ORIGINAL ARTICLES   

International Angiology 2012 June;31(3):289-96

Copyright © 2012 EDIZIONI MINERVA MEDICA

language: English

Catheter-directed thrombolysis with microplasmin for acute peripheral arterial occlusion (PAO): an exploratory study

Verhamme P. ^{1, 2}, Heye S. ³, Peerlinck K. ^{1, 2}, Cahillane G. ⁴, Tangelder M. ^{4, 5}, Fourneau I. ⁶, Daenens K. ⁶, Belmans A. ⁷, Pakola S. ⁴,Verhaeghe R. ¹, Maleux G. ³ ✉

¹ Department of Vascular Medicine and Hemostasis, University Hospitals Leuven, Leuven, Belgium; ² Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium; ³ Department of Radiology, University Hospitals Leuven, Leuven, Belgium; ⁴ Clinical Development, ThromboGenics NV, Leuven, Belgium; ⁵ Department of Vascular Surgery, University Medical Center Utrecht, the Netherlands; ⁶ Department of Vascular Surgery, University Hospitals Leuven, Leuven, Belgium; ⁷ Leuven Biostatistics and Statistical Bioinformatics Centre, University of Leuven, Leuven, Belgium

AIM: We performed an open-label, dose-ascending, single-centre, Phase IIa study to explore the safety and efficacy of catheter-directed thrombolysis (CDT) with microplasmin for infrainguinal arterial or bypass occlusions.
METHODS: Patients who presented with acute occlusions were subsequently treated with an intrathrombus infusion of five ascending doses of microplasmin: 0.3 mg/kg/h for 4 hours; 0.45 mg/kg/h for 4 hours; 0.6 mg/kg/h for 4 hours; 0.9 mg/kg/h for 4 hours or 0.6 mg/kg/h for 6 hours. Repeat angiograms were obtained to assess the degree of clot lysis. The primary outcome was complete thrombolysis defined as >95% thrombus volume reduction at the end of the microplasmin infusion. Safety evaluation included bleedings, adverse events and coagulation biomarkers.
RESULTS: Complete thrombolysis was obtained in 3 of the 19 treated patients at the end of microplasmin infusion. Thrombus volume reduction between 50% and 95% was achieved with all dosing regimens. Clinically significant distal embolization occurred in 8 patients. One major and two non-major bleedings occurred. Microplasmin depleted α2-anti-plasmin and decreased fibrinogen.
CONCLUSION: Intrathrombus infusion of microplasmin for 4 or 6 hours resulted in significant clot lysis. Distal embolization appeared the most important limitation.