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Patients with obstructive jaundice are conventionally described as hypocoagulable due to vitamin K malabsorption. However, associated underlying malignancy and synthetic liver dysfunction are mediators of hypercoagulability. The actual effect of biliary obstruction on the coagulation profile is not well characterised. This study aimed to define the coagulation status of patients with established biliary obstruction using rotational thromboelastometry (ROTEM). This prospective cohort study, conducted in an Australian metropolitan hospital, included patients with a total bilirubin level of >150 umol/L and biliary obstruction on imaging. The primary outcome was the coagulation profile assessed using ROTEM. 20 patients were included (median age 74.5 years), 15 were male and 17 had a malignant cause for biliary obstruction. The median bilirubin level was 209 umol/L (IQR: 175.0 umol/L – 255.8 umol/L). On ROTEM, all patients had normal or reduced clot formation times, and normal or increased maximum clot firmness. This confirmed all patients had a normal or hypercoagulable clotting profile, and none were auto-anticoagulated. Vitamin K administration before ROTEM did not vary the coagulation profile. Patients with established biliary obstruction and jaundice, predominantly due to malignancy, were normo or hypercoagulable. The belief that obstructive jaundice is associated with a hypocoagulable state should be questioned. [Display omitted] [ABSTRACT FROM AUTHOR]

Embolization is a leading cause of mortality, yet we know little about clot rupture mechanics. Fibrin provides the main structural and mechanical stability to blood clots. Previous studies have shown that altering the concentration of coagulation activators (thrombin or tissue factor (TF)) has a significant impact on fibrin structure and viscoelastic properties, but their effects on rupture properties are mostly unknown. Toughness, which corresponds to the ability to resist rupture, is independent of viscoelastic properties. We used varying TF concentrations to alter the structure and toughness of human plasma clots. We performed single-edge notch rupture tests to examine fibrin toughness under a constant strain rate and we assessed viscoelastic mechanics using rheology. We utilized fluorescent confocal and scanning electron microscopy (SEM) to quantify the fibrin network structure under varying TF concentrations. Our results revealed that increased TF concentration resulted in increased number of fibrin fibers with a reduction in network pore size, thinner and shorter fibrin fibers. Increasing TF concentration yielded a maximum toughness at mid-TF concentration, such that fibrin diameter and number of fibers underlie a complex role in influencing the rupture resistance of blood clots, resulting in a nonmonotonic relationship between TF and toughness. A simple mechanical model, built on our findings from our Fluctuating Spring (FS) computational model, adopted to estimate the fracture toughness (critical energy release rate) as a function of TF predicts trends that are in good agreement with experiments. The differences in mechanical responses point to the importance of studying the structure-function relationships of fibrin networks, which may be predictive of the tendency for embolization. Fibrin, a naturally occurring biomaterial, is the main mechanical and structural scaffold of blood clots that provides the necessary strength and stability to the clot, ensuring effective stemming of bleeding. The rupture of blood clots can result in the blockage of downstream vessels thereby blocking blood flow and oxygen supply. The fibrin network structure has been shown to influence the viscoelastic mechanical properties of clots, but has not been explored for fracture mechanics. Here, we modulate the fibrin network structure by varying the concentration of Tissue Factor (TF). Interestingly, the association between TF concentration and maximum toughness of the clots is non-monotonic. The variations in mechanical responses highlight the importance of studying the structure-function relationships of fibrin networks, as these may predict the tendency for embolization. [Display omitted] [ABSTRACT FROM AUTHOR]

Many studies have demonstrated the involvement of proteases in gut physiology and pathophysiology over the recent years. Among them, thrombin has appeared for a long time as an old player only involved in blood clotting upon tissue injury. The fact that thrombin receptors (Protease-Activated Receptors-1 and -4) are expressed and functional in almost all cell types of the gut, contributing to barrier, immune or motility functions, suggested that thrombin could actually be at the crossroad of intestinal physiology. Recent work has unraveled the constitutive release of active thrombin by intestinal epithelial cells, opening new research avenues on the role of thrombin in the gut. These roles are considered in the present review, as well as the regulation of thrombin in the gut. The potential of thrombin as a target for treatments of intestinal pathologies is also discussed here. • Physiology and Pathophysiology of Thrombin in the Intestine. • Thrombin: a Gut protease with pleiotropic mechanisms. • Thrombin is a major signal to microbiota and in inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Chitosan, a derivative of chitin derived from the gladius of the marine cephalopod Doryteuthis sibogae , has drawn interest in biomedical research because of its possible antibacterial effects on human infections and inhibition of blood clotting. Chitosan was extracted from chitin isolated from the gladius of D. sibogae via demineralization and deproteination. Chitosan was structurally characterized using FT-IR, XRD, and FESEM. Additionally, the disc diffusion method was used to investigate the antibacterial efficacy of chitosan against three human pathogens. Effective antibacterial activity was demonstrated against both Gram-positive and Gram-negative microorganisms. Chitosan is a potent anticoagulant in anticoagulant assays employing activated partial thromboplastin time (APTT) and prothrombin time (PT). [Display omitted] • Chitosan, deacetylated derivative of chitin was isolated from marine cephalopod. • Chitosan was structurally characterized through FT-IR, XRD, and SEM analysis. • Antibacterial efficacy of chitosan was analyzed. • Anticoagulant property of chitosan was evaluated by calculating APTT and PT. [ABSTRACT FROM AUTHOR]

