Platelet Hyperaggregability Research Articles

O-GlcNAcylation: Crosstalk between Hemostasis, Inflammation, and Cancer.

O-linked β-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients' healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network.

Clusters of patients with non-ST-segment elevation acute coronary syndrome depending on the laboratory data

Aim. To identify clusters of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) depending on the laboratory data, including platelet function tests.Material and methods. The study included 109 patients hospitalized in the cardiology department with NSTE-ACS. All patients underwent a standard examination, including a complete blood count. In addition, the platelet function was assessed using impedance aggregometry with various inducers (adenosine diphosphate (5 and 10 μmol/L), collagen (2 μmol/L)). We assessed the P-selectin expression level using flow cytometry. Patients were followed up for 6 months. As a statistical method, we performed сluster analysis by K-means algorithm.Results. We registered 18 adverse outcomes (myocardial infarction, unstable angina) during 6-month follow-up. Cluster analysis revealed 3 clusters. The first cluster included 39 (36%) patients with higher monocyte values and lower hemoglobin values, probably indicating chronic inflammation and a tendency towards anemia. The second cluster included 13 older patients (12%) with high comorbidity and high platelet function. Both the first and second clusters recorded 23% adverse outcomes. Third cluster, on the contrary, included mostly younger patients with fewer comorbidities, which had more favorable course of ACS (no signs of platelet hyperaggregation, chronic inflammation and anemia). This cluster included more than half (n=57, 52%) of all patients; adverse outcomes at 6 months in these patients developed 2-fold less frequently than in the other clusters (11% vs 23%).Conclusion. Among patients with NSTE-ACS, groups differing in laboratory parameters were identified, based on which clusters were formed using the k-means method. Clusters with high levels of platelet functional activity, monocyte count and low hemoglobin values included older patients with severe comorbidity and showed a tendency towards more frequent adverse outcomes of the disease.

Efficacy of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1h-1,2,4-triazol-4 bromide in the rat model of inferior vena cava thrombosis

Introduction. According to WHO, acute disorders of cerebral circulation are anticipated to become a predominant contributor to the global disease burden by 2030. The comprehensive management of vascular depression entails not only the use of antidepressants but also fundamental interventions. The development of a novel molecule based on thietane-containing heterocycles, merging the attributes of an antidepressant and an antiplatelet agent, holds promise for enhancing therapeutic efficacy in patients with acute cerebrovascular accidents through multimodal action. Objective is to conduct a preclinical assessment of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide concerning model thrombosis in rats. Materials and Methods. The investigation involved the evaluation of thrombosis processes and the haemostasis system in rats subjected to complete occlusion of the inferior vena cava within 24 hours post-thrombosis induction. Techniques employed included thromboelastography, Born aggregometry, standard clotting assays to appraise the coagulation facet of haemostasis, and morphological examinations. Results. The results demonstrate that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide mitigates thrombosis mass, restores platelet hyper aggregation, and counters hypercoagulation observed in acute inferior vena cava thrombosis in rats. Comparative analysis with reference drugs substantiates the superior effectiveness of the chosen compound in thrombosis prevention. Conclusion. The preclinical investigation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide unveils a fusion of established antidepressant and antithrombotic activities, laying groundwork for further drug development endeavours.

Delayed Rewarming Thrombocytopenia: A Suggested Preventable and Treatable Cause of Rewarming Deaths.

