The Effect of Sulfinpyrazone (Anturan) on Platelet Economy and Blood Coagulation in Man

Sulfinpyrazone (Anturan) administered in therapeutic doses over a period of several weeks produced prolongation of platelet survival and reduced turnover but with little change in blood coagulation. The changes in platelet survival and turnover were associated with reduced platelet adhesiveness. It is therefore possible to affect platelet economy in man significantly, without producing corresponding effects on blood coagulation.     

Blood Coagulation and Platelet Economy in Subjects with Primary Gout

Previous studies have suggested that there is an increased incidence of degenerative vascular disease in patients with gout and an increased rate of turnover of blood platelets in patients and animals with atherosclerosis. A disturbed uric acid metabolism and “secondary” gout have long been known to occur with bone marrow diseases. A study of platelet economy and blood clotting factors in subjects with primary gout was therefore undertaken.Twenty-two male subjects with gout but with no clinical evidence of vascular disease were studied. Half of these had a negative family history for vascular disease and half had less fortunate ancestors. The most striking differences were found when gouty patients with a negative family history for vascular disease were compared with similar control subjects. The mean platelet half-life was 2.85 days in the gouty subjects and 3.74 days in the controls. The mean platelet turnover (number/c.mm./day) was 58,750 in gouty subjects, 42,370 in controls. Platelet adhesiveness and plasma thromboplastic activity were correspondingly increased in the gouty subjects. Control subjects with a positive family history all showed relatively active clotting system and platelet turnover, similar to the values found in atherosclerotic subjects. The data indicated that there is increased platelet destruction and production in some patients with primary gout. The relation between this anomaly and the vascular disease, and disturbed urate metabolism in gouty subjects, remains to be investigated.     

Preliminary Investigation on the Effect of Dietary Supplemental Biotin and Palm Kernel Oil on Blood,Liver and Kidney Lipids in Chicks

Abstract

A total of 480 day-old broiler chicks were used in two trials conducted to investigate the performance and lipid contents of blood, liver and kidneys of birds when fed varying levels of palm kernel oil (0% and 2%) and biotin (40, 80, 120, 160, 200 and 240 mcg/kg feed) in a 2 × 6 factorial experimental design. The results showed that blood, liver and kidney lipid concentrations were significantly affected by dietary biotin treatments. While total lipid, free fatty acid, triglyceride and cholesterol contents were negatively correlated with dietary biotin level, phospholipid concentrations were positively correlated. Biotin-deficient chicks had significantly higher total lipid, free fatty acid, triglyceride and cholesterol but lower phospholipid contents in their blood and the two organs. Supplementation of the diet with 2% palm kernel oil significantly elevated blood phospholipid concentration, but depressed the accumulation of the other lipid fractions in both organs and the blood of birds. Blood, liver and kidney cholesterol concentrations were not affected by 2% fat supplementation. Observation on the lipid parameters coupled with the results on feed utilisation appeared to suggest that a minimum of 120 mcg of the vitamin per kilograme of diet was required by broiler chicks for optimum performance.     

The Blood Platelet as a Model for Regulating Blood Coagulation on Cell Surfaces and Its Consequences

Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of the large numbers of platelets that appear in the subendothelium where they become exposed to tissue factor and to molecules adhesive for platelets and normally found in the extracellular matrix. The complex of plasma factor VIIa with extravascular tissue factor both initiates and localizes thrombin production on platelets and on extravascular cells. Thrombin production at these sites in turn enhances platelet activation and the subsequent hemostatic plug formation to minimize bleeding. Thrombin production and platelet activation also initiate the process of wound healing requiring thrombin-dependent cell activation and platelet-dependent formation of new blood vessels (angiogenesis). Activated platelets release from their storage granules several proteins and other factors that regulate local thrombin formation and the responses of blood vessel cells to injury to assure hemostasis and effective wound healing. Failure to localize and adequately regulate thrombin production and/or platelet activation can have pathological consequences, including the development and propagation of atherosclerosis and enhancement of tumor development. The primary basis for the pathological consequences of the failure to adequately regulate thrombin production is that the multi-functional thrombin activates several types of cells to initiate their mitogenesis. Mitogenesis precedes many of the undesirable consequences of poorly regulated thrombin production and platelet activation. In addition, activated platelets release a variety of products which influence the functions of several cell types to the extent that inadequate regulation of platelet activation (by excessive thrombin production) could contribute to the pathogenesis of acute and chronic arterial thrombosis and to tumor development. Activated platelets participate in tumor development by releasing several factors that positively (and negatively) regulate blood vessel formation.     

