensive studies for the detection of other patients with mild bleeding disorders. The southeast of Iran (Sistan and Baluchestan Provinces) has the highest global incidence of FXIII deficiency, with 352 patients. Traditionally, FXIII deficiency is diagnosed by a clot solubility test in this province, as in other parts of the country [1]. After establishment of a molecular diagnosis for FXIII deficiency in the southeast of Iran, the number of patients dramatically increased, which highlighted the low sensitivity of the clot solubility test for the detection of FXIII deficiency [1,2]. In fact, a considerable number of patients with FXIII deficiency were undiagnosed through use of the clot solubility test. Although clinical presentations are strongly suggestive of FXIII deficiency, precise diagnosis of this disorder requires more-specific laboratory tests. For this purpose, an algorithm was recommended for the diagnosis and classification of FXIII deficiency. This algorithm includes plasma FXIII activity, FXIII-A2B2, FXIII-A, and FXIII-B antigen levels, as well as FXIII activity and FXIII-A antigen in platelets. Detection of autoantibodies against FXIII subunits, SDS-PAGE, and molecular diagnosis form other parts of this algorithm [3]. Although this algorithm presents a complete and convenient laboratory approach for the diagnosis and classification of FXIII deficiency, its application is limited in Iran. The low number of patients is the most important cause of this limitation, which leads to low investment for establishment of full laboratory tests for this bleeding disorder. Although factor activity and antigen assays for most other rare bleeding disorders are available in a number of coagulation laboratories, due to higher costs of the FXIII activity kit and the concentration of most patients in the southeast of Iran, the establishment of FXIII activity and antigen assays has been limited. 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 fam...

Effects of factor XIII deficiency on thromboelastography. Thrombelastography with calcium and lysis by addition of streptokinase is more sensitive than solubility tests

“…However, there is increasing evidence that more than 50% of patients with low pFXIII levels, but higher than 5%, could have bleeding complications after surgery, trauma or dental extraction7,8 because of a heterozygous deficiency condition, affecting either A or B subunits. Moreover, the patients with either congenital heterozygous or acquired FXIII deficiency, due to consumption or autoantibody inactivation, experience bleeding 9–12…”

“…The clot solubility test is an inexpensive procedure that has been used in hemostasis laboratories, but it has the limitation of detecting only homozygous or double heterozygous FXIII deficiency 6,9,13. Quantitative assays of FXIII activity and antigen are now recommended by experts because they can detect heterozygous congenital as well as mild acquired deficiencies, automate instruments can be used and then they can be better standardized 6.…”

Detection of Factor XIII deficiency: data from multicentre exercises amongst UK NEQAS and PRO‐RBDD project laboratories

“…However, despite this, the method is still employed in 25% and 43% of UK NEQAS BC and PRO‐RBDD centres, respectively, in most cases without concurrent availability of a specific assay. The solubility method is a low‐cost test which may be used by laboratories where budgetary restraints are an issue . We have previously reported that sensitivity of the solubility screen can be improved by modification of reagents used to clot and lyse plasma , and subsequent studies have confirmed this finding ; however, in the second exercise, 7/12 PRO‐RBDD centres continued to use the least sensitive reagent combination, of calcium and urea.…”

Diagnosis and Management of Congenital and Acquired FXIII Deficiencies

“…In exceptional cases, when one or two known causative mutations occur with high frequency in a country, like p.Arg77His and p.Trp187Arg in Iran, molecular genetic analysis might contribute to the diagnostic efficiency. 54 Obviously, in the case of known causative mutations in parents, prenatal genetic analysis is of high importance.…”