Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Glanzmann Thrombasthenia: Managing Gingival Bleeding Triggered by Tooth Eruption—A Rare Case Report

Glanzmann thrombasthenia (GT) is a rare and often underdiagnosed congenital bleeding disorder caused by mutations in the genes encoding glycoproteins GPIIb or GPIIIa, resulting in platelet dysfunction. Inherited in an autosomal recessive manner, GT is characterized by the inability of platelets to aggregate. Clinically, it presents with mucocutaneous bleeding, such as easy and extensive bruising, severe epistaxis, menorrhagia, gingival bleeding, postpartum hemorrhage, and unexpected bleeding following procedures, despite a normal platelet count. We present a case involving a 6-year-old male patient who experienced spontaneous gingival bleeding for the past 4 weeks due to the eruption of his first permanent molars. The bleeding was particularly severe at night, disrupting the child’s sleep. The patient had been diagnosed with GT at the age of 16 months. Dental management was pursued, and the use of tranexamic acid mouthwash, combined with meticulous oral hygiene, resulted in an excellent response.

Effects of Berbamine on PAF Production in Human Neutrophils and on Platelet Aggregation

The effects of berbamine, an alkaloid of dibenzylisoquinoline, on PAF produc tion in human neutrophils and on platelet aggregation induced by PAF were studied and compared with those of the calcium antagonist verapamil. Preincubation with berbamine (50 mmol / L, 100 mmol / L) or verapamil (10 mmol / L, 100 mmol / L) was shown to significantly inhibit A 23187 stimulated PAF synthesis. Berbamine and verapamil were found to inhibit platelet aggregation induced by PAF 70 pmol / L in a dose dependent manner. These results suggest that the inhibitory effects of berbamine and verapamil on A 23187 stimulated PAF synthesis in human neutrophils and PAF induced platelet aggregation are possibly brought about by inhibiting cellular calcium influx.

Inhibitory Effect of β-Elemene Emulsion on Platelet Aggregation and its Mechanism

为阐明β榄香烯的抗血小板作用，本文分别采用比浊法和放免法测定大鼠连续ｉｐ７ｄβ榄香烯乳６．２５～１２．５ｍｇ·ｋｇ－１·ｄ－１后对血小板聚集、血浆ｋｅｔｏＰＧＦ１α和ＴＸＢ２水平的影响。结果表明，本品分别使凝血酶、花生四烯酸和ＡＤＰ诱导血小板最大聚集率下降３８．３％～４２．６％，１４．７％～１９．１％和７．２％～１０．８％，血浆ＴＸＢ２从８８ｎｇ·Ｌ－１下降至７２ｎｇ·Ｌ－１，ｋｅｔｏＰＧＦ１α从１７．５ｎｇ·Ｌ－１增加至２０．９ｎｇ·Ｌ－１。提示ＴＸＢ２降低和ｋｅｔｏＰＧＦ１α值增加是其抑制血小板聚集的作用机制之一。

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation

Background:Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices.However,elevated von Willebrand factor(VWF)in cirrhosis improves platelet function and could decrease this risk.Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation(EVL).Methods:The assessment consisted of platelet count,antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity,and a platelet adhesion and aggregation test simulating vascular flow in vivo(Impact-RR)prior to EVL.Results:Totally 111 patients were divided into three groups according to platelet count:(1)<50×109/L(n=38,34.2%);(2)50×109/L to 100×109/L(n=47,42.3%);and(3)>100×109/L(n=26,23.4%).No statistically significant difference was found in the aggregate size of platelets[group 1:41.0(31.8–67.3)μm 2;group 2:47.0(33.8–71.3)μm 2;and group 3:47.0(34.0–66.0)μm 2;P=0.60]and no significant correlation was found between aggregate size and platelet count(Spearman r=0.07;P=0.47).Surface coverage was 4.1%(2.8%–6.7%),8.5%(4.0%–10.0%),and 9.0%(7.1%–12.0%)(P<0.001)in groups 1,2 and 3,respectively and correlated with platelet count(Spearman r=0.39;P<0.0001).There was no significant difference between groups in VWF or ADAMTS-13.Post-EVL bleeding occurred in six(5.4%)patients(n=2 in group 1,n=1 in group 2,and n=3 in group 3;P=0.32).Patients with bleeding had higher MELD scores[15.0(11.3–20.3)versus 12.0(10.0–15.0);P=0.025],but no difference was demonstrated for platelet function parameters.Conclusion:Platelet function is preserved even in the presence of thrombocytopenia,including in the patients with post-EVL bleeding.

EFFECTS OF NIMODIPINE ON PLATELET AGGREGATION AND THE ACTIVITY OF ENZYMES IN ARACHIDONIC ACID METABOLISM

The effects of nimodipine on platelet aggregation and arachidonic acid(AA)metabolism were studied in order to explore its effect on patients with thrombosis or cardiovas- cular disease.The results indicate that nimodipine(50-350μmol/L)significantly inhibits platelet aggregation induced by ADP,AA,and ionophore A23187 in a dose dependent manner.The inhibitory effects induced by ionophore A23187 could be partially antagonized by calcium(1 mmol/L).When the substrate was AA and the enzyme was supplied by pig lung microsomes,nimodipine(50-400μmol/L)significantly reduced the generation of TXB_2 and 6-keto-PGF_(1a) in parallel.When the substrate was prostaglandin endoperoxide, however,the levels of TXB_2 and 6-keto-PGF_(1a)were not significantly altered in the same concentration range.The results suggest that nimodipine is a cyclooxygenase inhibitor,and its ability to inhibit platelet aggregation is related to its calcium blocking effect.