Fibrin has unique biomechanical properties which are essential for its role as a scaffold for blood clots. Fibrin is highly extensible and demonstrates significant strain stiffening behaviour, which is essential for stress-distribution in the network. Yet the exact structures of fibrin at the sub-fibre level that contribute to its unique biomechanical characteristic are unknown. Here we show how truncations of the fibrinogen αC-region impact the biomechanical properties of fibrin fibres. Surprisingly, absence of the complete αC-region did not influence the low strain modulus of fibrin fibres but led to premature fibre rupture and decreased extensibility. Intermediate effects were observed with partial deletion of the αC-region, reflected by intermediate rupture stress and toughness. However, overall strain-stiffening behaviour remained even in absence of the αC-region, indicating that strain stiffening is not due to stress being transferred from the αC-region to the protofibril backbone. Upon stress-relaxation, decay constants and their relative contribution to the total relaxation remained similar at all strains, showing that a distinct relaxation process is present until fibre rupture. However, relative contribution of fast relaxation was maximal only in crosslinked fibres if the flexible αC-connector was present. These data show that the αC-region is not the main load-bearing structure within fibrin fibres and point to a critical role for the protofibril backbone instead. We present a revised structural model based on protofibril branching that fully explains the unique biomechanical behaviour of fibrin fibres, while the αC-region primarily acts as a safety latch at the highest of strains. The findings presented in this paper reveal critically important details about how the molecular structure of fibrin contributes to its unique mechanical properties which are essential to fulfil its function as the scaffold of blood clots. In this work we used engineered proteins with alterations in an important but highly disordered area of the molecule called αC-region and we provide direct evidence for the first time for how the absence of either the globular αC-domain, or the complete αC-region impacts the mechanical behaviour of individual fibrin fibres. Using these results we developed a new structural model of protofibril organisation within fibrin fibres that fully explains their strain stiffening, relatively low modulus and their high, largely variable, extensibility. [Display omitted] [ABSTRACT FROM AUTHOR]

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10 high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies. [Display omitted] • PMNs are a key source of coagulation factor X (FX) in the tumor microenvironment • PMN-derived FX directly fuels tumor growth and CRPC • CD84 marks F10 high Cxcr2 low PMNs in CRPC • High FX, CD84, and PAR2 levels predict poorer survival in PCa patients Calì et al. demonstrate that CD84+ immunosuppressive PMNs release in the tumor microenvironment of castration-resistant prostate cancer the coagulation factor X (FX). FX promotes androgen-independent cell proliferation and therapy resistance, independently from the coagulation cascade, by binding PAR2 on prostate cancer cells. This research reveals a new interplay between coagulation factors, immune cells, and cancer. [ABSTRACT FROM AUTHOR]

Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6–6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice. [Display omitted] • An improved adenovirus vector mediated efficient expression of FIX Fc fusion protein. • FIX Fc fusion protein, not wild-type FIX, was delivered from pregnant mice to fetuses. • Transplacental delivery of FIX to fetuses improved blood clotting ability in neonates. [ABSTRACT FROM AUTHOR]

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neoangiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, nonselective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors that lead to hypercoagulation is considered paramount. Hyperglycemia is a well-known prothrombotic factor, a fact that has received little attention in neuro-oncology. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time and activated partial thromboplastin time [aPTT]) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients who were operated on in 2 hospitals: Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia; and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ = –0.379; P = 0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ = –0.211; P = 0.0082). No connection was found between HbA1c and D-dimers or prothrombin time. Our results suggest that patients with hyperglycemia, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help to elucidate the vicious connection between glioblastomas and coagulation and to combat this deadly disease. [ABSTRACT FROM AUTHOR]

