Glycoprotein IIb/IIIa (GPIIb/IIIa) is the most abundant platelet surface receptor for fibrinogen and von Willebrand factor. Polymorphism PlA1/A2 in the gene of GPIIb/IIIa is among the risk factors for the development of arterial and venous thrombosis. The aim of this study is to evaluate the effect of the carriage of PlA1/A2 on the size, topographic features, and membrane stiffness of platelets from healthy controls and patients with deep venous thrombosis (DVT). Atomic force microscopy (AFM) imaging and nanoindentation (force-distance curves) were applied to investigate the morphological and nanomechanical properties (Young's modulus) of platelets immobilized on glass surface. The surface roughness (R a ) and height (h) of platelets from patients with DVT, carriers of mutant allele PlA2 (R a ¼ 30.2 + 6 nm; h ¼ 766 + 182 nm) and noncarriers (R a ¼ 28.6 + 6 nm; h ¼ 865 + 290 nm), were lower than those of healthy carriers of allele PlA2 (R a ¼ 48.1 + 12 nm; h ¼ 1072 + 338 nm) and healthy noncarriers (R a ¼ 49.7 + 14 nm; h ¼ 1021 + 433 nm), respectively. Platelets isolated from patients with DVT, both carriers and noncarriers, exhibit much higher degree of stiffness at the stage of spreading (E ¼ 327 + 85 kPa and 341 + 102 kPa, respectively) compared to healthy noncarriers (E ¼ 198 + 50 kPa). In addition, more pronounced level of platelet activation was found in polymorphism carriers. In conclusion, the carriage of PlA2 allele modulates the activation state, morphology, and membrane elasticity of platelets.

Summary Fetuin-A is a secretory liver glycoprotein with multiple physiological functions such as regulation of insulin resistance, tissue calcification, bone metabolism, cellular proteolytic activity, and self-proliferative signaling. Fetuin-A is a unique molecule which binds to the insulin receptor, modulating its sensitivity, and transducing “the physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inflammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate with reduced glucose tolerance and insulin resistance. Impaired insulin sensitivity leads to the development of metabolic syndrome, an increased risk for type 2 diabetes (T2DM), dyslipidaemias and cardiovascular diseases (CVDs). Furthermore, fetuin-A inversely correlates with inflammatory and activation biomarkers, e.g. in patients with T2DM. Thus, circulatory fetuin-A levels may have plausible predictive importance as a biomarker of risk of diabetes and negative acute phase protein. Dysregulated, it plays a crucial role in the pathogenesis of some metabolic disorders and clinical inflammatory conditions like metabolic syndrome, T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.