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Vascular endothelial growth factor C (Vegfc) is crucial for lymphatic and blood vessel development, yet its cellular sources and specific functions in heart development remain unclear. To address this, we created a vegfc reporter and an inducible overexpression line in zebrafish. We found vegfc expression in large coronary arteries, circulating thrombocytes, cardiac adipocytes, and outflow tract smooth muscle cells. Notably, although coronary lymphangiogenesis aligns with Vegfc-expressing arteries in juveniles, it occurs only after coronary artery formation. Vegfc overexpression induced ectopic lymphatics on the ventricular surface prior to arterial formation, indicating that Vegfc abundance, rather than arterial presence, drives lymphatic development. However, this overexpression did not affect coronary artery coverage, suggesting a specific role for Vegfc in lymphatic, rather than arterial, development. Thrombocytes emerged as the initial Vegfc source during inflammation following heart injuries, transitioning to endocardial and myocardial expression during regeneration. Lower Vegfc levels in an amputation model corresponded with a lack of lymphatic expansion. Importantly, Vegfc overexpression enhanced lymphatic expansion and promoted scar resolution without affecting cardiomyocyte proliferation, highlighting its role in regulating lymphangiogenesis and promoting heart regeneration. [ABSTRACT FROM AUTHOR]

Thrombocytopenia represents one of the most frequent causes of addressability for a hematological consultation. The purpose of the study is to establish a correlation between the degree of thrombocytopenia and the appearance of the mucocutaneous bleeding, with a therapeutic purpose. Materials and method: Our study is a retrospective observational study and was carried out on a group of 100 patients who were referred to the Hematology Clinic of Sp. St. Spiridon, Iași for a period of 12 months and who presented with isolated thrombocytopenia on admission. Other coagulopathy evolving with thrombocytopenia were excluded. To establish the correlation between the decrease in the number of platelets and the appearance of the hemorrhagic skin-mucosal syndrome, statistical methods were used - F Test - Two sample for Variance. Results and discussions: Thrombocytopenia was defined as the value of platelets below 150,000\mmc. 5 grades of thrombocytopenia were established: grade I (TR=150,000-100,000/mmc), grade II (TR= 100,000-50,000/mmc), grade III (TR=50,000-20,000/mmc), grade IV (TR= 20,000 -10,000/mmc), grade V (TR below 10,000/mmc)40% of the patients included in the study presented thrombocytopenia gr. I, 24% - grade II, 15% - grade III, 6% - grade IV and 15% presented severe thrombocytopenia (grade V). The mucocutaneous bleeding was manifested by: petechiae and ecchymosis, epistaxis, bleeding in the oral cavity (gingival bleeding, hemorrhagic bullae), menometrorrhagia, hematuria, melena. There is a statistical correlation between the number of platelets and the occurrence of mucocutaneous bleeding: p=0.000121 (p less than 0.001). The first clinical manifestations of the mucocutaneous bleeding appeared at the value of 70,000/mmc. No statistical correlation was obtained between the age of the patients and the number of platelets (p=0.0352). Conclusions: The occurrence of mucocutaneous bleeding is directly related to the decrease in the number of platelets. The oral cavity usually is involved in bleeding caused by the decrease in the number of platelets and requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Background: Platelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP. Methods: This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product). Discussion: DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study. Trial registration: NCT 06147531 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Introduction: Studies assessing the impact of preoperative and first-day postoperative values of leukocytes, thrombocytes, and platelet/leukocyte ratio (PLR) after radical cystectomy (RC) are sparse. We aimed to assess the impact of these factors on long-term survival after RC. Methods: An analysis of patients undergoing open RC from 2004 to 2023 at our center was performed. Leukocytosis was defined as ≥8,000 leukocytes/μL and thrombocytosis as ≥400,000 thrombocytes/μL. Similarly, the cutoff for PLR was set at 28. A multivariable Cox regression analysis was performed to assess the role of leukocytosis, thrombocytosis, and PLR on long-term survival after RC. For all analyses, hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. Results: A total of 1,817 patients with a median age of 70 years (interquartile range [IQR]: 62–77) were included. Overall, 804 (44%), 175 (10%), and 1,296 (71%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 preoperatively. Accordingly, 1,414 (78%), 37 (2%), and 249 (14%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 on the first day after RC. At a median follow-up of 26 months (IQR: 8–68) after RC, 896 (49%) patients died. In the multivariate Cox regression analysis after adjusting for major perioperative risk factors, only preoperative leukocytosis (HR: 1.3, 95% CI: 1.1–1.6, p = 0.01), as well as both preoperative and first-day thrombocytosis (HR: 2.1, 95% CI: 1.5–2.9, and HR: 2.8, 95% CI: 1.6–5.1, p < 0.001, accordingly) were associated with worse overall survival. Conclusion: PLR should not be used as a prognostic marker for survival after RC. On the contrary, preoperative leukocytosis, as well as preoperative and first-day thrombocytosis should raise awareness among clinicians performing RC since they were independently associated with worse survival after RC. [ABSTRACT FROM AUTHOR]

Imaging flow cytometry is an attractive method to investigate individual cells by optical properties. However, imaging flow cytometry applications with clinical relevance are scarce so far. Platelet aggregation naturally occurs during blood coagulation to form a clot. However, aberrant platelet aggregation is associated with cardiovascular disease under steady‐state conditions in the blood. Several types of so‐called antiplatelet drugs are frequently described to reduce the risk of stroke or cardiovascular diseases. However, an efficient monitoring method is missing to identify the presence and frequency of platelet–platelet aggregates in whole blood on a single cell level. In this work, we employed imaging flow cytometry to identify fluorescently labeled platelets in whole blood with a conditional gating strategy. Images were post‐processed and aligned. A convolutional neural network was designed to identify platelet–platelet aggregates of two, three, and more than three platelets, and results were validated against various data set properties. In addition, the neural network excluded erythrocyte–platelet aggregates from the results. Based on the results, a parameter for detecting platelet–platelet aggregates, the weighted platelet aggregation, was developed. If employed on a broad scale with proband and patient samples, our method could aid in building a future diagnostic marker for cardiovascular disease and monitoring parameters to optimize drug prescriptions in such patient groups. [ABSTRACT FROM AUTHOR]

