scholarly journals Is endothelial dysfunction a driving force of COVID-19 induced coagulopathy?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Dukhin ◽  
A Kalinskaya ◽  
I Molodtsov ◽  
A Maltseva ◽  
D Sokorev ◽  
...  
Keyword(s):  
Growth Rate ◽  
Platelet Aggregation ◽  
Endothelial Dysfunction ◽  
Endothelial Damage ◽  
Reference Ranges ◽  
Test Results ◽  
Plasma Coagulation ◽  
Funding Sources ◽  
Significant Difference ◽  
Induced Aggregation

Abstract Background/Introduction There are numerous reports regarding the direct endothelial damage by the SARS-CoV-2 that can lead to activation of both plasma hemostasis and platelet aggregation. However, the mechanism of interaction between endothelium and haemostasis in COVID-19 remains unclear. Purpose The aim of our study was to assess the relationship between each link of clot formation process (endothelial function, plasma coagulation, platelet aggregation) with the severity of the disease. Methods 58 COVID-19 patients were included in our study. Patients were divided into moderate (n=39) and severe (n=18) subgroups. All patients underwent a flow-mediated dilation (FMD) test, impedance aggregation, rotational thromboelastometry, thrombodynamics and von Willebrand factor antigen (vWF: Ag) quantification. All measurements were repeated on days 3 (point 2) and 9 (point 3) of hospitalization. Results COVID-19 patients demonstrated the enhanced plasma coagulation (clotting time, s 613,0 [480; 820], clot growth rate, μm/min 32,75 [29,3; 38,7]). At point 1 no significant difference in parameters of plasma coagulation between patients' subgroups was noted. At point 2 a significant decrease in the size (CS, μm 1278.0 [1216.5; 1356.5] vs 965.0 [659.8; 1098.0], p<0,01) and clot growth rate (μm/min 32,4 [29,2; 35,0] vs 17,7 [10,3; 24,4], p<0,01) under the influence of anticoagulants in the moderate subgroup compared with point 1 was observed. We didn't observe such phenomenon in severe subgroup. There was no significant difference in platelet aggregation between subgroups at point 1. During the course of the disease the patients in the moderate and severe subgroups demonstrated a significant increase in platelet aggregation induced by arachidonic acid and ADP (severe: AUC ARA 48,0 [25,0; 59,0] vs 77,5 [55,8; 92,7], p=0,04; AUC ADP 44,0 [41,0; 56,0] vs 58,0 [45,5; 69,0], p=0,04; moderate: AUC ARA 31,5 [19,8; 50,7] vs 56,0 [39,0; 76,0], p=0,01; AUC ADP 43,0 [20,0; 59,0] vs 56,6 [50,3; 70,5], p=0,04;), in moderate subgroup the significant increase in TRAP-induced aggregation was also noted (AUC TRAP 58,0 [41,0; 69,5] vs 76,0 [58,3; 81,5], p=0,048). There were no significant differences in the FMD-test results between the patient subgroups. FMD-test results were predominantly within the reference ranges (7,1 [4,0; 8,8]). Patients in the severe subgroup had significantly higher levels of vWF: Ag (228,0 [205,3; 240,7] vs 232,0 [226,0; 423,0], p=0,03). Conclusion SARS-CoV-2 infection was characterized by increased levels of vWF:Ag, that could represent the local endothelial damage, meanwhile there was no generalized endothelial dysfunction assessed via FMD-test in moderate to severe patients. At the same time the enhanced plasma coagulation in COVID-19 patients was observed. FUNDunding Acknowledgement Type of funding sources: None.

EFFECT OF Ca2+ and Mg2+ ON PLATELET ACTIVATING FACTOR (PAF) INDUCED AGGREGATION AND SPECIFIC BINDING TO HUMAN PLATELETS

1987 ◽  
Author(s):  
C M Chesney ◽  
D D Pifer
Keyword(s):  
Platelet Aggregation ◽  
Calcium Channel ◽  
Binding Sites ◽  
Competitive Inhibition ◽  
Specific Binding ◽  
Human Platelets ◽  
High Affinity ◽  
Specific Binding Sites ◽  
Significant Difference ◽  
Induced Aggregation

