Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients.
BACKGROUND
Thrombolytic therapy improves clinical outcome in patients with acute ischemic stroke but is compromised by symptomatic intracranial hemorrhage and an unpredictable therapeutic response. In vitro and in vivo data suggest that activation of procarboxypeptidase U (proCPU) inhibits fibrinolysis.


OBJECTIVE
To investigate whether the extent of proCPU activation is related to efficacy and safety of thrombolytic therapy in ischemic stroke patients.


METHODS
In twelve patients with ischemic stroke who were treated with intravenous (n=7) or intra-arterial (n=5) thrombolysis, venous blood samples were taken at different time points before, during and after thrombolytic therapy. ProCPU and carboxypeptidase U (CPU, TAFIa) plasma concentrations were determined by HPLC. The maximal CPU activity (CPU(max)) and the percentage of proCPU consumption during thrombolytic therapy were calculated. The efficacy and safety of the thrombolytic therapy were assessed by evolution of the clinical deficit, recanalisation, final infarct volume, thrombolysis-induced intracranial hemorrhage and mortality.


RESULTS
No correlations between CPU(max) or proCPU consumption and patient or stroke characteristics were found. However, CPU(max) is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume.


CONCLUSIONS
Irrespective of patient and stroke characteristics, CPU(max) and proCPU consumption during thrombolytic treatment for ischemic stroke are parameters for therapeutic efficacy and safety. Further evaluation of the clinical applicability of these parameters and further investigation of the potential role for CPU inhibitors as adjunctive therapeutics during thrombolytic treatment may be of value.
Brouns
Raf
R
Department of Neurology and Memory Clinic, ZNA Middelheim Hospital, Antwerp, Belgium.
Heylen
Evelien
E
Sheorajpanday
Rishi
R
Willemse
Johan L
JL
Kunnen
Jan
J
De Surgeloose
Didier
D
Hendriks
Dirk F
DF
De Deyn
Peter P
PP
D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D025901:Carboxypeptidase B2 / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D006801:Humans; D007238:Infarction / Q000175:diagnosis / Q000209:etiology; D020300:Intracranial Hemorrhages / Q000175:diagnosis / Q000209:etiology; D020767:Intracranial Thrombosis / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D015996:Survival Rate; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
D004792:Enzyme Precursors; D025901:Carboxypeptidase B2