Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.     

Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid

Hydroxytyrosol acetate (HT-AC) is a polyphenol present in virgin olive oil (VOO) at a proportion similar to hydroxytyrosol (HT) (160-479 micromol/kg oil). The present study was designed to measure the in vitro platelet antiaggregating activity of HT-AC in human whole blood, and compare this effect with that of HT and acetylsalicylic acid (ASA). The experiments were designed according to the standard procedure to investigate the activity of ASA. HT-AC and HT inhibited platelet aggregation induced by ADP, collagen or arachidonic acid in both whole blood and platelet-rich plasma (PRP). ASA and HT-AC had a greater effect in whole blood than in PRP when ADP or collagen was used as inducer. ASA and HT-AC had a greater effect in PRP+leucocytes than in PRP alone. All three compounds inhibited platelet thromboxane B2 and leucocyte 6-keto-prostaglandin F1alpha (6-keto-PF1 alpha) production. The thromboxane/6-keto-PGF1alpha inhibition ratio (as an indirect index of the prostanoid equilibrium) was 10.8 (SE 1) for HT-AC, 1.0 (SE 0.1) for HT and 3.3 (SE 0.2) for ASA. All three compounds stimulated nitric oxide production, although HT was a weaker effect. In our experiments only concentrations higher than 500 microm (HT) or 1 mm (HT-AC and ASA) inhibited 3-nitrotyrosine production. All three compounds inhibited the production of TNFalpha by leucocytes, with no significant differences between them. In quantitative terms HT-AC showed a greater antiplatelet aggregating activity than HT and a similar activity to that of ASA. This effect involved a decrease in platelet thromboxane synthesis and an increase in leucocyte nitric oxide production.     

血小板聚集率检测对行经皮冠脉介入术患者的临床意义探讨

目的研究血小板聚集率检测水平与行经皮冠脉介入（percutancous coronary intervention,PCI）术后患者心血管不良事件的相关性。方法用比浊法和阻抗法检测119例行PCI术服用阿司匹林和氯吡格雷超过7 d的患者的血浆或全血的血小板聚集率,促凝剂分别为终浓度为5μmo/lL的ADP或终浓度为2 mg/L的胶原。1年后随访,用SPSS13.0对未发生心血管不良事件及发生心血管不良事件组的患者的血小板聚集率平均值进行统计学分析。结果 13例发生心肌缺血等心血管不良事件组患者以ADP为促凝剂比浊法测定的血小板聚集率平均值（0.63±0.12）,与未发生心血管不良事件组患者的血小板聚集率平均值（0.48±0.18）比较,差异有统计学意义（P〈0.05）;两组患者以胶原为促凝剂阻抗法检测的血小板聚集率平均值（分别为8.3±3.8和5.2±3.3）比较,差异有统计学意义。两组患者以ADP为促凝剂阻抗法测定的血小板聚集率平均值,及以胶原为促凝剂比浊法检测的血小板聚集率平均值比较差异无统计学意义。结论以ADP为促凝剂比浊法,及以胶原为促凝剂阻抗法检测的血小板聚集率,与行PCI术常规服用阿司匹林和氯吡格雷抗血小板药的患者是否易发生心血管不良事件,有一定的相关性。     

不同剂量阿司匹林及氯吡格雷对冠心病患者阿司匹林抵抗的影响

目的 观察不同剂量阿司匹林及氯吡格雷对冠心病阿司匹林抵抗（AR）患者血小板聚集功能的影响。方法筛选出冠心病患者中发生AR的患者90例,随机分为3组,分别给予口服阿司匹林100mg,300mg及氯吡格雷75mg＋阿司匹林100mg治疗,4周后采用全血电阻法检测血小板聚集率。结果 阿司匹林100mg和阿司匹林300mg组患者的血小板聚集率比较差异无统计学意义,而加用氯吡格雷组患者血小板聚集率明显降低（P〈0.05）。结论 加大阿司匹林剂量不能明显改善冠心病患者的AR,而加服氯吡格雷能有效抑制血小板聚集,减少患者AR的发生率,同时对AR患者应加强临床观察和护理干预。     