Design and Synthesis of New Arylsulfonamide and Arylamide Derivatives for the Platelet Aggression Inhibitor

A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.

Effects of Total Flavone of Abelmoschl Manihot L.Medic on the Function of Platelets and Its Mechanism

Objective: To study the effects of total flavone of Abelmoschl Manihot L.Medic (TFA) on the function of platelets and to explore its mechanism. Methods: Rat models of artery-veins bypassing thrombus formation were used. The platelets of rabbits were collected. Platelet aggregation was induced by collagen and intracellular calcium ion concentration ([Ca 2+ ]i) was assayed by Fura-2 method. Results: TFA (25, 50, 100 mg/kg) significantly and dose-dependently reduced the weight of thrombus. TFA (0.025, 0.05, 0.1 mg/ml) possessed dose-dependant inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA significantly reduced the resting and CaCl 2-induced increase of free intracellular calcium concentration ([Ca 2+ ]i) in rabbit platelet in vitro . Conclusion: TFA has an antiplatelet effect via the inhibition on the influx of Ca 2+ .

Gender and tachycardia： independent modulation of platelet reactivity in patients with atrial fibrillation

Background Female patients with atrial fibrillation （AF） experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF （often associated with tachycardia） also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide （NO） signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Methods Interactions were sought in 87 AF patients between the extent of adenosine diphosphate （ADP）-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein （Txnip） was also evaluated. Results Analysis ofcovariance confLrmed the presence of physiological antagonism between platelet ADP and NO responses [F （1, 74） = 12.212, P 〈 0.01 ], while female sex correlated with impaired NO responses independent of platelet aggregability [F （2, 74） = 8.313, P 〈 0.01]. Admission heart rate correlated directly with platelet aggregation （r = 0.235, P 〈 0.05）, and inversely with NO response （r = -0.331, P 〈 0.01）. Txnip expression varied neither with gender nor with heart rate. Conclusions These results indicate, that gender and heart rate are independent determinants of platelet fimction. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.

EFFECT OF 764－3 ON AGGREGATION AND CALCIUM MOVEMENTS IN AEQUORIN－LOADED HUMAN PLATELETS

Washed human platelets were loaded with the Ca2+-sensitive photoprotein, aequorin. using hypoosmotic shock treatment-technique. Then aggregation and cytoplasmic ionized calcium concentration ( [Ca2+] i) changes in response to collagen or thrombin were measured simultaneously in the aequorin-loaded human platelets with a Platelet Ionized Calcium Aggregometer. 764-3. an active component isolated from the Chinese medicinal herb Salvia Miltiorrhiza Bge, inhibited platelet [Ca2+]i rise as well as aggregation evoked by collagen or thrombin in the presence of extracellular Ca2+. After the extracellular Ca2+. was removed by addition of EGTA, collagen or thrombin. causing no aggregation. still elicited platelet [Ca2+] i rise which reflected Ca2+ mobilization from intraplatelet stores. Under this condition, 764-3 could also suppress platelet [Ca2+] i rise. Analysis shows that 764-3 inhibrts platelet Ca2+ influx and Ca2+ mobilization with similar potency. which accounts for its suppression of platelet [Ca2+] i rise, and must contribute to its inhibition of platelet aggregation.

Mechanism Study of Endothelial Protection and Inhibits Platelet Activation of Low Molecular Weight Fucoidan from Laminaria japonica

Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline(0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. v WF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce v WF level in vascular endothelial injury rats and also significantly reduce v WF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and v WF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

Inhibitory effects and mechanisms of high molecular-weight phlorotannins from Sargassum thunbergii on ADP-induced platelet aggregation

We evaluated the effects of high molecular-weight phlorotannins from Sargassum thunbergii(STP) on ADP-induced platelet aggregation and arachidonic acid(AA) metabolism in New Zealand white rabbits and Wistar rats.The inhibition of STP on platelet aggregation was investigated using a turbidimetric method,and the levels of the terminal products of AA metabolism were measured using the corresponding kits for maleic dialdehyde(MDA),thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) by colorimetry and radioimmunoassay,as appropriate.We found that STP could inhibit ADP-induced platelet aggregation,and the inhibitory ratio was 91.50% at the STP concentration of 4.0 mg/mL.Furthermore,STP markedly affected AA metabolism by decreasing the synthesis of MDA(P<0.01) and increasing the synthesis of 6-keto-PGF1α,thus changing the plasma TXB2/6-keto-PGF1α balance when the platelets were activated(P<0.01).Therefore,STP altered AA metabolism and these findings partly revealed the molecular mechanism by which STP inhibits ADP-induced platelet aggregation.

