The significance of D-dimer levels and an elevated ESR in association with a hypercoagulable state in patients with cerebrovascular disease

Abstract

Background and purpose: Predictors of outcome in patients suffering cerebrovascular events (either stroke and/ or transient ischaemic attack) may be important determinants of those at risk for recurrent thrombotic cerebral episodes. Identification of patients with chronic underlying inflammatory processes, as opposed to generalised atheromatous disease, as causative factors in cerebrovascular disease, may have important therapeutic and preventative implications. Levels of D-dimers, markers for the detection of the activation of the coagulation and fibrinolytic systems, were analysed to assess whether patients suffering multiple events had ongoing evidence of a hypercoagulable state. To determine whether those patients with prolonged elevation of D-dimer levels had evidence of concurrent infection and inflammation, the erythrocyte sedimentation ratio (ESR), an inflammatory marker, was evaluated. Methods: Retrospective analysis was performed on 148 patients referred to the Haemostasis and Thrombosis Unit at the Johannesburg Hospital for evaluation of their thrombotic profiles. All had suffered either single or recurrent cerebrovascular events. A comprehensive history was taken and a complete physical and neurological examination performed, as well as cardiological assessment and neuroima Ang studies. In addition to the thrombotic profile, including D-dimer levels, haematologicai» vameters such as ESR, haemoglobin, white cell count, platelet count and others, were evaluated. The variable time interval between the date of most recent event and date of venesection was determined. Results: D-dimer levels remained elevated in some patients following a cerebrovascular event far in excess of the expected time frame of six weeks, suggesting ongoing thrombosis and fibrinolysis. Elevated D-dimers were not found to be of significant prognostic value in determining those at risk of recurrent episodes. O f the 47 patients assessed within two months of their most recent event, 53.19 % displayed elevated Ddimer levels, but 29.7 % had elevated levels in the group assessed after a two month time interval, p = 0.010. D-dimer elevations were not found to be of significant prognostic value in determining those at risk of recurrent episodes, with p = 0.216 when comparing patients suffering single, two or multiple events. However, elevated D-dimers correlate significantly with ESR levels, p = 0.0094, in all patients. This was particularly evident when comparing the 70 younger to the 78 older patients with elevated D-dimers (p = 0.0493) and the 48 Black to the 82 White patients (p = 0.0070) in the anterior cerebral territory of vascular supply (p = 0.0282). Both younger and Black patient groups have recognisably less widespread atheromatous disease than older and White patients. When assessing other markers of inflammation in association with elevated D-dimer levels and ESR, mean fibrinogen levels were significantly elevated at 6.56 g/1 (p = 0.0122). An elevated white cell count, as a categorical variable was significantly associated with a raised ESR (p = 0.0092). Conclusions: D-dimer elevations for prolonged periods after a thrombotic cerebrovascular episode were not of prognostic value in determining those patients at risk o f recurrent events. However, when evaluated together with markers of infective or inflammatory processes such as ESR, fibrinogen and white cell count, a significant association was demonstrated. Acquired abnormalities of coagulation and fibrinolysis, including chronic infection/ inflammation, may cause or contribute to stroke, especially in those patients at lower risk for generalised atheromatous disease by virtue of age or racial group. These findings have important implications relating to cerebrovascular disease aetiology, investigation, management and, ultimately, prevention.