Abstract
BackgroundLittle is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.MethodsIn 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.ResultsPolyhedrocytes content in contracted clots was positively correlated with glucose (r = 0.24, p = 0.028), glycated hemoglobin (r = 0.40, p = 0.024), total cholesterol (r = 0.22, p = 0.044), TBARS (r = 0.60, p = 0.0027), P-selectin (r = 0.54, p = 0.0078) and platelet factor-4, PF4 (r = 0.59, p = 0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥ 10th percentile) (n = 83, 85.6%) had higher glucose (+ 15.7%, p = 0.018), fibrinogen (+ 16.6%, p = 0.004), lower red blood cell distribution width (RDW, − 8.8%, p = 0.034), reduced plasma clot density (− 21.8% Ks, p = 0.011) and impaired fibrinolysis (+ 6.5% CLT, p = 0.037) when compared to patients with lesser amount of polyhedrocytes (< 10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r = 0.79, p = 0.036 and r = 0.67, p = 0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p = 0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR = 0.61, 95% CI 0.39–0.92).ConclusionsPoor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.
Highlights
Type 2 diabetes (T2D) is associated with a hypercoagulable state involving increased platelet activation, thrombin generation and unfavorable fibrin clot properties [1,2,3,4]
Polyhedrocytes content in contracted clots was positively correlated with glucose (r = 0.24, p = 0.028), glycated hemoglobin (r = 0.40, p = 0.024), total cholesterol (r = 0.22, p = 0.044), thiobarbituric acid reactive substances (TBARS) (r = 0.60, p = 0.0027), P-selectin (r = 0.54, p = 0.0078) and platelet factor-4, PF4 (r = 0.59, p = 0.0032), but not with thrombin generation, platelet count, permeation coefficient (Ks) or clot lysis time (CLT)
After adjustment for age, sex and fibrinogen, multiple regression analysis showed that red blood cell distribution width (RDW) was the only independent predictor of polyhedrocytes content in type 2 diabetes (T2D) (OR = 0.61, 95% confidence intervals (CI) 0.39–0.92)
Summary
Type 2 diabetes (T2D) is associated with a hypercoagulable state involving increased platelet activation, thrombin generation and unfavorable fibrin clot properties [1,2,3,4]. During clot formation platelets activated by thrombin form a platelet–fibrin mesh constituting the basic structure of thrombus in vivo or whole blood clot in vitro [16] Such clots undergo volume shrinkage [17] that is called clot contraction or retraction [18]. Reduced clot contraction has been demonstrated in subjects with a lower platelet count and/or dysfunction, elevated hematocrit, leukocytosis, increased plasma fibrinogen, and other changes in blood composition that may affect platelet function and properties of blood clots [20] [21]. Formation of polyhedrocytes in arterial thrombi has been associated with higher RBC count and both lower platelet count and plasma fibrinogen, but not with cardiovascular risk factors or the ischemia time [25]. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients
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