Significant Decrease In Platelet Count Research Articles

A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy.

Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort. We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children's hospital from 2017-2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS). Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p=0.034). Of those patients where the first filter change was unintended (n=33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p=0.002) or heparin (18) (p=0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p=0.003) or heparin (0.75) (p=0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT. Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.

Risk factors for bloodstream infection among patients admitted to an intensive care unit of a tertiary hospital of Shanghai, China

Blood flow infections (BSIs) is common occurrences in intensive care units (ICUs) and are associated with poor prognosis. The study aims to identify risk factors and assess mortality among BSI patients admitted to the ICU at Shanghai Ruijin hospital north from January 2022 to June 2023. Additionally, it seeks to present the latest microbiological isolates and their antimicrobial susceptibility. Independent risk factors for BSI and mortality were determined using the multivariable logistic regression model. The study found that the latest incidence rate of BSI was 10.11%, the mortality rate was 35.21% and the mean age of patients with BSI was 74 years old. Klebsiella pneumoniae was the predominant bacterial isolate. Logistic multiple regression revealed that tracheotomy, tigecycline, gastrointestinal bleeding, shock, length of hospital stay, age and laboratory indicators (such as procalcitonine and hemoglobin) were independent risk factors for BSI. Given the elevated risk associated with use of tracheotomy and tigecycline, it underscores the importance of the importance of cautious application of tracheostomy and empirical antibiotic management strategies. Meanwhile, the independent risk factors of mortality included cardiovascular disease, length of hospital stay, mean platelet volume (MPV), uric acid levels and ventilator. BSI patients exhibited a significant decrease in platelet count, and MPV emerged as an independent factor of mortality among them. Therefore, continuous monitoring of platelet-related parameters may aid in promptly identifying high-risk patients and assessing prognosis. Moreover, monitoring changes in uric acid levels may serve as an additional tool for prognostic evaluation in BSI patients.

A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates.

Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage. Six PCs prepared by the platelet-rich plasma method were assessed for free mtDNA copy number using quantitative real-time PCR and CD62P (P-selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined. Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5-7 and 0-3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, -0.72, -0.49, 0.81 and 0.77, respectively. The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.

An Assessment of the Viability of Haematological and Haemostatic Parameters of Blood under certain Storage Conditions at the Rivers State University Teaching Hospital Blood Bank in Port Harcourt, Nigeria

Introduction: Despite significant advances in transfusion medicine, concerns about the inherent risks of blood transfusion persist, even under optimal temperature and duration of storage. This makes the evaluation of blood viability a global task (1). Maintenance of adequate temperature is considered a key factor in the viability and quality of stored blood in healthcare institutions. Evaluating the haematological and haemostatic functionality of blood elements at different storage temperature and duration is therefore imperative for improving patient care and resource utilization in Rivers State University Teaching Hospital (RSUTH) blood bank in Port Harcourt.
 Methods: In this cohort study design, a total of sixteen (16) male and female blood donors in equal proportion of sex and ABO blood groups were randomly selected from the Port Harcourt blood donors' population and recruited as study subjects for this research. A well-structured questionnaire and the immunoassays were used to assess the donors' health and serological status respectively. Also the sample obtained were analayzed by automation and data statistically analyzed using ANOVA.
 Results: The results of this study shows a statistically significant decrease in white blood cell count from 4.93×109/L ± 0.33 to 2.79×109/L ± 1.68 (p=0.00) and platelet count from 227.38×109/L ± 32.17 to 153.75×109/L ± 58.39 (p=0.00) at day 7. Also, a significant decrease in platelet count from 227.38×109/L ± 32.17 to 141.50±60.92 at day 14. A significant decrease in Fibrinogen from 340.75mg/L±18.69 to 281.2575 mg/L ±46.41 at day 1 and day 14 respectively, and rise in PT and aPTT from 17.02s ±1.28 to 24.31s ±6.67 and 41.25s±3.23 to 46.63s±6.28 at day 14th to day 21 respectively (p=0.00).
 Conclusion and Implications for Translation: Pooled plasma at 4-60C contain clinically significant amount of coagulation factors up to day 21 in storage. The WBC and platelet is lost within seven day of storage at 4-60C. Lower temperatures, especially freezing at -60°C accelerate the loss of haematological viability of blood especially the depletion of white blood cells and platelets (p=0.00). Antihaemophilic factor and fibrinogen is maintained in FFP at 180 day in storage at -600C.