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care. Methods: We used fluorescence-activated cell sorting (FACS) with antibodies against CD61 for thrombocyte identification and CD62p or platelet activation complex-1 (PAC-1) to determine platelet activation. Aggregometry and automated platelet functioning analyzer (PFA-200) were employed to test thrombocyte reactivity. FACS and aggregometry samples were stimulated in vitro with arachidonic acid (AA) and adenosine diphosphate (ADP) to measure increase in CD62p-/PAC-1-expression or aggregation, respectively. Results: Between February and July 2023, 20 blood samples (n = 11 ischemic strokes; n = 7 hemorrhagic strokes; n = 2 controls) were acquired and analyzed within 24 h of symptom onset. N = 11 patients had taken ASA, n = 8 patients no APT and n = 1 ASA+clopidogrel. ASA intake compared to no APT was associated with lower CD62p expression after stimulation with AA on FACS analysis (median 15.8% [interquartile range {IQR} 12.6-37.2%] vs. 40.1% [IQR 20.3-56.3%]; p = 0.020), lower platelet aggregation (9.0% [IQR 7.0-12.0%] vs. 88.5% [IQR 11.8-92.0%]; p = 0.015) and longer time to plug formation with PFA-200 (248.0 s [IQR 157.0-297] vs. 121.5 s [IQR 99.8-174.3]; p = 0.027). Significant correlations were noted between AA-induced CD62p expression and aggregometry analysis (n = 18; ρ = 0.714; p < 0.001) as well as a negative correlation between CD62p increase and PFA clot formation time (n = 18; ρ = -0.613; p = 0.007). Sensitivity for ASA intake was highest for PFA (81.8% for values ≥155.5 s). The combination of ASA + clopidogrel also affected ADP-induced CD62p and PAC-1 expression. Conclusion: In the clinical setting it is feasible to use differentiated platelet analytics to determine alterations caused by antiplatelet therapy. Among the tests under investigation, PFA-200 showed the highest sensitivity for the intake of ASA in stroke patients. FACS analysis on the other hand might be able to provide a more nuanced approach to altered platelet reactivity. [ABSTRACT FROM AUTHOR]

Thrombocytes play an essential role in hemostasis and thrombosis. Moreover, the controlled activation of thrombocytes is required in reproduction and fertility. The platelet-activating factor and the controlled activation of platelets have important roles in folliculogenesis, ovulation, placental development, implantation and embryo development. Activated platelets accumulate in the follicular vessels surrounding the follicle and, due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters), locally increase oocyte maturation and hormone secretion. Furthermore, activated platelets are involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS) and preeclampsia. Low-dose aspirin can prevent OHSS during ovulation induction, while intrauterine or intraovarian administration of platelet-rich plasma (PRP) increases the endometrium thickness and receptivity as well as oocyte maturation. Activated thrombocytes rapidly release the contents of intracellular granules and have multiple adhesion molecules and receptors on their surface. Considering the numerous homeostatic endocrine functions of thrombocytes, it is reasonable to suppose a platelet-associated regulatory system (PARS) in reproduction. Although we are far from a complete understanding of the regulatory processes, the results of PARS research and the therapeutic application of aspirin and PRP during in vitro fertilization are promising. [ABSTRACT FROM AUTHOR]

Background: Phenobarbital (PB) is used as a first‐line treatment for recurrent epileptic seizures in cats. While hematologic abnormalities are well‐known side effects of antiepileptic therapy with PB in humans and dogs, little is known about such alterations in cats. Objectives: The aim of this retrospective study was to investigate the prevalence and clinical relevance of cytopenia during PB treatment in cats. Methods: In this single‐center, retrospective clinical study, 69 cats—with suspected idiopathic epilepsy admitted to the Small Animal Clinic of the University of Veterinary Medicine in Vienna (VMU)—were included. A complete blood count for each patient was performed, and changes in hematocrit, leukocytes, neutrophils, and thrombocytes were documented and graded. Results: Fifty‐three out of 69 cats (76.8%) showed cytopenias with a reduction of at least one cell fraction during PB treatment. The most frequent change was neutropenia (60%), followed by leukopenia (49.3%), thrombocytopenia (24.1%), and anemia (20.3%). Most of the changes were mild or moderate; only one patient (1.5%) showed severe leukopenia and neutropenia, and one was a life‐threatening neutropenia (1.5%) with a serum PB concentration within or even below the therapeutic range. These patients did not present with clinical symptoms other than those related to epileptic episodes. Cats who received combination therapy showed lower hematocrits than those who received monotherapy. A tendency for leukocytes and neutrophils to decrease during PB treatment was also seen. Conclusions: Blood cytopenias may frequently occur in cats on chronic PB therapy, even when serum drug levels are within the therapeutic range. However, clinical signs are typically mild to moderate and rarely severe. [ABSTRACT FROM AUTHOR]

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Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1–3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer® closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI − 97; − 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32). [ABSTRACT FROM AUTHOR]

PURPOSE: The study aimed to determine a simple diagnostic test that could predict the risk of anastomotic leakage in early postoperative period. METHODS: A single-center, retrospective study was conducted. The electronic medical records of patients who underwent resection for rectal tumor between January 1, 2016, and December 31, 2021, in University Hospital Olomouc, were reviewed. The data included risk factors for leakage and laboratory parameters commonly obtained. RESULTS: The decrease in platelets was signifi cant as for the possibility of being a marker of anastomotic leakage; OR = 0.980 (p = 0.036). A decrease of 34 or higher predicts leakage with a sensitivity of 45 % (95 % CI: 23.1–68.5 %) and specifi city of 81.1 % (95 % CI: 75.2–86.1 %). Postoperative leukocyte blood level (OR = 1.134; p = 0.019) and leukocyte level on postoperative day 1 (OR = 1.184; p = 0.023) were signifi cant predictors for leakage. WBC values ≥ 8.8 predict leakage with a sensitivity of 70.0 % (95 % CI: 45.7–88.1 %) and specifi city of 55.3 % (95 % CI: 48.4–62.0 %). Hemoglobin blood level ≤ 79.5 predicts leakage with a sensitivity of 70.0 % (95 % CI: 45.7–88.1 %) and specifi city of 62.2 % (95 % CI: 55.5–68.7 %). CONCLUSION: Despite the fact that the specifi city and sensitivity of the followed parameters are low, they could serve as markers useful for early diagnosis or suspicion for leakage (Tab. 5, Fig. 3, Ref. 14). Text in PDF www.elis.sk. [ABSTRACT FROM AUTHOR]

Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets. [ABSTRACT FROM AUTHOR]

To better characterize occurrence and extent of anticoagulant-associated pseudothrombocytopenia (PTCP) in the daily routine of a high-throughput clinical laboratory in order to draw conclusions on a more precise definition of this phenomenon. Concomitant platelet counts in both EDTA and citrate whole blood (WB) performed in our laboratory over a period of four years and 9 months, were analyzed, calculating the correlation, as well as the absolute difference in the results obtained from both materials, cross-referencing these measures with automated flags for platelet aggregates and the results of the visual examination for platelet aggregates of peripheral blood smears. Platelet counts in both materials were strongly correlated (ρ=0.86; p<0.0001) but are on average significantly higher in EDTA WB than in citrate WB (median difference: 11 ± 14.8/nL, p<0.0001). This is in spite of numerous instances of EDTA-associated PTCP recorded in our data, where the opposite is the case. The automated flag for possible platelet aggregates was shown to be very unspecific, while a machine-learning algorithm suggested the difference in platelet counts between EDTA and citrate WB as a predictor of platelet aggregates. EDTA-associated PTCP is a regular occurrence. Differences in platelet counts between EDTA and citrate WB appear to be a far better predictor of PTCP than automated flags. A clear and useful definition of PTCP is still missing, however, and cannot be derived from our data either, indicating the need for further research. [ABSTRACT FROM AUTHOR]

