Reduction In Platelet Count Research Articles

Relation of CXCL10 and CXCR3 Gene Polymorphisms with COVID-19 Severity and its Serum Biochemical Markers

CXCL10 (rs201830102) is a chemokine involved in immune cell recruitment, while its receptor, CXCR3 (rs779120264), mediates immune responses through the activation of T cells. These genes are critical in the immune response to viral infections, including COVID-19. The study aimed to explore the relationship between polymorphisms in the CXCL10 gene and CXCR3 receptor with disease severity in COVID-19 patients. In this cross-sectional analytical study, 100 COVID-19 patients were enrolled after ethical approval, and written informed consent was obtained from each participant. Polymorphisms in CXCL10 and CXCR3 were analyzed by sequencing, while biochemical and hematological parameters were assessed using appropriate methods. Descriptive and inferential statistics were employed to analyze continuous and categorical data. Significant associations were observed between severe COVID-19 cases and elevated levels of serum D-dimer, ferritin, random blood sugar (RBS), neutrophils, and erythrocyte sedimentation rate (ESR), along with reduced hemoglobin levels. Lymphocyte and platelet counts were significantly lower with increased disease severity. The wild genotype of CXCL10 was notably associated with elevated ferritin levels, suggesting that certain gene variants may offer protective effects. However, no significant correlation was found between CXCR3 and CXCL10 polymorphisms and other serum biomarkers. Our study confirmed a significant rise in serum D-dimer, ferritin, RBS, neutrophils, and ESR, along with a reduction in hemoglobin, lymphocyte, and platelet counts in severe COVID-19 cases compared to mild ones. Notably, mutations in the CXCL10 gene were linked to less severe COVID-19 outcomes.

Diagnostic Implications of CD63 and CD64 Expression Levels and FcγRIIIA 158 V/F Gene Polymorphism in Primary Immune Thrombocytopenia Adult Patients.

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by reduced platelet counts due to immune system dysregulation caused by many factors, including genetics, autoimmune diseases, infections, and inflammations. Therefore, the current study aimed to evaluate immunological markers such as the expression level of lysosomal associated membrane protein 3 (LAMP-3), also known as CD63, and the expression level of Fc-gamma receptor I (FcγRI), also known as CD64 and also investigate the association of Fc-gamma receptor IIIA (FcγRIIIA) 158 V/F polymorphism to the risk of ITP. A total of 180 subjects; 60 ITP patients, 60 patients with thrombocytopenia of other causes and 60 controls were enrolled into our study. The expression level of CD63 was done using reverse transcription quantitative PCR (RTqPCR), while CD64 expression level was done by flow cytometry. The polymorphism of FcγRIIIA 158 V/F gene was analyzed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. Finally, CD63 and CD64 protein-protein interactions were done by using the STRING online database. The expression of CD63 was significantly elevated in ITP patients than thrombocytopenia patients and healthy control. Also there was high expression level of CD64 on granulocytes and monocytes from ITP patients than other groups. Receiver operating characteristic curve (ROC curve) analysis of CD63 showed an area under the curve (AUC) revealed of 1.00, sensitivity of 100% and specificity of 100%; while for CD64 on granulocytes, AUC of 0.998 as well as a sensitivity of 96.66% and specificity of 93.33%. Regarding FcγRIIIa 158 V/F polymorphism, all patients and healthy volunteers included in this study showed the wild FF genotype. The expression of both CD63 and CD64 were significantly increased in ITP patients and could be good biomarkers to diagnose ITP. Additionally, there is no association between FcγRIIIa 158 V/F polymorphism and the risk of ITP disease.

Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C-reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial.

