Are Gamers Prone to eThrombosis during Long Gaming Sessions?

During the last two decades, several cases of venous thrombosis (VTE) after a prolonged period at a computer have been described, denominated as "eThrombosis". Video gaming on a computer has become very popular and can be a social activity where several players gather to play against each other or in a virtual environment for several days ("LAN (i.e., Local Area Network) parties") where the participants are sedentary and consuming calorie-rich food items. The aim of this study was to investigate potential coagulation activation during a 42 h LAN party. Nine male gamers volunteered for the LAN party. Citrated blood was sampled before and every 6 h, and plasma was analyzed for thrombin generation, thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. Thrombin generation increased slightly but not significantly during the LAN party, whereas the coagulation activation markers were unchanged. These results do not indicate that the coagulation system is activated significantly during 42 h of gaming with minimal physical activity. Although increased activity cannot be excluded, it does not directly indicate a risk of VTE in general.

Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy successfully treated with Eculizumab: A case report and review of the literature.

Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso-occlusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vaso-occlusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. Case Presentation A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vaso-occlusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy and refractory post-operative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. Conclusion Treatment with the anti-C5 monoclonal antibody eculizumab which targets and inhibits terminal complement system activation reversed the deleterious cascade of events in this patient with sickle cell disease.

A simplified HPLC-based method for measuring unconjugated bilirubin, bilirubin-monoglucuronide, bilirubin-diglucuronide, and delta-bilirubin in plasma with increased conjugated bilirubin.

Prolonged icterus is an important and common problem in neonatology and accurate determination of the different bilirubin species, including differentiation between delta-bilirubin and mono- and di-conjugated bilirubin, is useful for diagnostic purposes. However, most bilirubin measurements routinely performed in the clinical laboratory are hampered by the lack of separation of the four bilirubin fractions (unconjugated bilirubin, mono-conjugated bilirubin, di-conjugated bilirubin, and delta-bilirubin). Herein, we propose a high-performance liquid chromatography-based method, independent of commercially available standards or reliable molar absorption coefficients, for the determination of bilirubin fractions in blood samples from icteric patients. The method is a robust and reliable candidate for a semi-automatized setup for measuring the various bilirubin fractions in a specialized laboratory handling samples from clinics with expertise in biliary disease.

The Physiological and Cardiologic Effects of Long Video Gaming Sessions in Adult Males.

The effect of long gaming sessions on energy intake, caffeine intake, blood pressure, heart rate, heart rate variability, and biochemical cardiac injury markers is unknown. The objective of this exploratory study was to investigate the changes in healthy male adults during two consecutive 18-hour sedentary video gaming sessions. Nine participants were enrolled in the study. Energy intake was noted in food diaries. Heart rate variability was monitored continuously; blood pressure and cardiac injury markers were measured every three to six hours. During the 42-hour study, the participants had an energy and caffeine intake of 8004.9 kcal and 1354.4 mg, respectively. The participants had a significant decrease in energy intake in the second session (p=0.01). A strong, negative correlation was found between body mass index and total energy intake (R=-0.84, p=0.005) and waist circumference and total energy intake (R=-0.70, p=0.036) in the first session. No nightly dip in blood pressure or heart rate was observed. Based on this study, long-term adverse effects of gaming cannot be ruled out. The non-dip of HR and BP suggests that long gaming sessions could be detrimental to cardiovascular health long term.

Severe Peripheral Neuropathy From Treatment With Arsenic Trioxide in a Patient Suffering From Acute Promyelocytic Leukemia.

Treatment with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is standard treatment for patients suffering from acute promyelocytic leukemia (APL). Peripheral neuropathy is a common sign of arsenic poisoning but reports of peripheral neuropathy from patients treated with ATO for APL are limited. We here present a case of a woman treated with standard regimes of ATRA-ATO for APL, who subsequently developed severe peripheral neuropathy from ATO poisoning.

Use of genetic testing for hypolactasia trait in the North Denmark Region.