Aim: Recurrent pregnancy loss (RPL) is known to be associated with increased thrombophilia and oxidative toxicity. However, the mechanism of thrombophilia apoptosis and oxidative toxicity is still unclear. In addition, the treatment of heparin induced regulator roles on intracellular free Ca2+ ([Ca2+]i) and cytosolic reactive oxygen species (cytROS) concentrations in several diseases. TRPM2 and TRPV1 channels are activated by different stimuli, including oxidative toxicity. The aim of this study was to investigate the effects of low molecular weight heparin (LMWH) via modulation of TRPM2 and TRPV1 on calcium signaling, oxidative toxicity, and apoptosis in the thrombocytes of RPL patients. Study Design: Thrombocyte and plasma samples collected from 10 patients with RPL and 10 healthy controls were used in the current study. Main Findings: The [Ca2+]i concentration, cytROS (DCFH‐DA), mitochondrial membrane potential (JC‐1), apoptosis, caspase‐3, and caspase‐9 levels were high in the plasma and thrombocytes of RPL patients, although they were diminished by the treatments of LMWH, TRPM2 (N‐(p‐amylcinnamoyl)anthranilic acid) and TRPV1 (capsazepine) channel blockers. Conclusions: The current study results suggest that the treatment of LMWH is useful against apoptotic cell death and oxidative toxicity in the thrombocytes of patients with RPL, which seem to be dependent on increased levels of [Ca2+]i concentration via the activation of TRPM2 and TRPV1. [ABSTRACT FROM AUTHOR]

Leucocytozoon parasites remain poorly investigated in comparison to other haemosporidians. The host cell inhabited by their blood stages (gametocytes) remains insufficiently known. This study aimed to determine the blood cells inhabited by Leucocytozoon gametocytes in different species of Passeriformes and to test if this feature has a phylogenetic importance. We microscopically analyzed blood films stained with Giemsa from six different bird species and individuals and used PCR-based methods for parasite lineage identification. The DNA sequences obtained were applied for phylogenetic analysis. Leucocytozoon parasite from the song thrush Turdus philomelos (cytochrome b lineage STUR1), the blackbird Turdus merula (undetermined lineage), the garden warbler Sylvia borin (unknown lineage) inhabited erythrocytes, a parasite from the blue tit Cyanistes caeruleus (PARUS4) infects lymphocytes, while in the wood warbler Phylloscopus sibilatrix (WW6) and the common chiffchaff Phylloscopus collybita (AFR205) they were found inhabiting thrombocytes. Parasites infecting thrombocytes were closely related, while the parasites infecting erythrocytes were placed in three different clades, and the one found in lymphocytes was placed in a separate clade. This shows that the determination of host cells inhabited by Leucocytozoon parasites can be phylogenetically important and should be considered in future species descriptions. Noteworthy, phylogenetic analysis might be used for the prediction of which host cells parasite lineages might inhabit. [ABSTRACT FROM AUTHOR]

Pegagan embun (Hydrocotyle sibthorpioides Lam.) has been studied as an immunostimulant, increasing macrophage cell activity and phagocytosis capacity. Based on that circumstance, the study aims to prove the immunostimulating effect by measuring the activity of Hydrocotyle sibthorpioides Lam. extract in the capsule for the complete blood profile of healthy volunteers. The number of volunteers used was twenty people, and the volunteers were divided into two groups. The first group was given a placebo capsule without Hydrocotyle sibthorpioides Lam. extract. The second group was given a capsule with Hydrocotyle sibthorpioides Lam. extract with a dose of 67 mg, which was taken once a day for three days. Blood sampling was obtained before and after taking the capsule preparation. Observation of the complete blood profile was conducted by investigating changes in blood parameters such as haemoglobin levels, number of erythrocytes, number of leukocytes, hematocrit values, number of thrombocytes and the percentage of leukocyte types (banded neutrophils, segmented neutrophils, eosinophils, basophils, monocytes, and lymphocytes). The second group given Hydrocotyle sibthorpioides Lam. extract showed a significant effect on the increase in haemoglobin levels, number of thrombocytes and hematocrit values (p<0.05). The percentage of leukocyte type values showed that lymphocytes increased significantly (p<0.05). In contrast, the segmented neutrophil increased but did not show a significant difference with the percentage of banded neutrophils, eosinophils, basophils and monocytes (p>0.05). There was a nonsignificant result in all parameters for the first group, which was administrated with a placebo capsule without Hydrocotyle sibthorpioides Lam. extract.v [ABSTRACT FROM AUTHOR]

Background: Inflammation is important in the development of atherosclerosis. Research suggested sex-dependent differences for the value of inflammatory markers for risk stratification of stroke patients with internal carotid artery stenosis (ICAS). We investigated whether leukocytes and thrombocytes were associated with ≥50% ICAS in acute stroke and whether this was sex-dependent. Patients included in the Preventive Antibiotics in Stroke Study (PASS) were used. PASS is a randomized controlled trial that randomized between four days of preventive ceftriaxone intravenously or standard stroke care alone. It investigated whether ceftriaxone could improve functional outcome at three months after stroke. Methods: Patients included in PASS were evaluated for the predictive value of leukocytes and thrombocytes for ICAS. Ischemic stroke and TIA patients were selected out of PASS patients. Logistic regression analysis was performed adjusting for NIHSS and other covariates. Results: 2550 patients were included in PASS. 1413 of 2550 patients (55%) were evaluated in this sub study. Female patients showed a mean of 8.55 × 109/L for leukocytes and 259 × 109/L for thrombocytes. Men showed a mean of 8.29 × 109/L for leukocytes and 224 × 109/L for thrombocytes. Multivariate logistic regression analysis showed that leukocytes were independently associated with ICAS ≥ 50% in male patients (OR 1.094, p = 0.008), but not in female patients (OR 1.041, p = 0.360). Thrombocytes were not associated with ICAS. Conclusions: We conclude that blood leukocyte count independently predicts ICAS in men after acute stroke, but not in women. Clinical Trial unique identifier: ISRCTN66140176. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer (HNC) treatment poses several challenges in clinical practice, and treatment side effects can be debilitating due to the close proximity of important anatomical structures. Cancer recurrence post-treatment presents some of the most challenging HNC management issues. This prospective study identifies high-risk groups for recurrence of head and neck cancer, based on commonly accessible clinical parameters. In this study with 272 HNC patients, elevated pre- and post-treatment CRP levels, low BMI and advanced stage at admission indicate higher risk for recurrence of disease. Using these parameters, a risk model is proposed which may be useful for estimating the probability of cancer recurrence and allow the identification of high and low-risk patients. This prospective study identifies high-risk groups for recurrence of head and neck cancer by BMI and circulating inflammatory response markers. Head and neck cancer patients from three Swedish hospitals were included (n = 272). Leukocyte and thrombocyte counts, CRP levels, and BMI were measured pre-treatment and post-treatment. Associations between the four factors and treatment failure (residual tumor, loco-regional failure, general failure/distant metastasis) were assessed using a Cox proportional hazards model adjusted for sex, age at the initial visit, smoking status, cancer stage, and hemoglobin count. CRP level was the only significant single variable, with an average increase in risk of recurrence of 74% (p = 0.018) for every doubling. The predictive power of a combined model using all variables was highest during the initial months after treatment, with AUC under the ROC curve 0.75 at the 0–3 month timepoints. Patients with elevated pre- and post-treatment CRP levels are at higher risk for recurrence of disease. Male patients with low post-treatment BMI, advanced stage, and high CRP at any time post treatment are at high risk for recurrence. The combined model may be useful for stratifying post-treatment patients into low and high-risk groups, to enable more detailed follow-up or additional treatment regimens. [ABSTRACT FROM AUTHOR]