Risk Factors for Thrombocytopenia Induced by Capecitabine Plus Oxaliplatin Therapy in Patients With Colorectal Cancer.

Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients. Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores. Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×103/μl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients. Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC.

Familial Thrombocytopenia-Associated Germline ETV6 P214L Mutation Results in XPO1-Mediated Nuclear Export

In recent years, a number of heterozygous germline mutations in ETV6 have been associated with familial thrombocytopenia and predisposition to hematologic malignancies. While most of these missense mutations occur in the DNA-binding-domain of ETV6, the recurrent P214L mutation is unique in that it occurs in the central disordered region of the protein. The ETV6 P214L mutation has previously been shown to disrupt the nuclear localization of ETV6 and the ability of ETV6 to act as a transcriptional repressor. Unexpectedly, we have found that the P214L missense mutation creates a recognition motif for the nuclear export protein XPO1. We have demonstrated in cellular and protein reconstitution assays that XPO1 directly engages the P214L but not the wild-type ETV6 construct. Consistent with this mechanism, we are able to fully rescue the nuclear localization of ETV6 P214L in mammalian cells with small molecule XPO1 inhibitors. We have also found that once localized to the nucleus, the P214L mutant construct exhibits functional consequences indistinguishable from wild-type ETV6 in Ba/F3 transformation assays. When looking at the evolutionary conservation of the ETV6 amino acid sequence involved in the XPO1 recognition motif, we observed that the synonymous P216L mutation in the mouse ETV6 ortholog does not create a nuclear export signal. In order to study XPO1-mediated export of ETV6 P214L and its impact on hematopoiesis, we have generated a mouse model in which two point mutations (P216L and S211I) have been introduced into a single endogenous ETV6 allele, which precisely matches the sequence of this region in human P214L carriers. Using CRISPR-Cas9, we generated 3 transgenic mouse lines: Etv6 P216L, Etv6 S211I, and Etv6 S211IP216L. Immunofluorescence of fixed bone marrow shows that ETV6 is only mislocalized in megakaryocytes from ETV6 S211I P216L mice. Complete blood counts revealed a significant decrease in platelet counts in ETV6 S211I P216L heterozygotes (485 x 10 3/µL) compared to ETV6 S211I heterozygotes (1140 x 10 3/µL, p<0.0001), ETV6 P216L heterozygotes (1065 x 10 3/µL, p<0.0006), and wild-type littermates (1254 x 10 3/µL, p<0.0001). Flow cytometry phenotyping of bone marrow from the three transgenic lines and wild-type littermates shows a significant decrease in the absolute numbers of hematopoietic stem cells (HSCs) and megakaryocyte precursors (MkPs) in ETV6 S211I P216L mice. In summary, we have determined that XPO1-mediated nuclear export is the mechanistic basis for ETV6 P214L mislocalization. We developed a mouse model that recapitulates this export signal in the endogenous ETV6 allele and found that this model demonstrates a thrombocytopenic phenotype as seen in human patients. Reductions in HSCs and MkPs suggest both a decreased fitness of HSCs, as well as dysregulated megakaryopoiesis in this model.