Synthesis of Novel Ligustrazine Derivatives as Potential Platelet Aggregation Inhibitors

A series of novel ligustrazine derivatives were synthesized. These compounds have not been reported in literature, and their chemical structures were confirmed by IR, ^1H NMR and ESI-MS. The preliminary antiplatelet aggregation screening results demonstrated that the compounds 7a, 7b and 7c showed higher potency than ligustrazine.

Effect of pretreatment with aspirin and ticlopidine on the change of platelet aggregability after radiofrequency catheter ablation

Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thromboxane B 2(TXB 2) of the blood samples. Patients were divided into aspirin group A, ticlopidine group B, aspirin+ticlopidine group C and control group D. PAG and TXB 2 were increased clearly after RFCA in all groups (P<0.001). Treatment with aspirin or ticlopidine before operation could reduce the platelet aggregability caused by RFCA and the joint effect of two drugs(change rate of group A:52.51±12.51%; group B:54.78±11.27%;group C: 30.51±10.59%;group D:91.75±21.43%; P<0.05)was studied. The much decreased platelet aggregability after antiplatelet therapy was evidence of the potential benefit of the treatment in preventing thromboembolism after ablation. Pretreatment with aspirin and ticlopidine together is a good way to decrease palatelet aggregability after RFCA.

A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues

A convenient approach for the preparation of sarpogrelate hydrochloride was developed.Two series of sarpogrelate hydrochloride analogues were designed and synthesized in order to improve their platelet aggregation inhibitory activities, biological tests suggested that these compounds have platelet aggregation inhibitory activities to some extent.

Effect of SJAMP on ATP Release of Platelet

The aggregation and ATP release of placelet of normal subjects were measured by platelet lumi aggregometer. It was found that the aggregation curve induced by SJAMP at the concentration of 100 mg/L was a typical second phase aggregation. There existed a certain lag between platelet aggregation and secretion. The secretion actually began slightly after the second phase of aggregation, suggesting that the second phase aggregation induced by SJAMP is not dependent upon the release of contents of dense granule alone. If platelets were incubated with cyclo oxygenase inhibitor, the second phase aggregation was inhibited and no ATP was released. The results indicated that the aggregation and release reaction induced by SJAMP were dependent upon the generation of prostaglandin endoperoxides and TXA 2 in normal subjects. The amount of ATP release was 0.69±0.22 nmol/10 8 platelets as stimulated with SJAMP (100 mg/L). But the amount of ATP release were 1.60±0.25 and 1.37±0.15 nmol/10 8 platelets when platelets were stimulated with ADP (5 μmol/L) and collagen (5 mg/L). The amount of ATP release induced by SJAMP was significantly lower than that of ADP and collagen. These findings indicated that SJAMP was a weaker agonist than ADP in terms of platelets release reaction.

A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis.Serum NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol.The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Results:Cholesterol diet significantly increased serum levels of cholesterol and LDL,caused a remarkable platelet hyperaggregability,and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination.The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclerosis. Conclusion:The present study suggests that the endothelial dysfunction caused by enhanced serum cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.

Platelet aggregation responses in type 2 diabetic patients

Diabetes mellitus (DM) is associated with platelet dysfunction. In diabetic patients, alterations in platelet functions, especially increased platelet agregation, have been suggested to cause increasing in cardiovascular morbidity and mortality or in accelaretion of athersclerotic process. In this study, we aimed to investigate the platelet aggregation response alterations and the effects of DM duration, HbA1c, treatment options among the patients with Type 2 DM. Fortyfive patients (case group;21 male, 24 female) with Type 2 DM and forty-eight healthy individuals (control group;22 male, 26 female) were included in this study. Platelet aggregation was determinated with Chorono-log 500 (USA) named device by using Chorono-log/ADP, Chorono-log/ collagen and Chorono-log/epinephrine kits. ADP-induced platelet aggregation was significantly higher in the case group compared with control group (p 【0.05). Epinephrine induced platelet aggregation were significant in negatively correlation with the diabetes duration (P 【0.05). Platelet aggregation responses did not differ according to their treatment type (sulphonylurea or insulin) was statistically insignificiant among the case groups (p 】0.05). In conclusion, our findings supported that type 2 diabetes may interfere with platelet functions without any relationship age, gender, the treatment types and the regulation levels. These findings supports that existence potential new factors or mechanism affecting platelet agregation. The subject requires more detailed studies in the future.

Effects of procainamide on adenosine diphosphate-induced platelet aggregation and thromboxane B_2 production in rabbits in vitro

Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μmol L-1 inhibited ADP-induced platelet aggregation and TXB2 production, and theinhibition rates were 26. 7% -- 66. 7 % and 21. 4 % -- 70. 1 %, respectively. There was positive correlation between PA concentration and its efficiency in inhibiting the platelet aggregation and TXB2 production, and alsobetween the inhibition rates of platelet aggregation and that of TXB2 production. The three linear equationsand main parameters were The results indicate that PA could significantly inhibit ADP--induced platelet aggregation and TXB2 production in rabbits.

前列腺素E1对原发性肾病综合征作用初探(英文)

Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.