Background: Adult primary immune thrombocytopenia (ITP) is a rare bleeding disorder of unknown cause. Recent estimates of its incidence and trend over time were acquired for England. Method: The primary ITP population (using ICD 10 code D693 and excluding secondary ITP cases; positive predictive value: 82.6%) was sourced from NHS Digital inpatient and outpatient. Incidence rate (IR) for England and by age groups, sex, and regions were calculated and trends were assessed using average annual percent change (AAPC). Results: A total of 25 805 patients (mean age 59 years; females 57.8%) diagnosed between 2003 and 2014 was identified. IRs increased from 4.2/100 000 to 6.4/100 000 over this period (AAPC:4.3%). For all sex‐specific age groups, the IRs significantly increased over time, except 18–29 years males. The greatest increase was among females aged 30–39 (AAPC:8.7%). In contrast, among ≥70 years, ITP was more common in males (highest IR among ≥80 years males: 23.9/100 000). England's average annual IR was 6.1/100 000 for 2010–14. An estimated 2.5/100 000 (based on UKITP Registry data) was estimated to require 1st line treatment whereas 2.4/100 000 would have 1st and 2nd line treatments within 6 months from diagnosis. IRs for London and East Midlands were the highest (6.5/100 000). Conclusions: This study found a rising incidence of primary ITP, with sharp increases among young women and elderly men. These findings put in context the impact of ITP on patients' lives and the healthcare services in England, especially with 17%–50% who may develop chronic ITP and require long‐term care. [ABSTRACT FROM AUTHOR]

For almost a century, familial hypercholesterolemia (FH) has been considered a serious disease, causing atherosclerosis, cardiovascular disease, and ischemic stroke. Closely related to this is the widespread acceptance that its cause is greatly increased low-density-lipoprotein cholesterol (LDL-C). However, numerous observations and experiments in this field are in conflict with Bradford Hill's criteria for causality. For instance, those with FH demonstrate no association between LDL-C and the degree of atherosclerosis; coronary artery calcium (CAC) shows no or an inverse association with LDL-C, and on average, the life span of those with FH is about the same as the surrounding population. Furthermore, no controlled, randomized cholesterol-lowering trial restricted to those with FH has demonstrated a positive outcome. On the other hand, a number of studies suggest that increased thrombogenic factors—either procoagulant or those that lead to high platelet reactivity—may be the primary risk factors in FH. Those individuals who die prematurely have either higher lipoprotein (a) (Lp(a)), higher factor VIII and/or higher fibrinogen compared with those with a normal lifespan, whereas their LDL-C does not differ. Conclusions: Many observational and experimental studies have demonstrated that high LDL-C cannot be the cause of premature cardiovascular mortality among people with FH. The number who die early is also much smaller than expected. Apparently, some individuals with FH may have inherited other, more important risk factors than a high LDL-C. In accordance with this, our review has shown that increased coagulation factors are the commonest cause, but there may be other ones as well. [ABSTRACT FROM AUTHOR]

CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs. [ABSTRACT FROM AUTHOR]

In humans, splenectomy is performed to treat many clinical disorders, including immune thrombocytopenia. However, the incidence of splenectomies for immune thrombocytopenia as a therapeutic has significantly declined over the past decade due to the availability of new therapies. Infection and sepsis as a result of splenectomies are well documented, but other long-term effects are not well characterized. Evidence suggests that persons who have had a prior splenectomy may be at an increased risk of vascular conditions. Also, elevated levels of cell-derived microparticles appear to contribute to an increased risk of thrombosis and cardiovascular disease. However, in vivo studies on the increased levels of microparticles following splenectomy are limited. In order to understand the effects of splenectomies, we developed a protocol for splenectomy in adult zebrafish. After anesthesia, the spleen was removed under a stereomicroscope after making an incision on the ventral side of the fish. The spleen was removed by pulling with forceps. The incision was closed by Vetbond tissue glue. Blood collected from both splenectomized zebrafish and those that underwent sham surgeries was immunolabeled with polyclonal antisera against αIIb, followed by flow cytometry. We observed elevated levels of thrombocytes and their microparticles in splenectomized zebrafish. Finally, by injecting αIIb antibody intravenously into zebrafish, we found the thrombocyte counts decreased, suggesting the fish developed immune thrombocytopenia like conditions, which were then reversed by splenectomy. In summary, the model developed here should be useful to study molecular changes due to splenectomy. Also, the zebrafish will be useful in modeling treatment of immune thrombocytopenia like conditions. [ABSTRACT FROM AUTHOR]

Thrombocytes circulate in the blood of nonmammalian vertebrates and are involved in hemostasis; however, many detailed characteristics of thrombocytes remain unclear. Recently, we established an amphibian thrombocyte cell line. Here, we report the finding that thrombocytes produce integrin alpha IIb (CD41)‐positive extracellular vesicles (EVs), which include microRNAs (miRs). Flow cytometric analysis showed the expression of CD41+ and phosphatidylserine on the surface of EVs. Nanotracking analysis showed that these CD41+ EVs were approximately 100 nm in diameter. As CD41+ EVs were also observed from African clawed frogs, the production of CD41+ EVs might be common to amphibians. Microarray analysis showed that the CD41+ EVs contain many kinds of miRs. These CD41+ EVs were phagocytosed by endothelial cells and macrophages. qPCR analysis showed that many angiogenesis‐related genes were up‐regulated in CD41+ EV‐treated endothelial cells. Over‐expression of some miRs in the CD41+ EVs increased the proliferation of endothelial cells. These results indicated that thrombocytes produced CD41+ EVs, including miRs, that were received by endothelial cells to induce the expression of angiogenesis‐related genes. These results indicated that the CD41+ EVs produced from thrombocytes act as signaling molecules to repair damaged blood vessels. [ABSTRACT FROM AUTHOR]