The lack of a consensus of accepted prognostic factors in hypothermia suggests an additional factor has been overlooked. Delayed rewarming thrombocytopenia (DRT) is a novel candidate for such a role. At body temperature, platelets undergoing a first stage of aggregation are capable of progression to a second irreversible stage of aggregation. However, we have shown that the second stage of aggregation does not occur below 32°C and that this causes the first stage to become augmented (first-stage platelet hyperaggregation). In aggregometer studies performed below 32°C, the use of quantities of ADP that cause a marked first-stage hyperaggregation can cause an augmented second-stage activation of the platelets during rewarming (second-stage platelet hyperaggregation). In vivo, after 24 hours of hypothermia, platelets on rewarming seem to undergo second-stage hyperaggregation, from ADP released from erythrocytes, leading to life-threatening thrombocytopenia. This hyperaggregation is avoidable if heparin is given before the hypothermia or if aspirin, alcohol or platelet transfusion is given during the hypothermia before reaching 32°C on rewarming. Many of the open questions existing in this field are explained by DRT. Prevention and treatment of DRT could be of significant value in preventing rewarming deaths and some cases of rescue collapse. Performing platelet counts during rewarming will demonstrate potentially fatal thrombocytopenia and enable treatment with platelet infusions aspirin or alcohol.

Deep vein thrombosis: does platelet hyperaggregation have any role?

Deep vein thrombosis: does platelet hyperaggregation have any role?

The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD's early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products. Capillarization leads to ischemic changes in hepatocytes, triggering pro-inflammatory responses in Kupffer cells (KCs) and activating hepatic stellate cells (HSCs). Capillarized LSECs show a pro-inflammatory phenotype through adhesion molecule overexpression, autophagy loss, and increased cytokines production. Platelet interaction favors leucocyte recruitment, NETs formation, and liver inflammatory foci. Liver fibrosis is facilitated by reduced nitric oxide, HSC activation, profibrogenic mediators, and increased angiogenesis. Moreover, platelet attachment, activation, α-granule cargo release, and NETs formation contribute to MASLD progression. Platelets foster fibrosis and microthrombosis, leading to parenchymal extinction and fibrotic healing. Additionally, platelets promote tumor growth, epithelial-mesenchymal transition, and tumor cell metastasis. MASLD's prothrombotic features are exacerbated by insulin resistance, diabetes, and obesity, manifesting as increased von Willebrand factor, platelet hyperaggregability, hypo-fibrinolysis, and a prothrombotic fibrin clot structure. Improving LSEC health and using antiplatelet treatment appear promising for preventing MASLD development and progression.

Relationships of apolipoprotein E genotypes with a cluster of seven in persons with type 2 diabetes.

The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes (2/2, 2/3, 2/4, 3/3, 3/4, and 4/4) for each member of the cluster of seven associated with type 2 diabetes (T2D). The cluster of seven includes abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDL-C) and increased plasma levels of triglycerides)), increased low-density lipoprotein (LDL) oxidation, and increased inflammation. Forty-six patients with well-controlled T2D participated in the study. Abdominal obesity (assessed by waist circumference), hypertension (measured by manual sphygmomanometry), platelet hyperaggregability (measured by bleeding time), hyperglycemia (by enzymatic kit and spectrophotometry), decreased plasma levels of HDL-C and increased plasma levels of triglycerides (by enzymatic kit and spectrophotometry), increased LDL oxidation (measured by LDL conjugated dienes using spectrophotometry) and increased inflammation measured by C-reactive protein (CRP) (by EIA kit) were determined. All genotypes, except 2/2 were found in the population studied. Abdominal obesity did not vary significantly across the five genotypes. However, glucose levels trended progressively higher going from 2/3 to 2/4 to 3/4 to 4/4. Systolic blood pressure was higher in 3/4 compared to 2/4 and trended higher in 3/4 compared to 3/3. Diastolic blood pressure trended higher in 3/3 vs 2/4 and significantly higher in 3/4 compared to 2/4. Triglycerides trended higher in 3/4 vs 3/3 while HDL-C came close to trending downward in 4/4 compared to 2/4. Bleeding time was unaffected by genotype. Plasma LDL conjugated dienes trended higher in 3/4 vs 2/4 and were significantly higher in 3/4 vs 3/3. CRP trended higher in 4/4 vs 2/3. We can conclude that those with at least one 4 allele in the presence of another allele being 2, 3 or 4 is potentially (in the case of trends) deleterious or is deleterious in terms of hyperglycemia, hypertension (systolic and diastolic blood pressure), dyslipidemia, LDL conjugated dienes and CRP levels.

