Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: an exploratory observational study

Abstract

Background Thrombus formation is an important factor affecting cardiovascular events and venous thromboembolism in type 2 diabetes. However, it is unclear whether glycemic control reduces thrombogenicity. We investigated the effect of short-term glycemic control (STUDY 1) and hypoglycemia (STUDY 2) on thrombus formation using an automated microchip flow chamber system. Methods For STUDY 1, we recruited 10 patients with type 2 diabetes. Before and after 2 weeks of treatment, blood glucose was analyzed with a continuous glucose monitoring system, and thrombogenicity was analyzed with an automated microchip flow chamber system. For STUDY 2, we recruited 10 subjects without diabetes who underwent an insulin tolerance test. We evaluated the change in thrombogenic potential with hypoglycemia. Results STUDY1: The mean blood glucose level reduced from 10.1 ± 2.6 to 6.9 ± 0.97 mM ( P < 0.01). T10, an indicator of thrombogenicity, significantly attenuated after glycemic control (338 ± 65 vs. 425 ± 117 s, P < 0.05). The attenuation in T10 was significantly correlated with changes in mean blood glucose level after treatment ( r = − 0.718, P < 0.05). STUDY 2: Platelet function was enhanced with decreasing blood glucose; increased platelet function was strongly correlated with an increase in epinephrine. Conclusions We demonstrated attenuation in thrombogenicity with short-term comprehensive diabetes care and enhancement in thrombogenicity with hypoglycemia, using a new flow chamber system. Trial registration UMIN-CTR UMIN 000019899 , registered 26-Jan-2015 (STUDY 2). Electronic supplementary material The online version of this article (10.1186/s12959-019-0206-8) contains supplementary material, which is available to authorized users.

A modified microchip-based flow chamber system for evaluating thrombogenicity in patients with thrombocytopenia

“…The flow rate was set at 10 μL/min, which corresponds to initial wall shear rates of approximately 1500, 1100, and 600 s − 1 in the 50-, 60-, and 80-μm-deep chambers, respectively. The intra-assay coefficient of variation of the AUC was 1.24% when using conventional flow chambers and whole blood from healthy volunteers [ 25 ] .…”

Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis

“…Hypoglycemia is also associated with increased thrombus formation based on platelet activation, quantitative and qualitative alterations of coagulants, as well as impaired fibrinolysis [ 62 , 63 ]. In T2DM patients, platelet function increased with decreasing blood glucose and increasing epinephrine, suggesting that hypoglycemia induces platelet activation by sympathetic stimulation [ 64 ]. Hypoglycemia also promotes coagulant and fibrinolytic dysfunction by inducing pro-inflammatory reactions and impairing endothelial function in patients with DM [ 65 ].…”

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk—A Systematic Review

“…Mean platelet volume (MPV) and D-dimer measurements can also be used to predict thrombotic status [12]. The blood glucose test was also undertaken by Yamamoto et al [13]. In addition to glycaemic control, they also analysed hypoglycaemia using T-TAS and, more precisely, its effect on clot formation.…”

“…Then, a decrease in blood glucose was observed which increased the activity of platelets, what is associated with an increase of adrenaline. Therefore, scientists suggest that glycaemic control is important in critical situations and that it is relevant to avoid hypoglycaemia [13]. In diabetes, platelet dysfunction occurs due to intracellular hyperglycaemia related to insulin-independent glucose transporters in the platelet cell membrane.…”