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Background: Thrombocytopenia is a common condition in hospitalised critically ill children and most platelet transfusions are given as prophylaxis to non‐bleeding children prior to invasive procedures such as central venous catheterisation and lumbar puncture. Platelet transfusion may reduce bleeding complications but have also been associated with potential adverse effects and variation in clinical practice exist. To direct future research, we aim to assess the current evidence regarding prophylactic platelet transfusion prior to procedures in hospitalised thrombocytopenic children. Methods: We will conduct a scoping review of all study designs in accordance with the Preferred Reporting Items for Systematic and Meta‐Analyses (PRISMA) statement. We will include studies on hospitalised children undergoing invasive procedures where the prevalence of thrombocytopenia and the predefined outcome measures, including bleeding, transfusion‐related adverse events and use of blood products and life support are reported. We will provide descriptive analyses of the included studies/trials and the quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Conclusion: The outlined scoping review will provide an overview on the benefits and harms of prophylactic platelet transfusion prior to invasive procedures in thrombocytopenic hospitalised children. [ABSTRACT FROM AUTHOR]

Thrombocytes are blood cells that protect fish by aggregation to hinder hemorrhages and play a role on pathogen phagocytosis. Moreover, there is a lack of information regarding to the population of thrombocytes and its relationship with fish ploidy. The goal of this work was to determine the thrombocyte numbers and its aggregation capacity in adult diploid and triploid rainbow trouts Oncorhynchus mykiss by flow cytometry screening using monoclonal antibody and magnetic separation. As expected, thrombocytes were in similar proportions between ploidies with 15.26 ± 6.77% in diploid and 13.11 ± 6.37% in triploid blood samples; however, with thrombocytes of triploid trouts showing less aggregation activity when exposed to collagen (85.59 ± 3.36% vs. 95.51 ± 1.25%). In conclusion, triploid thrombocytes have lower aggregation capacity than the diploid ones. This response is possibly related to the deficiency of receptors on the surface of thrombocytes of triploid trouts, which requires further studies for confirmation. [ABSTRACT FROM AUTHOR]

Objectives: There is scarce evidence about the effectiveness of anti‐bleeding measures in hematological outpatients experiencing persistent severe thrombocytopenia. We aim to describe clinical practice and clinicians' considerations on the administration of prophylactic platelet transfusions and tranexamic acid (TXA) to outpatients with acute leukemia, myelodysplastic syndrome (MDS), or aplastic anemia (AA) in the Netherlands. Methods: We conducted an online survey among members of the Dutch Society for Hematology. Results: The survey was filled out by 73 respondents. Prophylactic platelet transfusions are widely used in acute leukemia and MDS outpatients receiving disease‐modifying treatments (87%‐98% of respondents). TXA is predominantly prescribed in case of bleeding (tendency) (71%‐88% of respondents). Conditions potentially increasing bleeding risks highly variably influence clinicians' decision making on anti‐bleeding regimens, which includes a wide range in adhered platelet thresholds. Conclusion: Considering that both the contribution of prophylactic platelet transfusions as well as TXA to limiting bleeding is insufficiently evidence‐based, there is an urgent need for trials on optimal anti‐bleeding strategies in this outpatient population, which should encompass efficacy, logistic, financial, and quality‐of‐life aspects. [ABSTRACT FROM AUTHOR]

Background: The examination of a peripheral blood smear is mandatory in case of unexplained thrombocytopenia or thrombocytosis. First, the number of platelets should be estimated in order to confirm the platelet count determined by the haematology analyser, and to rule out causes of spuriously low or elevated platelet counts. Second, the size and morphological features of the platelets, which may provide information on the underlying cause of the low or enhanced platelet count, have to be assessed. Content: This review summarizes the physiological and pathological features of platelet size and morphology, circulating megakaryocytes, micromegakaryocytes and megakaryoblasts, and provides an overview of current guidelines on the reporting of platelet morphology. Summary: In the diagnostic work-up of a patient with thrombocytopenia, the size of the platelets is of diagnostic relevance. Thrombocytopenia with small platelets is suggestive of a defect in platelet production, whereas the presence of large platelets is more likely to be associated with enhanced platelet turnover or hereditary thrombocytopenias. Morphological platelet abnormalities may affect the granulation and the shape and are frequently associated with abnormalities of platelet size. Platelet anomalies can be found in various haematologic disorders, such as myelodysplastic syndromes, myeloproliferative neoplasms, acute megakaryoblastic leukaemia or hereditary thrombocytopenias. [ABSTRACT FROM AUTHOR]

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Objectives: Primary immune thrombocytopenia (ITP) is a bleeding disorder characterised by an isolated thrombocytopenia in the absence of an alternative diagnosis. The condition is highly heterogeneous with some patients requiring multiple of therapy before achieving response. In this study, we collected data on a large cohort of primary ITP patients with the objective of identifying variables which may predict treatment requirements. Methods: We collected data on 379 patients, 275 with a confirmed diagnosis of primary ITP included demographics, baseline laboratory results and treatments. These were compared against treatment responses and lines of therapy. Results: Patients who presented with a platelet count of <30 × 109/L or bleeding symptoms were observed to require more subsequent lines of therapy (P‐value <0.001). 32% of patients (n = 87) received no treatment, and these patients had a significantly higher median count compared to those with required >2 lines of therapy (P‐value <0.001). Superior response rates were demonstrated with thrombopoietin receptor agonists when compared with other agents irrespective of baseline characteristics. Conclusions: Platelet counts at diagnosis are a potentially strong predictive indicator of subsequent lines of therapy. Patients with bleeding symptoms at diagnosis were more likely to have lower median platelets counts. [ABSTRACT FROM AUTHOR]

Background: Endotoxemia is a common and severe disease of horses. Most previous studies have monitored changes caused by a bolus dose of endotoxin over short time periods. Objectives: We aimed to describe inflammatory responses to endotoxin with inflammatory and hematologic markers monitored over a longer time than has been performed in the past using more prolonged endotoxin exposures. Methods: Escherichia coli O55:B5 endotoxin was administered as a 6‐hour continuous intravenous infusion of lipopolysaccharide (LPS) to eight horses. Blood cell counts, and prostaglandin F2α‐metabolite (PGM), serum amyloid A (SAA), and serum total iron concentrations were monitored for up to 3 or 6 days. Results: An immediate and severe decrease in neutrophils and monocytes occurred in all horses, which subsequently changed to a moderate to strong neutrophilia and monocytosis that persisted for more than 78 hours postinfusion (PI) of LPS. Lymphocyte and eosinophil numbers decreased gradually and then normalized after 66‐ and 78‐hours PI, respectively. Mild to moderate, biphasic thrombocytopenia occurred. A pronounced, transient increase in PGM occurred between 1 and 7 hours, peaking at 2 hours. Serum amyloid A began to increase after 6 hours PI and remained elevated after 72 hours PI. Serum iron was decreased between 6 and 48 hours. The clinical signs were most prominent during the first 24 hours PI and subsided within 48 hours PI. Conclusions: Neutrophilia, monocytoses, and high SAA concentrations were present in horses even after the clinical signs had subsided. Serum iron normalized before SAA. Knowledge of these findings is imperative when interpreting laboratory results in horses with possible endotoxin exposure. [ABSTRACT FROM AUTHOR]

