胰岛素依赖型糖尿病及其并发症患者血小板超微结构的形态计量学研究

采用形态计量学方法，分析胰岛素依赖型糖尿病（ＩＤＤＭ），及其并发视网膜病变患者血小板外形和超微结构的量的变化。与对照组比较，ＩＤＤＭ患者血小板平均体积增大，ａ颗粒、致密体、线粒体和糖原区含量增多，ａ颗粒和致密体平均直径、体积增大，并发微血管病变组改变尤为显著。从结构上证明ＩＤＤＭ患者血小板是属于细胞器丰富的高敏大体积血小板，在微血管病变的发生和发展中起重要作用。     

血小板参数与2型糖尿病微血管病变的关联研究

选取62例2型糖尿病患者作为病例组研究对象,并分为无微血管病变组(27例)与有微血管病变组(35例),选取30例健康者作为对照组,比较三组对象之间的血小板参数。结果 2型糖尿病患者的MPV、PDW显著高于健康者,PLT显著低于健康者,有微血管病变组的MPV、PDW显著高于无微血管病变组,PLT显著低于无微血管病变组,差异均有统计学意义(P0.05)。结论 2型糖尿病微血管病变患者存在血小板参数异常,动态了解血小板参数对及早发现并控制糖尿病微循环障碍具有重要临床意义。     

糖化血红蛋白和血小板参数联合检测在老年糖尿病患者微血管病变时的意义

目的探讨糖化血红蛋白（GHb）及血小板参数联合检测在糖尿病微血管病变时意义。方法应用全自动血细胞分析仪和生化分析仪，测定96例老年糖尿病患者（其中有微血管病变者50例，无微血管病变者46例）及42名健康对照者的GHb、血小板平均体积（MPV）、血小板分布宽度（PDW）、血小板计数（PLT），分析它们在正常人和糖尿病患者不同时期的变化。结果糖尿病患者GHb、MPV、PDW明显高于健康对照组（P〈0．01），有微血管病变者明显高于无微血管病变者（P〈0．01），正常人和糖尿病患者的PLT无显著变化（P〉0．05）。结论GHb、MPV、PDW联合检测对糖尿病患者微血管病变的早期诊断具有重要价值。     

糖尿病血小板功能异常与微血管病变

糖尿病为全身系统性疾病，微血管病变是其常见的慢性并发症，包括糖尿病肾病（diabetic nephropathy）和糖尿病视网膜病变（diabetic retinopathy）和神经病变（diabetic neuropathy）等。许多研究证实，糖尿病患者的血小板功能异常在未出现微血管病变时已经存在，且血小板异常活化程度以有微血管病变者更为显著。血小板异常活化是糖尿病微血管病变的始动因素。笔者就糖尿病血小板功能异常与微血管病变作一综述。     

2型糖尿病并微血管病变患者血小板参数、凝血指标、D-二聚体变化及其临床意义

目的分析2型糖尿病并微血管病变患者血小板参数、凝血指标、D-二聚体变化及其临床意义。方法选取同济大学附属同济医院2014年5月—2016年5月收治的2型糖尿病患者100例,根据微血管病变情况分为A组(并发微血管病变)和B组(未并发微血管病变),每组50例;另选取同期体检健康者50例作为对照组。比较3组受试者血小板参数、凝血指标及D-二聚体。结果 A组患者血小板计数(PLT)低于B组、对照组(P0.05),平均血小板体积(MPV)、血小板分布宽度(PDW)、血小板压积(PCT)高于B组、对照组(P0.05);B组患者PLT低于对照组(P0.05),而B组与对照组MPV、PDW、PCT比较,差异无统计学意义(P0.05)。A组患者凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)短于B组、对照组,纤维蛋白原(FIB)、D-二聚高于B组、对照组(P0.05);B组患者PT、APTT、TT短于对照组,FIB、D-二聚体高于对照组(P0.05)。结论 2型糖尿病并微血管病变患者血小板参数、凝血指标、D-二聚体异常,存在微循环障碍,血小板参数、凝血指标、D-二聚体可作为诊断2型糖尿病患者微血管病变的参考指标。     

