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| Haemostatic changes damaging to stroke outcome |
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15 June 2006
Stroke-induced changes in haemostasis may be detrimental to patient outcome, even after successful treatment with thrombolysis, say researchers. "Our findings illustrate the limitations of current thrombolytic treatment paradigms, which affect stroke within a narrow time window, while thrombin generation, inflammation, and impaired endogenous fibrinolysis may persist to worsen outcomes," they observe.
Dr David Tanne (Chaim Sheba Medical Centre, Tel-Hashomer, Israel) and colleagues conducted a post-hoc analysis of haemostasis markers in 465 patients who participated in the National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rt-PA) Stroke study.
The investigators report that levels of thrombin-antithrombin complex (TAT), reflecting elevated thrombin, and levels of t-PA antigen peaked at around 2 hours after rt-PA treatment, while fibrinogen levels fell at this time and remained low for 24 hours. Analysis revealed that thrombolysis-treated patients who had higher levels of t-PA antigen at 24 hours after stroke onset had a reduced odds ratio (OR) of 0.34 for a favourable 3-month outcome compared with those with lower levels. Similarly, thrombolysis-treated patients with higher levels of thrombomodulin and all patients with elevated levels of TAT were more likely than other patients to die within 3 months of stroke onset, with ORs of 4.45 and 1.72, respectively.
The latter finding suggests that "increased thrombin generation may reflect more complicated and thrombogenic atherosclerotic lesions or a sustained hypercoagulable state that threatens the integrity of cerebral reperfusion," the authors note. Writing in the journal Stroke, they conclude: "On the basis of these findings, there is a rationale to investigate the safety and efficacy of protocols in which rt-PA is complemented by agents that are antithrombotic and enhance fibrinolysis."
Reference:
Stroke 2006; Epub ahead of print.
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