Gel filtered human platelets (GFP) collected in Tyrode's buffer containing 0.5 mM Ca+2, ImM Mg+2, and 0.35% albumin exhibit high affinity binding of 3H-PAF with a Kd of 0.109 α 0.029 nM (mean α SD; n=13) and 267 α 70 sites per platelet. When fibrinogen (1.67 mg/ml final concentration) is added to these GFP preparations biphasic aggregation is observed with PAF (4 nM). Normal aggregation is also observed with other platelet agonists including ADP, epinephrine, collagen, arachidonic acid, A23187 and thrombin. If GFP is prepared without added Ca+2 or Mg+2 in the presence of 3mM EDTA, platelets do not aggregate in response to PAF. However the number of specific binding sites remains unchanged (387 per platelet) with some decrease in affinity of binding (Kd = 0.2l4nM). In the presence of ImM Mg+2 there is no significant difference in binding kinetics over a range of Ca+2 concentrations (0-2mM). On the other hand the calcium channel blocker verapamil (5-10uM) exhibits competitive inhibition of 3H-PAF as analyzed by Lineweaver-Burk plots. Specific binding of 3H-PAF to GFP in the presence of ImM Mg+2 and ImM EGTA shows Kd of 0.l66nM but with increase in specific binding sites to 665. Despite increase in number of sites and no change in binding affinity, GFP under these conditions does not exhibit platelet aggregation with PAF in doses up to 80 nM.From these data it appears that external Ca+2 is not necessary for specific binding of 3H-PAF to its high affinity receptor. However, calcium does appear to be necessary for second wave aggregation with PAF. While Mg+2 appears to enhance 3H-PAF binding to platelets Mg+2 cannot substitute for Ca+2 in PAF induced platelet aggregation. Although verapamil appears to competitively inhibit binding of PAF to GFP it is not clear whether the inhibition is due to competition at or near the actual PAF receptor or at a site involving the calcium channel.

Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry

2014 ◽  
Vol 111 (02) ◽  
pp. 266-272 ◽  
Author(s):  
Philipp Diehl ◽  
Katharina Schnabel ◽  
Patrick Weik ◽  
Qian Zhou ◽  
Christoph Bode ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Aggregation ◽  
Whole Blood ◽  
Antiplatelet Agents ◽  
Platelet Inhibition ◽  
Current Standard ◽  
Antiplatelet Effect ◽  
P2y12 Antagonists ◽  
Significant Difference ◽  
Induced Aggregation

SummaryThe current standard of antiplatelet therapy of patients after myocardial infarction includes the P2Y12 receptor antagonists clopidogrel, prasugrel or ticagrelor. This study aimed to compare the antiplatelet effect of clopidogrel, prasugrel and ticagrelor in patients after myocardial infarction. In a single-centre registry the antiplatelet effect of clopidogrel, prasugrel and ticagrelor was investigated by aggregometry in patients after myocardial infarction. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 μM). To specifically quantify the effect of P2Y12 antagonists, whole blood was stimulated with 6.4 μM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n=58), prasugrel (n=65), ticagrelor (n=115)]. The r-ADP-agg was 35 ± 14% for patients receiving clopidogrel, 28 ± 10% for patients receiving prasugrel and 26 ± 11% for patients receiving ticagrelor. The r-ADP-agg was significantly lower in patients treated with prasugrel (p=0.0024) or ticagrelor (p<0.0001) compared to clopidogrel. There was no significant difference between patients receiving prasugrel or ticagrelor (p=0.2559). In conclusion, prasugrel and ticagrelor provide a stronger platelet inhibition compared to clopidogrel in patients after myocardial infarction. No significant difference in platelet inhibition was detected between prasugrel and ticagrelor. (registry for patients after Myocardial Infarction Treated with AntiPlatelet agents; DRKS00003146).

The Common PAR4 Ala120Thr Variant Has a Major Effect on Platelet Reactivity to Thrombin and These Effects Are Enhanced with PAR1 and P2Y12 Inhibition

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 709-709
Author(s):  
Michael J. Whitley ◽  
Joanne Vesci ◽  
Michael Holinstat ◽  
Leonard C. Edelstein ◽  
Paul F. Bray
Keyword(s):  
Platelet Aggregation ◽  
Dose Response ◽  
Platelet Reactivity ◽  
Genotype Effect ◽  
Intermediate Phenotypes ◽  
Functional Variants ◽  
Cox Inhibitor ◽  
Significant Difference ◽  
The Common ◽  
Induced Aggregation