Surgical removal of an impacted third molar is one of the most common oral surgical procedures performed in dental offices. The postoperative phase is often associated with severe inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually prescribed to manage postoperative discomfort. NSAIDs have been associated with gastrointestinal bleeding, renal function disturbances, and platelet count reductions. Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars.This study aimed to correlate and compare the impact of aescin and diclofenac on salivary PGE2 levels and serum C-reactive protein levels after surgical extraction of the mandibular third molar. The study will also evaluate and compare the effectiveness of individual drug therapy in managing postoperative pain, swelling and mouth opening. The planned study is a single-center, double-blind, randomized, parallel, prospective clinical trial. Each patient will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day to be taken orally in divided doses for five days after surgically removing the impacted mandibular third molar.Pain will be assessed using a visual analog scale. Facial swelling and mouth opening will be recorded using a metric scale with standardized reference points. ELISA (enzyme-linked immunosorbent assay (ELISA) will be employed to measure salivary Prostaglandin E2 and serum C-reactive protein levels. All parameters will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2). The proposed study is expected to show a clinically acceptable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery.The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C-reactive protein, which are reliable inflammatory markers.The outcome of this study may provide an efficacious and safe alternative to conventional nonsteroidal anti-inflammatory drugs for managing postoperative discomfort following third molar surgery.

Genetically predicted plasma metabolites mediate the causal relationship between gut microbiota and primary immune thrombocytopenia (ITP).

Primary immune thrombocytopenia (ITP) is an immune-mediated hematologic disorder characterized by a reduction in platelet count, increasing the risk of bleeding. Recent studies have indicated a close association between alterations in gut microbiota and the development of ITP. However, the mechanisms by which gut microbiota influence the occurrence and progression of ITP through plasma metabolites remain poorly understood. Evidence suggests extensive interactions between gut microbiota and plasma metabolites, implying a potential role for gut microbiota in influencing ITP through alterations in plasma metabolites, which requires further investigation. In this study, summarized GWAS data (including 211 gut microbiota taxa, 1,400 plasma metabolites or ratios, and an ITP patient cohort) were retrieved from the MiBioGen and GWAS Catalog databases. Using a two-sample Mendelian randomization (MR) approach, we screened gut microbiota and plasma metabolites potentially causally related to ITP. We further identified plasma metabolites serving as mediators through which gut microbiota affect ITP and calculated the strength of the mediation effect. To ensure result stability, we primarily used the inverse variance weighted (IVW) method as the main judgment index. We also utilized MR Egger and inverse variance weighted methods to detect heterogeneity in the results, and employed MR-Egger and MR-PRESSO methods to assess the presence of pleiotropy. Though two-sample MR analysis, 8 gut microbiota taxa were found to have causal relationships with ITP. After excluding six plasma metabolites with pleiotropy, 39 plasma metabolites were found to be causally related to ITP (P < 0.05). Eleven plasma metabolites were identified as having causal relationships between gut microbiota and plasma metabolites. Finally, using the delta method, it was calculated that Sphingomyelin levels (8.0%, 95%CI: 0.9% to 11.5%, P = 0.047) and Glucose-to-mannose ratio (6.5%, 95%CI: 0.7% to 9.5%, P = 0.039) are intermediates for Intestinimonas influencing ITP, while Bilirubin (Z,Z) to etiocholanolone glucuronide ratio (5.6%, 95%CI: 4.7% to 6.9%, P = 0.043) is an intermediate for Senegalimassilia influencing ITP. Gut microbiota can influence the development of ITP through changes in plasma metabolites. Sphingomyelin levels, Glucose-to-mannose ratio, and Bilirubin (Z,Z) to etiocholanolone glucuronide ratio are newly discovered intermediates through which gut microbiota influence ITP, providing potential indicators and targets for clinical diagnosis and treatment. This study highlights the intricate relationship between gut microbiota and plasma metabolites in the context of ITP, suggesting new avenues for clinical diagnosis and treatment.

Salvianolic acid B improves the microcirculation in a mouse model of sepsis through a mechanism involving the platelet receptor CD226.