老年2型糖尿病患者血浆血小板α-颗粒膜蛋白的变化

目的 观察老年２型糖尿病患者血浆血小板α－颗粒膜蛋白（ＧＭＰ－１４０）的变化。方法 采用放免法,检测２０例正常人和４０例老年２型糖尿病患者（２２例无微血管病变,１８例有微血管病变）血浆ＧＭＰ－１４０的变化,同时观察了患者用己酮可可减治疗后上述指标的变化。结果 糖尿病患者ＧＭＰ－１４０显著高于正常对照组,己酮可可碱治疗后ＧＭＰ－１４０则明显下降,伴微血管病变者比无微血管病者变化,结果 糖尿病患者ＧＭ     

糖尿病患者平均血小板体积和血脂变化的研究

糖尿病患者平均血小板体积和血脂变化的研究赵淑好王中心杨立勇潘时中严孙杰刘东晖张松菁近年来研究表明糖尿病患者血小板平均体积增大，在糖尿病微血管病变的发生和发展过程中起重要作用。本文对９０例糖尿病患者平均血小板体积（ＭＰＶ）、血小板压积（ＰＣＴ）、血小板...     

糖尿病微循环障碍的特征

糖尿病微循环障碍是导致微血管病变的病理基础,而血液流变学的变化是微循环状态的重要指征。糖尿病脂代谢的紊乱对血液流变学及血小板功能的影响已有报告,而对红细胞膜的作用尚未研究。本文作者研究了糖尿病患者血小板自身凝     

糖尿病患者的血小板表面糖蛋白

我们测定了21例糖尿病微血管病变患者、27例糖尿病无并发症患者的血小板表面糖蛋白,以探讨血小板表面糖蛋白与糖尿病血小板功能改变及微血管病变的关系。 一、对象:糖尿病并微血管病变患者21例(男9例,女12例),年龄42～82岁,平均58.2±12.0岁,病程1个月～17年,血糖7.98±3.04mmol/L(±s);21     

营养和代谢疾病

994289 糖尿病患者血小板活人状态和纤溶活性的变化/林东平…//实用医学杂志-1999,15(6).425～426 检测正常人20例,Ⅱ型DM40例(无微血管病变22例,微血管病变18例)。结果:DM患者血小板α-颗粒膜蛋白(GMP-140)、血栓素B_2、血小板聚集率     

Effect of infusing rat monoclonal antibodies to the murine GPIb-IX-V complex on platelet and megakaryocyte morphology in mice

In the Bernard-Soulier syndrome, the absence of GPIb-IX-V leads to thrombocytopenia and giant platelets. In autoimmune thrombocytopenia in man, anti-platelet antibodies are associated with changes in megakaryocyte (MK) morphology and platelet size heterogeneity. We have compared the ultrastructural changes in mature MK following the infusion of rat monoclonal antibodies (MoAbs) to different epitopes of the murine GPIb-IX-V complex in mice. Blood and marrow samples were examined during both the acute thrombocytopenic phase and during the recovery phase. A MoAb to GPV induced neither thrombocytopenia nor changes in platelet morphology. During the acute thrombocytopenic phase with anti-GPIb f MoAbs, the size of residual platelets was heterogeneous and included large forms and platelets with few granules. During recovery, platelet size heterogeneity continued, and some platelets showed signs of activation. But only rare platelets were giant forms with ultrastructural defects resembling BSS. Megakaryocytopoiesis during acute thrombocytopenia was already abnormal, with some mature cells often showing vacuoles and an irregular development of the demarcation membrane system which varied in extent. These changes continued into the recovery phase. The anti-GPV MoAb had no effect on MK. Thus, anti-platelet antibodies can induce a different medullary response even when binding to the same receptor.     

Effect of infusing rat monoclonal antibodies to the murine GPIb-IX-V complex on platelet and megakaryocyte morphology in mice

In the Bernard-Soulier syndrome, the absence of GPIb-IX-V leads to thrombocytopenia and giant platelets. In autoimmune thrombocytopenia in man, anti-platelet antibodies are associated with changes in megakaryocyte (MK) morphology and platelet size heterogeneity. We have compared the ultrastructural changes in mature MK following the infusion of rat monoclonal antibodies (MoAbs) to different epitopes of the murine GPIb-IX-V complex in mice. Blood and marrow samples were examined during both the acute thrombocytopenic phase and during the recovery phase. A MoAb to GPV induced neither thrombocytopenia nor changes in platelet morphology. During the acute thrombocytopenic phase with anti-GPIbalpha MoAbs, the size of residual platelets was heterogeneous and included large forms and platelets with few granules. During recovery, platelet size heterogeneity continued, and some platelets showed signs of activation. But only rare platelets were giant forms with ultrastructural defects resembling BSS. Megakaryocytopoiesis during acute thrombocytopenia was already abnormal, with some mature cells often showing vacuoles and an irregular development of the demarcation membrane system which varied in extent. These changes continued into the recovery phase. The anti-GPV MoAb had no effect on MK. Thus, anti-platelet antibodies can induce a different medullary response even when binding to the same receptor.     