Various apolipoprotein E genotypes relate to responsiveness to flaxseed lignan complex in older persons with type 2 diabetes mellitus.

Objective. The objective of the study was to determine if there would be statistically significant differences or trends among apolipoprotein E genotypes in the responsiveness of members of a cluster of seven measures in older persons with type 2 diabetes mellitus (T2DM) consuming flaxseed lignan complex (FLC). The cluster of seven are abdominal obesity, hypertension, platelet hyperaggregability, hyperglycemia, dyslipidemia (decreased plasma levels of high-density lipoprotein cholesterol (HDLc), and increased plasma levels of triglycerides), increased low-density lipoprotein (LDL) oxidation and increased inflammation. All cluster members exacerbate T2DM. Methods. Sixteen patients with well-controlled T2DM participated in this double-blind randomized, placebo-controlled crossover study consisting of four visits. Apolipoprotein E genotyping was done at visit one. The cluster of seven, diet, exercise, smoking and medication use were assessed at each visit. Results. The 3/4 genotype showed a stronger downward trend in systolic blood pressure compared to the 3/3 genotype with no trend or significant difference in the 2/4 genotype. There was a downward trend in diastolic blood pressure in genotype 3/3 compared genotype 2/4, which showed no significant difference or trend. Only genotype 3/4 showed a significant drop in diastolic pressure compared to genotypes 2/4 and 3/3. HDLc only showed a downward trend in 3/4 relative to genotypes 2/4 and 3/3. LDL apolipoprotein B oxidation (LDL-Box) only showed an upward trend in 3/3 compared to genotypes 2/4 and 3/4. There were no other significant differences or trends by genotype in the cluster of seven. Conclusions. It appears that those with the 2/4 genotype may not benefit from FLC, those with 3/3 and 3/4 genotypes may benefit only in terms of systolic and diastolic pressures, those with the apo E 3/4 genotype should perhaps avoid FLC to manage HDLc, and those with the 3/3 genotype should perhaps avoid FLC to manage LDL apolipoprotein B oxidation.

Correlation Between P-Selectin Level and Platelet Aggregation in Cerebral Venous Sinus Thrombosis Patients

One of the causes of cerebral venous sinus thrombosis (CVST) is platelet hyperactivity. Adhesion and secretion are the beginning of platelet activation, which is indicated by a change in the Platelet-selectin (P-selectin) level. The end result of platelet activation is platelet aggregation. However, it is unknown whether the beginning of platelet activation ends with platelet aggregation. This study aimed to discover the correlation between P-selectin level and platelet aggregation in CVST. This study used a cross-sectional escriptive observational correlative approach. Subjects were the CVST outpatients visiting the Neurology Department of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, from July to September 2021. A total of 49 subjects met the inclusion and exclusion criteria. This study used citrate plasma samples for platelet aggregation and serum for P-selectin assessment. Platelet aggregation were assessed using the light transmission platelet aggregation method while P-selectin was assessed using Enzyme-linked immunosorbent assay (ELISA). Platelet aggregation median was 10.6% (range 0.2–82.4%), which reflected normoaggregation. Platelet hyperaggregation were seen in 9 samples (8.4%). Median of P-selectin was 2.4 ng/mL (range 0.1–10.1 ng/mL) which were normal. High P-selectin level was observed in 16 (32.7%) with 4/16 (25%) experiencing platelet hyperaggregation. Statistical analysis showed a weak negative correlation between P-selectin and platelet aggregation (r=-0.012; p=0.467). In conclusion, no correlation is seen between P-selectin and platelet aggregation, which may be due to the fact that platelets are influenced by many factors that are not examined in this study.