Impaired platelet aggregation and thromboxane generation in essential fatty acid-deficient rats

ADP-induced platelet aggregation and thrombin-induced thromboxane B2 generation in diluted whole blood from rats fed a fat-free diet supplemented with 10% (by weight) hydrogenated coconut oil [essential fatty acid (EFA) deficient] were significantly lower than that in animals fed 10% safflower oil [(SFO) rich in linoleic acid] or 10% marine oil (rich in eicosapentaenoic acid and docosahexaenoic acid). Plasma fibrinogen levels were significantly lower and liver function was impaired in the EFA-deficient group compared with the other two groups. Platelet responsiveness to ADP was restored when plasma from the EFA-deficient rats was replaced by plasma obtained from rats fed a nonpurified diet. ADP responsiveness and thrombin-stimulated thromboxane B2 production in diluted whole blood were also restored after 2 wk of injections of 100 mg ethyl linoleate every 48 h, and partially restored by injections of 100 mg ethyl alpha-linolenate. When ADP-induced platelet aggregation was examined in washed platelets, the impaired ADP aggregation (found when platelets of the EFA-deficient rats were suspended in their own plasma) was not observed at either high (9.5 microM) or low (1.0 microM) ADP concentrations. Although thrombin-stimulated thromboxane B2 production in washed platelets in the EFA-deficient rats was lower than that in the SFO-fed rats, the magnitude of aggregation was not different. In addition, inhibition of thrombin-induced platelet aggregation by apyrase (0.06 U/mL) was identical in the two groups. These results suggest that impaired platelet aggregation in EFA deficiency is related more to plasma factors than to inherent platelet properties and that restoration of normal liver function is associated with normal platelet function.(ABSTRACT TRUNCATED AT 250 WORDS)     

The rate of acetylsalicylic acid non-respondents among patients hospitalized for acute coronary disease, previously undergoing secondary salicylic acid prophylaxis

The authors determined the rate of acetylsalicylic acid (ASA) non-responders among patients receiving secondary prevention due to cardiovascular diseases at the appearance of acute coronary events. The non-responders were defined as: patients who have been treated with ASA because of acute coronary syndrome, but the subsequently performed platelet aggregation study did not confirmed an appropriate platelet inhibition. Among the 75 patients being investigated (44 male, 31 female, average age: 61.3 ys) 21 were hospitalized due to acute myocardial infarction and 54 for unstable angina, respectively. The daily doses of ASA were 200-325 mg. The aggregation of platelets was measured within 24 h after the admission. The investigations were performed with different amounts of 4 different inducers (ADP, arachidonic acid, epinephrine and collagen) taking dose-response curves. The antiaggregatory treatment with ASA was considered to be ineffective if the typical aggregation curves were obtained above the following final concentrations of the inducers: ADP: > 5 microM, epinephrine: > 5 microM, arachidonic acid: > 250 microM, collagen: > 2 micrograms/ml. These upper-threshold concentrations of the inducers were determined with the help of the data of healthy drug free volunteers. Twenty-six of the 75 patients (34%) were found to be non-responder to ASA, whereas the antiaggregatory effect of ASA was proven in 49 cases. No differences were found in gender. The compliance was proven with the HPLC-determination of urinary metabolites of ASA performed immediately after the upon admission. Seven patients (10.9%) showed a non-compliance, not showing any traces of ASA-metabolites in their urine. The authors emphasizing the importance of the laboratory control even of the prophylactic ASA treatment in order to continue the effective antiaggregatory therapy with other effective drugs.     

Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation

Epidemiological studies indicate a J-shaped relationship linking coffee consumption and cardiovascular risk, suggesting that moderate coffee consumption can be beneficial. Platelet aggregation is of critical importance in thrombotic events, and platelets play a major role in the aetiology of several CVD. The aim of this study was to evaluate the effect of coffee drinking on platelet aggregation ex vivo, using caffeine as control. A crossover study was performed on ten healthy subjects. In two different sessions, subjects drank 200 ml coffee, containing 180 mg caffeine, or a capsule of caffeine (180 mg) with 200 ml water. Platelets were separated from plasma at baseline and 30 and 60 min after coffee drinking. Platelet aggregation was induced with three different agonists: collagen, arachidonic acid and ADP. Coffee drinking inhibited collagen (P < 0.05 from baseline at time 30 min) and arachidonic acid (P < 0.05 from baseline at time 60 min) induced platelet aggregation. Caffeine intake did not affect platelet aggregation induced by the three agonists. Coffee consumption induced a significant increase of platelet phenolic acids (likely present as glucuronate and sulphate derivatives), caffeic acid, the principal phenolic acid in coffee, raising from 0.3 (SEM 0.1) to 2.4 (SEM 0.6) ng/mg (P < 0.01). Caffeine was not detectable in platelets. Coffee drinking decreases platelet aggregation, and induces a significant increase in phenolic acid platelet concentration. The antiplatelet effect of coffee is independent from caffeine and could be a result of the interaction of coffee phenolic acids with the intracellular signalling network leading to platelet aggregation.     

Acidic peptides enhanced genistein-dependent inhibition of human platelet aggregation: potential protective effect of digestible peptides plus genistein against atherosclerosis

The leading cause of death in the United States and European countries is coronary heart disease. We hypothesized that the ingestion of soy compounds may not only have beneficial effects on atherosclerotic risk by lowering lipid compounds, but also by reducing platelet aggregability. Therefore, we analyzed in vitro the influence of defined and digestible peptides, frequently found in glycinin and β-conglycinin as important proteins of soy bean, on platelet aggregation of 180 healthy volunteers with or without the isoflavone genistein by aggregometry and flow cytometry. (i) The predominating share of amino acids and acidic, neutral, and basic di- and tripeptides of up to 2 mmol/L did not modify platelet aggregation induced by collagen, adenosine diphosphate, epinephrine, or arachidonic acid. (ii) Genistein inhibited agonist-induced platelet aggregation dose dependently. (iii) In the presence of the acidic peptides glutamate-glutamate and aspartate-aspartate-aspartate (1 mmol/L each), genistein reduced collagen- and ADP-dependent platelet activation stronger than 250 μmol/L of this isoflavone alone. Other peptides were less effective (eg, glutamate-glutamate-glutamate) or ineffective (eg, asparagine-asparagine). (iv) Glutamate-glutamate-glutamate (1 nmol/L), glutamate-glutamate (1 μmol/L), and aspartate-aspartate-aspartate (1 μmol/L) enhanced the inhibition of genistein on platelet aggregation induced by arachidonic acid. Thus, the results of the present in vitro investigation allow the assumption that nutrition with specific compounds of soy—acidic peptides together with genistein—might protect against coronary atherosclerosis by attenuating platelet activity. In vivo studies are warranted to check this assumption.     

Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study

Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertaken. Subjects ingested a soup containing either a high or a low amount of quercetin. Plasma quercetin concentrations and platelet aggregation and signalling were assessed after soup ingestion. The high-quercetin soup contained 69 mg total quercetin compared with the low-quercetin soup containing 5 mg total quercetin. Plasma quercetin concentrations were significantly higher after high-quercetin soup ingestion than after low-quercetin soup ingestion and peaked at 2.59 (sem 0.42) mumol/l. Collagen-stimulated (0.5 mug/ml) platelet aggregation was inhibited after ingestion of the high-quercetin soup in a time-dependent manner. Collagen-stimulated tyrosine phosphorylation of a key component of the collagen-signalling pathway via glycoprotein VI, Syk, was significantly inhibited by ingestion of the high-quercetin soup. The inhibition of Syk tyrosine phosphorylation was correlated with the area under the curve for the high-quercetin plasma profile. In conclusion, the ingestion of quercetin from a dietary source of onion soup could inhibit some aspects of collagen-stimulated platelet aggregation and signalling ex vivo. This further substantiates the epidemiological data suggesting that those who preferentially consume high amounts of quercetin-containing foods have a reduced risk of thrombosis and potential CVD risk.     

