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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.

Fungal hyphae constitute a special challenge for the immune system, since they are too large to be phagocytosed. This review summarizes our current knowledge on those immune cells that are able to attack and eliminate hyphae and we discuss the different means that are employed by these cells in order to kill hyphae., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recently, ketamine has been investigated as a potential antidepressant option for treatment resistant depression. Unlike traditional drugs, it yields immediate effects, most likely via increased glutamatergic transmission and synaptic plasticity. However, ketamine administration in humans is systemic and its long-term impact on blood parameters has not yet been described in clinical studies. Here we investigated potential sustained effects of ketamine administration (0.5 mg/kg ketamine racemate) on hematological and biochemical values in plasma and serum in a randomized double-blinded study. 80 healthy young participants were included and whole blood samples were collected 5 days before, and 14 days after the infusion. To assess the group effect, repeated measure analyses of co-variance (rmANCOVA) were conducted for the following blood parameters: levels of sodium, potassium, calcium, hemoglobin and number of erythrocytes, lymphocytes, and thrombocytes. RmANCOVA revealed a significant time by treatment effect on thrombocyte levels (F 1, 74 = 13.54, p < 0.001, eta = 0.155), driven by an increase in the ketamine group (paired t-test, t = -3.51, df = 38, p = 0.001). Specificity of thrombocyte effect was confirmed by logistic regression, and in addition, no other coagulation parameters showed significant interaction. Moreover, the relative increase in the ketamine group was stable across sexes and not predicted by age, BMI, smoking, alcohol or drug use, and contraception. Our results describe aftereffects of sub-anesthetic ketamine administration on blood coagulation parameters, which should be considered especially when targeting psychiatric populations with relevant clinical comorbidities., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

The critical care and perioperative settings are high consumers of blood products, with multiple units and different products often given to an individual patient. The recommendation of this review is always to consider the risks and benefits for a specific blood product for a specific patient in a specific clinical setting. Optimize patient status by treating anemia and preventing the need for red blood cell transfusion. Consider other options for correction of anemia and coagulation disorders and use an imperative non-overtransfusion policy for all blood products., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide ( MTAB GNRs). Interestingly, even after cellular accumulation of high amounts of MTAB GNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro. In vivo, after intravenous administration, the majority of GNRs accumulated in mouse spleen followed by lungs and liver. Microscopic examination of the blood and spleen showed that GNRs interacted with white blood cells (mononuclear and polymorphonuclear leukocytes) and thrombocytes, and were delivered to the spleen red pulp mainly as GNR-thrombocyte complexes. Importantly, no acute toxic effects of MTAB GNRs administered as 10 or 50 μg of gold per mice, as well as no pathological changes after their high accumulation in the spleen were observed, indicating good tolerance of MTAB GNRs by living systems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The historical concentration of thrombocytes is an average of three subsequent concentrations of thrombocytes before donation (during two years) in blood of donors. The evaluation was applied to characteristics of historical concentration of thrombocytes concerning concentration of thrombocytes in blood of 99 regular donors before every donation of apheresis thrombocytes. It is established that less than 20% dispersion between historical concentration of thrombocytes and value obtained in day of donation is observed in 96% of regular donors. The average concentration of thrombocytes before three subsequent donations of apparatus apheresis in males is statistically higher than in females: 235,2±6,7 and 222,1±11,0 (× 109 cells/l) correspondingly (p < 0,05). The concentration of thrombocytes has no relationship with intervals between donations. There is no statistically significant differences between historical concentration of thrombocytes and concentration of thrombocytes before fourth donation and in general and between separate donations both in males and females. It is appropriate to analyze quality of concentrates of thrombocytes received through program accounting historical concentration of thrombocytes., Competing Interests: The authors declare no conflict of interest.

Background: Platelets are responsible for primary haemostasis. Patients with suspected platelet dysfunction require prompt clinical assessment when qualifying for emergency surgical procedures. The purpose of this article is to present our experience in platelet function assessment using whole-blood multiple electrode aggregometry (MEA) in various clinical conditions., Case Reports: Retrospective analysis of three patients with thrombocytopathy associated with normal platelet counts was performed using standard laboratory tests complemented by MEA. In two cases, platelet dysfunction was due to antiplatelet drugs, while in one other case it was caused by chronic kidney disease., Conclusions: Anaesthesiologists strive to make the perioperative period as safe as possible. Platelet function assessment should be considered in every patient in whom haemostatic disturbances are suspected. MEA provides support for clinical decision-making, especially in patients who undergo haemodialysis or require antiplatelet therapy, and are in need of emergency surgery.

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., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Platelets display a number of properties besides the crucial function of repairing a damaged vascular endothelium and stopping bleeding. Platelets constitutively express molecules that are classically acknowledged to function in primary haemostasis. Platelets specialize in pro-inflammatory activities, and can secrete a large number of molecules, many of which display biological response modifier functions. Recently, platelets expressing receptors for infectious and possibly noninfectious danger signals were shown to be involved in pathophysiological reactions including an immune-inflammatory response. In sepsis, platelets play a key role in immunothrombosis, participate in the formation of NETs (neutrophil extracellular trap) resulting in the trapping and killing of pathogens and are one of the main factors influencing mortality.

Neutrophils are an key part of the innate immune system in the host's defences against pathogens. Circulating neutrophils are recruited at the sites of infection or sterile inflammation in response to pathogen and host-derived inflammatory mediators. In addition to phagocytosis and degranulation, neutrophils display the release of NETs in order to restrain infection. NETs are able to entrap and kill microbes, and display proinflammatory and prothrombotic properties.

