Treatment of Nonhealing Leg Ulcers With Fibrin-Stabilizing Factor XIII: A Case Report

Hildenbrand, Tanja; Idzko, Marco; Panther, Elisabeth; Norgauer, Johannes; Herouy, Yared

doi:10.1046/j.1524-4725.2002.02106.x

Cited by 14 publications

(16 citation statements)

References 6 publications

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“…However, clinical and experimental evidence suggests that coagulation factor FXIII has a role in this process. For example, patients affected by CVU, as well as patients with congenital FXIII deficiency, are characterized by wound healing impairment, 1,2, 17 several plasma factors or growth factors (FXIII, platelet‐derived growth factor, epidermal growth factor, and transforming growth factor‐β) are poorly represented or abnormally distributed in the local ulcer area because of anomalous extravascular exchanges due to modified capillary permeability, especially in post‐thrombotic CVU, 17,18, 25 and topical FXIII treatment improves healing in CVU patients 18,19, 26 . In addition, we recently reported FXIII concentrate effectively counteracts the detrimental effects of Clostridium histolyticum collagenase in human fibroblast cultured cells, 20 significantly reducing the ECM components degraded by MMP's action, considered a unique step in venous ulcer formation 11–14 …”

Section: Discussionmentioning

confidence: 99%

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension

Gemmati

Tognazzo

Serino

et al. 2004

Wound Repair Regeneration

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Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII-treated fibroblasts. In addition, a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly increases the activity and modifies the cross-linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195 healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were determined by immuno-electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p= 0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n= 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p < 0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm(2,)+/- 23.6; VL = 6.1 cm(2,)+/- 6.9; LL = 4.1 cm(2,)+/- 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA

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Section: Discussionmentioning

confidence: 99%

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension

Gemmati

Tognazzo

Serino

et al. 2004

Wound Repair Regeneration

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“…However, in the latter study, 11% of the cases had moderate FXIII deficiency (FXIII-A antigen Յ0.65 U/mL). Although only a relatively small number of patients were recruited for the four studies evaluating the effect of topical treatment of CVLU with FXIII concentrate, the studies unanimously reported a beneficial effect (131,134,297,380). Accelerated wound surface reduction, shorter healing time, improved availability of granulation tissue, and decreased secretion and bleeding tendency were observed following daily local administration of the concentrate in CVLU, but not in arterial-venous mixed disease (380).…”

Section: A Clinical Data and Animal Experiments Supporting The Involmentioning

confidence: 99%

Factor XIII: A Coagulation Factor With Multiple Plasmatic and Cellular Functions

Muszbek

Bereczky

Bagoly

et al. 2011

Physiological Reviews

412

437

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Factor XIII (FXIII) is unique among clotting factors for a number of reasons: 1) it is a protransglutaminase, which becomes activated in the last stage of coagulation; 2) it works on an insoluble substrate; 3) its potentially active subunit is also present in the cytoplasm of platelets, monocytes, monocyte-derived macrophages, dendritic cells, chondrocytes, osteoblasts, and osteocytes; and 4) in addition to its contribution to hemostasis, it has multiple extra- and intracellular functions. This review gives a general overview on the structure and activation of FXIII as well as on the biochemical function and downregulation of activated FXIII with emphasis on new developments in the last decade. New aspects of the traditional functions of FXIII, stabilization of fibrin clot, and protection of fibrin against fibrinolysis are summarized. The role of FXIII in maintaining pregnancy, its contribution to the wound healing process, and its proangiogenic function are reviewed in details. Special attention is given to new, less explored, but promising fields of FXIII research that include inhibition of vascular permeability, cardioprotection, and its role in cartilage and bone development. FXIII is also considered as an intracellular enzyme; a separate section is devoted to its intracellular activation, intracellular action, and involvement in platelet, monocyte/macrophage, and dendritic cell functions.

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“…A positive effect was observed after topical and intravenous administration to patients with venous ulcers and pressure sores, respectively. The effect is believed to be mediated through the vessel‐sealing effect of pFXIII, which reduces MMP leakage, thus resulting in limited fibrinolysis .…”

Section: Potential Clinical Use Of Fxiiimentioning

confidence: 99%

Tissue-regenerating functions of coagulation factor XIII

Soendergaard

Kvist

Seidelin

et al. 2013

Journal of Thrombosis and Haemostasis

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To cite this article: Soendergaard C, Kvist PH, Seidelin JB, Nielsen OH. Tissue-regenerating functions of coagulation factor XIII. J Thromb Haemost 2013; 11: 806-16. Summary. The protransglutaminase factor XIII (FXIII) has recently attracted attention within the field of tissue regeneration, as it has been found that FXIII significantly influences wound healing by exerting a multitude of functions. It supports hemostasis by enhancing platelet adhesion to damaged endothelium, and by its cross-linking activity it stabilizes the formed fibrin clot. Furthermore, FXIII limits bacterial dissemination from the wound and incorporates macromolecules of importance for cellular infiltration, supporting cell migration and survival. FXIIImediated complex formation of the vascular endothelial growth factor receptor 2 and a V b 3 integrin is important for angiogenesis, supporting the formation of granulation tissue. Chronic inflammatory conditions involving bleeding and activation of the coagulation cascade have been shown to lead to reduced FXIII levels in plasma. Of particular importance for this review is the fact that patients suffering from inflammatory bowel disease (IBD) have reduced FXIII antigen levels and activity. Furthermore, these patients show impaired mucosal healing, which supports the inflammatory state of the disease. This review summarizes the role of FXIII in the healing of wounds, and briefly summarizes the previous use of FXIII in clinical settings. Moreover, it addresses the potential role for FXIII as a therapeutic agent in the healing of persistent wounds during chronic conditions, with an emphasis on IBD.

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Treatment of Nonhealing Leg Ulcers With Fibrin-Stabilizing Factor XIII: A Case Report

Cited by 14 publications

References 6 publications

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension

Factor XIII: A Coagulation Factor With Multiple Plasmatic and Cellular Functions

Tissue-regenerating functions of coagulation factor XIII

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