In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation. [Display omitted] • MBPs experienced a significant decrease in FXIII levels from the time of admission up to 24 h after surgery. • Abnormal low levels of FXIII could not be detected by other coagulation tests. • FXIII deficiency could be partly responsible for massive intraoperative bleeding in MBPs. • Most of the factors studied showed a decrease at 24 h suggesting a fluid resuscitation-driven dilution mechanism. • Normal ROTEM parameters in the early stages could be due to a compensated dilution of procoagulant and anticoagulant factors. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) exert immunomodulatory effects, primarily through released extracellular vesicles (EVs). For the clinical-grade manufacturing of MSC-EV products culture conditions need to support MSC expansion and allow the manufacturing of potent MSC-EV products. Traditionally, MSCs are expanded in fetal bovine serum-supplemented media. However, according to good manufacturing practice (GMP) guidelines the use of animal sera should be avoided. To this end, human platelet lysate (hPL) has been qualified as an animal serum replacement. Although hPL outcompetes animal sera in promoting MSC expansion, hPL typically contains components of the coagulation system that need to be inhibited or removed to avoid coagulation reactions in the cell culture. Commonly, heparin is utilized as an anticoagulant; however, higher concentrations of heparin can negatively impact MSC viability, and conventional concentrations alone do not sufficiently prevent clot formation in prepared media. To circumvent unwanted coagulation processes, this study compared various clotting prevention strategies, including different anticoagulants and calcium chloride (CaCl 2)-mediated declotting methods, which in combination with heparin addition was found effective. We evaluated the influence of the differently treated hPLs on the proliferation and phenotype of primary bone marrow-derived MSCs and identified the CaCl 2 -mediated declotting method as the most effective option. To determine whether CaCl 2 declotted hPL allows the manufacturing of immunomodulatory MSC-EV products, EVs were prepared from conditioned media of MSCs expanded with either conventional or CaCl 2 declotted hPL. In addition to metric analyses, the immunomodulatory potential of resulting MSC-EV products was assessed in a recently established multi-donor mixed lymphocyte reaction assay. Our findings conclusively show that CaCl 2 -declotted hPLs support the production of immunomodulatory-active MSC-EV products. [ABSTRACT FROM AUTHOR]

Double-filtration plasmapheresis (DFPP) can be used to remove circulating pathogenic molecules. By reclaiming filtered albumin, DFPP reduces the need for albumin and plasma replacement. Large proteins, such as fibrinogen, are removed. Our institution adopts a DFPP treatment protocol consisting of active surveillance of coagulation profiles and prophylactic supplementation of blood products containing fibrinogen. This study aims to investigate the effects of consecutive DFPP treatments on serial coagulation profiles and the risk of bleeding under this protocol. Serial laboratory data and bleeding events at a single tertiary medical center were prospectively collected. Prophylactic transfusion of cryoprecipitate or fresh frozen plasma (FFP) was instituted if significant coagulopathy or a clinically evident bleeding event was observed. After the first treatment session, plasma fibrinogen levels decreased from 332 ± 106 mg/dL to 96 ± 44 mg/dL in the 37 study patients. In the following sessions, plasma fibrinogen levels were maintained at around 100 mg/dL under prophylactic transfusion. No major bleeding events were recorded, but five (14%) patients experienced minor bleeding. DFPP treatment might be performed safely along with active monitoring of coagulation profiles and prophylactic transfusion of cryoprecipitate or FFP. [ABSTRACT FROM AUTHOR]

• We discuss the available literature on thrombus architecture and structure in relation to ischaemic stroke. • Implications of thrombus structure for thrombectomy and thrombolysis is also discussed. • The role of clot contraction is highlighted, in addition to areas for future study. Ischaemic stroke is a major cause of morbidity and mortality worldwide. Blood clotting and thromboembolism play a central role in the pathogenesis of ischaemic stroke. An increasing number of recent studies indicate changes in blood clot structure and composition in patients with ischaemic stroke. In this review, we aim to summarise and discuss clot structure, function and composition in ischaemic stroke, including its relationships with clinical diagnosis and treatment options such as thrombolysis and thrombectomy. Studies are summarised in which clot structure and composition is analysed both in vitro from patients' plasma samples and ex vivo in thrombi obtained through interventional catheter-mediated thrombectomy. Mechanisms that drive clot composition and architecture such as neutrophil extracellular traps and clot contraction are also discussed. We find that, while in vitro clot structure in plasma samples from ischaemic stroke patients are consistently altered, showing denser clots that are more resistant to fibrinolysis, current data on the composition and architecture of ex vivo clots obtained by thrombectomy are more variable. With the potential of advances in technologies underpinning both the imaging and retrieving of clots, we expect that future studies in this area will generate new data that is of interest for the diagnosis, optimal treatment strategies and clinical management of patients with ischaemic stroke. [ABSTRACT FROM AUTHOR]