Cytotoxic Stress Transiently Increases the Contribution of Platelet-Biased Hematopoietic Stem Cells to Platelet Production

While hematopoietic stem cells (HSCs) and megakaryocyte (Mk)/platelet lineages exhibit substantial phenotypic and transcriptional overlap, direct Mk production from HSCs is still under investigation. In particular, the hypothesis that specific HSC clones might facilitate rapid megakaryopoiesis and their physiological roles are yet to be elucidated. Previous clonal studies using either single cell transplantations (Yamamoto, Cell 2013; Carrelha, Nature 2018) or barcoding assays (Pei, Cell Stem Cell 2020; Rodriguez-Fraticelli, Nature 2020) have identified subsets of HSCs with Mk-biased output, designated as Mk-biased HSCs or platelet-biased HSCs (P-HSCs), in contrast to multi-lineage HSCs (MUL-HSCs) with balanced output. Moreover, P-HSCs exhibit up-regulated platelet-lineage gene expression and chromatin accessibility, and they generate platelets at a faster rate than MUL-HSCs, pointing towards a direct platelet formation pathway (Rodriguez-Fraticelli, Nature 2020; Meng, 2023 Nat Cell Biol). Notably, under inflammatory stress, direct Mk progenitor (MkP) production and Mk formation from HSCs have been shown to accelerate (Haas, Cell Stem Cell, 2015; Morcos, Nat Commun 2022), suggesting that P-HSCs could drive rapid platelet production during hematopoietic emergencies. To probe this premise, we re-analysed previously published RNA-seq data on HSC subtypes and discovered that the gene Vldlr is markedly expressed in MUL-HSCs relative to P-HSCs. We subsequently created a Vldlr-Cre transgenic mouse model for lineage tracing of platelet production from MUL-HSCs and P-HSCs. Flow cytometry analysis across the HSC-MPP2-preMegE-MkP-platelet developmental sequence revealed a notable increase in the percentages of Tomato- HSCs and platelets, in comparison to MPP2-preMegE-MkP, suggesting that Tomato- HSCs significantly bypass the conventional MPP2-preMegE-MkP pathway in platelet formation. Transplantation of labelled and non-labelled HSCs confirmed that Vldlr-Cre predominantly labelled MUL-HSCs, whilst Tomato- HSCs were rich in P-HSCs and largely generated Tomato- platelets, implying that platelets derived from the direct P-HSC pathway can be identified as Tomato- through Vldlr-Cre lineage tracing. We exploited this model to examine the distinct roles of classical and direct pathways during emergency thrombopoiesis, induced by either antibody-mediated platelet depletion mimicking immune thrombocytopenia or a cytotoxic drug 5-fluorouracil (5-FU) that causes severe hematopoietic disruption. Both interventions precipitated a significant decrease in platelet counts, as previously demonstrated. However, the proportion of Tomato- platelets did not change during platelet recovery following antibody intervention, while the percentage of Tomato- platelets rose up to four-fold in early recovery stage following 5-FU treatment, suggesting an acceleration of the direct pathway under this stressor. The percentage of Tomato- platelets returned to baseline following platelet count normalization. Further analysis of bone marrow progenitors post-intervention revealed that the proportion of Tomato- MkP was maintained during recovery from antibody treatment but significantly expanded after 5-FU treatment. Nevertheless, the fraction of Tomato- HSCs remained unaltered under both interventions, indicating that neither reagent selectively activates P-HSCs or MUL-HSCs. We hypothesize that the 5-FU treatment, by significantly eliminating bone marrow progenitors, permits P-HSCs to rapidly replenish the MkP pool and platelets due to their faster platelet formation kinetics, whereas progenitors are not affected by the antibody, leaving both pathways to contribute to platelet recovery. In summary, our findings suggest that P-HSCs provide a fast-track for platelet formation, enabling them to contribute to platelet recovery more rapidly following progenitor depletion induced by cytotoxic stress.

