Department of Coronary Artery Disease and Heart Failure, Jagiellonian University Medical College, Prądnicka 80 St., 31-202, Kraków, Poland.
John Paul II Hospital, Prądnicka 80 St., Kraków, Poland.
Cardiovasc Diabetol. 2018 Nov 22;17(1):146. doi: 10.1186/s12933-018-0789-6.
Little 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.
In 97 patients with long-standing T2D [median HbA, 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 (K), 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.
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), 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, K 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% K, 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).
Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.
关于影响特定疾病中凝结血红细胞形态变化的因素，我们知之甚少。我们研究了 2 型糖尿病（T2D）患者血红细胞聚集体（polyhedrocytes）在血液凝块中的含量及其决定因素。
在 97 名患有长期 T2D 的患者中（中位 HbA1c，6.4%（四分位间距 5.9-7.8）），我们通过扫描电子显微镜测量了体外血液凝块的组成，包括聚集体覆盖的血凝块面积，并测量了红细胞压缩指数（ECI），定义为平均聚集体面积与平均原生红细胞面积的比值。此外，还测定了血浆纤维蛋白凝块通透性（K）、凝块溶解时间（CLT）、凝血酶生成、氧化应激[总蛋白羰基（total PC）、总抗氧化能力和硫代巴比妥酸反应物质（TBARS）]和血小板活化标志物。评估了葡萄糖浓度对聚集体形成的体外影响。
收缩凝块中聚集体的含量与葡萄糖（r = 0.24，p = 0.028）、糖化血红蛋白（r = 0.40，p = 0.024）、总胆固醇（r = 0.22，p = 0.044）、TBARS（r = 0.60，p = 0.0027）、P-选择素（r = 0.54，p = 0.0078）和血小板因子 4（PF4，r = 0.59，p = 0.0032）呈正相关，但与凝血酶生成、血小板计数、K 或 CLT 无关。形成更多聚集体（≥第 10 百分位数）（n = 83，85.6%）的患者血糖水平更高（+15.7%，p = 0.018），纤维蛋白原水平更高（+16.6%，p = 0.004），红细胞分布宽度（RDW）更低（-8.8%，p = 0.034），血浆凝块密度降低（-21.8%K，p = 0.011），纤维蛋白溶解受损（+6.5%CLT，p = 0.037），与聚集体含量较低（<第 10 百分位数）的患者相比。ECI 和聚集体含量与总 PC 呈强相关（r = 0.79，p = 0.036 和 r = 0.67，p = 0.0004）。体外葡萄糖浓度增加 10 mmol/L 与聚集体含量增加 94%相关（p = 0.033），与基线（7.1 mmol/L）相比。调整年龄、性别和纤维蛋白原后，多元回归分析显示 RDW 是 T2D 患者聚集体含量的唯一独立预测因子（OR = 0.61，95%CI 0.39-0.92）。
血糖控制不佳，加上血小板活化和氧化应激增强，增加了 T2D 患者血液凝块中聚集体的含量。
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