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Title: Haemostatic function and cerebrovascular disease
Author: Barber, Jonathan Mark
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2004
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Early clinical progression of ischaemic stroke is common and is associated with increased risk of death and dependency. It was hypothesised that activation of the coagulation system may be an important contributor in early cases of deterioration. A study was designed with the aim of characterising alterations in circulating haemostatic markers in patients with progressing stroke. A number of validation projects were also undertaken around this main study. Consecutive acute ischaemic stroke admissions were recruited to the haemostasis in\ progressing ischaemic stroke study and had haemostatic markers measured within 24 hours of symptom recognition. Fifty four (25%) of the 219 patients recruited met criteria for progressing stroke. Prothrombin fragments 1+2 (Fl+2)(median 1.28 v. 1.06 nmol/1, p=0.01), thrombin-antithrombin complex (TAT)(5.28 v. 4.07 mug/1, p < 0.01), D-dimer (443 V. 194 ng/ml, p < 0.001) and von Willebrand factor (216 v. 198 iu/dl, p < 0.05) levels were higher in these patients than stable/ improving patients. In logistic regression analysis, with all important clinical and laboratory variables included, only natural log D-dimer (odds ratio 1.88, p=0.0001) and mean arterial blood pressure (odds ratio 1.26 per 10 mmHg change, p=0.01) remained independent predictors of progressing stroke. In conclusion, there is evidence of excess thrombin generation and fibrin turnover in patients with progressing ischaemic stroke. Further research is required to determine whether such patients benefit from acute interventions aimed at modifying haemostatic function. Atrial fibrillation (AF) is associated with cognitive impairment and dementia. It was hypothesised that haemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against cognitive decline. Recruitment was from an observational cohort study of AF. Cognitive function was assessed using both a telephone interview and an informant questionnaire. In 218 subjects assessed D-dimer, Fl+2 and TAT levels were higher in AF subjects with dementia compared to those without (geometric means 97.1 v. 62.0 ng/ml, p=0.008; 0.74 v. 0.53 nmol/1, p=0.006; and medians 1.78 v. 1.44 mug/l, p=0.003 respectively). Dementia was less common in those treated with warfarin; 18%, v. 32%, p=0.023. In conclusion, the results were consistent with increased thrombin generation and fibrin turnover in subjects with AF and dementia compared to those without dementia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available