Acute effects of ingestion of black tea on postprandial platelet aggregation in human subjects

Results of population studies suggest that black tea can reduce cardiovascular risk. Effects of black-tea polyphenols to reduce platelet aggregability may help to explain any benefits. Given that black tea is often consumed with and after meals, and man spends much of his life in the postprandial state, the objective of the present study was to investigate the acute effects of ingestion of black tea on postprandial platelet aggregation ex vivo. Twenty healthy participants had platelet aggregation and blood lipids assessed before and 4 h after the ingestion of 50 g dairy fat on two occasions in random order, corresponding to black tea or hot water. Black tea or hot water (one cup) was consumed immediately following the dairy fat, then after 15 and 30 h. Platelet aggregation ex vivo was assessed in platelet-rich plasma in response to three concentrations of collagen (0.2, 0.6, 20 microg/ml) and ADP (2, 4, 8 microM). Urinary concentrations of 4-O-methylgallic acid were used as an indicator that tea polyphenols were absorbed. Serum total cholesterol and triacylglycerol concentrations increased significantly 4 h after ingesting the dairy fat, but there was no significant difference between black tea and hot-water treatments on the cholesterol or triacylglycerol responses. Urinary 4-O-methylgallic acid concentrations were significantly increased following ingestion of black tea (P=0.0001) but not water. Black tea in comparison to hot water did not inhibit collagen or ADP-induced postprandial platelet aggregation. The results of this study do not support the suggestion that reduced postprandial platelet aggregability contributes to any benefits of black tea on cardiovascular risk.     

Effect of D-003 on intravascular platelet aggregation induced with collagen in rats

D-003 is a mixture of higher aliphatic primary acids purified from sugar-cane (Saccharum officinarum L.) wax that inhibits platelet aggregation induced ex vivo by addition of agonists to platelet-rich plasma (PRP) of rats, guinea pigs, and healthy human volunteers. Because the ex vivo platelet aggregation model does not mimic properly platelet aggregation occurring inside the arteries, since all blood factors regulating the formation of a platelet aggregate or thrombus are not present in PRP, this work was undertaken in order to investigate the effects of different oral doses of D-003 on platelet aggregation induced by collagen in vivo in rats. Effects of single (5, 25, 100, and 200 mg/kg) or repeated doses (1, 5, 25, 100, and 200 mg/kg during 10 days) of D-003 on in vivo platelet aggregation in rats were studied. D-003 (5-200 mg/kg) orally administered as single or repeated doses inhibited significantly and dose-dependently collagen-induced platelet aggregation in rats. The minimal dose investigated effective in both single and repeated administration schemes was 5 mg/kg. The highest dose assessed in both cases was 200 mg/kg, causing inhibitions of 61.5% (single doses) and 74.4% (repeated doses). Thus, the effects of repeated doses were more pronounced than those obtained with single administration. The mean 50% effective dose of D-003 in both schemes was 2.3 mg/kg, which indicates a promising anti-thrombotic potential of D-003.     

Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels

A randomized, placebo-controlled double-blind trial was conducted on 20 adults to assess the effect of vitamin E (800 IU/d 727 mg/d for 5 wk) on platelet function, arachidonic acid metabolism, and prostacyclin generation. Platelet aggregation was measured in response to collagen, arachidonic acid, and adenosine diphosphate. Thromboxane B2 was assayed in serum and in the supernatant plasma after platelet aggregation. Platelets were labeled with [3H]arachidonic acid to assess production and release of cyclooxygenase products (MDA, TXB2, and HHT), a lipoxygenase product (12-HETE), and arachidonic acid in response to stimulation by thrombin or collagen. Prostacyclin was measured in plasma and in blood collected from bleeding-time incisions by a sensitive HPLC-RIA procedure. Despite marked increases in plasma and erythrocyte vitamin E levels in the vitamin E group, there were no significant differences between the vitamin E and placebo groups in any of the variables measured.     