重症肺炎影响极低出生体重儿血小板及凝血功能的研究

目的:通过观察我院收治的极低出生体重新生儿肺炎的临床治疗,研究重症肺炎对该类疾病患儿的血小板及凝血功能的影响,探讨其临床研究价值.方法:将47例一般肺炎的极低出生体重新生儿设为对照组,45例重症肺炎的极低出生体重新生儿设为实验组,对比分析两组患儿的血小板参数的检测指标并行患儿凝血功能检查.结果:在血小板参数方面,实验组在MPV和PDW的数据较对照组高,而在PLT明显较低;在凝血功能方面,实验组在PT、APTT和TT等方面的数据较对照组高,而在FIB方面明显较低.结论:临床上对动态监测重症肺炎患儿血小板的变化情况,对判断该疾病患儿的预后具有积极的参考与预警意义,而对重症肺炎患儿出现凝血系统功能紊乱及时把握具体发病机制,对症进行凝血功能恢复治疗,值得临床进一步研究与探讨.     

Effect of Dietary Lipids on Phospholipase D Activity in Rat Brain

Phospholipase D (PLD) is emerging as a major player in many novel signaling pathways. Based on recent studies correlating membrane composition with enzyme function, we speculated that feeding of dietary lipids to the newborns has a major impact on brain PLD activity. To test this hypothesis, the rat dams were fed fat-free powder containing either safflower oil or fish oil, and a control powdered chow. The pups were weaned onto the diet and sacrificed at 30 days of age. PLD activity was measured by transphosphatidylation assays using rat brain membranes. This study shows that microsome GTPS-dependent PLD activity in rats fed safflower oil or fish oil was significantly reduced by 38% and 30% respectively compared to controls. Oleate-dependent PLD activity in the safflower oil group, however, was significantly increased by 38%. In contrast, synaptosome membrane (P2) GTPS-dependent PLD activity in rats consuming safflower oil was significantly increased by 29%, but there was no difference in oleate-dependent PLD activity. Likewise, no difference was observed in microsome oleate-dependent PLD and P2 GTPS-dependent PLD activity between the fish oil and the control groups. These results indicate that dietary lipid intake appears to modulate phospholipid metabolism and differential expression of PLD isozymes in the brain.     

Circadian Variations in Blood Coagulation Parameters, Alpha-Antitrypsin Antigen and Platelet Aggregation and Retention in Clinically Healthy Subjects

Ten clinically healthy subjects (5 men and 5 women), 31 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.     

不同海拔地区藏族就诊人群血脂、血液黏度、HCY水平与心血管疾病的相关性研究

目的:探讨不同海拔地区藏族就诊人群血脂、血液黏度、HCY水平与心血管疾病的相关性。方法:采用回顾性分析的方法,将328例来自不同海拔地区的藏族就诊患者为三组,高海拔组(纳入99例),中海拔(纳入120例)和低海拔组(纳入109例),比较不同海拔高度组患者血压、血脂、血液黏度、HCY、疾病类型的差异,采用多元Logistic回归模型分析藏族就诊人群心血管疾病发病的影响因素。结果:不同海拔组收缩压、舒张压、血清HCY、TC、TG、HDL-C、LDL-C水平、全血黏度低切、中切、高切、血浆黏度和红细胞压积比较差异均有统计学意义(P0.05),随着海拔升高,收缩压、舒张压、血清HCY、TC、TG以及LDL-C、全血黏度低切、中切、高切、血浆黏度和红细胞压积水平显著升高(P0.05),而血清HDL-C水平显著下降。41.8%(137/328)的就诊者至少患有一种心血管疾病,和非心血管组比较,心血管疾病组年龄明显偏高,居住主要分布在中度及高度海拔地区,合并高血糖、高血脂、高HCY的比例均明显较高,差异均有统计学意义(P0.05)。年龄、海拔、高血糖、高血脂、高HCY均和心血管疾病相关(r=-0.230~0.334,P0.05)。多元Logistic回归分析显示年龄、居住地海拔、HCY水平、全血低切粘度、TG水平、LDL-C等因素是心血管疾病发生的危险因素,HDL-C是保护因素。结论:来自不同海拔地区的就诊人群在血压、血脂、血液黏度、HCY水平以及心血管疾病患者占比不同。年龄、居住地海拔、HCY水平、血液黏度、血脂水平等增加可能使高原藏族人群心血管疾病发生风险增加。     