Hydroxysafflor yellow A inhibits the hyperactivation of rat platelets by regulating the miR-9a-5p/SRC axis

Pathological platelet activation plays a vital role in the prevalence of cardiovascular diseases. Hydroxysafflor yellow A (HSYA) has been shown to have significant anti-platelet aggregation and anti-activation effects, but its mechanism of action is unclear. Our study showed that HSYA inhibited the expression of platelet surface glycoproteins IIβ/III α (GPIIβ/III α) and thromboxane A2 (TXA2) during platelet activation and reduced platelet Ca2+ accumulation. HSYA significantly reduced the number of platelets and inhibited adrenaline-induced platelet hyperaggregation in rats. Transcriptomic analysis of platelets suggested that HSYA significantly suppressed SRC and MAPK3 (ERK1/2) gene expression. YEEI peptide, an SRC activator, could significantly reverse the inhibition of HSYA on the phosphorylation of SRC/PLCγ2/PKCδ/MEK/ERK1/2 pathway proteins and reverse the effect of HSYA on platelet activation-related markers GPIIβ/IIIα protein, TXA2 and cAMP. The SRC genes were further predicted by transcriptome analysis of HSYA-regulated miRNAs combined with bioinformatics techniques. The results suggested that HSYA could significantly upregulate the expression level of the miR-9a-5p gene and further confirmed that miR-9a-5p had a targeted regulatory relationship with SRC by dual-luciferase activity reporter and cell transfection experiments. The inhibitory effect of HSYA on the SRC/PLCγ2/PKCδ/MEK/ERK1/2 pathway was significantly reversed after platelets were transfected with the miR-9a inhibitor, while SRC siRNA attenuated the effect of the miR-9a inhibitor. SRC siRNA was able to attenuate the effect of the miR-9a inhibitor. In conclusion, this study suggests that HSYA can inhibit the activation of the SRC/PLCγ2/PKC δ/MEK/ERK1/2 axis by upregulating platelet miR-9a-5p, thereby reducing the activation of platelets and inhibiting platelet aggregation.

Platelet miRNA Expression in Patients with Sticky Platelet Syndrome

Abstract Sticky platelet syndrome (SPS) is a disorder with familial occurrence and autosomal dominant trait characterized by platelet hyperaggregability in response to a low concentration of adenosine diphosphate (ADP) and/or epinephrine (EPI). The etiology of SPS may be associated with platelet microRNAs (miRNAs), which are considered as potential biomarkers of platelet function and antiplatelet therapy. We were monitoring the expression of platelet miRNAs in patients with laboratory diagnosed SPS and healthy controls. We have found a statistically significant increased expression of both miR-423-5p and miR-338-3p as well as a statistically significant decreased expression of miR-425-5p between the group of patients with diagnosed SPS type II and the group of healthy controls, which seems to be an interesting issue for a further research.

The Effect of 4-Methylcatechol on Platelets in Familial Hypercholesterolemic Patients Treated with Lipid Apheresis and/or Proprotein Convertase Subtilisin Kexin 9 Monoclonal Antibodies.

Elevated low-density lipoprotein (LDL) cholesterol levels lead to atherosclerosis and platelet hyperaggregability, both of which are known culprits of arterial thrombosis. Normalization of LDL cholesterol in familial hypercholesterolemia (FH) is not an easy task and frequently requires specific treatment, such as regularly performed lipid apheresis and/or novel drugs such as proprotein convertase subtilisin kexin 9 monoclonal antibodies (PCSK9Ab). Moreover, a high resistance rate to the first-line antiplatelet drug acetylsalicylic acid (ASA) stimulated research of novel antiplatelet drugs. 4-methylcatechol (4-MC), a known metabolite of several dietary flavonoids, may be a suitable candidate. The aim of this study was to analyse the antiplatelet effect of 4-MC in FH patients and to compare its impact on two FH treatment modalities via whole-blood impedance aggregometry. When compared to age-matched, generally healthy controls, the antiplatelet effect of 4-MC against collagen-induced aggregation was higher in FH patients. Apheresis itself improved the effect of 4-MC on platelet aggregation and blood from patients treated with this procedure and pretreated with 4-MC had lower platelet aggregability when compared to those solely treated with PCKS9Ab. Although this study had some inherent limitations, e.g., a low number of patients and possible impact of administered drugs, it confirmed the suitability of 4-MC as a promising antiplatelet agent and also demonstrated the effect of 4-MC in patients with a genetic metabolic disease for the first time.