Salvianolic acid B (SalB) demonstrates diverse clinical applications, particularly in cardiovascular and cerebral protection. This study primarily investigated the effects of SalB on sepsis. The model of sepsis via caecal ligation puncture (CLP) was established in male C57BL/6 mice. Therapeutic effects of SalB on hepatic and pulmonary injury, inflammatory responses and microcirculatory disturbances in sepsis were evaluated. Platelet aggregation and adhesion were measured via flow cytometry and an adhesion test. After overexpression of platelet-related activating molecules by 293T cells, the efficient binding of SalB and platelet CD226 molecules was further evaluated. Finally, neutralizing antibody experiments were used to assess the mechanism of SalB in alleviating the progression of sepsis. SalB mitigated hepatic and pulmonary impairments, reduced inflammatory cytokine levels and enhanced mesenteric microvascular blood flow in septic mice. SalB enhanced CLP-induced reduction of platelet count and platelet pressure cumulative volume. SalB reduced platelet adhesion to endothelial cells and platelet aggregation to leukocytes. A high binding efficiency was observed between SalB and the platelet adhesion molecule CD226. Ex vivo, interactions between SalB and platelets from CD226-knockout mice were markedly decreased. In vivo administration of CD226 neutralizing antibodies significantly delayed disease progression and enhanced mesenteric microcirculation in septic mice. In our murine model of sepsis, treatment with SalB improved the microcirculatory disturbance and hindered the progression of sepsis by inhibiting platelet CD226 function. Our results suggest SalB is a promising therapeutic approach to the treatment of sepsis.

The Establishment of a Novel Murine Model of Immune Thrombocytopenia in Pregnancy and the Impacts of Thrombopoietin Receptor Agonist on Platelet Production.

Objective Immune thrombocytopenia (ITP) is frequently associated with pregnancy. However, treatment options for ITP in pregnancy are limited, and there are few animal models available for the establishment of treatments. Here, we aimed to establish a novel murine pregnant model of ITP and to investigate the impacts of thrombopoietin receptor agonist (TPO-RA) on platelet production and reproductive outcomes. Methods Anti-glycoprotein Ib-alpha (GPIbα) antibody, which binds to megakaryocytes and platelets, was subcutaneously administered to pregnant mice in order to develop an ITP model (ITP group). TPO-RA was given in doses of 1 µg/kg, 10 µg/kg, and 100 µg/kg (low-dose group, mid-dose group, and high-dose group, respectively) for the treatment of ITP in pregnancy. Results The ITP group showed a significant reduction of platelet counts of less than 15% of healthy pregnant mice (control group) and also showed a significant increase in miscarriage rate (control group, 3.8%; ITP group, 44.4%; p < 0.05). Striking increases in platelet counts were observed in every TPO-RA group without any negative effects on fetal growth and placental pathology. No abnormality was noted in the external examination of fetal mice. Interestingly, a significant recovery of miscarriage rate was observed in the mid-dose group (23.5%) compared with the ITP group (p < 0.05). Conclusion A novel ITP model in pregnant mice was induced by injection of an anti-GPIbα antibody, and sufficient effects of TPO-RA on platelet production were observed in the present study. Furthermore, the positive impacts of TPO-RA on reproductive outcomes were revealed in the ITP model.

Association Between Cerebral Microbleeds and Neurological Outcomes in Patients Who Underwent Extracorporeal Membrane Oxygenation.

Cerebral microbleeds (CMBs) are common and varied in patients receiving extracorporeal membrane oxygenation (ECMO). Here, the authors describe CMB findings in patients receiving ECMO and their association with clinical factors. A total of 138 patients receiving ECMO were enrolled and categorized as venovenous and venoarterial. Blood coagulation profiles during ECMO support and Glasgow Coma Scale (GCS) scores within 7 days were recorded. Patients with CMBs exhibited prolonged activated clotting time (P<0.001), decreased fibrinogen levels (P<0.001), reduced platelet counts (P<0.001), and extended prothrombin time (P<0.001). A significant correlation (P<0.05) was observed between the presence of CMBs and most coagulation parameters among all patients. Patients with venoarterial ECMO had significantly higher activated partial thromboplastin time, activated clotting time, and prothrombin time compared with those with venovenous ECMO (all P<0.05). Patients with a less severe CMB burden exhibited higher GCS scores and better neurological injury outcomes at both 7 and 90 days. CMB burden in all patients with ECMO was significantly correlated (P<0.05) with most blood coagulation profiles and neurological injury. CMB burdens after ECMO are common, varied, and associated with a variety of clinical conditions. These findings may guide ECMO management.

Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a lack of a specific targeted treatment and a complex, partially unexplored pathophysiology. Common comorbidities associated with HFpEF are hypertension, atrial fibrillation, obesity and diabetes. These comorbidities, combined with advanced age, play a crucial role in the initiation and development of the disease through the promotion of systemic inflammation and consequent changes in cardiac phenotype. In this context, we suggest platelets as important players due to their emerging role in vascular inflammation. This review provides an overview of the role of platelets in HFpEF and its associated comorbidities, including hypertension, atrial fibrillation, obesity and diabetes mellitus, as well as the impact of age and sex on platelet function. These major HFpEF-associated comorbidities present alterations in platelet behaviour and in features linked to platelet size, content and reactivity. The resulting dysfunctional platelets can contribute to further increase inflammation, oxidative stress and endothelial dysfunction, suggesting an active role of these cells in the initiation and progression of HFpEF. Recent evidence shows that reduced platelet count and elevated mean platelet volume are associated with worsening heart failure in HFpEF patients. However, the specific mechanisms by which platelets contribute to HFpEF development and progression are still largely unexplored, with only a few studies investigating platelet function in HFpEF. We discuss the limited yet significant body of research investigating platelet function in HFpEF, emphasizing the need for more comprehensive studies. Additionally, we explore the potential mechanisms through which platelets may influence HFpEF, such as their interactions with the vascular endothelium and the secretion of bioactive molecules like cytokines, chemokines and RNA molecules. These interactions and secretions may play a role in modulating vascular inflammation and contributing to the pathophysiological landscape of HFpEF. The review underscores the necessity for future research to elucidate the precise contributions of platelets to HFpEF, aiming to potentially identify novel therapeutic targets and improve patient outcomes. The evidence presented herein supports the hypothesis that platelets are not merely passive bystanders but active participants in the pathophysiology of HFpEF and its comorbidities.

Compound K Promotes Megakaryocytic Differentiation by NLRP3 Inflammasome Activation.

Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer's disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production. Compound K (CK), a major bioactive metabolite of ginsenosides from Panax ginseng, has demonstrated anti-cancer and neuroprotective properties. In this study, we investigated the effects of CK on megakaryocytic differentiation and apoptosis in chronic myeloid leukemia (CML) cell lines K562 and Meg-01. CK treatment significantly upregulated the mRNA expression of key megakaryocytic differentiation markers, including CD61, CD41, and CD42a, and promoted the formation of large, multinucleated cells in K562 cells. Additionally, flow cytometry analysis revealed that CK at 5 µM induced apoptosis, a critical process in thrombocytopoiesis, in both K562 and Meg-01 cells. RT2 Profiler PCR array analysis further identified a marked increase in the expression of genes associated with the activation of the NLRP3 inflammasome in CK-treated K562 and Meg-01 cells. This study is the first to demonstrate that CK promotes megakaryocytic differentiation and apoptosis through the activation of the ERK/EGR1 and NLRP3 inflammasome pathways. These findings suggest that CK may enhance platelet production, indicating its potential as a therapeutic candidate for platelet-related disorders and other associated diseases.

