Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay

Abstract

Diabetes is a risk factor for the development of atherothrombosis and venous thromboembolism (VTE). We investigated whether plasma from patients with type 2 diabetes has an imbalance of pro- versus anti-coagulation resulting in hypercoagulability despite normal conventional coagulation tests. We analyzed blood samples from 60 patients with type 2 diabetes and 60 gender- and age-matched healthy subjects (controls) for the levels of pro- and anti-coagulant factors, for thrombin generation and for the numbers of cell-derived circulating microparticles bearing such pro-coagulant triggers as tissue factor and negatively charged phospholipids. The levels of pro- or anti-coagulants as measured with conventional coagulation tests or single factor measurements were similar to those of the control population. In contrast, the median (range) of the height of the thrombin peak (taken as an index of thrombin generation) was higher in patients [205 nM (126-352)] than controls [151 nM (41-289)], P < 0.001. The median numbers of circulating microparticles were higher for patients [5,041/μl (1,821-13,132)] than for controls [1,753/μl (554-13,308)], P < 0.001 and their values were correlated with the height of the thrombin peak (ρ = 0.66, P < 0.001). In conclusion, plasma from patients with type 2 diabetes possesses an imbalance of pro- versus anti-coagulation resulting in hypercoagulability that can be detected by thrombin generation tests, but not by the measurement of the single pro- or anti-coagulant factors. This hypercoagulability is associated with increased numbers of circulating microparticles bearing endogenous pro-coagulant triggers. These findings might explain the relatively high risk of atherothrombosis and VTE described in these patients.

Beyond Hyperglycemia in Diabetes: Role of Statin Treatment on Thrombogenesis Triggered by Inflammation

“…A hypercoagulable state, detected by thrombin generation tests, was reported in patients with T2D, explaining, at least partially, the high incidence of vascular events in these patients [9].…”

“…Improved glycemic control is the only significant predictor of a decrease in blood thrombogenicity, irrespective of treatment allocation [7]. Enhanced levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) have been shown in T2D patients in comparison with healthy subjects [8].A hypercoagulable state, detected by thrombin generation tests, was reported in patients with T2D, explaining, at least partially, the high incidence of vascular events in these patients [9].Platelets of patients with DM are characterized by dysregulation of several signaling pathways, leading to an hyperreactive phenotype with enhanced adhesion, aggregation, and activation [10]. Chronic hyperglycemia has been clearly identified as a causal factor for in vivo platelet activation [11].…”

The Significance of Thrombin Generation Test in Recurrent Early Pregnancy Loss

“…'nın venöz tromboemboli için yüksek riske sahip diabetes mellituslu hastalarda yaptığı çalış-mada, TGA testi ile venöz tromboembolinin ön-görülebileceği ve verilen mevcut tedavilerin veya trombini ve aktive F X'u inhibe etmeye yönelik Turkiye Klinikleri J Med Sci 2013;33 (3) yeni antikoagülan tedavilerin bu hastalarda faydalı olabileceği öne sürülmüştür. 36 Bizim çalışma-mızda da TA'da önemli bir yeri olan trombofilili hastalarda ve rutin testlerle trombofili göstergesi saptanamayan hastalarda ETP değerinin yüksek olmasının önemli olabileceğini, TA'sı olan hastalarda antikoagülan tedavi başlanmasında ve tedavinin takibinde bu testin yol gösterici olabileceğini düşünmekteyiz. Açıklanamayan TA'sı olan hastalarda antikoagülan kullanımına yönelik yapılan çalışmalarda TGA testi kullanıldığı takdirde hiperkoagülabilite tespit edilen hastaların ayrıca değerlendirilmesinin sonuçları etkileyebileceği kanaatindeyiz.…”

Novel measurements of blood coagulability for assessing the risk of thrombosis

“…When thrombin is generated, the substrate is cleaved and makes a fluorescent signal, and several parameters are derived from the serial changes in the thrombin generation. It is considered that the TGA has the advantage of better detecting hypercoagulability than the aPTT or PT, and several clinical studies have shown its utility for detecting the hypercoagulability [6,7].…”