Platelet dropping, bleeding and new treatment requirements in ITP patients after inactivated COVID-19 vaccination

Significant decreases in platelet counts and ITP relapses have been documented in ITP patients receiving COVID-19 mRNA vaccines; however, the effect of the inactivated COVID-19 vaccine on ITP patients remains unclear. The present study aimed to investigate the impact of inactivated COVID-19 vaccines on ITP patients, with a focus on platelet dropping events, bleeding events/scores, and the requirement of a new round of treatment. A total of 118 ITP patients, with 97 chronic ITP and 21 persistent ITP, who received inactivated COVID-19 immunization were investigated retrospectively. Following vaccination (within 1 month), ITP patients reported platelet dropping (31.36 %), new bleeding events (22.88 %), increases in bleeding scores (23.73 %), and new treatment requirements (22.03 %). Among them, persistent ITP patients with disease duration of 3–12 months had higher ratios of the above adverse events (71.43 %, 57.14 %, 61.90 % and 71.43 %, respectively) than chronic ITP patients with duration > 1 year (22.68 %, 15.46 %, 15.46 % and 11.34 %, respectively); patients’ disease duration was negatively correlated with platelet dropping events and new treatment requirements. Furthermore, logistic regression analysis also supported the above findings, revealing that persistent ITP patients had 9.40–9.70, 7.24–10.08, and 27.17–28.51 times incidence of having platelet dropping events, new bleeding events, and new treatment requirements after vaccination, respectively, when compared to chronic ITP patients. In conclusion, the present study demonstrates that after receiving inactivated COVID-19 vaccines, ITP patients may experience platelet dropping, which may lead to new bleeding events and the requirement of a new round of treatment for ITP recurrence. As a result, platelet level monitoring is crucial for ITP patients during the vaccination, especially those with persistent ITP.

Evaluation of the Role of Serum Vimentin as a Diagnostic Biomarker for Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is a major unresolved medical issue, which is considered as the seventh most common cancer globally and the fourth leading cause of cancer deaths, with approximately 700,000 deaths per year. Aim of the Work The aim of this study; to evaluate the role of serum vimentin as a diagnostic biomarker in patients with HCC. Patients and Methods This case control study enrolled 60 patients; divided into two groups: Group (I): included 20 patients with liver cirrhosis without HCC as a control group and Group (II): 20 patients divided into 2 subgroups: (IIa): includes 20 patients with HCC and serum AFP is high and (IIb): includes 20 patients with HCC and serum AFP is normal. Results The present study found statistical significant decrease in Hb level in group IIb compared to group I, there was high statistical significant decrease in platelet count in patients of group IIa and IIb compared to control group. a statistical significant elevation of total bilirubin and INR with decrease of albumin in group II compared to control group.There was high statistical significant elevation in AFP in group IIa and IIb compared to control group and in group IIa compared to group IIb, a high statistical significant elevation in Vimentin level in group IIa and IIb compared to control group while there was no statistical significant difference between group IIa and group IIb. Conclusion Vimentin can be considered as an important independent and discriminative serological biomarker for detecting early stage HCC in patients with normal serum AFP.

Secondary thrombocythemia with ST-segment elevation myocardial infarction as the first manifestation: a case report.

An 80-year-old woman was admitted with cardiogenic shock due to post-activity chest pain. She was started on aspirin and clopidogrel antiplatelet therapy, then replaced aspirin with indolibuprofen, which has relatively few side effects. There was no significant decrease in platelet counts during treatment. Secondary thrombocythemia, characterized by nonspecific symptoms, is difficult to diagnose. Secondary thrombocytosis with acute myocardial infarction as the first symptom is uncommon, but is very urgent and associated with a poor prognosis. What's more, cause-specific treatment counts for secondary thrombocythemia. Therefore it is important to search for the causal factor of secondary thrombocytosis. Secondary thrombocytosis caused by cephalosporins is rare. There is a need to arouse the attention of clinicians to the ST caused by cephalosporins and to provide a guide of treatment to these patients. After a thorough analysis of the pertinent literature, we discovered that several retrospective studies demonstrated the effectiveness of cytoreductive therapy in significantly reducing platelet counts. Based on this finding, we prescribed hydroxyurea to our patient, which led to a gradual decrease in platelet count and ultimately resulted in a return to normal levels.