Meta‐analyses and Mendelian randomization (MR) may clarify the associations of smoking, blood cells and myeloproliferative neoplasms (MPN). We investigated the association of smoking with blood cells in the Danish General Suburban Population Study (GESUS, n = 11 083), by meta‐analyses (including GESUS) of 92 studies (n = 531 741) and MR of smoking variant CHRNA3 (rs1051730[A]) in UK Biobank, and with MPN in a meta‐analysis of six studies (n (total/cases):1 425 529/2187), totalling 2 307 745 participants. In the meta‐analysis the random‐effects standardized mean difference (SMD) in current smokers versus non‐smokers was 0·82 (0·75–0·89, P = 2·0 * 10−108) for leukocytes, 0·09 (−0·02 to 0·21, P = 0·12) for erythrocytes, 0·53 (0·42–0·64, P = 8·0 * 10−22) for haematocrit, 0·42 (0·34–0·51, P = 7·1 * 10−21) for haemoglobin, 0·19 (0·08–0·31, P = 1·2 * 10−3) for mean corpuscular haemoglobin (MCH), 0·29 (0·19–0·39, P = 1·6 * 10−8) for mean corpuscular volume (MCV), and 0·04 (−0·04 to 0·13, P = 0·34) for platelets with trends for ever/ex‐/current smokers, light/heavy smokers and female/male smokers. Analyses presented high heterogeneity but low publication bias. Per allele in CHRNA3, cigarettes per day in current smokers was associated with increased blood cell counts (leukocytes, neutrophils), MCH, red cell distribution width (RDW) and MCV. The pooled fixed‐effects odds ratio for MPN was 1·44 [95% confidence interval (CI): 1·33–1·56; P = 1·8 * 10−19; I2 = 0%] in current smokers, 1·29 (1·15–1·44; P = 8·0 * 10−6; I2 = 0%) in ex‐smokers, 1·49 (1·26–1·77; P = 4·4 * 10−6; I2 = 0%) in light smokers and 2·04 (1·74–2·39, P = 2·3 * 10−18; I2 = 51%) in heavy smokers compared with non‐smokers. Smoking is observationally and genetically associated with increased leukocyte counts and red blood cell indices (MCH, MCV, RDW) and observationally with risk of MPN in current and ex‐smokers versus non/never‐smokers. [ABSTRACT FROM AUTHOR]

In vitro pharmacodynamic models are used to optimize in vivo dosing regimens in antimicrobial drug development. One limiting factor of such models is the lack of host factors such as corpuscular blood components as erythrocytes which have already been shown to impact activity of antibiotics and/or growth of the pathogen. However, the impact of thrombocytes has not previously been investigated. We set out to investigate if the addition of thrombocytes (set to physiological concentrations in blood of healthy human, i.e., 5 × 105 thrombocytes/μL standard growth media Mueller Hinton Broth, MHB) has an influence on bacterial growth and on the efficacy of antibiotics against Gram+ and Gram− bacteria. Growth assays and time-killing-curves (TKC) were performed with ATCC-strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa in triplicate over 24 h. The same approach was followed for 5 clinical isolates of Escherichia coli. Meropenem, ciprofloxacin, and tigecycline were tested as representatives of broad-spectrum antibiotics, and concentrations several-fold above and below the minimal inhibitory concentration (MIC) were simulated. No significant impact of thrombocytes was found on bacterial growth or antimicrobial stability for the investigated agents. Bacteria reduced thrombocyte content to different degree, indicating direct interaction of pathogens and thrombocytes. Impact on bacterial killing was observed but was not fully reproducible when thrombocytes from different donors where used. While interaction of bacteria and thrombocytes was evident in the present study, interaction between antibiotic activity and thrombocytes seems unlikely. Whether variability was caused by different thrombocyte concentrates needs further investigation. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate that the use of platelet-rich plasma (PRP) enhances both the quality of healing and the time required for wound healing at a skin graft donor site. Methods: Patients who had dermo-epidermal skin grafts taken from the thigh area were included in a prospective, randomised clinical study. PRP was applied to one donor site and then covered with Vaseline-impregnated, open-weave gauze and gauze, while the contralateral donor site on the other thigh served as a control and was covered with the open-weave gauze and gauze without PRP. Results: A total of 24 patients took part in the study, of which three developed infections and were thus removed from the study. Use of PRP reduced the wound healing time of the dermo-epidermal graft donor sites by a mean 17.8% and median 18 days. On average, the treated donor sites healed in 14.9 days compared with 18.4 days for the control group. The median was 14 days compared with 18 days in the control group (p=0.026). In one patient, healing was slower on the side where PRP was applied. In 20 patients, healing of the donor site was accelerated where PRP was applied. Conclusion: The study demonstrated a beneficial effect of PRP, as healing time was shortened. Using PRP to heal wounds could be beneficial for patients for whom commonly available wound healing therapies have failed, as well as for high-risk patient groups for whom problematic wound healing may be expected. [ABSTRACT FROM AUTHOR]

Platelets play roles in malignancy, wound healing, and immunity. Nevertheless, their significance in postoperative outcomes is not established. This is a retrospective cohort study of 100,795 patients undergoing cancer surgery in 2010 and 2014 in >500 hospitals. Patients were stratified into five groups based on preoperative platelet counts. Multivariable logistic regression was used to determine the risk of 30-day mortality, morbidities, readmission, and prolonged hospitalization using the mid-normal group as a reference. We adjusted for demographic variables, comorbidities, and operation complexity. In the 2014 cohort, multivariable analysis showed that mortality was higher in patients with thrombocytopenia (OR 1.49, 95% CI [1.23–1.81]), high-normal platelets (OR 1.29, [1.06–1.55]), and thrombocytosis (OR 1.78, [1.45–2.19]). Composite postoperative morbidity followed a similar trend with thrombocytopenia (OR 1.34, [1.25–1.43]), high-normal counts (OR 1.41, [1.33–1.49]), and thrombocytosis (OR 2.20, [2.05–2.36]). Concordantly, the risks of prolonged hospitalization and 30-day readmission followed the same pattern. These results were validated in a large colon cancer cohort from the 2010 database. In conclusion, platelet count is a prognostic indicator in cancer surgeries. This could be related to the role of platelets in wound healing and immunity on one hand, and propagating malignancy on the other. [ABSTRACT FROM AUTHOR]

Objective: Evans syndrome, the combination of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) or autoimmune neutropenia, is associated with a high rate of relapsed/refractory disease. There are limited data on the efficacy of splenectomy for this condition. We reviewed patient outcomes after splenectomy for Evans syndrome compared to ITP at our institution. Methods: We performed a retrospective analysis of patients who underwent splenectomy for autoimmune cytopenias over a 23‐year period with the intention of comparing disease relapse rates after splenectomy in patients with Evans syndrome and in those with ITP. Results: During the study period, 77 patients underwent splenectomy for ITP and seven underwent splenectomy for Evans syndrome. In the Evans cohort, splenectomy led to an 85.7% initial response rate with a 42.8% rate of relapse within one year and a long‐term (one‐year) response rate of 42.8%. In the ITP cohort, the initial response rate was 90.9% with a long‐term response rate of 70.1%. Conclusion: Our data suggest that long‐term remission rates after splenectomy are lower in adults with Evans syndrome compared to those with ITP, although splenectomy may still be an acceptable treatment for certain patients with Evans syndrome. Our findings underscore the need for further research and development of additional therapeutic strategies for this patient population. [ABSTRACT FROM AUTHOR]

