High functional levels of thrombin-activatable fibrinolysis inhibitor are associated with an increased risk of first ischemic stroke.
OBJECTIVE
Several studies have suggested that thrombin-activatable fibrinolysis inhibitor (TAFI) levels are associated with the risk of arterial thrombosis, but results have been contradictory. We studied functional TAFI levels and TAFI gene polymorphisms in 124 patients with a recent ischemic stroke and 125 age- and sex-matched controls to establish the role of TAFI in ischemic stroke.


RESULTS
Functional TAFI levels, defined as TAFI-related retardation (RT), the difference in clot lysis time (LT) in the absence or presence of a specific activated TAFI inhibitor (potato carboxypeptidase inhibitor [PCI]), were higher in patients than controls (19.5 +/- 4.2 vs. 17.7 +/- 3.7 min, P < 0.005). Clot LTs in the presence of PCI, which were independent of TAFI, were also increased in ischemic stroke patients. This indicates that in these patients fibrinolysis is impaired not only by high TAFI levels, but also by other mechanisms. Individuals with functional TAFI levels in the highest quartile had an increased risk of ischemic stroke compared with the lowest quartile [odds ratio (OR) 4.0, 95% confidence interval (CI): 1.6-9.8]. In an unselected group of 36 of the 125 stroke patients functional TAFI levels were also measured at 3 months, and were persistently high. This indicates that increased functional TAFI levels after stroke are not caused by an acute phase reaction. No difference was found between patients and controls with respect to TAFI genotype distribution.


CONCLUSIONS
Increased functional TAFI levels, resulting in decreased fibrinolysis, are associated with an increased risk of ischemic stroke.
Leebeek
F W G
FW
Department of Hematology, Erasmus University Medical Center, Rotterdam. f.leebeek@erasmusmc.nl
Goor
M P J
MP
Guimaraes
A H C
AH
Brouwers
G-J
GJ
Maat
M P M
MP
Dippel
D W J
DW
Rijken
D C
DC
D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology / Q000209:etiology*; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005342:Fibrinolysis; D005838:Genotype; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000209:etiology*; D044465:White People
D025901:Carboxypeptidase B2