Toxicological Effect of Green Tea (Camelia sinensis) on Haematological Parameters in Wistar Rats

Introduction: Green tea, derived from the leaves of Camellia sinensis, has gained significant attention due to its potential health benefits. It contains various bioactive compounds, such as polyphenols, flavonoids, and catechins, which have antioxidant, anti-inflammatory, and anticancer properties. Despite its widespread consumption and positive reputation, limited information is available regarding the potential toxicological effects of green tea. In this study, the toxicological impact of green tea extract on haematological parameters was investigated using Wistar rats as an animal model.
 Method: Forty-eight adult male rats were randomly divided into four groups (n=12 per group). The control group received a vehicle solution, while the treatment groups were orally administered different doses of green tea extract (low dose: 100 mg/kg, moderate dose: 200 mg/kg, high dose: 400 mg/kg) once daily for 28 consecutive days. Haematological analysis was performed at baseline (day 0) and on days 7, 14, 21, and 28 of the study. Blood samples were collected from the retro-orbital plexus under light isoflurane anaesthesia, and various haematological parameters were assessed using automated Hematology analyzers.
 Results: The results of the haematological analysis showed that the administration of green tea extract did not significantly affect haemoglobin levels, packed cell volume, red blood cell count, eosinophil count, lymphocyte count, and neutrophil count compared to the control group throughout the study period. However, the white blood cell (WBC) count and its differential count exhibited some variations among the treatment groups. The low and moderate doses of green tea extract resulted in a slight increase in the WBC count compared to the control group, although the difference was not statistically significant. On the other hand, the high dose of green tea extract led to a slight decrease in the WBC count compared to the control group. Regarding platelet count, the low and moderate doses of green tea extract resulted in a significant increase compared to the control group. In contrast, the high dose of green tea extract caused a significant decrease in platelet count.
 Conclusions: Based on the findings of this study, it can be concluded that the administration of green tea extract did not have significant adverse effects on the assessed haematological parameters in Wistar rats, except for some minor variations in the WBC count and platelet count at higher doses. These results suggest that green tea consumption may not cause significant haematological toxicity in rats. However, further studies are warranted to evaluate the long-term effects and safety of green tea consumption in humans.

Clinical features and treatment effect of HIV-associated immune thrombocytopenia—single center Ten-Years data summary

Thrombocytopenia represents one of the most prevalent hematologic complications observed in patients infected with the human immunodeficiency virus (HIV). In this study, we sought to analyze the clinical characteristics and treatment outcomes of patients with coexisting HIV and thrombocytopenia. Specifically, we retrospectively examined the medical records of 45 patients diagnosed with HIV/AIDS and thrombocytopenia at the Yunnan Infectious Diseases Specialist Hospital between January 2010 and December 2020, all of whom received highly active antiretroviral therapy (HAART) with/without glucocorticoids. The median follow-up period was 79 days, ranging between 14 and 368 days, the total platelet count was higher after receiving treatment than before (Z = −5.662, P < .001). Among the cohort, 27 patients (60.0%) responded to treatment, with 12 patients (44.44%) experiencing relapse during the follow-up period. The response rate (80.00%) of newly diagnosed ITP were significantly higher than of persistent ITP (28.57%) and chronic ITP (38.46%) ( \\x 2 = 9.560, P = .008) and the relapse rate of the newly diagnosed ITP (30.00%) was significantly lower than the persistent ITP and chronic ITP (100.00%, 80.00%) ( \\x 2 = 6.750, P = .034). Notably, we found that the number of CD4+ T cells, duration of HIV infection, selection of HAART and type of glucocorticoids administered displayed no statistically significant effect on platelet count, treatment response, or relapse rate. However, we observed a significant decrease in platelet count in hepatitis C virus-positive individuals coinfected with HIV compared to those with HIV alone (Z = −2.855, P = .003). Our findings suggest that patients diagnosed with HIV and thrombocytopenia exhibit a low response rate to treatment and have an increased likelihood of relapse.