OBJECTIVE: Lactose intolerance (LI) may be considered in patients with unspecific gastrointestinal symptoms, but there is no clear consensus on when and how to diagnose the disorder. The LCT-13910 CC genotype is associated with acquired primary lactase deficiency (adult-type hypolactasia; ATH). We aimed to describe the number of tests and test results in the North Denmark Region considering patient age, geographical origin and repeated testing. METHODS: Retrospective evaluation of the polymerase chain reaction-based LCT-13910 genotype tests registered in the clinical laboratory information system (LABKA II) with data linkage to Danish nationwide registers. RESULTS: Between 18 May 2007 and 31 December 2018, a total of 23,560 individuals were tested. There was a sevenfold increase in the number of tests performed during the study period. About 9.8% of the tests performed in 2018 were repeated testing in the same individuals. Overall, 8.8% of tested individuals were younger than 5 years, 90.7% were of Danish origin and 5.5% originated from outside of Europe. The LCT-13910 CC genotype was identified in 13.3% of all tested individuals, in 16.0% of children younger than 5 years, in 6.8% of Danish individuals and in 90.9% originating from outside of Europe. CONCLUSIONS: In the North Denmark Region, a marked increase in the use of genetic testing for hypolactasia was observed and repeated testing was frequent. Furthermore, the use of the test and the test results were dependent on patient age and geographical origin. Results inform the debate on when and how to use genetic testing in the diagnosing of LI.

Elevated blood plasma levels of tissue factor-bearing extracellular vesicles in patients with atrial fibrillation.

BACKGROUND: The risk of thrombus formation in the left atrial appendage (LAA) in patients with atrial fibrillation (AF) may result from blood stasis, local endocardial changes, and/or changed blood composition. Extracellular vesicles (EVs), especially subtypes exposing tissue factor (TF), have procoagulant capacity. We hypothesized that blood concentrations of TF-bearing EVs and other procoagulant biomarkers are elevated in AF patients, particularly in the LAA lumen. METHODS: From 13 AF patients and 12 controls a venous blood sample was drawn prior to cardiac surgery. Intraoperatively, venous blood and blood directly from the LAA was drawn. Plasma levels of EVs, including TF- and cell type specific antigen-bearing EVs, were measured using a protein microarray platform. Plasma levels of TF, von Willebrand factor (vWF), cell free deoxyribonucleic acid (cf-DNA), procoagulant phospholipids (PPLs), and total submicron particles were also evaluated. RESULTS: Significantly higher EV levels, including a several-fold higher median level of TF-bearing EVs were measured in AF patients compared with controls. Median concentrations of TF and vWF were approximately 40% and 30% higher, respectively, in the AF group than in the control group, while no significant differences in levels of cf-DNA, PPLs, or total submicron particles were observed. No significant differences in levels of any of the measured analytes were observed between intraoperative venous and LAA samples. CONCLUSIONS: Increased plasma concentrations of TF in AF patients are accompanied and probably at least partly explained by increased levels of TF-bearing EVs, which may be mechanistically involved in increased thrombogenicity in AF patients.

Postprandial Increase in Blood Plasma Levels of Tissue Factor-Bearing (and Other) Microvesicles Measured by Flow Cytometry: Fact or Artifact?

Tissue factor (TF)-bearing microvesicles (MVs) and exosomes may play a role in hemostasis and thrombosis. MVs may be quantified by flow cytometry (FC)-based detection of phosphatidylserine (PS)-positive submicron particles carrying specific antigens, although interference from lipoproteins complicates this approach. In this study, we evaluated the effect of food intake on blood levels of TF-bearing particles measured by FC and small extracellular vesicles (EVs) measured by a protein microarray-based test termed EV Array. Platelet-free plasma (PFP) was obtained from 20 healthy persons in the fasting state and 75 minutes after consumption of a meal. Postprandial changes in the concentration of PS-positive particles, including subgroups binding labeled antibodies against TF, CD41, CD146, and CD62E, respectively (FC), small EVs (EV Array), and TF antigen and procoagulant phospholipids (PPLs) were measured. Furthermore, we tested the effect on FC results of in vitro addition of lipoproteins to fasting PFP. We found significantly increased plasma concentrations of PS-positive particles and all examined subgroups postprandially, while no changes in small EVs, PPL, or TF antigen levels were found. Levels of all types of particles measured by FC were also elevated by lipoprotein spiking. In conclusion, meal consumption as well as in vitro addition of lipoproteins to fasting plasma induces increased levels of PS-positive particles as measured by FC, including TF-positive subtypes and subtypes exposing other antigens. While the observed postprandial increase may to some extent reflect elevated MV levels, our results indicate a substantial interference from lipoproteins.