Background: Macrothrombocytopenia is a well‐known anomaly in Cavalier King Charles Spaniels (CKCSs), a breed also highly predisposed to develop myxomatous mitral valve disease (MMVD). Thromboelastography (TEG) has been shown to be a valuable instrument for whole blood hemostatic evaluation in dogs and correlates well with different physiologic and pathologic situations. Objectives: We aimed to assess the influence of macrothrombocytopenia and the severity of MMVD on hemostatic function as measured by TEG. Methods: Associations between TEG variables (R, K, α, MA, and G) and dog characteristics, heart rates, systolic blood pressures, MMVD severities (healthy, mild or moderate, and severe), echocardiographic variables, platelet variables (platelet count, mean platelet volume [MPV], and plateletcrit), and hematocrits were evaluated in 47 prospectively recruited privately owned CKCSs. Blood samples were analyzed using a computerized thromboelastograph and an Advia 2120 hematology analyzer. Results: Univariable and multiple regression analyses showed an effect of left ventricular (LV) fractional shortening (FS%) on all TEG variables, an effect of LV FS% and age on TEG α, and an effect of LV FS% and MPV on TEG MA and TEG G. TEG MA and G increased with increasing MPV, but the associations were generally weak. No significant differences were detected in the TEG variables between the MMVD severity groups. Conclusion: Macrothrombocytopenia and increased LV FS%, of which the latter commonly increases in various positive inotropic states, were both associated with a more hypercoagulable hemostatic system, according to the TEG results, in the present study. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that medical options without splenectomy, such as rituximab (RTX) or thrombopoietin receptor agonists (TPO-RAs), can be effective to treat persistent or chronic primary immune thrombocytopenia (ITP). However, it remains to be determined which of these strategies should be the first choice after the first-line treatment for newly diagnosed ITP. We performed a systematic review and network meta-analysis to establish a clinically meaningful hierarchy of the efficacy and safety of medical treatments for persistent or chronic ITP in adults. Randomized controlled trials (RCTs) evaluating medical treatments were included. Reviewers independently extracted data and assessed the risk of bias. The main outcome was the overall response (platelet≥ 50 × 109/L); incidence of bleeding episodes, necessity of rescue treatments, and therapy-related adverse events including thrombosis were the secondary endpoints. A total of 12 randomized controlled trials (N= 1306) were included in this study. Our main finding was an improved overall response in TPO-RA arms (both Eltrombopag and Romiplostim) compared with that of RTX or placebo. There were no significant differences between Eltrombopag and Romiplostim. Moreover, clinically significant bleeding episodes were decreased in TPO-RA arm compared with placebo. Therapy-related adverse events showed similar profiles, and were tolerable in all treatment arms. In conclusion, TPO-RAs can be first choices for the treatment of persistent and chronic ITP, rather than RTX, as alternatives to splenectomy. Future head-to-head trials including TPO-RAs vs. RTX or Eltrombopag vs. Romiplostim are necessary to validate our study findings and determine the most suitable therapy for persistent/chronic ITP. [ABSTRACT FROM AUTHOR]

A study has been made of the structure and properties of erythrocyte and thrombocyte membranes in patients with diabetes mellitus type 2 by the atomic-force-microscopy method. The influence of the temperature and the incubation time on the local mechanical properties of blood cells and the aggregation properties of erythrocytes has been assessed. The critical temperature and the incubation time for erythrocytes have been established, at which irreversible changes in the properties of erythrocyte membranes occur. It has been shown that thrombocytes are characterized by the higher thermally stable local mechanical properties of the membrane than erythrocytes. [ABSTRACT FROM AUTHOR]

Urosepsis is a severe condition often caused by Escherichia coli that spontaneously have ascended the urinary tract to the kidneys causing pyelonephritis and potentially bacteraemia. The number of sepsis cases has been steadily increasing over the last decades, and there are still no specific, molecular supportive therapies for sepsis to supplement antibiotic treatment. P2X1 receptors are expressed by a number of immune cells including thrombocytes, which presently have been established as an important player in the acute immune response to bacterial infections. P2X1 receptor-deficient mice have been shown to be relatively protected against urosepsis, with markedly reduced levels of circulating proinflammatory cytokines and intravascular coagulation. However, here we show that continuous intravenous infusion with P2X1 receptor antagonist markedly accelerates development of a septic response to induced bacteraemia with uropathogenic E. coli. Mice exposed to the P2X1 receptor antagonists die very early with haematuria, substantially elevated plasma levels of proinflammatory cytokines, massive intravascular coagulation and a concomitant reduction in circulating thrombocytes. Interestingly, infusion of P2X1 receptor antagonists causes a marked acute reduction in circulating thrombocytes and a higher number of bacteria in the blood. These data support the notion that the number of functional thrombocytes is important for the acute defence against bacteria in the circulation and that the P2X1 receptor potentially could be essential for this response. [ABSTRACT FROM AUTHOR]

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Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease that can be triggered by different events, including viral infections. It presents as thrombotic microangiopathy and can lead to severe complications that often require management in the intensive care unit (ICU). We report a patient who presented with acquired TTP following COVID-19 infection. A 44-year-old woman presented to the emergency department with severe anemia, acute kidney injury and respiratory failure due to COVID-19. Clinical and laboratory findings were suggestive for thrombotic microangiopathy. On day 8 laboratory tests confirmed the diagnosis of acquired TTP. The patient needed 14 plasma exchanges, treatment with steroids, rituximab and caplacizumab and 18 days of mechanical ventilation. She completely recovered and was discharged home on day 51. Acquired TTP can be triggered by different events leading to immune stimulation. COVID-19 has been associated with different inflammatory and auto-immune diseases. Considering the temporal sequence and the lack of other possible causes, we suggest that COVID-19 infection could have been the triggering factor in the development of TTP. Since other similar cases have already been described, possible association between COVID and TTP deserves further investigation. [ABSTRACT FROM AUTHOR]

The present study was conducted on blood cells of thirty healthy domestic fowl, duck and quail, ten birds of each group. The basophilic granules showed strong positive reaction in fowl while moderate in duck and weak in quail when the blood smears were stained with toluidine blue in the form of blue coloured granules. PAS reaction for glycogen was moderate in heterophil and weak in thrombocyte of fowl. The reaction was strong in heterophil and moderate in thrombocyte of duck and quail, respectively. Eosinophil of fowl and duck showed strongly positive reaction in the form of black granules for Sudan Black B while the reaction was weak in quail. [ABSTRACT FROM AUTHOR]

