Document Detail


Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients.
MedLine Citation:
PMID:  18980797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: 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. AIMS: 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.
Authors:
Raf Brouns; Evelien Heylen; Rishi Sheorajpanday; Johan L Willemse; Jan Kunnen; Didier De Surgeloose; Dirk F Hendriks; Peter P De Deyn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-02
Journal Detail:
Title:  Clinical neurology and neurosurgery     Volume:  111     ISSN:  1872-6968     ISO Abbreviation:  Clin Neurol Neurosurg     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-26     Completed Date:  2009-03-09     Revised Date:  2009-10-14    
Medline Journal Info:
Nlm Unique ID:  7502039     Medline TA:  Clin Neurol Neurosurg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  165-70     Citation Subset:  IM    
Affiliation:
Department of Neurology and Memory Clinic, ZNA Middelheim Hospital, Antwerp, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Aged
Brain Ischemia / drug therapy*,  physiopathology
Carboxypeptidase U / blood*
Chromatography, High Pressure Liquid / methods
Enzyme Precursors / blood
Female
Humans
Infarction / diagnosis,  etiology
Intracranial Hemorrhages / diagnosis,  etiology
Intracranial Thrombosis / complications,  drug therapy
Male
Middle Aged
Stroke / drug therapy*,  physiopathology
Survival Rate
Thrombolytic Therapy / adverse effects,  methods*,  mortality
Time Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Enzyme Precursors; EC 3.4.17.20/Carboxypeptidase U

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