Effect of oral vitamin B6 supplementation on in vitro platelet aggregation

A randomized, double-blind study was conducted with 12 healthy adult males to determine the effects of oral pyridoxine supplementation on in vitro platelet aggregation. Following a 4-wk baseline period, half the subjects received 100 mg/day of pyridoxine X HCl while the remaining subjects received a placebo for 6 wk. In vitro platelet responses to ADP and collagen and the plasma pyridoxal 5'-phosphate (PLP) concentrations were measured at biweekly intervals. Plasma PLP concentrations increased significantly (p less than 0.001) for those receiving the vitamin B6 compared to baseline values or compared to those receiving the placebo. However, there was no significant effect of increased levels of plasma PLP on collagen-stimulated platelet aggregation and only a slight effect on ADP-stimulated aggregation. Acute administration of 100 mg pyridoxine X HCl failed to alter the in vitro response of platelets to either ADP or collagen. Reevaluation of conclusions based solely on in vitro studies suggesting the use of pyridoxine as an effective in vivo antithrombotic agent may be warranted.     

Changes in oxidative stress and hemostatic parameters in the course of thrombolytic therapy of pulmonary embolism

Acute pulmonary embolism is the third most common cause of cardiovascular mortality. Thrombolytic treatment of massive pulmonary embolism can be complicated with haemorrhage, re-thrombosis and oxidative stress. Aims: The purpose of this study was to evaluate the changes in platelet aggregation, haemostatic, leukocyte function parameters and oxidative stress in patients with acute pulmonary embolism treated with thrombolytics. Methods: Fifteen patients undergoing thrombolysis with ultra-high dose streptokinase ( n = 8), or alteplase ( n = 7) treatment were studied. Arterial blood samples were taken before (baseline) and after thrombolysis between the 4th and 24th hour at every four hours, on the second day twice a day and daily on the 3rd, 4th, 5th and 30th day. Platelet aggregation was examined as spontaneous and induced aggregation with adrenaline, collagen and adenosine diphosphate. D-dimer and fibrinogen were measured 8 hourly on the first day and later at the same time intervals as above. To analyse oxidative stress, blood samples were collected prior to thrombolysis, and then 8 hours, 1, 3, 5 and 30 days after treatment. Malondialdehyde, reduced glutathion, plasma sulphydryl groups levels, superoxide dismutase and myeloperoxidase enzyme activities were measured in plasma or whole blood for monitoring of the oxidative stress markers. Production of reactive oxygen species in whole blood was measured by luminol dependent chemiluminescence. Flow cytometry was used to determine CD11a, CD18, and CD97 surface antigen expression on leukocytes. Results: In streptokinase group, adrenaline induced platelet aggregation decreased at the 4th and 8th hour ( p < 0.03) and was significantly lower than in the alteplase group at the 36th hour and on the 3rd day. Platelet aggregation induced by adenosine diphosphate was lower at the 4th hour than at baseline in streptokinase group ( p < 0.05). Collagen induced platelet aggregation was lower at the 4th and 8th hour than at baseline ( p < 0.05) in streptokinase group. Compared to baseline, fibrinogen levels decreased in both groups after thrombolysis. D-dimer levels elevated significantly in both therapeutic groups at the 8th hour. Spontaneous platelet aggregation was not detectable and major bleeding or re-embolism was not documented. The elevated malondialdehyde, reactive oxygen species and myeloperoxidase, decreased reduced glutathion and plasma sulphydryl levels indicated the presence of oxidative stress in patients with pulmonary embolism. Malondialdehyde significantly increased, reduced glutathion significantly decreased following thrombolysis. Reactive oxygen species production peaked on the 3rd and 5th days. Thrombolysis was accompanied by significant decrease in granulocyte and monocyte CD11a and CD18 as well as in granulocyte CD97 expression ( p < 0.05). Conclusion: Massive/submassive pulmonary embolism and thrombolysis injures inducible platelet aggregation. The changes in fibrinogen levels correlate significantly with the improvement of pulmonary perfusion which shows the effect of thrombolysis. Pulmonary embolism induced oxidative stress was detected on patients before thrombolysis. Thrombolytic treatment of pulmonary embolism augmented the increase of oxidative stress response and leukocyte activation following reperfusion, and these parameters normalised only on the 30th day.     