Intraflagellar transport (IFT) proteins are vital for the genesis and maintenance of cilia. Our identification of ift122 transcripts in zebrafish thrombocytes that lack primary cilia was unexpected. IFT proteins serve transport in cilia, whose narrow dimensions may have necessitated the evolution of IFT from vesicular transport in ancestral eukaryotes. We hypothesized that IFTs might also facilitate transport within the filopodia that form when thrombocytes are activated. To test this possibility, we knocked down ift122 expression by injecting antisense Morpholino oligonucleotides (MOs) into zebrafish embryos. Laser-induced arterial thrombosis showed prolonged time to occlusion (TTO) of the vessel, as would be expected with defective thrombocyte function. Acute effects in adult zebrafish were evaluated by Vivo-Morpholino (Vivo-MO) knockdown of ift122. Vivo-MO morphants showed a prolonged time to thrombocyte aggregation (TTA) in the plate tilt assay after thrombocyte activation by the following agonists: ADP, collagen, PAR1 peptide, and epinephrine. A luminescence assay for ATP revealed that ATP secretion by thrombocytes was reduced in collagen-activated blood of Vivo-MO ift122 morphants. Moreover, DiI-C18 labeled morphant thrombocytes exposed to collagen showed reductions in filopodia number and length. Analysis of ift mutants, in which cilia defects have been noted, also showed prolongation of TTO in our arterial laser thrombosis assay. Additionally, collagen activation of wild-type thrombocytes led to a concentration of IFT122 both within and at the base of filopodia. Taken together these results, suggest that IFT proteins are involved in both the extension of filopodia and secretion of ATP, which are critical in thrombocyte function. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Platelets, or thrombocytes, are important players in inflammation, wound healing, initiation of immune response and regeneration in the organism. Disruption of the blood-brain barrier occurs during certain neurological disorders, such as brain trauma, Alzheimer’s disease or stroke, when blood cells including platelets can invade nervous tissue. However, the role of platelets in the context of neuroinflammation remains understudied. Recent studies have shown that activated platelets release a wide set of coagulative and vascular factors during neurovascular pathologies in the central nervous system. Moreover, platelets stimulate immunity and regulate inflammation in the central nervous system. Trophic and growth factors stored in platelets may play a role in neuronal regeneration. Activated platelets release neurotransmitters, serotonin, dopamine, histamine, and glutamate, and can modify neuronal cell activity in neuropathologies. This review focuses on the major aspects and mechanisms of platelet functions in neuroinflammation, and therapeutic potential of platelets for treatment of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Objective: There are currently 2 representative diagnostic criteria for essential thrombocythemia (ET), the 2014 British Committee for Standards in Hematology Guidelines (BCSH) criteria and the 2016 World Health Organization (WHO) criteria. We compare and discuss the advantages and disadvantages of the 2 criteria. Method: We applied the 2 criteria to 403 patients with thrombocytosis and suspected myeloproliferative neoplasms (MPN) and compared patient populations. Results: The BCSH criteria diagnosed ET in 279 patients (BCSH-ET) whereas the WHO criteria diagnosed ET in 203 patients (WHO-ET). There were 83 patients diagnosable only by the BCSH criteria (BCSH-only-ET), of which under the WHO classification, 69 patients fell under the category of MPN, unclassifiable (MPN-u), 12 patients were PMF, prefibrotic/early stage (pre-PMF), and 2 patients were polycythemia vera. Patient characteristics such as age, hemoglobin, hematocrit, platelet counts, lactate dehydrogenase levels, JAK2V617F allele burdens, prevalence of myelofibrosis and splenomegaly, and frequencies of thrombotic events and treatment did not differ between WHO-ET and BCSH-only-ET, but BCSH-only-ET patients showed higher WBC counts and higher JAK2V617F mutation frequencies. Conclusion: The BCSH criteria diagnosed ET in a broader range of patients encompassing a significant number of patients who would otherwise be diagnosed as pre-PMF or MPN-u. [ABSTRACT FROM AUTHOR]

Sphingosine‐1‐phosphate (S1P) is a bioactive lysosphingolipid that is found in relatively high concentration in human plasma. Erythrocytes, endothelial cells, and activated platelets are the main sources of circulating S1P. The majority of plasma S1P is transported bound to high‐density lipoprotein (HDL) and albumin. In recent years, HDL‐bound S1P attracted much attention due to its cardioprotective and anti‐atherogenic properties. We have previously found that endurance‐trained athletes are characterized by higher plasma S1P concentration compared to untrained individuals. This finding prompted us to examine the effect of endurance training on S1P metabolism in blood. Thirteen healthy, untrained, male subjects completed an 8‐week training program on a rowing ergometer. Three days before the first, and 3 days after the last training session, blood samples were drawn from an antecubital vein. We found that total plasma S1P concentration was increased after the training. Further analysis of different plasma fractions showed that the training selectively elevated HDL‐bound S1P. This effect was associated with activation of sphingosine kinase in erythrocytes and platelets and enhanced S1P release from red blood cells. We postulate that increase in HDL‐bound S1P level is one of the mechanisms underlying beneficial effects of regular physical activity on cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background and objective In regenerative dentistry, platelet preparations are applied to stimulate bone healing and periodontal regeneration. Here, we pursue a strategy where bone substitutes are used as carriers for platelet-released supernatants. The mitogenic capacity and release kinetics of loaded bone substitutes were assessed. Material and Methods Platelet-released supernatants of washed platelets (washed PRS) and platelet-released supernatants of unwashed platelets (unwashed PRS) were lyophilized onto the bone substitutes deproteinized bovine bone mineral, hydroxyapatite and β-tricalcium phosphate. Scanning electron microscopy images were taken. Supernatants of bone substitutes were collected at hours 1, 3, 6, 24, and 48 and medium was replaced. We evaluated the protein content with the bicinchoninic acid assay and the effect on proliferation using bioassays with human periodontal fibroblasts. Release of growth factors from the loaded bone substitutes was measured based on the platelet-derived growth factor isoform ( PDGF- BB) and thrombin immunoassays. Furthermore, we assessed DNA and RNA content of washed PRS and unwashed PRS. Results Unwashed PRS showed higher total protein concentrations than washed PRS, while the concentration of PDGF- BB, thrombin, DNA, RNA and their mitogenic effect was not significantly different. The bone substitute materials adsorbed protein over time but no significant changes in overall appearance was found. Supernatants collected from unwashed PRS-loaded bone substitute after 1 h induced a potent mitogenic response in periodontal fibroblasts. This pro-mitogenic capacity of the supernatants decreased over the observation period. Supernatants of washed PRS-loaded bone substitutes did not induce a substantial mitogenic effect. Levels of PDGF- BB, thrombin and protein were higher in supernatants of unwashed PRS-loaded bone substitutes than of washed PRS-loaded bone substitutes. Conclusion Bone substitutes loaded with unwashed PRS, but not bone substitutes loaded with washed PRS show continuously declining release kinetics. These data suggest that plasma components in platelet preparations can modify the release kinetics profile. [ABSTRACT FROM AUTHOR]