Biology of Factor XIII and clinical manifestations of Factor XIII deficiency

Levy, Jerrold H.; Greenberg, Charles S.

doi:10.1111/j.1537-2995.2012.03865.x

Cited by 75 publications

(70 citation statements)

References 89 publications

(110 reference statements)

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“…Acquired FXIII deficiency is thought to be much more common than congenital deficiency [1]. Acquired FXIII deficiency could result as a consequence of hemorrhage or dilutional changes [6], from the development of inhibitory autoantibodies against FXIII [1,5,6], or from diseases associated with overconsumption or reduced synthesis of FXIII [5,6]. …”

Section: Introductionmentioning

confidence: 99%

“…Congenital FXIII deficiency is a rare hereditary bleeding disorder estimated to affect one in every 1-5 million live births, which occurs with higher frequency in consanguineous families [1,3,4,5,6]. Patients suffering from FXIII deficiency can manifest severe bleeding conditions as early as a few days after birth, with umbilical cord bleeding occurring in 80% of cases of severe FXIII deficiency [3].…”

Section: Introductionmentioning

confidence: 99%

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Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Solomon

Korte

Fries

et al. 2016

Transfus Med Hemother

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Background: Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. Methods: Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. Results: Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. Conclusion: Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Solomon

Korte

Fries

et al. 2016

Transfus Med Hemother

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“…Factor XIII activity should be increased to 20 to 30% to prevent surgical bleeding and poor wound healing, and an activity level of less than 50% adequately responds to treatment with FXIII concentrate 8,11 .…”

Section: Discussionmentioning

confidence: 99%

“…A purified concentrate of FXIII has been marketed in Europe for more than 20 years. Replacement therapy with that concentrate is a widely accepted treatment for acquired and congenital deficiency of FXIII, as well as, supportive therapy in cases of poor wound healing 8,11,14 . Similarly, desmopressin acetate…”

Section: Introductionmentioning

confidence: 99%

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Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

et al. 2015

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PURPOSE:To investigate hemostatic effects of supplementary factor XIII and desmopressin (DDAVP) in resuscitation of uncontrolled bleeding. METHODS:Fifty-four rabbits were randomized in nine groups: G1: Sham; G2: FXIII and normotensive resuscitation (NBP); G3:FXIII and permissive hypotension (PH) (MAP 60% baseline); G4: FXIII/DDAVP/NBP; G5: FXIII/DDAVP/PH; G6: NBP only; G7:FXIII no hemorrhage; G8: FXIII/DDAVP no hemorrhage; G9: PH only. Thromboelastometry and intra-abdominal blood loss were assessed. Scanning electron microscopy (EM) of the clots was performed. RESULTS:Compared to Sham, only G8 (FXIII/DDAVP w/o hemorrhage) showed clotting time (CT) significantly lower (p<0.05). NBP alone (G6) resulted in significantly prolonged CT compared to G2, G3 and G5 (p<0.05). Similarly, median alpha angle was significantly larger in G3,4,5, and 9 compared to G6 (p<0.05). Area under the curve was significantly greater in G5 than G2. Intra-abdominal blood loss was lower in G5 and G9 compared to G2 and G6. FXIII/DDAVP and PH resulted in more robust fibrin mesh by EM. CONCLUSIONS:Normotensive resuscitation provokes more bleeding and worsens coagulation compared to pH, that is partially reversed by factor XIII and desmopressin. FXIII and DDAVP can synergistically improve coagulation. Permissive hypotension reduces bleeding regardless of those agents.

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In VitroSecretion Deficits are Common Among Human Coagulation Factor XIII Subunit B Missense Mutants: Correlations with Patient Phenotypes and Molecular Models

Biswas¹,

Thomas²,

Bevans

et al. 2013

Human Mutation

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Coagulation factor XIII (FXIII) proenzyme circulates in plasma as a heterotetramer composed of two each of A and B subunits. Upon activation, the B subunits dissociate from the A subunit dimer, which gains transglutaminase activity to cross-link preformed fibrin clots increasing mechanical strength and resistance to degradation. The B subunits are thought to possess a carrier/protective function before FXIII activation. Mutations in either A or B subunits are associated with pathological patient phenotypes characterized by mild to severe bleeding. In vitro expression of FXIII B subunit (FXIIIB) missense variants in HEK293T cells revealed impaired secretion for all seven variants studied. To investigate the likely molecular environments of the missense residues, we created molecular models of individual FXIIIB Sushi domains using phylogenetically similar complement factor H Sushi domain structural templates. Assessment of the local molecular environments for the models suggested surface or buried positions for each mutant residue and possible pathological mechanisms. The in vitro expression system and in silico analytical methods and models we developed can be used to further investigate the molecular basis of FXIIIB mutation pathologies.

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Biology of Factor XIII and clinical manifestations of Factor XIII deficiency

Abstract: ABBREVIATIONS: CD = Crohn's disease; CFT = clot formation time; IBD = inflammatory bowel disease; ROTEM = rotational thromboelastography; SLE = systemic lupus erythematosus; TEG = thromboelastography; TGT = thrombin generation test; UC = ulcerative colitis.

Cited by 75 publications

References 89 publications

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Clotting Factor XIII and desmopressin improve hemostasis in uncontrolled bleeding

In VitroSecretion Deficits are Common Among Human Coagulation Factor XIII Subunit B Missense Mutants: Correlations with Patient Phenotypes and Molecular Models

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