Abstract Introduction: Human platelets express two thrombin receptors, protease activated receptor (PAR) 1 and PAR4 with different affinities for thrombin and different signaling properties. PAR1 and PAR4 have non-identical tissue expression patterns and repertoire of protease activators. We have shown a significant difference in activation kinetics and calciummobilization between platelets from healthy white and black subjects stimulated with PAR4-AP (Nat Med 2013). Part of these racial differences appears to be mediated by PAR4 signaling through Gq to Rap1 and PKC (ATVB 2014). Given the importance of platelet thrombus formation in ischemic arterial disease, these findings may contribute to the known worse outcomes in blacks compared to whites after acute coronary syndromes. Genomic approaches demonstrated that ~50% of the racial variance in PAR4-AP-induced platelet aggregation and calcium flux is caused by an Ala120Thr substitution in PAR4 (encoded by rs773902) and that the Thr120 variant is the "hyperreactive" compared to Ala120 (Blood 2014). Importantly, the Thr120 allele frequency is 63% in blacks and 19% in whites. However, the effect of the physiologic activator, thrombin, on this platelet PAR4 variant (independent of race) has not been characterized. The goals of this work were to perform a detailed characterization of the PAR4 Ala120Thr effect on thrombin-induced platelet function, and to assess pharmacogenetic effects of the PAR4 Ala120Thr variant on standard anti-platelet agents and novel PAR4 inhibitors. Results:We recruited 130 healthy, multi-racial donors and genotyped for rs773902. Subjects were excluded who had reduced arachidonic acid aggregation or who had the rare PAR4 Val296 variant. Preliminary studies showed heterozygotes had intermediate phenotypes to all assays, so most comparisons were between washed platelets homozygous for Thr120 or Ala120. The thrombin dose response curve for Thr120 homozygotes was left-shifted relative to Ala120 homozygotes (p=0.022 for genotype effect; n=10 per genotype). The concentration of thrombin required to produce 50% maximal aggregation (ED50) was 17% lower for Thr120 homozygotes than for Ala120 homozygotes (0.041 ± 0.002 U/mL vs. 0.049 ± 0.002 U/mL, respectively; p<0.001). The PAR4-AP dose response for Thr120 homozygotes was also left-shifted compared to Ala120 homozygotes (p<0.0001 for genotype effect; n=11 per genotype), as would be expected for functional variants in PAR4. The PAR4-AP ED50 was 2.5-fold lower for Thr120 homozygotes than for Ala120 homozygotes (41.0 uM ± 5.0 uM vs. 101.0 ± 4.5 uM respectively; p<0.001) Compared to Ala120 homozygotes, Thr120 homozygote platelets showed higher thrombin-induced ATP release and P-selectin exposure, indicating higher levels of dense and alpha granule release, and higher calcium mobilization, indicating Gq coupling (n=4-7 per genotype). Next, washed platelets were incubated with varying concentrations of YD-3 (PAR4 blocker), ASA (COX inhibitor), 2-MeSAMP (P2Y12 antagonist) or the PAR1 antagonist, vorapaxar, and assessed for aggregation after stimulation with 0.1 U/mL thrombin. The concentration of vorapaxar required to inhibit 50% of maximal platelet aggregation (IC50) was 2.6 fold lower for Ala120 homozygotes relative to Thr120 homozygotes (45.5 ± 7.6 nM vs. 118.6 ± 40.9 nM, p<0.0001; n=3 per genotype). The IC50 of 2-MeSAMP was substantially lower for Ala120 homozygotes relative to Thr120 homozygotes (4.0 ± 5.0 uM vs. 10.9 ± 4.8 uM, p=0.056; n=4 per genotype). YD-3 and ASA were unable to inhibit thrombin-induced aggregation regardless of the PAR4 variant. Conclusions: These data indicate that the common Ala120Thr variant alters platelet reactivity to physiologic agonists, that the Thr120 variant has decreased sensitivity to PAR1 and P2Y12 inhibition, and predict the PAR4 Thr120 variant would alter the risk-benefit of PAR1 inhibition. Since current antiplatelet therapy is based largely on platelet studies done with white subjects, novel PAR4 inhibitors may provide improved anti-thrombotic therapy for patients with the Thr120 risk allele. Disclosures No relevant conflicts of interest to declare.