The Cause and Effect of Immune Thrombocytopenia (ITP) on Individuals

Immune thrombocytopenia is a rare blood disorder in which an individual has a decreased level of platelets due to the immune system destroying the blood-clotting platelets. Platelets function in the body to help clot the blood, but in people with ITP, the body produces antibodies that disrupt and attack the creation, leading to lower levels. The average platelet count ranges from 150,000-400,000 per microliter of blood, but in individuals with ITP, the platelet count is less than 100,000 [1]. This significant decrease in platelet count can cause easy bruising, bleeding, and fatigue, among various symptoms that can disrupt an individual's life. The current diagnosis of ITP is centered on presumptions and excludes other causes of thrombocytopenia due to a variety of acquired and inherited that can present similar symptoms. In some cases, ITP may not cause symptoms, and for most children and adults, ITP is not severe. Acute ITP will typically go away on its own without the need for extensive therapy. In individuals with more advanced cases, or chronic ITP, one may receive a wide range of treatments. The stage of the disorder, current medical history, and genetics all have significant roles in determining the treatment an individual will receive.

Decreased Platelet Reactivity and Function in a Mouse Model of Human Pancreatic Cancer.

Cancer patients have increased thrombosis and bleeding compared with the general population. Cancer is associated with activation of both platelets and coagulation. Mouse models have been used to study the dysregulation of platelets and coagulation in cancer. We established a mouse model of pancreatic cancer in which tissue factor-expressing human pancreatic tumors (BxPC-3) are grown in nude mice. Tumor-bearing mice have an activated coagulation system and increased venous thrombosis compared to control mice. We also showed that tumor-derived, tissue factor-positive extracellular vesicles activated platelets ex vivo and in vivo. In this study, we determined the effect of tumors on a platelet-dependent arterial thrombosis model. Unexpectedly, we observed significantly reduced carotid artery thrombosis in tumor-bearing mice compared to controls. In addition, we observed significantly increased tail bleeding in tumor-bearing mice compared to controls. These results suggested that the presence of the tumor affected platelets. Indeed, tumor-bearing mice exhibited a significant decrease in platelet count and an increase in mean platelet volume and percentage of reticulated platelets, findings that are consistent with increased platelet turnover. Levels of the platelet activation marker platelet factor 4 were also increased in tumor-bearing mice. We also observed decreased platelet receptor expression in tumor-bearing mice and reduced levels of active αIIb/β3 integrin in response to PAR4 agonist peptide and convulxin in platelets from tumor-bearing mice compared with platelets from control mice. In summary, our study suggests that in tumor-bearing mice there is chronic platelet activation, leading to thrombocytopenia, decreased receptor expression, and impaired platelet adhesive function.

Epidemiological, clinical and hematobiochemical studies on hemotoxic snakebite in bovines

Snakebite is a conflict between venomous snakes and humans as well as livestock and considered as neglected tropical disease. The present study aimed to investigate the hospital prevalence, clinical and hemato-biochemical aspects of hemotoxic snakebite in bovines. The overall hospital prevalence of hemotoxic snakebite in bovines was found to be 0.93%. Highest prevalence of hemotoxic snakebite in bovines was observed in August month during monsoon season in female bovines with higher cases in buffaloes. The highest occurrence was reported in native Marathwadi buffalo, non-descript and Deoni cattle of &gt; 4 years and 1-4 years age group in forelimbs and hindlimbs during morning and evening hours. Ascending swelling over limbs extending upward and lameness in case of bite on limbs while asymmetrical swelling in case of bite over face, occasional signs of bleeding like melena, hematuria, epistaxis and bleeding from the site of bite were the prominent clinical signs observed in hemotoxic snakebite affected bovines. Highly significant increase in heart rate and respiration rate, while decrease in rumen motility was observed in snakebite affected bovines. Hemato-biochemial analysis showed highly significant increase in leukocyte count, erythrocyte count and PCV, significant increase in granulocyte and monocyte count, highly significant decrease in platelet count while increase in capillary blood clotting time, bilirubin, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and creatine kinase levels compared to healthy bovines.