Monitoring the Antiplatelet Therapy Efficacy in Patients with Acute Ischemic Stroke.

Stroke is one of the leading causes of morbidity and mortality in populations of developed countries. Ischemic strokes account for 85 - 90% of all strokes, with the majority of strokes of non-cardioembolic pathogenesis. Platelet aggregation plays a key role in arterial thrombus formation. Therefore, effective antiplatelet therapy plays a key role in secondary prevention. Acetylsalicylic acid (ASA) is the main drug of choice, and clopidogrel therapy is another recommended treatment option. Monitoring of the efficacy of antiplatelet therapy has been intensively studied in patients with coronary artery disease in the context of coronary stent implantation. It is not yet part of the routine procedure in patients with stroke [1-3]. This study investigated the efficacy of antiplatelet therapy with ASA and clopidogrel using optical and impedance aggregometry in 42 consecutive patients with acute ischemic stroke. Patients were treated with throm-bolysis at baseline and platelet function was examined 24 hours after administration, focusing on the occurrence of platelet hyperaggregability and assessing the efficacy of any chronically administered antiplatelet therapy. Subsequently, patients were administered a loading dose of ASA or clopidogrel followed by a check of its efficacy 24 hours after administration. In the following days, the maintenance dose of the drug was continued and regular laboratory monitoring of treatment efficacy was performed every 24 hours. In patients with atherothrombotic stroke indicated for antiplatelet therapy, monitoring of residual platelet activity allowed for detection of potentially atrisk patients. These were 35% (9% borderline ineffective) of patients taking ASA and 55% (18% borderline ineffective) of patients treated with clopidogrel. The dose was adjusted, increased the administered treatment and no recurrence of stroke was observed in this study group at 1-year follow-up. Personalized antiplatelet therapy based on platelet function tests appears to be a useful method to reduce the risk of recurrent vascular events.

Aspirin Administration Mitigates Platelet Hyperaggregability After Splenectomy in a Murine Model

IntroductionPatients who undergo splenectomy (SPLN) have an estimated 10%-35% risk of venous thromboembolic events; however, the underlying mechanism and strategy for prevention have yet to be identified. The goals of this study were to 1) investigate platelet aggregation after SPLN, 2) examine if aspirin administration could mitigate this effect, and 3) determine if concomitant hemorrhage would affect post-SPLN platelet function and response to aspirin. MethodsMurine models of operative SPLN and submandibular bleed (SMB) were utilized. Mice were randomized to eight groups as follows: untouched, SPLN, sham (laparotomy only), SMB, SPLN + SMB, SPLN + aspirin (ASA), SMB + ASA, and SPLN + SMB + ASA. Aspirin (50 mg/kg) was administered on postoperative days (PODs) one and two via oral gavage. Mice were euthanized on POD 3, platelet counts were obtained, and blood samples were analyzed via rotational thromboelastometry and impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. ResultsBy POD 3, SPLN mice displayed a significant thrombocytosis compared to untouched, SMB, and sham SPLN mice. Clotting time and clot formation time were significantly decreased in SPLN and SPLN + SMB cohorts compared to untouched and sham controls with elevated mean clot firmness. SPLN mice also displayed a significant increase in ADP- and AA-mediated platelet aggregability compared to untouched controls, SMB, and SPLN + SMB. ASA significantly decreased platelet aggregation via both ADP and AA signaling in SPLN and SPLN + SMB cohorts without affecting viscoelastic coagulation testing. ConclusionsPlatelet hyperaggregability after SPLN is mediated by both ADP and AA signaling. Early aspirin administration may prevent increased platelet aggregation exacerbated after polytrauma.

Primary Thrombophilia XVII: A Narrative Review of Sticky Platelet Syndrome in México.

