Abstract
BackgroundStroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (df)) ex-vivo, real-time clot formation time (TGP) and blood clot strength (elasticity at the gel point (G’GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention.MethodsIn a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2–4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy.Results75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: df (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G’GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in df (p = 0.02), G’GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for df (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values.ConclusionPatients with ischaemic stroke have denser and stronger clot structure as detected by df and G’GP. The effect of thrombolysis on clot microstructure (df) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.
Highlights
Stroke is the second largest cause of death worldwide
123 patients with suspected first-ever ischaemic stroke were recruited between May 2012 and February 2014. 48 patients were excluded for various reasons (18 had stroke mimics such as Bell’s palsy, sepsis and brain tumour; 8 transient ischemic attacks (TIA); 8 had a haemorrhagic stroke; 4 previous strokes; 6 found to have been given loading aspirin prior to blood collection; 1 renal failure and 3 cancers)
The changes in df may seem small, it is very important to recognize that df has a non-integer value with very narrow range and non-linear relationship with the amount of fibrin mass incorporated within the incipient clot (Figure 2), which means substantial increases in mass are required to generate even small increments of df [20,22,23]
Summary
Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. This has been reported in haemorrhagic stroke [3] but it Stanford et al BMC Neurology (2015) 15:35 These factors and standard coagulation tests have limited clinical use in stroke [7,8] as they are functional time-based end point assays based on plasma incubation with exogenous reagents to activate the coagulation cascade [9,10]. Recent studies [13,14,15,16] have highlighted new biomarkers of haemostasis that measure these viscoelastic and structural changes These biomarkers rely on the rheometrical measurement of blood as it clots and strict criteria for assessing when an incipient clot has formed. This study aims to compare these biomarkers in patients with ischaemic stroke and healthy individuals and assess changes in clot microstructure ex-vivo following therapeutic intervention
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