Effects of COVID-19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia.

Coronavirus disease 2019 (COVID-19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C-AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID-19 vaccination on platelet counts and bleeding in a single-center series of 2 C-AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS-CoV2 vaccination was safe in C-AYA with ITP in this small cohort.

A PROSPECTIVE STUDY ON EFFECT OF FLUOXETINE ON PRIMARY HEMOSTASIS OF PATIENTS HAVING MAJOR DEPRESSIVE DISORDER

Objectives: The objectives of the study were to study the effect of fluoxetine on bleeding time, clotting time and platelet count of depressed patients. Methods: Patients diagnosed with major depressive disorder were included in the study to fulfill a sample size of 60. Before starting the treatment with fluoxetine, laboratory tests were done which included bleeding time, clotting time, and platelet count. Patients were requested to return for follow-up after 4 weeks of treatment and the laboratory tests were repeated. All the study end point analysis was analyzed based on per-protocol population. Continuous variables were expressed as mean and standard deviations, paired t-test was used for within group comparison and unpaired t-test was used for between group comparisons. p&lt;0.05 was considered to be significant. For categorical variable, frequency and percentage were calculated. For continuous variable, that is, bleeding time, clotting time, and platelet count, mean and standard deviation were calculated. Results: At the end of 4 weeks, it was observed that there was a significant increase in bleeding time from 1.35±0.08 min to 1.46±0.08 min**. Similarly, there was a significant increase in clotting time from 3.30±0.15 min to 3.38±0.15 min**. It was also observed that there was a significant decrease in platelet count from 3.07±0.67 lakh cells/cu mm to 2.86±0.63 lakh cells/cu mm**. Conclusion: Fluoxetine has shown to increase bleeding time, clotting time, and decrease platelet count. Hence, fluoxetine induced risk of bleeding and its cardio protective action has to be considered while individualizing therapy in management of depression.

Poly(2-methoxyethyl acrylate) (PMEA) improves the thromboresistance of FRED flow diverters: a thrombogenic evaluation of flow diverters with human blood under flow conditions.

Surface modification of flow-diverting stents has been explored to reduce thrombus-related complications that may arise under clinical use. This study investigated the thromboresistant properties of the flow redirection endoluminal device (FRED) X, a flow diverter treated with a copolymer of poly(2-methoxyethyl acrylate) (PMEA; X Technology). The performance of FRED, FRED X, and Pipeline Flex with Shield Technology (sPED) was evaluated in an in vitro blood loop model. Blood activation level was assessed by the concentration of thrombin-antithrombin complex (TAT), β-thromboglobulin (β-TG), and platelet count, and qualitatively by scanning electron microscopy (SEM). Cellular adhesion characteristics were measured using human aortic endothelial cells that were seeded on flat sheets mimicking the surface of FRED, FRED X, and sPED, and evaluated with fluorescence microscopy. Statistical comparisons were conducted using one-way analysis of variance (ANOVA) with Tukey post hoc tests. FRED X, sPED, and control blood loops showed significantly reduced blood activation levels (TAT and β-TG) compared with FRED (p<0.01). Consequently, FRED showed a significant decrease in platelet count compared with FRED X, sPED, and control loops (p<0.01). SEM imaging showed the lowest accumulation of blood cell-like deposits on FRED X compared with sPED and FRED, while FRED had the highest accumulation. Endothelial cells adhered and were widely spread on X Technology-treated sheets, while minimal cell adhesion was observed on phosphorylcholine-treated sheets. The X Technology surface modification of FRED X demonstrated superior thromboresistant properties over untreated FRED while maintaining comparable cellular adhesion. Taken together, these properties may help mitigate material-related thromboembolic complications.

