Measurement of factor XIII activity in plasma

Katona, Éva; Pénzes, Krisztina; Molnár, Éva; Muszbek, László

doi:10.1515/cclm-2011-0730

Cited by 35 publications

(50 citation statements)

References 51 publications

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“…Patients with less severe FXIII deficiency (with levels from 2%‐50% activity) are rarely symptomatic, and may only be diagnosed after an invasive procedure or other hemostatic challenge. Traditionally, FXIII deficiency has been assessed qualitatively by plasma clot solubility in concentrated urea, acetic acid, or monochloroacetic acid . However, since clot solubility assays detect only low levels of FXIII activity (<3.0%), moderate deficiencies were frequently missed .…”

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confidence: 99%

Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures

et al. 2014

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BACKGROUND:Patients with congenital Factor XIII (FXIII) deficiency have impaired fibrin stabilization and are at high risk for surgical bleeding. Data regarding the use of FXIII concentrates before and during surgery are lacking. The objective of this study was to report the use of plasma-derived FXIII concentrate (Corifact in the United States; Fibrogammin P in other countries) in patients with congenital FXIII deficiency undergoing surgical procedures. STUDY DESIGN AND METHODS: FXIII concentrate at preoperative doses ranging from 25 to 40 U/kg was administered to six patients with congenital FXIII deficiency undergoing major or minor surgeries. RESULTS: FXIII concentrate was administered immediately before surgery for five surgical cases; three of these patients achieved excellent hemostasis during and after surgery, while two had intraoperative bleeding. In one surgical case, a regular prophylactic dose of FXIII concentrate was administered to the patient 1 week before minor surgery. FXIII concentrate provided rapid replacement of FXIII activity. In all but one of the patients given a dose of FXIII designed to increase FXIII levels more than 50%, there was satisfactory intraoperative and postoperative hemostasis. One patient undergoing aortic valve replacement on cardiopulmonary bypass (CPB) was the exception. Intraoperative bleeding in this patient was associated with lower-than-expected blood levels of FXIII. CONCLUSION: Preoperative plasma-derived FXIII concentrate allowed for sufficient hemostasis in most patients with FXIII deficiencies. Additional doses were necessary to achieve hemostasis in one patient who underwent a CPB procedure. F actor XIII (FXIII) deficiency is a rare autosomal recessive congenital bleeding disorder resulting from defects in genes encoding the "A"-chain or "B"-chain subunits of the FXIII coagulation protein.1 FXIII is capable of cross-linking a variety of proteins, but its function in cross-linking fibrin is crucial for clot stabilization and the prevention of bleeding. The incidence of severe FXIII deficiency (<1% FXIII) is estimated to be one in 5 million people, 2 but the true incidence of FXIII deficiency is unknown, as heterozygous patients will have higher baseline FXIII levels and may not exhibit overt symptoms.1 Patients with severe FXIII deficiencies usually present with umbilical cord bleeding, mucosal bleeding, poor wound healing, primary intracranial hemorrhage, or spontaneous miscarriage. Patients with less severe FXIII deficiency (with levels from 2%-50% activity) are rarely symptomatic, and may only be diagnosed after an invasive procedure or other hemostatic challenge. Traditionally, FXIII deficiency has been assessed qualitatively by plasma clot solubility in concentrated urea, acetic acid, or monochloroacetic acid.3 However, since clot solubility ABBREVIATION: CPB = cardiopulmonary bypass. Although not licensed in Canada, Fibrogammin P has been widely used under the Special Access Programme of Health Canada. In 2013, the US Food and Drug Administration approve...

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Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures

et al. 2014

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“…In a second step, this binary complex can undergo two different subsequent reactions: (i) the primary amine group of a lysine residue from another gamma chain fibrin molecule breaks the binary complex thioester bond in a transglutaminase reaction and reacts with the glutamine residue, forming a glutaminyl‐lysyl bond (Figure B); (ii) a free amine group reacts with the binary complex, resulting in an isopeptide glutamine‐amine bond (Figure C). These reactions, including ammonia release, transglutaminase reaction, and incorporation of a free amine group into the glutamine‐FXIIIa complex, result in gamma chain fibrin to fibrin dimerization and cross‐linking, and form the fundamental basis for laboratory assays measuring FXIII activity via specific products released during these steps …”

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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“…From the literature on FXIII deficiency no clear association between clinical severity, laboratory phenotype and genotype could be revealed. This is mainly due to the use of qualitative clot solubility test or quantitative ammonia release assay without plasma blank correction for the determination of FXIII activity . Studies including genetic analysis and complete laboratory work‐up based on adequate methodology are required for establishing such association.…”

Section: Resultsmentioning

confidence: 99%

Factor XIII deficiency: complete phenotypic characterization of two cases with novel causative mutations

et al. 2013

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Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A₂B₂) in the plasma and as dimer (FXIII-A₂) in cells. Activated FXIII mechanically stabilizes fibrin and protects it from fibrinolysis by cross-linking fibrin chains and α₂-plasmin inhibitor to fibrin. FXIII is essential to maintaining haemostasis, and its deficiency causes severe bleeding diathesis. Due to improper laboratory practices, FXIII deficiency is considered the most under-diagnosed bleeding disorder. The aim of this study was to demonstrate in two cases how FXIII deficiency is properly diagnosed and classified, and to compare results of laboratory analysis and clinical symptoms. FXIII activity from plasma and platelets was measured by a modified ammonia release assay, while FXIII-A₂B₂, FXIII-A and FXIII-B antigens were determined by ELISA. The exon-intron boundaries and the promoter region of F13A1 gene were amplified by PCR and the amplified products were analysed by direct fluorescent sequencing. FXIII-A mRNA in platelets was determined by RT-qPCR. Two children with severe bleeding symptoms were investigated. In both cases FXIII activity and FXIII-A antigen were undetectable in the plasma and platelet lysate. In the plasma no FXIII-A₂B₂ antigen was found, while FXIII-B antigen was >30% in both cases. Proband1 was a compound heterozygote possessing a known missense mutation (c.980G>A, p.Arg326Gln) and a novel splice-site mutation (c.1112+2T>C). Proband2 was homozygote for a novel single nucleotide deletion (c.212delA) leading to early stop codon. The discovered mutations explain the severity of clinical symptoms and the laboratory data. Methods precise in the low activity/antigen range are required to draw valid conclusion on phenotype-genotype relationship.

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Measurement of factor XIII activity in plasma

Cited by 35 publications

References 51 publications

Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures

Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures

Factor XIII deficiency diagnosis: Challenges and tools

Factor XIII deficiency: complete phenotypic characterization of two cases with novel causative mutations

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