In vitro effects of trace elements on blood clotting and platelet function. A--Iron, copper, and gold.

The present in vitro study of the effects of iron on the blood coagulation mechanism in rats showed that addition of ferrous sulphate to pooled rat plasma resulted in inhibition of blood coagulation, as shown by prolongation of the clotting parameters tested, an effect which was dose-dependent. In vitro addition of ferrous sulphate to rat PRP in doses of 2-5 mg/ml significantly decreased platelet aggregation in response to ADP, while collagen-induced aggregation was significantly diminished in presence of the higher doses of ferrous sulphate (4-5 mg/ml). Also, preincubation of ferrous sulphate with thrombin or with pure fibrinogen indicated that iron could produce decrease of thrombin activity as well as impairment of fibrinogen clottability. In vitro addition of copper sulphate (300-1000 micrograms/ml) elicited an anticoagulant effect, though thrombin time was markedly shortened with all tested concentrations of copper sulphate. Addition of copper sulphate to PRP produced inhibition of platelet aggregation in response to PRP produced inhibition of platelet aggregation in response to ADP and to collagen. Preincubation of copper sulphate with thrombin resulted in slight enhancement of thrombin activity followed by inhibition, while preincubation of copper sulphate with pure fibrinogen caused only minimal impairment of fibrinogen clottability. Also, addition of gold chloride in doses of 50-500 micrograms/ml to plasma in vitro produced a dose-dependent progressive prolongation of all clotting parameters tested, the effects reaching a maximum after 30 min. incubation. Further the in vitro addition of gold chloride to rat PRP resulted in marked inhibition of platelet aggregation in response to both ADP and collagen. In addition, preincubation of gold chloride with thrombin or with pure fibrinogen showed that gold exerted an antithrombin action and prolonged the fibrinogen clotting time indicating impaired fibrinogen clottability.     

Necrobiosis lipoidica without diabetes mellitus (diagnostic and therapeutic possibilities)

The goal of the present study was to follow the clinical behaviour of 6 non diabetic patients (5 females and 1 male, aged 23-68) suffering from necrobiosis lipoidica. Thickening of the basalmembrane of capillaries could be confirmed by electron microscopy, although the histological structure of skin alterations are not different from those observed in diabetes mellitus. Three patients (2 females and one male) showed impaired glucose tolerance, 2 other patients had increased levels of total cholesterol, whereas one patient suffered from both metabolic disturbances. After treatment with ASA (acetylsalicylic acid, 1.0 g/day) and dipyridamole (200 mg/day) for six weeks, the decrease of platelet in vitro aggregation in platelet rich plasma could be observed by stimulation with arachidonic acid, epinephrine, ADP and collagen, respectively. Healing of the exulceration of skin lesion could be detected by the use of the combined treatment of ASA and dipyridamole in 4 cases.     