A novel snake venom C-type lectin-like protein modulates blood coagulation by targeting von Willebrand factor and coagulation factor IX

Snake venom C-type lectin-like proteins (CLPs) belong to the nonenzymatic proteins. To date, no CLP with both platelet and coagulation factors activating activities has been reported. In this study, a novel CLP, termed protocetin, with molecular weight of 29.986 kDa, was purified from the Protobothrops mucrosquamatus venom (PMV). It consists of α- and β-chains, with 67% similarity in their N-terminal sequence. Protocetin activates glycoprotein Ib (GPIb) by binding to von Willebrand factor (vWF), inducing platelet aggregation. It also activates the intrinsic coagulation pathway by binding to coagulation factor IX. After injection of protocetin into mice at dose of 0.5 µg/g or 1.5 µg/g, it resulted in activation of platelets, a notable reduction in platelet count and prolonged tail bleeding time. Additionally, the plasma activated partial thromboplastin time (APTT) was significantly extended, and the fibrinogen concentration was markedly reduced. Thrombelastogram comfirmed the anticoagulation effect of protocetin. Notably, no microthrombosis was observed in tissues of lung, liver and kidney within 1 h after injection of protocetin into the mice at dose of 0.5 µg/g. This study revealed protocetin as a novel CLP from PMV that has dual functions in activating platelet and coagulation factor IX, thereby modulates coagulation in vivo. This work contributes to a better understanding of the structure and function of snake venom CLP.

Clinical Characteristics and Risk Factors of Sepsis in Patients with Liver Abscess.

Aims/Background Liver abscess (LA) is a serious medical condition that predisposes patients to sepsis. However, predicting sepsis in LA patients has rarely been explored. This study employed univariate and multivariate logistic regression analyses to identify independent risk factors for sepsis, which would provide guidance for clinical diagnosis and treatment. Methods A total of 122 patients with LA treated in Peking University People's Hospital from 1 January 2016 to 31 October 2022 were recruited. Among the cases, 35 patients had sepsis (sepsis group) while the remaining 87 did not have sepsis (non-sepsis group). Clinical data were collected for all enrolled cases. Univariate analysis was performed to identify potential predictors, which were tested in multivariable logistic analysis to pinpoint the independent risk factors for sepsis in LA patients; these findings were utilized to develop a prediction model. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the prediction model. Informed consent to participate was obtained from the patients or their relatives. Results The incidence of shivering in the sepsis group was significantly higher than that in the non-sepsis group (p < 0.05). Through the univariate analysis, it was found that the reduction in platelet count and prothrombin time activity and the elevation of glycosylated hemoglobin (HbAlc) and procalcitonin (PCT) were more significant in the sepsis group than in the non-sepsis group (p < 0.05). Multivariate logistic regression analysis revealed that PCT and HbAlc were independent risk predictors of sepsis in LA patients within the derivation cohort (p < 0.05). Conclusion Elevated levels of HbAlc and PCT were independent risk factors for sepsis associated with LA. Patients with LA exhibiting elevated PCT levels demonstrated a 21% increased susceptibility to sepsis, and those with elevated HbAlc levels showed a 38% heightened risk for sepsis.

Long-term safety and effectiveness of romiplostim for chronic idiopathic thrombocytopenic purpura in real-world settings.

Idiopathic thrombocytopenic purpura (ITP), an autoimmune hematologic disorder characterized by severe platelet count reduction, can be treated with romiplostim. However, post-marketing safety and effectiveness data for romiplostim in Japan are scarce. This prospective, observational, post-marketing Specified Use-Results Survey evaluated the real-world safety and effectiveness of romiplostim for 2years. All patients treated with romiplostim during the survey period were eligible. Of the 1622 patients in the safety analysis set, 94.08% (1526/1622) had chronic ITP. The mean single dose of romiplostim was stable after 12weeks and remained < 6μg/kg in approximately 70% of patients until 104weeks. Within 2years, 14.92% of patients discontinued romiplostim because of adverse events, while 6.47% discontinued because of suspected adverse drug reactions. In contrast, 14.00% of patients discontinued romiplostim because of symptom improvement. Before romiplostim initiation, platelet count was < 2.0 × 104/µL in 60.54% of patients, and the mean platelet count was 2.84 ± 5.76 × 104/µL. Platelet count was 9.19 ± 13.01 × 104/µL after 4weeks, and remained between 10.34 ± 10.72 and 12.38 ± 12.63 × 104/µL from 8 to 104weeks of treatment. No specific concerns were revealed regarding the safety and effectiveness of romiplostim in chronic ITP; the findings demonstrated a favorable risk-benefit balance for romiplostim in this population. Trial registration: UMIN000047864 ( www.umin.ac.jp/ctr ).

