Comparison of assays measuring extracellular vesicle tissue factor in plasma samples: communication from the ISTH SSC Subcommittee on Vascular Biology.

Background: Scientific and clinical interest in extracellular vesicles (EVs) is growing. EVs that expose tissue factor (TF) bind factor VII/VIIa and can trigger coagulation. Highly procoagulant TF-exposing EVs are detectable in the circulation in various diseases, such as sepsis, COVID-19, or cancer.

Extracellular vesicles from activated platelets possess a phospholipid-rich biomolecular profile and enhance prothrombinase activity.

Background: Extracellular vesicles (EVs), in particular those derived from activated platelets, are associated with a risk of future venous thromboembolism.

Objectives: To study the biomolecular profile and function characteristics of EVs from control (unstimulated) and activated platelets.

Methods: Biomolecular profiling of single or very few (1-4) platelet-EVs (control/stimulated) was performed by Raman tweezers microspectroscopy.

Enhanced Blood Clotting After Rewarming From Experimental Hypothermia in an Intact Porcine Model.

Due to functional alterations of blood platelets and coagulation enzymes at low temperatures, excessive bleeding is a well-recognized complication in victims of accidental hypothermia and may present a great clinical challenge. Still, it remains largely unknown if hemostatic function normalizes upon rewarming. The aim of this study was to investigate effects of hypothermia and rewarming on blood coagulation in an intact porcine model.

A rapid, sensitive, and specific assay to measure TF activity based on chromogenic determination of thrombin generation.

Background: Most tissue factor (TF) activity assays are based on measurement of factor X (FX) activation by TF in the presence of factor VII (FVII)/FVIIa. This requires long incubation, which may result in TF-independent activity of FX and inaccurate measurement of TF activity.

Aim: To develop a sensitive and specific TF activity assay, which does not register a non-specific TF activity, using commercial coagulation factors.

Anti-β-glycoprotein I autoantibodies influence thrombin generation parameters via various mechanisms.

Introduction: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by recurrent thrombotic events, pregnancy loss and thrombocytopenia and the presence of antiphospholipid antibodies (APL). The exact pathomechanism of APS is still unknown, thus we investigated the effect of anti-β-glycoprotein I (anti-βGPI) on thrombin generation in different plasma samples.

Methods: For the separation of anti-βGPI IgG, overall 12 APS patients were selected.

Detection of tissue factor in platelets: why is it so troublesome?

Tissue factor (TF) is the most important trigger for the extrinsic coagulation pathway. TF, earlier denoted as thromboplastin, has always been a mystery since its discovery due to its abundant presence in most human tissues but not blood. The latter has been extensively studied in a vast quest for possible sources of blood-borne TF yielding many conflicting findings and confusing conclusions regarding the presence of TF mRNA, protein or functional procoagulant activity in virtually all blood cells.

Improving scientific practice in sports-associated drug testing.

Antidoping work is heavily based on scientific analyses of biological material, such as urine and blood. Because of the high stakes both for sports and for the athletes involved it is important that analyses are performed and interpreted in agreement with established scientific standards and professional norms. This is not always the case, as we document here.

Cold-pressed minke whale oil reduces circulating LDL/VLDL-cholesterol, lipid oxidation and atherogenesis in apolipoprotein E-deficient mice fed a Western-type diet for 13 weeks.

Background: Long-chain n3-polyunsaturated fatty acids (LC n3-PUFA) are well known for their anti-inflammatory activity and their impact on cardiovascular disease. Cold-pressed whale oil (CWO) has half the amount of LC n3-PUFA compared to cod liver oil (CLO). Still, there has been observed more pronounced beneficial effects on cardiovascular disease markers from intake of CWO compared to intake of CLO in human intervention studies.

Antioxidant and Anti-Inflammatory Activities in Extracts from Minke Whale () Blubber.