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

Association of Genetic Variability in Selected Genes with Platelet Hyperaggregability and Arterial Thrombosis

Abstract Introduction: Inherited platelet hyperaggregability, so called “Sticky platelet syndrome” (SPS), is a prothrombotic platelet disorder. The syndrome contributes more often to arterial than venous thrombosis. The most common localization of arterial occlusion involves cerebral or coronary arteries. However, SPS may also lead to thrombosis in the atypical sites of the circulation. This qualitative platelet alteration causes platelet hyperaggregability after a very low concentration of platelet inducers – adenosine diphosphate (ADP) and/or epinephrine (EPI). The precise genetic background of the syndrome has not been defined. In the present study we aimed to determine the association between selected single nucleotide polymorphisms (SNPs) within genes for platelet endothelial aggregation receptor 1 (PEAR1) and murine retrovirus integration site 1 (MRVI1) and the risk for arterial thrombosis in patients with SPS. The products of these selected genes play an important role in platelet aggregation. Patients and methods: We examined 69 patients with SPS and a history of arterial thrombosis and 69 healthy blood donors who served as controls. SPS was confirmed by a light transmission aggregometry (LTA) according to the method and criteria described by Mammen and Bick. We assessed two SNPs within PEAR1 gene (rs12041331, rs1256888) and two SNPs within MRVI1 gene (rs1874445, rs7940646). Results: Selected PEAR1 and MRVI1 polymorphisms seem not to be a risk factor for the development of SPS as the syndrome with an arterial thrombosis phenotype. However, in the subgroup of SPS1 patients there was found a decreased frequency of the minor A allele of SNP rs12041331 in PEAR1 gene (borderline p value, p=0.061) that can be hypothesized as protective against arterial thrombosis. In the same SPS1 subgroup the haplotype TA in PEAR1 gene also showed a decreased frequency with a borderline insignificance (p=0.056). We can theorize also about its protective role in SPS1 patients. We did not confirm the protective effect of polymorphism (T/T of rs 12566888) in PEAR1 against arterial thrombosis in SPS patients and SPS subgroups. Conclusion: Our results support the idea that examined genetic variability of the selected SNPs in PEAR1 and MRVI1 genes is not associated with platelet hyperaggregability manifested as arterial thrombosis. The possible protective role of the minor A allele of SNP rs12041331 as well as a role of haplotype TA in PEAR1 gene related to the arterial thrombosis found in the subgroup of SPS1 patients needs to be verified in further research.

Does platelet aggregation have any importance in fetal growth restriction pregnancies?

The aim of the study was to evaluate platelet (PLT) concentration, mean platelet volume (MPV), PLT aggregation and its velocity in pregnancy complicated with fetal growth restriction (FGR) and to analyze the PLT aggregation according to the gestational age and Doppler velocimetry. The study group included 29 pregnant women diagnosed with FGR. The control group-consisted of 27 females in uncomplicated pregnancy. Then both groups were divided according to the gestational week (< and ≥ 36 weeks) and Doppler velocimetry results. The adenosine diphosphate (ADP) induced PLT aggregation was performed with the help of the electrical impedance. There was a significant positive correlation between gestational age and PLT aggregation and between gestational age and velocity of PLT aggregation in FGR. Patients with FGR ≥ 36 weeks of gestation had 73% higher PLT aggregation than control group. Within the FGR group, the PLT aggregation was 135% higher in pregnancies ≥ 36 weeks as compared to < 36 weeks of gestation. In FGR pregnancies ≥ 36 weeks with impaired flow in both uterine arteries (UtA), 2.3-fold higher PLT aggregation was found as compared to FGR patients with normal flow or abnormal flow in one UtA. The increased PLT aggregation in FGR is related to gestational week and occurs in pregnancies ≥ 36 weeks of gestation. The PLT hyperaggregability in growth-restricted pregnancies is associated with abnormal Doppler velocimetry in both UtA, comparing to patients with altered blood flow in one UtA or normal pulsatility index in both UtA, suggesting the PLT activation due to impaired uteroplacental circulation.

A new decade awaits sticky platelet syndrome: where are we now, how do we manage and what are the complications?