Investigation of Platelet Functions in Chronic Myeloproliferative Disorders by Optical and Luminesance Method.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4766-4766
Author(s):  
Meltem O. Akay ◽  
Fezan S. Mutlu ◽  
Zafer Gulbas
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Reference Range ◽  
Platelet Rich Plasma ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Myeloproliferative Disorders ◽  
Test Results ◽  
Chronic Myeloproliferative Disorders ◽  
Significant Difference

Abstract Background: Bleeding and thrombosis are common causes of morbidity and mortality in patients with myeloproliferative disorders (MPD). Qualitative platelet abnormalities are frequently found in these patients and range from platelet hypofunction as demonstrated by defective invitro platelet aggregation, acquired storage pool disease and/or platelet membrane defects, in addition to enhanced platelet aggregation, increased plasma beta thromboglobulin levels or shortened platelet survival. In this study we aimed to perform platelet aggregation studies by optical method (on platelet rich plasma=PRP) and luminesance method (on whole blood) in chronic myeloproliferative disorders. Methods:A total of twenty-five patients with MPD (17 chronic myeloid leukemia, 6 polycythemia vera, 2 essential thrombocytosis) were enrolled. Median age was 54,4 (29–76). Platelet aggregation was measured using the optic and luminesance method. The agonists used were adenosine diphosphate (ADP), arachidonic acid (AA) ristocetin and collagen. Platelets were considered to be hyperactive if at least one result (i.e. aggregation or ATP release with one agonist) was above the reference range, and hypoactive if at least one result (i.e. aggregation or ATP release) was below the reference range. Mixed hypo- and hyperactive platelets were considered present when at least one result (i.e. aggregation or ATP release) was below and above the reference range respectively. Results:Platelet aggregation test results by two methods in myeloproliferative disorders were shown in Table 1. The percent for detection of platelet function abnormality by luminesance method was found to be higher than the optic method and a significant difference was shown between two methods (p&lt;0,05). Conclusion Our findings suggest that;1. Luminesance platelet aggregation study is more valuable than optic platelet aggregation study for invitro assessment of platelet function in patients with MPD. 2. The use of luminesance platelet aggregation study appears useful to select patients for antiplatelet therapy. Platelet aggregation test results in myeloproliferative disorders (n=25) Normal Hypofunction Hyperfunction Mix Total abnormality Luminesance method 1(%4) 4(%16) 8(%32) 11(%44) 24(%96) Optic method 9(%36) 11(%44) 2(%8) 3(%12) 16(%64)

13-Azaprostanoic Acid Potentiates Prostacyclin Induced Platelet Deaggregation

1981 ◽  
Author(s):  
L V Parise ◽  
D Venton ◽  
G C Le Breton
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Present Report ◽  
The Other ◽  
Calcium Sequestration ◽  
Significant Difference ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Stimulation Of

13-Azaprostanoic acid (13-APA), a specific thromboxane/endoperoxide receptor antagonist, reverses platelet aggregation stimulated by the endoperoxide analog U46619. The present report demonstrates that 13-APA also potentiates prostacyclin (PGI2) reversal of U46619-induced aggregation. Human platelet rich plasma was aggregated with 3 × 106M U46619. Deaggregation was induced 2 min. sitosequent to the addition of aggregating agent and was measured over a 3 min. period. Concentrations of 13-APA (4 × 10-4M) and PGI2(4 × 10-9M) were chosen such that each agent individually induced approximately 20% deaggregation. Addition of half of the above concentrations of these agents i.e. 2 × 10-4M 13-APA plus 2 × 10-9M PGI2resulted in 62% deaggregation, demonstrating that the observed response was supraadditive. Only 8% deaggregation was induced by 2 × 10-4M 13-APA alone and 0% by 2 × 10-9M PGI2 alone. PGI2 causes platelet deaggregation presumably through elevation of cAMP. 13-APA, however, did not increase cAMP levels even at concentrations of 13-APA as high as 1.2 × 10-3M i.e. 9.8 ± 1.3 pmoles/ml for control and 10.8 ± 1.2 for 13-APA. Nevertheless it is possible that the observed potentiation of deaggregation was the result of 13-APA facilitating PGI2 stimulation of adenylate cyclase. Measurement of cAMP during deaggregation, however, showed no significant difference between treatment with PGI2 alone and treatment with PGI2 plus 13-APA i.e. 11.3 ± 0.4 pmoles/ml for control, 11.4 ± 0.3 pmoles/ml for 13-APA, 16.1 ± 0.5 pmoles/ml for PGI2 and 16.5 ± 0.8 pmoles/ml for PGI2 plus 13-APA. These results clearly establish that 13-APA and PGI2deaggregate platelets by distinctly separate mechanisms. In this regard we propose that PGI2 causes platelet deaggregation by stimulating intraplatelet calcium sequestration through a cAMP dependent process. 13-APA, on the other hand, blocks the ability of U46619 to mobilize intraplatelet calcium. The combination of these two mechanisms presumably results in the observed potentiation of deaggregation.

