• 2018-07
  • 2018-10
  • 2018-11
  • Obstructive sleep apnoea hypopnoea syndrome OSAHS affects


    Obstructive sleep apnoea hypopnoea syndrome (OSAHS) affects 2–4% of middle-aged adults [1–3]. It is associated with various adverse cardiovascular outcomes [4,5] and appears an independent factor for arterial [6] and possibly venous thrombosis [7]. However, studies focusing on mechanisms to explain the dysfunctional haemostasis in OSAHS are scarce and inconsistent. Recent research highlights the role of static fibrin (clot) microstructure in abnormal clot development and its direct relation to the increased risk of cardiovascular events in OSAHS [8]. The formation of an initial fibrin network has been shown as the primary templating microstructural component of a blood clot formation (Incipient clot formation) [9,10]. The clotting process starts the activation of time-based coagulation pathways which result in the development of clot microstructural fibrinopeptide A and B cleaved by thrombin from fibrinogen, and the resulting fibrin monomers bind together to create oligomers and subsequently two-stranded protofibrils [11]. Protofibrils aggregate axially to build up a fibre that droperidol gels via lateral aggregation [12]. This cross-linking therefore determines the elasticity and mechanical strength of the developing fibrin architecture. Fibres become thicker due to lateral aggregation and branch that leads to a sample-spanning network (i.e., gel). Fibrin network conformation and fibrin fibre diameter also influence fibrinolysis speed. Therefore, fibrin clots built of thin fibres are dissolved at a slower rate than clots with the thick fibres [13], and the resulting formation of tight, rigid and space-filling fibrin network structures with small pores is associated with premature coronary artery disease (CAD) [14,15]. Furthermore, Mills et al. [16] found that healthy male relatives of patients with premature CAD had fibrin clots which polymerized more quickly, had thicker fibres and were less permeable than controls matched for traditional CAD risk factors [16]. The initial fibrin network acts as a template for how the clot develops and determines the clot׳s eventual physical properties. According to Wolberg [17], the conditions i.e., inflammatory and physiological alterations affect how fibrinogen is converted to fibrin determines fibre thickness, branching and network density of the clot development and morphology. Hence, measuring initial clot microstructure and its dynamic development would determine a meaningful marker of coagulation in pro-coagulable states. Incipient clot microstructure is associated with significant changes in blood viscoelasticity (a measure of a material’s viscous and elastic properties). Recent studies of viscoelastic properties are among the most sensitive measures of fibrin polymerization and blood clot microstructure and its mechanical properties [18,19]. Fractal analysis is an established method that allows the testing of a viscoelastic fluid, such as blood by applying a stress (small amplitude oscillatory shear) that varies harmonically with time, and then measuring the response. This technique generates a phase angle (δ) which is a measure of the ratio between the material׳s viscous and elastic properties. An incipient clot is formed at the Gel Point (GP) [20,21] just as the blood turns from viscoelastic liquid to a viscoelastic solid. Therefore, rheological analysis explains in a dynamic way the process of clot initiation to clot formation. We have shown that incipient clots form in healthy whole blood within a narrow range represented by a fractal dimension (d) value derived from the GP and δ. A higher d is suggestive of a more pro-coagulable state. The measurement of d in a healthy state is maintained within remarkably narrow limits at 1.74±0.07 [22]. Hypoxic events and diurnal changes in catecholamines and blood pressure can affect the mechanistic changes in clot structure thereby causing increased cardiovascular events in OSAHS. In the general population, myocardial infarction (MI) and sudden cardiac death peak in incidence between 06:00 and 12:00 [23] but the frequency of MI in people with OSAHS is significantly higher than in non-OSA patients (32% vs. 7%; p= 0.01) between 00:00 and 06:00 [8]. The purpose of this pilot study was to infer if T, d and G׳ are altered in OSAS patients compared to symptomatic comparators. Our secondary aim was to see if any diurnal variation existed in the standard laboratory screening tests in the above groups.