Factor XIII in Ulcerative Leg Disease: Background and Preliminary Clinical Results

Abstract

The therapy concept of topical factor XIII application was developed on the basis of clinical and experimental investigations on improvement of wound healing, as well as on the morphological and pathophysiological topical site of venous ulcers. Topical treatment with factor XIII is special with regard to mode of application as well as efficacy, since a lot of other medications used for local wound treatment contain a fibrinolytic component. In the last 32 months, 23 inpatients (17 female, 6 male) averaging 62.9 +/- 14.1 years and suffering ulcerative leg disease were treated with topically applied factor XIII. The average period of distal venous ulcer in these patients was 3.3 +/- 2.04 years. The extent of the ulcer surface ranged between 2.5 x 3.0 cm (minimum) and 18.5 x 8.0 cm (maximum). All patients had been in medical consultation for several years. The venous ulcers were based upon a "postthrombotic syndrome" in 15 patients. Six patients were suffering from ulcerations due to arterial and venous mixed disease, and there were 2 patients with ulcerations of unknown etiology. In 5 patients, 2 with unknown etiology and 3 with arterial and venous mixed disease, local treatment with factor XIII was discontinued after 4 weeks because there was definitely no improvement in wound healing. Additionally, 3 patients with ulcerations due to arterial and venous mixed disease were treated for a maximum of 6 weeks with only moderate improvement in healing. Twelve of the 15 patients (79.3%) with extended, chronic ulceration on the basis of a postthrombotic syndrome showed such a distinct improvement of topical site after an average of only 3.15 +/- 1.14 weeks that they were released for further ambulatory treatment. Three patients had to be treated for a maximum period of 6 weeks, also with distinct improvement in wound healing. Apart from a wound surface reduction and a clinically documentable improvement of granulation tendency, there was a marked reduction of secretion and bleeding tendency within the ulcer area observed in all patients. None of the patients showed any systemic or local allergic reactions.

Identification of factor XIII-A as a marker of alternative macrophage activation

“…On the other hand, impaired wound healing is frequently observed in FXIII-A-defi cient patients [18][19][20] and the same observation was made in studies on FXIII-A gene knock-out mice [47]. FXIII-A treatment is also known to facilitate wound healing in different clinical and experimental conditions [48,49]. To elucidate the contradiction between the above observations, one must hypothesize that FXIII-A is not necessarily required for all types of phagocytosis.…”

Transglutaminase and Vascular Biology: Physiopathologic Implications and Perspectives for Therapeutic Interventions

“…Even more relevant to the present discussion on the links between transglutaminases, and vascular biology/ cardiovascular diseases are the recent observations that statins are powerful inducers of the TG2 [114], in light of the ability of the enzyme to protect against "progression" of atheromasic plaques [112,113]. These protective effects of transglutaminases as stabilizers of atherosclerotic lesions and the benefits brought about by topical application of Factor XIII for the therapy of venous ulcers [152], are promising since both conditions are frequently major clinical vascular complications in aged people.…”

Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

“…In line with these findings, the studies conducted so far on the application of FXIII as a treatment option in dermal wound treatment are promising. Accelerated wound surface reduction, shorter healing time, improved availability of granulation tissue, and decreased secretion, and bleeding tendencies were all reported following daily local administration of FXIII concentrate on clear, noninfected wounds of chronic venous leg ulcers and on pyoderma gangrenosum lesions [24, 95–99]. …”