Quantitative and functional changes in platelets and fibrinogen following cardiopulmonary by-pass in children

IntroductionCardiopulmonary bypass (CPB) causes coagulopathy, increasing the risk of postoperative bleeding and mortality. The underlying causes of post-CPB coagulopathy and the factors associated with its occurrence are not yet fully understood. This study assesses platelet and fibrinogen concentration and function following CPB in children with congenital heart diseases (CHD).MethodsWe analyzed prospective data from 104 patients aged 0–16 years who underwent CPB surgery for CHD. Blood samples were collected before surgery and within 30 min of CPB completion. In addition to usual coagulation tests, functional analyses were performed using point of care systems with thromboelastometry and impedance aggregometry.ResultsPlatelet count, fibrinogen concentration, and platelet and fibrinogen activities significantly decreased after CPB. The duration of CPB was directly associated with a reduction in platelet count and fibrinogen level (r = −0.38, p &amp;lt; 0.001; r = −0.21, p = 0.03, respectively), but not with their measured activity. Postoperative percentages of baseline values for platelet count (58.36% [43.34–74.44] vs. 37.44% [29.81–54.17], p &amp;lt; 0.001) and fibrinogen concentration (73.68% [66.67–82.35] vs. 65.22% [57.89–70.83], p &amp;lt; 0.001) were significantly higher in patients who did not experience hypothermia during surgery. Age was inversely associated with the decrease in platelet count (r = 0.63, p &amp;lt; 0.001), TRAPTEM AUC (r = 0.43, p &amp;lt; 0.001), fibrinogen concentration (r = 0.44, p &amp;lt; 0.001) and FIBTEM MCF (r = 0.57, p &amp;lt; 0.001).ConclusionPost-CPB coagulopathy is multifactorial and not solely attributed to hemodilution. It also involves functional changes in coagulation cascade components, which can be demonstrated by thromboelastometry and impedance aggregometry. Young children, patients requiring prolonged CPB surgery, or those experiencing hypothermia are particularly affected.

Development of a large diameter invitro flow loop thrombogenicity test system.

To accommodate a wider range of medical device sizes, a larger invitro flow loop thrombogenicity test system using 9.5 -mm inner diameter (ID) tubing was developed and evaluated based on our previously established 6.4 -mm ID tubing system. Four cardiopulmonary bypass roller pumps were used concurrently to drive four flow loops during testing. To ensure that each pump produced a consistent thrombogenic response for the same material under the same test conditions, a novel dynamic roller occlusion setting method was applied. Five materials with varying thrombogenic potentials were tested: polytetrafluoroethylene (PTFE), silicone, 3D-printed nylon, latex, and nitrile rubber (BUNA). Day-old bovine blood was heparinized to a donor-specific concentration and recirculated through the flow loops containing test materials at 20 rpm for 1 h at room temperature. Material thrombogenicity was characterized by measuring the thrombus surface coverage, thrombus weight, and platelet (PLT) count reduction. The larger tubing system can differentiate thrombogenic materials (latex, BUNA) from the thromboresistant PTFE material. Additionally, silicone and the 3D-printed nylon exhibited an intermediate thrombogenic response with significantly less thrombus surface coverage and PLT count reduction than latex and BUNA but more thrombus surface coverage than PTFE (p < 0.05). The 9.5 -mm ID test system can effectively differentiate materials of varying thrombogenic potentials when appropriate pump occlusion settings and donor-specific anticoagulation are used. This system is being assessed in an interlaboratory study to develop standardized best practices for performing invitro dynamic thrombogenicity testing of medical devices and materials.

