Diurnal variation in thrombotic and fibrinolytic status in healthy volunteers

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): East and North Hertfordshire NHS Trust Background Previous studies assessing markers of fibrinolysis in healthy volunteers and patients with coronary artery disease (CAD) indicate circadian variation, primarily attributable to changes in plasminogen activator inhibitor-1 (PAI-1) concentrations, the main inhibitor of fibrinolysis, peaking between midnight and 06:00 hrs, with a nadir at 01:00 hrs. Whether the elevated PAI-1 translates into a global impairment of fibrinolysis, is not known. Purpose It was our aim to assess diurnal variation in global fibrinolytic activity in healthy subjects. Methods A single centre, prospective, observational study was conducted in healthy volunteers. Blood samples were obtained at two different time points on the same day, with a minimum inter-sample interval of 8 hours and a maximum of 12 hours. Venous blood was assessed to determine global thrombotic and fibrinolytic status in native whole blood status using the automated, point-of-care Global Thrombosis Test (GTT). This utilises non-anticoagulated blood to assess the time taken to form an occlusive thrombus under high shear (occlusion time) and the time taken for spontaneous restart of flow as a measure of endogenous fibrinolysis (lysis time). Results A total of 25 healthy volunteers (36% male), aged 34±12 y were included. All were non-smokers with a BMI of 25 (22.3 – 27.5) kg/m². The median interval between samples was 8:05 [hh:mm] (IQR 8:30 – 9:10). Occlusion time was similar in the morning and evening samples (median 451s [389 – 590] vs. 524s [428 – 597], p=0.207). Lysis time was also similar between morning and evening (median 1792s [1622 -2097] vs. 1726s [IQR 1517 – 1891], p=0.265). Conclusion Compared to the known circadian variation of thrombotic and fibrinolytic activity attributable to PAI-1, global thrombotic and fibrinolytic status do not appear to exhibit diurnal variation. Further studies are needed to assess how this correlates to t-PA and PAI-1 levels and the status in patients with cardiovascular disease.