Influence of low density lipoprotein from insulin-dependent diabetic patients on platelet functions.

In the present work we studied in vitro the action of low density lipoproteins (LDL) isolated from normolipemic insulin-dependent diabetic (IDDM) patients on transmembrane cation transport, nitric oxide synthase (NOS) activity, and aggregating response to stimuli of platelets from healthy subjects to elucidate whether the modified interaction between circulating lipoproteins and cells might be one of the pathogenetic mechanisms of the increased platelet activation in IDDM. LDL were obtained by discontinuous gradient ultracentrifugation from 15 IDDM out-patients and 15 sex- and age-matched healthy subjects and used for incubation experiments with control platelets. Lipid composition and hydroperoxide concentrations were studied in LDL. Platelet aggregation responses to ADP, NOS activity, cytosolic Ca2+ concentrations, and platelet membrane Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) and Ca2+-ATPase activities were measured after incubation. IDDM LDL showed an increased lysophosphatidylcholine content compared with that of control LDL. IDDM LDL significantly increased the platelet aggregating response to ADP, cytosolic Ca2+ concentrations, and plasma membrane Ca2+-ATPase activity and significantly reduced NOS activity and platelet membrane Na+/K+-ATPase activity compared with those of platelets incubated in buffer or cells incubated with control LDL. The effects exerted by IDDM LDL on platelet suspensions from healthy subjects mimic the alterations observed in platelets from diabetic subjects in basal conditions. Both the decreased activity of NOS and the higher cytoplasmic concentrations of Ca2+ might cause increased platelet activation, as observed in IDDM. In conclusion, the present study suggests a new mechanism with a potential role in the early development of atherosclerosis in diabetic patients, i.e. an altered interaction between circulating lipoproteins and platelets.     

Platelet hyperreactivity and vasculopathy in insulin dependent diabetes mellitus

Platelet functions were studied in 10 patients with insulin dependent diabetes mellitus (IDDM) with vasculopathy, and in age and sex-matched normal controls. The patient group at presentation showed increased circulating platelet aggregates, greater platelet factor III availability and increased aggregation of platelets in response to various agonists (shorter latent period, greater rate of aggregation, greater degree of aggregation, p < 0.05- < 0.001). This platelet hyperreactivity remained unchanged even after normalisation of blood glucose. In contrast, similar platelet hyperreactivity seen by us earlier in patients with uncontrolled IDDM without vasculopathy reversed to normal after metabolic control. In view of the postulated role of hyperreactivity of platelets in the pathogenesis of vasculopathy in IDDM, our results imply that once vasculopathy sets in, a vicious cycle starts between platelet hyperreactivity and vasculopathy. Proper and early treatment of IDDM at a stage when vasculopathy is not present, would therefore be important in reversing the platelet hyper-function and may possibly delay the development of vasculopathy.     

Platelet ultrastructural abnormalities in three patients with type 2B von Willebrand disease

Several reports have described the presence of giant platelets in patients with type 2B von Willebrand disease (VWD). We have now characterized the ultrastructural changes in platelets from three unrelated patients with type 2B VWD and different mutations within exon 28 of the von Willebrand factor (VWF) gene. Electron microscopy showed that each of these subjects had an increased proportion of large platelets when compared with those of a patient with type 2A VWD or control subjects. Immunogold labelling for VWF was performed. Large masses detected by anti-VWF antibody were seen not only on the platelet surface, but also inside the platelet surface-connected canalicular system (SCCS) when ultrathin sections were labelled. This suggested translocation of the abnormally bound VWF from the platelet surface. Labelling of the alpha-granules was eccentric as for normal platelets. Labelling for glycoprotein (GP) Ib was seen on the surface and within the SCCS, suggesting co-localization with the bound VWF. However, there was no evidence for VWF in endosomes or other endocytic vesicles. The presence of platelet-bound VWF was not accompanied by high levels of platelet activation, as detected by electron microscopy, or by using monoclonal antibodies against P-selectin or activation-dependent determinants on GP IIb-IIIa in flow cytometry. Intriguingly, platelet ultrastructure often resembled that seen in patients with congenital thrombocytopathies characteristic of giant platelet syndromes.     