The small noncoding RNA Vaultrc5 is dispensable to mouse development.

Vault RNAs (vtRNAs) are evolutionarily conserved small noncoding RNAs transcribed by RNA polymerase III. Vault RNAs were initially described as components of the vault particle, but have since been assigned multiple vault-independent functions, including regulation of PKR activity, apoptosis, autophagy, lysosome biogenesis, and viral particle trafficking. The full-length transcript has also been described as a noncanonical source of miRNAs, which are processed in a DICER-dependent manner. As central molecules in vault-dependent and independent processes, vtRNAs have been attributed numerous biological roles, including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAs in vivo, we generated a mouse line with a conditional Vaultrc5 loss-of-function allele. Because Vaultrc5 is the sole murine vtRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null for Vaultrc5 are viable and histologically normal but have a slight reduction in platelet counts, pointing to a potential role for vtRNAs in hematopoiesis. This work paves the way for further in vivo characterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specific Vaultrc5 deletion and of the physiological requirements for an intact Vaultrc5 during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.

Biomedical application of TiO2NPs can cause arterial thrombotic risks through triggering procoagulant activity, activation and aggregation of platelets.

Titanium dioxide nanoparticles (TiO2NPs) are widely used in medical application. However, the relevant health risk has not been completely assessed, the potential of inducing arterial thrombosis (AT) in particular. Alterations in platelet function and susceptibility to arterial thrombosis induced by TiO2NPs were examined using peripheral blood samples from healthy adult males and an in vivo mouse model, respectively. Here, using human platelets (hPLTs) freshly isolated from health volunteers, we demonstrated TiO2NP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiO2NP treatment increased the levels of glycoprotein IIb/IIIa and P-selectin leading to aggregation and activation of hPLTs, which were exacerbated by providing physiology-mimicking conditions, including introduction of thrombin, collagen, and high shear stress. Interestingly, intracellular calcium levels in hPLTs were increased upon TiO2NP treatment, which were crucial in TiO2NP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiO2NP treatment a reduction in mouse platelet (mPLT) counts, disrupted blood flow, and exacerbated carotid arterial thrombosis with enhanced deposition of mPLT. Together, our study provides evidence for an ignored health risk caused by TiO2NPs, specifically TiO2NP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.

Navigating Primary Immune Thrombocytopenia During Pregnancy With Management Strategies and Considerations: A Comprehensive Review.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduction in platelet count due to autoantibody-mediated platelet destruction. ITP presents unique challenges during pregnancy, affecting both maternal and fetal health. This comprehensive review explores the pathophysiology, diagnosis, and management strategies of ITP in pregnant women, emphasizing the importance of individualized care. The incidence of ITP in pregnancy is significant, with potential complications including maternal hemorrhage and neonatal thrombocytopenia. Effective management is crucial to minimize these risks and ensure optimal outcomes. First-line treatments typically include corticosteroids and intravenous immunoglobulin (IVIG), with second-line options such as immunosuppressive agents and thrombopoietin receptor agonists. This review highlights the significance of multidisciplinary care and the need for careful monitoring and adjustment of treatment plans based on the severity of thrombocytopenia and the pregnancy stage. This review aims to enhance clinical decision-making and improve maternal and fetal outcomes in pregnancies complicated by ITP by providing a detailed analysis of current practices and emerging therapies.

Phytochemical analysis and effect of short-term administration of aqueous seed extract of Aframomum melegueta on haematologic indices of female albino rats