The physical load provokes reliable alterations in the blood coagulation system, specifically increasing of blood coagulability, including increasing of thrombus formation. However, the long-term alterations in the blood coagulation system in sportsmen are still unexplored. The article demonstrates that in sportsmen parameters за aggregation capacity of thrombocytes have significant long-term alterations during annual training competition macro-cycle. The maximal alterations have to do with value of lag-phase and area under the curve of aggregation of thrombocytes. The lag-phase no the curve of aggregation of thrombocytes under stimulation with collagen is significantly increased in termination of competition period; it decreases up to control values during resting time in transition period and significantly falls down below control group indices during preparatory period. The area under the curve of aggregation of thrombocytes under stimulation with collagen is reliably decreased as to control values at the termination of competition period. It exceeds the control level during transition period and it has no reliable differences against control values during preparatory period. The alterations of functional activities of thrombocytes significantly effect functioning of immune system that modulates course of processes of adaptation to sport activities in general., Competing Interests: The authors declare no conflict of interest.

Background: This study strives to define prognostic models for outcome after surgery for malignant pancreatic neuroendocrine tumors., Methods: Forty-one patients were included. Prognostic models for mortality and disease recurrence were developed with multivariate binary logistic regression., Results: The proposed prognostic model for tumor recurrence risk after surgery in percentage (AUROC = 0.774, 95%CI = 0.611-0.937) is: Risk in % = Exp(Y)/(1 + Exp(Y)), with Y = -4.360 + (0.015 × tumor diameter in cm) + (0.010 × preoperative platelet count in thousand/μl) + (1.077 × distant metastases, if yes = 1; if no = 0) + (-0.026 × Ki-67-positive cells in %) + (-1.086 × upper abdominal pain, if yes = 1; if no = 0). The proposed prognostic model for observed 3-year survival probability after surgery in % (AUROC = 0.932, 95%CI = 0.857-0.999) is: Survival probability in % = Exp(Y)/(1 + Exp(Y)), with Y = -12.492 + (0.054 × preoperative platelet count in thousand/μl) + (0.112 × minimal distance of the resection margin from the tumor in mm) + (-1.574 × number of positive lymph nodes) + (2.292 × histological tumor infiltration, if yes = 1; if no = 0) CONCLUSIONS: The platelet count was identified as a relevant risk factor. Proposed prognostic models with good model-fit display properties that indicate potential clinical usefulness., (© 2015 Wiley Periodicals, Inc.)

Sepsis is a life-threatening condition characterized by a systemic response to microbial infection. Despite considerable progress in intensive care medicine, the incidence of sepsis and the number of sepsis-related deaths are increasing world-wide. There is a complex relationship between the coagulation, immune and inflammatory systems in sepsis. Activation of the coagulation cascade in sepsis is a result of a pathogen invasion and is a part of a immuno-inflammatory host response. In sepsis, the close cooperation of the immune and coagulation systems through cross signalling results in immunothrombosis. According to a recently described new theory, immunothrombosis is a immune response in which the local activation of coagulation facilitates the recognition and destruction of pathogens. Small amounts of clot formation are beneficial for the host because of bacteria trapping and prevention of the systemic spread of infection. Sepsis is a dynamic syndrome and in all patients with sepsis coagulation changes may progress from a normal profile to hypercoagulability and hypofibrinolysis, hyperfibrinolysis, and ultimately hypocoagulability.

Fish health is a growing concern as pets, education, and aquaculture evolves. For the veterinary staff, fish handling, diagnostics, medicine, and surgery may require specialized training and equipment in comparison with terrestrial and arboreal animals, simply because of their aquatic nature and diversity. Fish hematology is one diagnostic tool that may not require additional equipment, may be inexpensive, and provide useful information in guiding treatment options. Challenges involving hematology may include handling and restraint, venipuncture, evaluation, and interpretation. In this article, strategies for these challenges are discussed for teleost (bony fish) and elasmobranch (cartilaginous fish) fish types., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts either as an intracellular messenger or as a ligand for its membrane receptors. S1P is a normal constituent of blood, where it is found both in plasma and blood cells. Compared with other cell types, sphingolipid metabolism in erythrocytes and platelets has unique features that allow the erythrocytes and platelets to accumulate S1P. In plasma, S1P is bound mainly to HDLs and albumin. Of note, metabolism and biological activity of S1P is to a large extent affected by the type of its carrier. Plasma S1P is characterized by a short half-life, indicating rapid clearance by degradative enzymes and the presence of high-capacity sources involved in maintaining its high concentration. These sources include blood cells, vascular endothelium, and hepatocytes. However, the extent to which each of these contributes to the plasma pool of S1P is a matter of debate. Circulating S1P plays a significant physiological role. It was found to be the key regulator of lymphocyte trafficking, endothelial barrier function, and vascular tone. The purpose of this review is to summarize the present state of knowledge on the metabolism, transport, and origin of plasma S1P, and to discuss the mechanisms regulating its homeostasis in blood., (Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.)

Unlabelled: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life., Methods: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose-response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design., Results: Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K(+), Ca(2+), and PO4 (3-) was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg(2+), prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values., Conclusion: Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In contrast, BP-C1 corrected abnormalities. No hematological and biochemical toxicity was observed.

Birds often suffer from skin injuries of different aetiology. Platelet-rich plasma (PRP) is successfully used for improvement of wound healing in humans and in some mammalian species (e.g. horses, dogs and cats), but experience with its application in avian patients has not yet been published. Therefore, the aim of this study was to test a quick method for the counting of isolated avian platelets and mononuclear leukocytes and to find an appropriate carrier for their application to the wounds of birds. It seems that flow cytometry can be used for the quick counting of isolated cells and the discrimination of thrombocytes, lymphocytes and eventually monocytes or debris. Of the tested gels and sponges routinely used for improvement of wound healing, a gelatin sponge (Gelaspon®) providing the highest numbers and viability of isolated cells proved to be the best carrier.