阿藿烯对血栓形成的影响及其机制

目的探讨阿藿烯对血栓形成的影响及其机制。方法将SD大鼠随机分为正常对照组、阳性对照组、阿藿烯低、中、高剂量共5组,灌胃7d后采用动-静脉旁路血栓形成法制作大鼠血栓模型,测量血栓湿重,检测血清P-选择素(Ps)和血管细胞黏附分子-1(VCAM-1)水平;并以花生四烯酸(AA)作诱导剂,观察阿藿烯对兔血小板聚集的作用。结果低、中、高剂量组阿藿烯均可显著抑制血栓形成(P0.01或P0.05),显著降低血小板最大聚集率及血清Ps水平(P0.01);中、高剂量组阿藿烯还可显著减少VCAM-1含量(P0.01)。结论阿藿烯能够抑制大鼠动-静脉旁路的血栓形成,其机制与减少血小板聚集,抑制VCAM-1和Ps的表达有关。     

丁胺卡那霉素对抗凝剂依赖性血小板假性减少症血小板的解离作用及血小板功能的影响

目的研究丁胺卡那霉素对抗凝剂依赖的假性血小板减少症血小板聚集的解离作用及其功能的影响。方法①在确诊为抗凝剂依赖的假性血小板减少症患者的EDTA-K2抗凝血和枸橼酸钠抗凝血内加入丁胺卡那霉素(6.5mg/ml血),在不同时间段作血小板计数,以原液(不加丁胺卡那霉素的抗凝血)作对照。②观察血小板聚集释放的情况:在不加丁胺卡那霉素、抽血后即加丁胺卡那霉素和1小时后加丁胺卡那霉素,用胶原、ADP、花生四烯酸诱导血小板聚集释放。结果用EDTA-K2、枸橼酸钠抗凝的血小板计数随着时间的延长呈下降趋势,观察血片均有血小板聚集现象,在上述两种抗凝剂中加入丁胺卡那霉素(6.5mg/ml血),血小板计数2小时内稳定;加入丁胺卡那霉素的血小板聚集释放试验比不加丁胺卡那霉素的聚集释放试验的结果稍高。结论丁胺卡那霉素可以抑制和解离由于EDTA-K2、枸橼酸钠依赖引起的血小板聚集,对血小板的聚集释放没有影响。     

The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters.

OBJECTIVE: The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians. DESIGN: Cross-sectional comparison of habitual meat-eaters and habitual vegetarians. SETTING: Free living subjects. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods. RESULTS: Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity. CONCLUSIONS: Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.     

Effect of atorvastatin treatment on the hemorheologic and hemostatic parameters in chronic cerebrovascular patients

Hemorheologic and hemostatic parameters are known to be altered in cerebrovascular diseases. Statin therapy is an effective treatment in the prevention of ischemic stroke, the beneficial effects may also involve lipid-independent mechanisms. AIMS: In their publication the authors review the references based on the effect of atorvastatin on stroke prevention, hemorheologic and hemostatic parameters, referred to in their previous study, investigating the short-term effect of low-dose atorvastatin on hemorheologic parameters, and endothelial dysfunction, platelet aggregation. METHODS: 27 chronic cerebrovascular patients (mean age: 61 +/- 8 years) with hyperlipidemia were investigated for serum lipid levels, hemorheologic parameters (hematocrit, plasma fibrinogen level, plasma and whole blood viscosity, red blood cell aggregation and deformability) and platelet aggregation at baseline, and after one and three months treatment with 10 mg atorvastatin daily. Endothelial dysfunction, characterized by von Willebrand factor activity was measured before and after 1-month treatment. RESULTS: The mean decrease of plasma total cholesterol level was 28% both after 1 and 3 months ( p < 0.001), that of LDL-cholesterol was 40% and 38% ( p < 0.001) compared to baseline values. Atorvastatin significantly improved whole blood viscosity after 3-month treatment and red blood cell deformability even after 1-month treatment ( p < 0.05). Collagen induced platelet aggregation provided a significant ( p < 0.001) decrease compared to that of baseline values beside unaltered antiplatelet therapy. Von Willebrand factor activity was also improved significantly ( p < 0.05) after 1-month treatment. CONCLUSIONS: Data of the literature and findings of the authors show that the beneficial effects of atorvastatin are complex. Besides lipid lowering, atorvastatin can improve hemorheologic parameters, platelet aggregation and endothelial dysfunction after short-term and low-dose therapy.