Factor XIII Assays and Associated Problems for Laboratory Diagnosis of Factor XIII Deficiency: An Analysis of International Proficiency Testing Results

Hsu, Peihong; Zantek, Nicole D.; Meijer, Piet; Hayward, Catherine P.M.; Brody, Judith; Zhang, Xinmin; Smock, Kristi J.; Cott, Elizabeth M. Van

doi:10.1055/s-0034-1365841

Cited by 24 publications

(29 citation statements)

References 15 publications

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“…The R‐ELISA FXIII method is a one‐step sandwich ELISA with good sensitivity (as low as 0.1%) and suitable for monitoring substitution therapy . Other methods, including EIA and RIA, are used infrequently due to lower sensitivity, laborious procedures, or because they may produce artifacts …”

Section: Resultsmentioning

confidence: 99%

Factor XIII deficiency diagnosis: Challenges and tools

Karimi

Peyvandi

Naderi

et al. 2017

Int J Lab Hematology

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Factor XIII deficiency (FXIIID) is a rare hereditary bleeding disorder arising from heterogeneous mutations, which can lead to life-threatening hemorrhage. The diagnosis of FXIIID is challenging due to normal standard coagulation assays requiring specific FXIII assays for diagnosis, which is especially difficult in developing countries. This report presents an overview of FXIIID diagnosis and laboratory methods and suggests an algorithm to improve diagnostic efficiency and prevent missed or delayed FXIIID diagnosis. Assays measuring FXIII activity: The currently available assays utilized to diagnose FXIIID, including an overview of their complexity, reliability, sensitivity, and specificity, as well as mutational analysis are reviewed. The use of a FXIII inhibitor assay is described. Diagnostic tools in FXIIID: Many laboratories are not equipped with quantitative FXIII activity assays, and if available, limitations in lower activity ranges are important to consider. Clot solubility tests are not standardized, have a low sensitivity, and are therefore not recommended as routine screening test; however, they are the first screening test in almost all coagulation laboratories in developing countries. To minimize the number of patients with undiagnosed FXIIID, test quality should be improved in less well-equipped laboratories. Common country-specific mutations may facilitate diagnosis through targeted genetic analysis in reference laboratories in suspected cases. However, genetic analysis may not be feasible in every country and may miss spontaneous mutations. Centralized FXIII activity measurements should also be considered. An algorithm for diagnosis of FXIIID including different approaches dependent upon laboratory capability is proposed. K E Y W O R D Sfactor XIII, factor XIII deficiency, factor XIII deficiency diagnosis, FXIII assays, laboratory assays | INTRODUCTIONInherited factor XIII deficiency (FXIIID) is a rare bleeding disorder affecting the final stage of the coagulation system and resulting in a bleeding diathesis.1 The worldwide incidence of FXIIID, inherited as an autosomal recessive disorder, is approximately one per 1-3 million people. Its prevalence depends on geographic region and is higher in areas in which consanguineous marriage is common; however, there is no difference worldwide in affected ethnicity or race. The molecular defects in FXIIID arise from heterogeneous mutations, which can be country-specific, facilitating methods to confirm FXIIID diagnosis in such areas. 2-4Signs and symptoms of FXIIID range from life-threatening hemorrhage such as intracranial hemorrhage to mild forms, including skin bleeding. Umbilical cord bleeding and soft tissue hematoma are the most common and often the first symptom of FXIIID. 3,5,6 In women with severe FXIIID, recurrent miscarriage is common. Heterozygous carriers may show a bleeding tendency upon provocation such as traumatic injury or invasive procedures, and in some cases, umbilical cord bleeding, menorrhagia, miscarriages, or postpartum ble...

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Section: Resultsmentioning

confidence: 99%

Factor XIII deficiency diagnosis: Challenges and tools

Karimi

Peyvandi

Naderi

et al. 2017

Int J Lab Hematology

View full text Add to dashboard Cite

show abstract

“…2 The Malay-and Indian-specific intervals appeared broader partly due to the small sample sizes, and the upper limits were higher compared to the Chinese limit. The post hoc analysis of pairwise comparisons showed that FXIII activity was statistically higher by approximately 18% in Malays and Indians when separately compared to Chinese.…”

Section: Relevance Of Ethnic Differences In Factor XIII Activity On Lmentioning

confidence: 98%

“…Separate ethnicity-specific reference intervals were obtained using the robust calculation. 2 The Malay-and Indian-specific intervals appeared broader partly due to the small sample sizes, and the upper limits were higher compared to the Chinese limit. The lower limit of the Chinese-specific interval was 41% compared to the Malay and Indian limits of 38% and 57%, respectively.…”

Section: Relevance Of Ethnic Differences In Factor XIII Activity On Lmentioning

confidence: 98%

Relevance of ethnic differences in factor XIII activity on laboratory reference ranges

Wong

Tan

et al. 2017

Int J Lab Hematology

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“…Qualitative methods such as a clot solubility test are frequently used for screening, especially in some countries with limited resources, but a significant number of patients are undiagnosed . Moreover, this semiquantitative functional method detects only severe FXIIID and not heterozygous deficiency, and it is poorly standardized . Heterozygous FXIIID is better diagnosed by a quantitative assay, such as amine incorporation and ammonia release assays . The Berichrom ® FXIII chromogenic assay from Siemens is a functional activity assay based on ammonia release which is commonly used for FXIII testing in France.…”

Section: Introductionmentioning

confidence: 99%