Prospects and limitations of antibody-mediated clearing of lipoproteins from blood plasma prior to nanoparticle tracking analysis of extracellular vesicles.

Introduction: Nanoparticle tracking analysis (NTA) enables measurement of extracellular vesicles (EVs) but lacks the ability to distinct between EVs and lipoproteins which are abundantly present in blood plasma. Limitations in ultracentrifugation and size exclusion chromatography applied for EV isolation may result in inadequate EV purification and preservation. In this proof of concept study, we aimed to evaluate the potential of antibody-mediated removal of lipoproteins from plasma prior to extracellular vesicle (EV) analysis by nanoparticle tracking analysis (NTA). Methods: Ten platelet-free plasma (PFP) samples from healthy fasting subjects were incubated with magnetic beads coated with antibodies against apolipoprotein B-48 and B-100 (ApoB). Plasma samples were analysed with NTA before and after application of the bead procedure. Four fasting PFP samples were analysed with an ELISA specific for human ApoB to estimate the degree of removal of lipoproteins and EV array analysis was used for identification of possible EV loss. Results: The magnetic bead separation procedure resulted in a median reduction of the particle concentration in plasma by 62% (interquartile range 32-72%). The mean size of the remaining particles generally increased. ApoB concentration was reduced to a level close to the background signal, whereas a median reduction of the EV content by 21% (range 8-43%) was observed. Conclusion: Anti-ApoB antibody coated magnetic beads may hold potential for removal of lipoproteins from human PFP prior to EV measurement by NTA but some artefactual effect and EV loss may have to be endured.

Preanalytical, analytical, and biological variation of blood plasma submicron particle levels measured with nanoparticle tracking analysis and tunable resistive pulse sensing.

BACKGROUND: Nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS) enable measurement of extracellular vesicles (EVs) in blood plasma but also measure other particles present in plasma. Complete isolation of EVs from similarly sized particles with full EV recovery is currently not possible due to limitations in existing isolation techniques. AIM: This study aimed to evaluate preanalytical, analytical, and biological variation of particle measurements with NTA and TRPS on blood plasma. METHODS: Blood from 20 healthy subjects was sampled in the fasting and postprandial state. Platelet free plasma (PFP) was analyzed immediately and after a freeze-thaw cycle. Additionally, the effect of prandial state and a freeze-thaw cycle on EV-enriched particle fractions obtained via size-exclusion chromatography (SEC) was examined. RESULTS: We observed analytical linearity in the range of 1.0-10.0 × 10(8) particles/mL for NTA and 1.0 × 10(8)-1.8 × 10(9) particles/mL for TRPS. The analytical variation was generally below 10%. A considerable intra- and inter-individual variation was demonstrated with estimated reference intervals of 1.4 × 10(11)-1.2 × 10(12) particles/mL for NTA and 1.8 × 10(8)-1.6 × 10(9) particles/mL for TRPS. Food intake and to a lesser extent a freeze-thaw cycle affected particle populations in PFP and, similarly, in EV-enriched fractions. CONCLUSION: In this study NTA and TRPS enabled acceptably precise concentration and size measurement of submicron particles in PFP. An appreciable intra- and inter-individual biological variation was observed. In studies on particle populations in PFP or EV-enriched fractions, we recommend analysis of fresh, fasting samples.