Particulate matter inhalation during hay storing activity induces systemic inflammation and platelet aggregation

The aim of this study was to investigate possible pathomechanisms behind the cardiovascular morbidity caused by inhalation of particulate matter (PM₁₀). For that purpose, healthy volunteers were exposed to high PM₁₀ concentrations during a 2 h hay storing activity. Blood was drawn in the evening before and after PM₁₀ exposure and in the morning and evening of the day after exposure. The leukocyte count increased after PM₁₀ exposure with an initial increase of segmented neutrophils followed by banded forms. C-reactive protein increased over time. Fibrinogen and plasma viscosity became increased in the evening of the day after PM₁₀ exposure. Platelet aggregation was increased in the evening after PM₁₀ exposure. At the same time von Willebrand factor and factor VIII were increased, reflecting endothelial activation. These results confirm that acute inhalative exposure to high PM₁₀ concentrations during hay storage activity leads to a systemic inflammatory reaction, endothelial activation, and platelet aggregation.     

The effects of coronary artery disease severity on time-dependent changes in platelet activation indices in stored whole blood

Background Platelets play a pivotal role in the pathogenesis of the thrombotic complications in cardiovascular disease (CVD). Abnormal platelet activation indices are evolving as potentially useful markers in CVD risk stratification. Whilst there has been some investigation into the effects of storage time on several of these indices, the effects of underlying disease severity on these temporal changes have not been previously studied. Methods Using the ADVIA^TM120 haematology analyser, we assessed the effects of time-dependent storage of whole blood in EDTA, on a number of platelet activation indices: mean platelet volume (MPV), mean platelet component (MPC, measure of platelet density) and platelet component distribution width (PCDW, a marker of platelet shape change. We studied three age- and sex-matched patient groups: (i) healthy controls (n = 10), (ii) stable patients with coronary artery disease (CAD, n = 9); and (iii) patients with acute myocardial infarction (n = 8). Whole blood samples were processed at exactly 5 min following venesection and at 15, 30, 60 and 120 min later in storage in EDTA tubes at room temperature. Results There was a significant and stepwise increase in MPV (P = 0.01) and decrease in PCDW (P = 0.03), with a non-significant trend to increasing MPM and decreasing MPC with increasing underlying disease (that is healthy, ‘stable’ and ‘acute’ artery disease). There was a significant time-dependent increase in MPV and decrease in MPC and PCDW (all P < 0.05), which were all significant on ‘post-hoc’ analyses by 30 min. There were no significant changes in platelet count or MPM with time. There was no interaction of underlying disease with whole-blood storage time for any of the platelet indices reported (P = NS). Conclusion There is a temporal increase in MPV and decrease in MPC and PCDW in venous blood stored over 2 h in EDTA. These changes are not influenced by the underlying CVD disease severity.     

Survival in vivo of platelets stored for 48 hours in the buffycoat at 4°C compared to platelet rich plasma stored at 22°C

Summary High speed centrifugation allows separation of whole blood into cell free plasma, a buffy coat and leukocyte poor red cells. The buffy coat can be used for the preparation of platelet concentrates. High lactate production at 22°C requires storage of the buffy coat at 4°C. Survival in vivo of platelet concentrates prepared from buffy coats stored at 4°C for 48 h (BC-PC) was compared with the survival in vivo of platelet concentrates from platelet rich plasma stored at 22°C for 48 h (PRP-PC). Both methods were studied in the same healthy volunteers (n=8) using⁵¹Cr labeled autologous platelets. The mean ±SD recovery 15 min after reinfusion of the BC-PC was 30.5%±13.3% and for PRP-PC 41.4%±7.9% (p<0.0001). The survival in vivo for BC-PC was 2.4 days ±0.4 days and for PRP-PC 7.0 days ±1.4 days (p<0.0001).Since the survival in vivo is significantly less for platelets derived from the buffy coat stored at 4°C, we advocate storage of platelets at 22°C.     

骨盆骨折患者围术期血小板相关指标及炎性指标的变化

目的:分析盆骨骨折患者围手术期血小板相关指标及炎性指标的变化.方法:收集来本院就诊的盆骨骨折患者90例,作为盆骨骨折组,纳入同时期健康志愿者90例作为对照组.对比对照组和盆骨骨折患者术前及术后第1、3、7天凝血功能指标、血液流变学相关指标和血清炎症因子水平进行检测,比较组间差异及组内围手术期变化.结果:盆骨骨折组术前及术后第7天各项凝血功能和血液流变学相关指标对照组相比,差异无统计学意义(P＞0.05).术后第1、3天,盆骨骨折组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)明显短于对照组和术前,血清纤维蛋白原(FIB)、D-二聚体(D-D)、C反应蛋白(CRP)、白介素-1(IL-1)和肿瘤坏死因子-α(TNF-α)和全血高切黏度、全血低切黏度、全血中切粘度、血浆粘度、红细胞聚集指数则明显高于对照组和术前,IL-6则明显低于对照组和术前,差异具有统计学意义(P＜0.05),术后第7天这些指标开始恢复正常.结论:盆骨骨折患者术后血小板聚集活化、血液处于高凝状态,另外机体应激性刺激分泌大量的炎症因子.     