Abstract 2174: Increased Platelet Aggregability In Obstructive Sleep Apnea Syndrome Patients Is Improved By Nasal Continuous Positive Airway Pressure Treatment

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hisanori Horiuchi ◽  
Kensuke Sumi ◽  
Arata Tabuchi ◽  
Ryoji Taniguchi ◽  
Toru Oga ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Platelet Aggregation ◽  
Sleep Apnea ◽  
Platelet Aggregability ◽  
Nasal Cpap ◽  
Obstructive Sleep ◽  
Significant Difference ◽  
Induced Aggregation

Background and aim: Obstructive sleep apnea (OSA) is a risk factor for cerebrovascular diseases. One cause for them is an occlusive arterial thrombus triggered by local platelet activation. Whether OSA is an independent risk factor for increased platelet aggregability is unclear. Methods: We enrolled 124 patients with snoring or daytime sleepiness in whom 3% oxygen desaturation index (3%ODI), a principal marker of the severity of intermittent hypoxia and reoxygenation (IHR), was measured. We studied ex vivo ADP- and collagen-induced aggregation of platelet-rich plasma using an optical aggregometer. The agonist concentration giving half maximal aggregation was defined as the platelet-aggregation threshold index (PATI) value. Therefore, the lower PATI value implicates the higher aggregability. In 23 patients who underwent nasal CPAP, platelet aggregability was followed until 90 days. Results: There was a significant difference in the PATI value for ADP-induced aggregation between 66 patients with non-to-mild OSA (3%ODI≤15) (1.04±0.07 μM, mean±SE) and 58 patients with moderate-to-severe OSA(3%ODI>15) (0.78±0.09 μM)(p=0.029). Multiple linear model revealed that 3%ODI strongly significantly contributed to the PATI values for ADP (p<0.001) and collagen (p=0.0026) among the 59 subjects with a cardiovascular risk factor such as smoking, hypertension, diabetes mellitus or hyperlipidemia. However, the percentage of time of arterial O2 saturation<90% during sleep did not significantly contribute to the PATI values for ADP (p=0.21) and collagen (p=0.20). After initiation of nasal CPAP therapy, the PATI values for ADP-induced aggregation significantly worsened transiently on day 30 (p=0.035), and then it recovered and improved at day 90 and the PATI for collagen-induced aggregation improved at day 90 without the transient exacerbation. Conclusions: OSA patients had increased platelet aggregability. Severity of IHR more significantly contributed to platelet aggregation than total hypoxic time. Among OSA patients with conventional cardiovascular risk factors, the effects of IHR on the platelet aggregability was prominent. Nasal CPAP initially induced a transient hyperaggregable state of platelets, after which it continued to improve.

scholarly journals Hypercholesterolemia as a factor in the risk stratification of patients with hypertension depending on the ITGA2 gene polymorphism

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V Netiazhenko ◽  
A V Liakhotska
Keyword(s):  
Platelet Aggregation ◽  
Gene Polymorphism ◽  
Included Study ◽  
Control Group ◽  
Genotype Group ◽  
Coronary Syndrome ◽  
Funding Sources ◽  
Increased Risk ◽  
Angioplasty And Stenting ◽  
Induced Aggregation

Abstract   Mutation C807 in the ITGA2 gene is associated with the risk of early myocardial infarction, ischemic stroke, embolism, thrombosis after angioplasty and stenting of coronary arteries. Aim To study the relationship between ITGA2 gene polymorphism and increased risk of CAD in patients with hypertension and hypercholesterolemia Materials and methods 72 patients were included. Study involved patients with ACS, which developed on the background of hypertension, 32 patients also had coronary angiography and stenting. We used analysis of spontaneous and induced platelet aggregation, polymorphism of C807T of the ITGA2 gene was determined by polymerase chain reaction. Results At 82.5% of patients with ACS genotype ITGA 2 C/T was prevalent – 40.3%, T/T – 31.9%. Aggregation capability research in the studied groups has shown that patients of all groups had their degree of spontaneous aggregation significantly exceeding limits of control. Wherein, the highest indices were recorded in the T/T genotype group, which exceeded reference values by 3,02 times. AA-induced aggregation in the group of patients with T/T genotype exceeded indexes of the C/C group by 17.3%, while C/T group's rates-by 16.5% (p&lt;0.05 in both cases). Studying the degree of collagen-induced aggregation, it was noted that the highest rates were recorded in T/T genotype group – 1.68 times higher than control group. Conclusion It is found that T allele of ITGA2 carrier is typical for 72.1% of patients with acute coronary syndrome and combined with spontaneous acceleration of platelet aggregation and increases sensitivity of platelets to ADP and collagen. Results allow us to consider the carrier of the T-allele as a marker of predisposition to thrombophilia. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Effects of tranexamic acid and exogenous fibrin monomer on the liver injury area and systemic circulation in pharmacological suppression of platelet function in an experiment