Platelet activation in diabetic microangiopathy

Platelet activation and hyperreactivity are known to be associated with a rapid development and progression of diabetic angiopathy. The present study attempts to clarify whether IDDM patients without diabetic complications have an increased platelet activation and whether in vivo platelet activation is altered in the presence of diabetic microangiopathy. Platelet activation was assessed by flow cytometry analysis in 50 healthy controls (c) and in 41 patients with insulin-dependent diabetes mellitus (IDDM type 1) who were screened for diabetic complications. Sixteen of these patients (0) showed no evidence of microangiopathic organ lesions as assessed by an established standard battery of clinical tests, whereas the other 25 patients had diabetes derived microvascular complications (dmc). Patients with macroangiopathy were ruled out. Platelet activation was evaluated by flow cytometric detection of four activation-dependent platelet surface markers (lysosomal GP53, thrombospondin, P-selectin and ligand-induced binding site-1 of GPIIb-IIIa). A higher percentage of thrombospondin-positive platelets was detected in the IDDM patients without complications: 8.6 +/- 0.9% (0) vs 6.1 +/- 0.4% (c) vs 5.4 +/- 0.4% (dmc), P < 0.05, respectively. A decrease in GP53-, P-selectin-, and LIBS-1-positive platelets was observed in the IDDM group with dmc: for GP53 17.4 +/- 1.0% (dmc) vs 23.4 +/- 1.0% (c), P < 0.05; for P-selectin 5.5 +/- 0.6% (dmc) vs 8.0+/-0.7% (c), P < 0.01 and for LIBS-1 8.3 +/- 0.9% (dmc) vs 15.8 +/- 1.3% (c), P < 0.01. No differences in these markers were found in controls and IDDM patients without complications. In addition, no correlations were found between the glucose metabolism and platelet activation. These findings indicate (i) that the platelet system is pre-activated in IDDM , and (ii) that an increased consumption of activated platelet may occur in the vessels of IDDM patients with diabetic microangiopathy.     

Do determinants of platelet function co-segregate with genetic markers of type 1 diabetes mellitus?

This study examined the significance of selected parameters of primary haemostasis to discriminate between relatives of children with insulin-dependent diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and agonist-induced platelet activation (CD62), platelet consumption (microparticles) and clumping (aggregates), as well as selected parameters of the fibrinolytic system (t-PA and PAI-1), were studied in IDDM children ( n = 45), their parents ( n = 65), siblings ( n = 17) and unrelated healthy controls ( n = 51). The fraction of activated platelets circulating in whole blood amounted to 4.3 +/- 2.1% in IDDM children, and significantly exceeded the level found in parents (1.3 +/- 0.7%, P < 0.002), siblings (1.2 +/- 1.0%, P < 0.002), and controls (1.2 +/- 0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles was observed in the IDDM group, both in resting platelets and also when platelets were stimulated with thrombin. Significantly decreased total PAI-1 occurred in IDDM children ( P < 0.02 versus parents); also slightly lowered active PAI-1 and t-PA antigen were noticed in IDDM subjects compared to other groups, however, the differences were not statistically significant. To assess dissimilarities between the groups of subjects we applied the forward stepwise model of discriminant function analysis, which included platelet flow cytometry parameters. The best separation and the highest discrepancy (expressed as the so called squared Mahalanobis distances, d ) was M revealed between controls and IDDM patients ( P < < 0.0001) and between controls and parents ( P < < 0.0001). The values of d found between IDDM children and their siblings (P < 0.001), as well as parents ( P < 0.01), were M of much lower significance. The finding that the control group, representing unrelated subjects, remains particularly well separated from the other groups, more or less clustered together, implies the possible involvement of genetic factor(s) which might potentially affect platelet activation and reactivity. In addition, the distinguished distribution of HLA DQAI(52) and HLA DQBI(57) genotypes in the groups further validates the suspicion that the altered platelet function and response in diabetes might be associated with some independent genetic factor(s), and is not likely to result from HLA DQAI(52) and HLA DQBI(57) impact.