Platelet phenotype changes associated with breast cancer and its treatment

Platelets and their granular contents influence both angiogenesis and breast cancer progression. This study was performed to assess the effect of breast cancer and its treatment on platelet biology and the response to inhibition of the platelet P2Y12 receptor. Receptor-specific platelet activation and inhibition was studied for three platelet-associated proteins important in cancer angiogenesis and progression, vascular endothelial growth factor (VEGF), thrombospondin1 (TSP1), and transforming growth factor beta 1 (TGF-β1).

Twenty-four women with active breast cancer and 10 healthy controls not receiving antiplatelet therapy participated in the study. Ex vivo activation of platelets in whole blood was accomplished using PAR1AP, PAR4AP, convulxin, and ADP. Platelet inhibition was accomplished using the P2Y12 receptor antagonist cangrelor (the in vitro equivalent of clopidogrel). VEGF, TSP1, and TGF-β1 were measured using standard ELISA.

Platelet activation by ADP, PAR1, PAR4, and collagen receptors increased VEGF, TSP1, and TGF-β1 secretion in patients with breast cancer. Agonist-induced release of VEGF was greater in cancer patients as compared to healthy controls (p = 0.02 for ADP, p < 0.001 for PAR1AP, PAR4AP, and convulxin) despite a decrease in the efficiency of VEGF secretion in patients with breast cancer. These differences were not observed for TSP1 and TGF-β1 secretion. P2Y12 receptor inhibition decreased VEGF, TSP1, and TGF-β1 secretion. In patients with cancer, cangrelor inhibited TSP1 release to a greater extent than VEGF and TGF-β1 release. In patients with breast cancer, the magnitude of platelet inhibition achieved by cangrelor was greater than that achieved with healthy controls for all agonists and platelet proteins studied.

While platelets are known to influence progression of breast cancer, our results show that breast cancer and its treatment influence the platelet phenotype by increasing the secretion of pro-angiogenic proteins following platelet activation, modulating the efficiency of platelet protein release as well as increasing the response to antiplatelet therapy.     

Effect of dealcoholized beer (Bitburger Drive) consumption on hemostasis in humans

BACKGROUND: The beneficial effect of moderate alcohol consumption in lowering the risk of cardiovascular disease has been shown in several epidemiologic studies. Such studies have also shown, however, that the protective effect of alcoholic beverages like wine and beer is not only due to the ethanol content but also to the presence of nonalcoholic constituents. The positive effect of alcoholic beverages has been attributed to changes in lipoprotein metabolism, but there is substantial evidence that effects on hemostasis play an important role. Whether the effects of alcoholic beverages on hemostasis are due exclusively to ethanol or are due, in part, to nonalcoholic components, is still under debate. METHODS: We have examined the hemostatic effects of 3 liters of beer, dealcoholized beer, and ethanol/water (v/v 4%), consumed over a period of 3 hr, in 12 young healthy volunteers. Platelet parameters CD62, PAC-1, and monocyte platelet aggregates were analyzed using flow cytometric measurements. The activity of factor VII was determined with a prothrombin time (PT) assay and plasminogen activator inhibitor activity using a chromogenic substrate. Thrombin generation was determined according to the method of Hemker. RESULTS: All three fluids administered, dealcoholized beer, beer, and ethanol, reduced the expression of activated fibrinogen receptor, the platelet activation marker CD62, and the formation of monocyte-platelet-aggregate. In addition, dealcoholized beer also showed significant inhibitory effects on thrombin generation, whereas beer and ethanol showed procoagulatory effects. CONCLUSIONS: This study has shown that the acute consumption of dealcoholized beer inhibits thrombogenic activity in young adults. This action could have a beneficial effect on the development of coronary artery disease. Thus, the consumption of dealcoholized beer could provide cardiovascular benefit without the negative effects of alcohol.     

Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (−37%, P<0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH patients were combined (r=−0.48, P=0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r=−0.59, P=0.03; normal and FH data, r=−0.49, P=0.004) but positively with high-density lipoprotein (HDL) (FH, r=0.79, P=0.001; normal and FH, r=0.37, P=0.03). Collagen (5–160 μg/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 μg/ml collagen, −40%, P<0.05) and accompanied by increased collagen EC₅₀ values (P<0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.