不同全自动凝血仪检测结果的分析研究

目的:探讨不同全自动凝血分析仪检测结果是否具有可比性,同时对其检测结果临床可接受性进行评估,使不同全自动凝血分析仪检测结果标准化.方法:连续30天用SYSMEX CA- 1500及CA-7000全自动凝血分析仪同时检测并比对仪器配套定值质控物的PT、INR、APTT、FIB、TT值;同时连续30天利用两台仪器检测并对比新鲜血标本的PT、INR、APTT、FIB、TT值.结果:SYSMEX CA- 1500及CA-7000日间质控物各检测项目:PT、INR、APTT、FIB、TT变异系数均小于5％.CA- 1500及CA-7000全自动凝血分析仪检测新鲜血标本:PT、INR、APTT、FIB、TT统计分析结果,t检验其P值均＞0.05;相关系数r在0.993-0.999之间;两台仪器的偏差均符合1/2美国CLIA’88能力验证分析质量要求.结论:两台仪器PT、INR、APTT、FIB、TT的检测结果具有很好的相关性,经统计分析两台仪器检测结果无统计学意义.对不同凝血分析仪进行比对分析,不仅能够及时发现仪器存在的系统误差.而且使其检测结果具有很好的一致性,给临床可提供一个准确、可靠一致的实验室检测结果,使临床对疾病的诊断、疗效观察有一个统一的评判标准.     

Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function

Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO₂ ⁻) and nitrate (NO₃ ⁻) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 µM inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes.     

不同化疗方案对非小细胞肺癌患者凝血纤溶功能及血小板参数的影响及其临床意义

目的:探讨不同化疗方案对非小细胞肺癌患者凝血纤溶功能及血小板参数的影响及临床意义。方法:回顾性分析2013年2月至2016年2月于我院进行治疗的96非小细胞肺癌患者的临床资料,按照化疗方案的不同分为TP组(50例)及GP组(46例),TP组患者给予多西他赛联合卡铂方案(TP方案)进行化疗,GP组患者给予吉西他滨联合卡铂方案(GP方案)进行化疗,另选择45例健康体检者作为对照组。比较三组治疗前者血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血浆凝血酶时间(TT)、血浆纤维蛋白原含量(FIB)以及D-二聚体(D-dimer)、血小板数(PLT)、血小板比积(PCT)、血小板平均体积(MPV)、血小板体积分布宽度(PDW)以及大体积血小板比率(P-LCR)及TP组和GP组治疗后以上指标的差异。结果:TP组和GP组患者化疗前PT、APTT、TT、FIB、D-dimer、PLT、PCT、MPV、PDW以及P-LCR水平均明显高于对照组(P0.05),而TP组与GP组以上指标比较无显著差异(P0.05)。治疗后,TP组和GP组患者PT、APTT、TT、FIB、D-dimer、PLT、PCT、MPV、PDW以及P-LCR水平均较治疗前有所下降,且GP组TT明显长于TP组(P0.05),PLT、PCT明显低于TP组(P0.05)。结论:凝血纤溶功能及血小板参数对于评价不同化疗方案治疗非小细胞肺癌患者预后具有积极的临床价值,不同化疗方案选择对于患者凝血系统均具有一定的影响。