Preeclampsia has an association with both platelet count and mean platelet volume: A systematic review and meta-analysis.

BackgroundPreeclampsia (PE) is a pregnancy-specific disorder characterized by endothelial dysfunction, and activation of the coagulation system. Alteration of PLT parameters is the common hematological abnormality observed in women with PE. The main aim of this study was to systematically review previous studies from around the world to generate evidence about the relationship between platelet count (PC) and PE, as well as mean platelet volume (MPV) and PE, by calculating the pooled weighted mean difference (WMD) of PC and MPV between PE and normotensive (NT) groups.MethodsRelevant articles which were published in the English language from January 10, 2011, to January 10, 2021, were systematically searched through PubMed, Web of Science, and African journals online. In addition, reference probing of published articles searching was employed through Google Scholar and Google for searching grey literature. The methodological qualities of articles were assessed using Joana Brigg’s institute critical appraisal checklist. A random-effects model was used to estimate pooled WMD of PLT parameters between the two groups with the respective 95% confidence intervals (CI) using Stata version 11.0. The I2 statistics and Egger’s regression test were used to assess heterogeneity and publication bias among included studies, respectively.ResultsA total of 25 articles were included in this systematic review and meta-analysis. Of which, 23 studies were used in each PC and MPV analysis. The overall pooled WMD of PC and MPV between PE and NT groups were -41.45 × 109/L [95% CI; -51.8, -31.0] and 0.98 fl [95% CI; 0.8, 1.1], respectively. The pooled WMD revealed that PC decreased significantly in the PE group compared to the NT group while MPV increased significantly in the PE group.ConclusionsThis systematic review and meta-analysis indicated that there is a significant decrease in PC and a significant increase in MPV during PE development among pregnant women. As a result, a change in these parameters among pregnant women may indicate the development of PE.

A Systematic Review on the Effect of Common Medications on Platelet Count and Function: Which Medications Should Be Stopped Before Getting a Platelet-Rich Plasma Injection?

Background:Platelet-rich plasma (PRP) exerts its effect through the release of growth factors and cytokines from the platelet concentrate. Certain medications may affect platelet count or function, resulting in decreased efficacy of PRP injections.Purpose:To systematically review the literature regarding common medications and their effects on platelets to establish guidelines for which medications should be stopped before obtaining a PRP injection.Study Design:Systematic review; Level of evidence, 2.Methods:This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search for studies assessing the effect of common medications on platelet count or platelet function was performed of the PubMed, Cochrane Library, Web of Science, and OpenGrey databases. Inclusion criteria were as follows: drug studied was aspirin, acetaminophen, a nonsteroidal anti-inflammatory drug (NSAID), a statin, or gabapentin; human participants; and article in the English language. Risk of bias was assessed using the Cochrane Risk of Bias tool and the Risk of Bias in Non-randomised Studies—of Interventions tool.Results:A total of 1711 studies were identified through the initial search, with 20 studies meeting all inclusion criteria. No studies involving gabapentin met all inclusion criteria. Patients treated with aspirin (268 patients) or acetaminophen (13 patients) showed a significant decrease in platelet aggregation. Statin therapy (73 patients) did not result in a significant decrease in platelet aggregation. Patients who took NSAIDs (172 patients) demonstrated significantly decreased platelet aggregation only when treated with nonselective formulations. Those treated with cyclooxygenase (COX)-2–selective NSAIDs showed no significant difference in platelet aggregation. Treatment with aspirin, acetaminophen, statins, or NSAIDs did not lead to a significant decrease in platelet count.Conclusion:Aspirin, acetaminophen, and nonselective NSAIDs should be considered for suspension before a PRP injection because of their potential to diminish the effects of the injection. COX-2–selective NSAIDs and statins do not need to be withheld before a PRP injection.