ABSTRACT Introduction Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial. Areas covered The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: ‘sticky platelet syndrome’ – ‘platelet hyperreactivity’ – ‘platelet hyperaggregability’). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems. Expert Opinion Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.

Cardiovascular protection effect of a Northeastern Brazilian lyophilized red wine in spontaneously hypertensive rats

• Northeastern Brazilian lyophilized red (LRW-RSCS) wine lowers blood pressure in SHR. • LRW-RSCS reduced endothelial dysfunction and improved vascular remodeling in SHR. • In SHR, LRW-RSCS attenuated platelet hyper aggregation and generation of ROS. • The cardioprotective effects of LRW-RSCS in SHR may be linked to a reduction in ROS. Moderate consumption of wine has a protective effect on the cardiovascular system. This study proposes to investigate the cardiovascular protective effect of the lyophilized red wine RIO SOL Cabernet-Sauvignon (LRW-RSCS), produced in Northeastern Brazil, in SHR. Sixteen different phenolic compounds, such as gentisic acid, catechin, and resveratrol were identified in LRW-RSCS using high-performance liquid chromatography. LRW-RSCS presented anti-radical activity. Six-week treatment of SHR with LRW-RSCS (100 or 300 mg/Kg/day intra-gastrically) reduced blood pressure and hypercontractility, and improved mesenteric resistance artery endothelial function. The protective effect of LRW-RSCS on endothelial function, mediated relaxation involving both higher endothelial-NO and -EDHF. LRW-RSCS intake reduced vessel wall thickness, media-to-lumen ratio, collagen vascular deposition, and vessel oxidative stress. LRW-RSCS also attenuated platelet hyper aggregation and ROS generation. The results demonstrate that LRW-RSCS from Northeastern Brazil presents cardiovascular protective effect in SHR, at least in part by decreasing oxidative stress.

Dose-dependent effects of anthocyanin supplementation on platelet function in subjects with dyslipidemia: A randomized clinical trial.

BackgroundDyslipidemia induces platelet hyperactivation and hyper-aggregation, which are linked to thrombosis. Anthocyanins could inhibit platelet function in vitro and in mice fed high-fat diets with their effects on platelet function in subjects with dyslipidemia remained unknown. This study aimed to investigate the effects of different doses of anthocyanins on platelet function in individuals with dyslipidemia.MethodsA double-blind, randomized, controlled trial was conducted. Ninety-three individuals who were initially diagnosed with dyslipidemia were randomly assigned to placebo or 40, 80, 160 or 320 mg/day anthocyanin groups. The supplementations were anthocyanin capsules (Medox, Norway). Platelet aggregation by light aggregometry of platelet-rich plasma, P-selectin, activated GPⅡbⅢa, reactive oxygen species (ROS), and mitochondrial membrane potential were tested at baseline, 6 weeks and 12 weeks.FindingsCompared to placebo group, anthocyanins at 80 mg/day for 12 weeks reduced collagen-induced platelet aggregation (-3.39±2.36%) and activated GPⅡbⅢa (-8.25±2.45%) (P < 0.05). Moreover, compared to placebo group, anthocyanins at 320 mg/day inhibited collagen-induced platelet aggregation (-7.05±2.38%), ADP-induced platelet aggregation (-7.14±2.00%), platelet ROS levels (-14.55±1.86%), and mitochondrial membrane potential (7.40±1.56%) (P < 0.05). There were dose-response relationships between anthocyanins and the attenuation of platelet aggregation, mitochondrial membrane potential and ROS levels (P for trend <0.05). Furthermore, significantly positive correlations were observed between changes in collagen-induced (r = 0.473) or ADP-induced (r = 0.551) platelet aggregation and ROS levels in subjects with dyslipidemia after the 12-week intervention (P < 0.05).InterpretationAnthocyanin supplementation dose-dependently attenuates platelet function, and 12-week supplementation with 80 mg/day or more of anthocyanins can reduce platelet function in individuals with dyslipidemia.