Background and aims: Aframomum melegueta (Alligator pepper) is a dietary spice widely used for entertainment, religious rites, food flavor enhancer, possessing erythropoietic potentials, and many other medicinal uses. Women are included in eating this widely used spice. This experiment determined the health risk or benefit of short-term administration of aqueous seed extract of A. melegueta on haematologic indices of female albino rats. Methods: Thirty adult female albino rats weighing 160 to 200 g were used for the study. Male rats were introduced into the female rat cages of groups II-V within 12h at the expected estrous phase for mating and withdrawn afterward. Groups I, II, and III were orally administered distilled water only, while groups IV and V received oral doses of 5 µg/kg b.w. Cabergoline and 3000 mg/kg b.w. aqueous seed extract of A. melegueta respectively 24 hours postpartum and once daily by oral gavage for three days. Results: Fourier-transform infrared spectroscopy (FTIR) identified twelve functional groups in the seed extracts, namely –OH, -NH2 , CH, -NH3 +, -CH3 , -OH, -N=C=O, -C≡N, -C=C=C, -NH, -CH3 and -1,3,5-trisubstituted benzenes, while gas chromatography with flame ionization detector (GCFID) determined 15 bioactive components namely kaempferol, naringenin, Sapogernin, flavanones, anthocyanin, flavan-3-ol, cyanogenic glycoside, ribalinidine, rutin, catechin, resveratrol, spartein, epicatechin, steroid and phytate. Non-significant alterations in hemoglobin, packed cell volume (PCV), and red blood cell count were observed. There was a significant (P&lt;0.05) decrease in WBC during pregnancy, but it was improved postpartum. However, platelet count was significantly (P&lt;0.05) reduced after extract administration. Conclusion: The results indicate no adverse anemic condition elicited during pregnancy and delivery on haematologic parameters, namely red blood cells, hemoglobin, and PCV, with a significant decrease in WBC during pregnancy as well as reduction in platelet counts (thrombocytopenia) of extract treated animals post-partum likely due to the flavonoid, resveratrol as well as rutin and (–)-epicatechin components of A. melegueta and thus may increase the risk of bleeding disorders but reflects a positive anti-atherogenic and cardioprotective effect.

RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means

AbstractRed blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5′-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50 × 103/μL) but not severe (10 × 103/μL) thrombocytopenia in vitro. Reduction in hematocrit by 45% increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote shear-induced platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood and vessel wall interface and in the fluidic phase of circulation.

Mustard oil consumption and Harris platelet syndrome: unveiling a dietary link to thrombocytopenia in the Indian subcontinent

Background and objectives: Asymptomatic thrombocytopenia, characterized by a reduced platelet count without bleeding symptoms, is notably prevalent in certain regions of India and Bangladesh, presenting a diagnostic challenge. A significant portion of healthy blood donors from Bangladesh and various parts of India, particularly West Bengal, exhibit this condition, termed Harris platelet syndrome (HPS). This review explores the potential correlation between mustard oil consumption, a common dietary staple in these regions, and the incidence of HPS. Methods: A comprehensive narrative review was conducted using systematic search strategies across databases such as Google Scholar, MEDLINE, PubMed, and Scopus. Keywords included "Harris platelet syndrome," "mustard oil consumption," "thrombocytopenia," and "erucic acid." Studies were selected based on relevance and quality, focusing on the epidemiology of HPS, dietary habits, and the thrombocytopenic effects of erucic acid. Results: HPS shows a significant geographical prevalence in the Indian subcontinent, notably in regions like West Bengal, Kashmir, and Assam. The review identifies a higher prevalence of thrombocytopenia in areas with predominant mustard oil usage. Studies highlight the association between dietary erucic acid from mustard oil and thrombocytopenia, with notable effects observed in patients treated with Lorenzo’s Oil, which contains erucic acid. Conclusions: The review highlights a significant association between mustard oil consumption and asymptomatic thrombocytopenia in the Indian subcontinent. The similarity in hematological profiles between HPS and erucic acid-induced thrombocytopenia underscores the need for further research. This includes measuring erucic acid levels in patients, conducting controlled dietary interventions, and genetic analyses to differentiate between genetic and environmental factors. July 2024; Vol. 18(2):009. DOI:https://doi.org/10.55010/imcjms.18.021 *Correspondence: Wasim Md MohosinUl Haque, Department of Nephrology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), 122 Kazi Nazrul Islam Avenue, Dhaka-1000, Bangladesh. Email: wmmhaque@live.com