Intake of long-chain omega-3 polyunsaturated fatty acids (LC-n3-PUFA) is commonly recognized to reduce cardiovascular disease (CVD). In previous studies, cold-pressed whale oil (CWO) and cod liver oil (CLO) were given as a dietary supplement to healthy volunteers. Even though CWO contains less than half the amount of LC-n3-PUFA of CLO, CWO supplement resulted in beneficial effects on anti-inflammatory and CVD risk markers compared to CLO.

Laboratory characterization of leukemic cell procoagulants.

Background: In acute myeloid leukemias, there is an increased chance to develop thrombotic disorders. We hypothesized that in addition to leukemic promyelocytes, monocytic leukemia cells may also have a higher procoagulant activity.

Methods: Fibrin formation was assessed by a one-stage clotting assay using a magnetic coagulometer.

Doping and drug testing: Anti-doping work must be transparent and adhere to good scientific practices to ensure public trust.

Controversial decisions to ban athletes and the Russian doping scandal have raised doubts about the reliability of doping controls in professional sports. To ensure fairness and due process, doping tests must be transparent and adhere to the best scientific standards. [Image: see text]

The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2.

Background: Barettin is a marine natural compound with reported anti-inflammatory and antioxidant properties. The combination of these effects led us to explore barettin further as an inhibitor of atherosclerosis development.

Methods: The effect of barettin on MCP-1 and IL-10 secretion from activated immune cells was detected by ELISA.

The key roles of complement and tissue factor in Escherichia coli-induced coagulation in human whole blood.

The complement system and the Toll-like (TLR) co-receptor CD14 play important roles in innate immunity and sepsis. Tissue factor (TF) is a key initiating component in intravascular coagulation in sepsis, and long pentraxin 3 (PTX3) enhances the lipopolysaccharide (LPS)-induced transcription of TF. The aim of this study was to study the mechanism by which complement and CD14 affects LPS- and Escherichia coli (E.

Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia. A randomised, placebo-controlled study.

Tetraplegic patients have increased risk of venous thrombosis despite anti-thrombotic prophylaxis. Moreover, they have blunted plasma variations in melatonin and altered diurnal variation of several haemostatic markers, compared with able-bodied. However, whether healthy individuals and tetraplegic patients, with or without melatonin, display abnormalities in thrombin generation during a 24-hour (h) cycle, is unknown.

Procoagulant and proinflammatory effects of red blood cells on lipopolysaccharide-stimulated monocytes.

Background: We aimed to evaluate the mechanisms underlying the effects of red blood cells (RBCs) on the reactivity of monocytes to lipopolysaccharide (LPS) stimulation.

Methods: Measurements of tissue factor (TF) antigen and activity were performed on freshly isolated white blood cells (WBCs)/platelets resuspended in heparinized plasma, as well as cultured monocytic cells.

Results: In a dose-dependent manner, RBCs significantly enhanced LPS-induced TF activity and antigen levels in blood monocytes; potentiation of TF activity by both human and murine RBCs did not require the presence of neutrophils and/or platelets.

Alterations in markers of coagulation and fibrinolysis in patients with Paroxysmal Nocturnal Hemoglobinuria before and during treatment with eculizumab.

Background: Paroxysmal Nocturnal Hemoglobinuria is characterized by complement-mediated hemolysis and an increased thrombosis risk. Eculizumab, an antibody to complement factor C5, reduces thrombotic risk via unknown mechanisms. Clinical observations suggest that eculizumab has an immediate effect.

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.

Study Design: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia.

Objectives: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement.

Pro- and anti-inflammatory effects of histamine on tissue factor and TNFα expression in monocytes of human blood.

Background: Histamine is classified as an inflammatory mediator and has been reported to have anti- as well as pro-inflammatory properties. The aim of this study was to explore the role of histamine on the production of LPS-induced tissue factor (TF) activity and TNFα in monocytes of whole blood in the absence and presence of TNFα or PMA.

Methods: Human blood anticoagulated with Fragmin was subjected to stimulation by LPS in the presence and absence of TNFα or PMA and various concentrations of histamine.