2021 ◽  
Vol 102 (5) ◽  
pp. 642-653
Author(s):  
V M Vdovin ◽  
A P Momot ◽  
I I Shakhmatov ◽  
I P Bobrov ◽  
D A Orekhov ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Liver Injury ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Morphological Features ◽  
Fibrinogen Concentration ◽  
Fibrin Monomer ◽  
Significant Difference ◽  
Induced Aggregation ◽  
Injury Area

Aim. To identify and compare the morphological, hemostatic and hemostasiological consequences of intravenous administration of tranexamic acid and fibrin monomer in controlled liver injury against drug-induced thrombocytopathy. Methods. The morphological features of fibrin formation in the area of liver injury after spontaneous bleeding arrest combined with the indicators of blood loss in the animals treated with intravenous placebo, tranexamic acid or fibrin monomer was studied in 69 male rabbits. The effects of these drugs were assessed against thrombocytopathy associated with the combined use of acetylsalicylic acid and clopidogrel. Platelet number and function (adnosine diphosphate-induced aggregation), the data of thromboelastometry and calibrated automated thrombogram, fibrinogen concentration and D-dimer level were considered in the blood test. The feature distribution in the samples was assessed using the ShapiroWilk test. Depending on the distribution, Student's t-test, MannWhitney U test or Wilcoxon signed-rank test were used to test for a significant difference between the features. Differences in mortality rate were established by using Fisher's exact test. The differences were considered statistically significant at p 0.05. Results. A model of thrombocytopathy which showed decreased platelet aggregation function (by 4.5 times), increased blood loss (by 40%), and high mortality (53.9%) was reproduced. Only a small accumulation of thrombotic material was noted on the injured surface of such animals. The use of tranexamic acid led to decreased post-traumatic bleeding (2.5 times) and animal mortality (20%). The latter was provided on the wound surface by increasing the thickness of both thrombotic deposits and fibrin strands. When fibrin monomer was used, the phenomenon of an overcompensated decrease in blood loss (by 6.7 times) accompanied by zero mortality was noted despite a pronounced decrease in platelet aggregation. The maximum increase in the thickness of thrombotic material and fibrin strands was morphologically determined in the injury area compared with other animal groups. Conclusion. Morphological features of traumatic hemostatic effect at the injured area when using tranexamic acid and fibrin monomer have a number of differences despite the similarity of the achieved results in minimizing blood loss.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig

1992 ◽  
Vol 68 (05) ◽  
pp. 500-505 ◽  
Author(s):  
Ch M Samama ◽  
Ph Bonnin ◽  
M Bonneau ◽  
G Pignaud ◽  
E Mazoyer ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Femoral Artery ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Flow Reduction ◽  
Cyclic Flow ◽  
Left Femoral Artery ◽  
Before And After ◽  
The Right ◽  
Induced Aggregation

SummaryWe investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 µg kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions in all animals and epinephrine did not restore any cyclic flow reduction. On the right femoral artery, cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (>15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal. Aspirin 5 mg kg-1 (n = 6) abolished cyclic flow reductions in only 3 animals and epinephrine always restored it. Aspirin 100 mg kg-1 (n = 3) was unable to abolish cyclic flow reductions. On the right femoral artery, aspirin did not significantly prevent cyclic flow reductions which occurred in all animals after one (n = 14) or two injuries (n = 1), except for one animal. Basal bleeding time was lengthened but it shortened rapidly, reaching its basal value after 24 h. ADP-induced aggregation was not significantly inhibited, whereas arachidonic acid induced aggregation was always inhibited. Clopidogrel appears as a more potent antithrombotic drug than aspirin in this model, in treating and preventing spontaneous or epinephrine-induced cyclic flow reductions and lengthening bleeding time.

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