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


CONCLUSIONS
Intrathrombus infusion of microplasmin for 4 or 6 hours resulted in significant clot lysis. Distal embolization appeared the most important limitation.
Department of Vascular Medicine and Hemostasis, University Hospitals Leuven, Leuven, Belgium. peter.verhamme@med.kuleuven.be
P
P
Verhamme
S
S
Heye
K
K
Peerlinck
G
G
Cahillane
M
M
Tangelder
I
I
Fourneau
K
K
Daenens
A
A
Belmans
S
S
Pakola
R
R
Verhaeghe
G
G
Maleux
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D057785:Catheters; D005260:Female; D005341:Fibrinolysin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage*; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D010865:Pilot Projects; D015912:Thrombolytic Therapy / Q000379:methods*; D055815:Young Adult
D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin