Intermittent intravenous urokinase for critical limb ischemia in diabetic foot ulceration

Abstract

Patients with diabetic foot ulceration and critical limb ischemia have a high risk of major amputation, especially if limbs can not be revascularized. Urokinase is effective in improving microcirculation in critical limb ischemia and might improve outcomes. There are no data on the efficacy and safety of urokinase treatment (survival free of major amputation, ulcer healing and the rate of minor and major bleeding). Therefore, we aimed to investigate the effect of urokinase treatment in a phase II clinical trial. We performed an open, prospective, non-controlled, multicenter phase II cohort study in 77 type-2 diabetic patients with critical limb ischemia and diabetic foot ulceration. Patients had no surgical or endovascular treatment option based on interdisciplinary consensus. Urokinase (1 Mio IU if plasma fibrinogen >or=2.5 g/l, 0.5 Mio IU if fibrinogen <2.5 g/l) was administered for 21 days as an intravenous infusion over 30 minutes. Each patient was followed up for 12 months. Treatment for a median of 21 days resulted in 33% of patients being alive, having no major amputation and completely healed ulcers after 12 months. Total survival rate was 84.6%, amputation-free survival 69.2% and rate of major amputation 21.1%. Eighty-two percent of patients experienced at least once a complete ulcer healing within the course of study. Three serious adverse events were urokinase-related. Urokinase treatment in diabetic patients with critical limb ischemia appears to be effective, feasible and safe. Although this calls for a larger, randomized and controlled trial, the results are highly relevant for clinical practice to prevent these patients from receiving major amputation due to diabetic foot syndrome.

Noninvasive management of the diabetic foot with critical limb ischemia: current options and future perspectives

“…Hyperfibrinogenemia with the resulting increase in plasma viscosity and erythrocyte aggregation has been demonstrated in patients with coronary heart disease and PAD [Leschke et al 1986[Leschke et al , 1997Peters et al 1999;Partsch and Jochmann, 1993;Weck et al 2008;Rietzsch et al 2008]. The increase in plasma viscosity, in particular, can be a flowlimiting factor and a critical determinant of oxygen supply in the poststenotic microcirculation of myocardium and diabetic foot.…”

“…However, studies on the effect of intravenous urokinase treatment in patients with CLI and diabetic foot lesions are mostly retrospective in small patient cohorts. Therefore, we performed an open, prospective, noncontrolled, multicenter cohort study in 77 type 2 diabetic patients with CLI and diabetic foot ulceration [Weck et al 2008]. Patients had no surgical or endovascular treatment option based on interdisciplinary consensus.…”

Therapieresistente Wunden der unteren Extremität

“…Prostaglandin E 1 ist für die Behandlung der kritischen Extremitäten-ischämie zugelassen. Für eine fibrinolytische Therapie mit Urokinase bei Hyperfibrinogenämie und nicht rekonstruierbarer kritischer Ischämie liegen positive Ergebnisse einer Phase-II-Studie vor [18]. Die Substitution von Zink [19] und Vitamin C wird bei älteren Patienten bei entsprechenden Mangelzuständen empfohlen.…”

Application of the Combined Phototherapy in Complex Treatment of Patients with Complications of Diabetic Foot Syndrome

“…Ведущими факторами риска развития ос-ложнений диабетической язвы стопы являются: длительный стаж диабета, нейропатия, пора-жение периферических сосудов, деформация стоп с формированием зон высокого давления, высокий уровень гликозилированного гемогло-бина, курение, использование неадекватной обуви [12,13,14].…”

“…Облучение может вызывать три различные фотохимические реакции: фотоокисление ли-пидов в клеточных мембранах, фотореактива-цию фермента супероксиддисмутазы, фотолиз комплексов окиси азота [7,14].…”