It is crucial to develop a long-term therapy that targets hemophilia A and B, including inhibitor-positive patients. We have developed an Adeno-associated virus (AAV) based strategy to integrate the bypass coagulation factor, activated FVII (murine, mFVIIa) gene into the Rosa26 locus using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 mediated gene-editing. AAV vectors designed for expression of guide RNA (AAV8-gRNA), Cas9 (AAV2 neddylation mutant-Cas9), and mFVIIa (AAV8-mFVIIa) flanked by homology arms of the target locus were validated in vitro. Hemophilia B mice were administered with AAV carrying gRNA, Cas9 (1 × 1011 vgs/mouse), and mFVIIa with homology arms (2 × 1011 vgs/mouse) with appropriate controls. Functional rescue was documented with suitable coagulation assays at various time points. The data from the T7 endonuclease assay revealed a cleavage efficiency of 20–42 %. Further, DNA sequencing confirmed the targeted integration of mFVIIa into the safe-harbor Rosa26 locus. The prothrombin time (PT) assay revealed a significant reduction in PT in mice that received the gene-editing vectors (22 %), and a 13 % decline in mice that received only the AAV-FVIIa when compared to mock treated mice, 8 weeks after vector administration. Furthermore, FVIIa activity in mice that received triple gene-editing vectors was higher (122.5mIU/mL vs 28.8mIU/mL) than the mock group up to 15 weeks post vector administration. A hemostatic challenge by tail clip assay revealed that hemophilia B mice injected with only FVIIa or the gene-editing vectors had significant reduction in blood loss. In conclusion, AAV based gene-editing facilitates sustained expression of coagulation FVIIa and phenotypic rescue in hemophilia B mice. AAV mediated gene editing using CRISPR/Cas9 facilitates integration of a bypass coagulation factor VIIa and rescues bleeding phenotype in hemophilia B mice. Image created using Biorender.com. [Display omitted] • CRISPR/Cas9 mediated targeting of Rosa26 locus was found to have 20-42% efficiency in vitro. • Successful insertion of murine activated factor VII (mFVIIa) into the Rosa26 locus was achieved by CRISPR/Cas9 gene editing. • AAV mediated knock-in of bypass clotting factor mFVIIa using CRISPR/Cas9 mitigated bleeding phenotype in hemophilia B mice. • Increased FVIIa activity and shortened prothrombin time was attained after gene editing therapy in hemophilia B mice. [ABSTRACT FROM AUTHOR]

Use of anabolic-androgenic steroids (AAS) is associated with adverse cardiovascular (CV) effects, including potential prothrombotic effects. This study aimed to assess platelet activation and aggregation, coagulation, and fibrinolysis, in long-term AAS users compared to non-using strength-trained athletes. Thirty-seven strength-trained men using AAS were compared to seventeen non-using professional strength-trained athletes at similar age (median 33 years). AAS use was verified by blood and urine analyses. Platelet Function Analyzer 100 (PFA-100) and whole blood impedance aggregometry with thrombin, arachidonic acid, and ADP as agonists, were performed to evaluate platelet aggregation. ELISA methods were used for markers of platelet activation. Fibrinogen, D-dimer, the coagulation inhibitors protein S and C activity, and antithrombin were measured by routine. Fibrinolysis was evaluated by Plasminogen Activator Inhibitor-1 (PAI-1) activity. There were no significant differences in platelet aggregation between the two groups. Von Willebrand factor was lower among the AAS users (p < 0.01), and P-Selectin was slightly higher (p = 0.05), whereas CD40 Ligand, β-thromboglobulin, and thrombospondin did not differ significantly. No differences were found in the assessed coagulation inhibitors. Higher D-dimer levels (p < 0.01) and lower PAI-1 activity (p < 0.01) were found among the AAS users. The investigated long-term users of AAS did not exhibit elevated platelet activity compared to strength-trained non-using athletes. However, AAS use was associated with higher D-dimer levels and lower PAI-1 activity. These findings suggest that any prothrombotic effect of long-term AAS use may predominantly involve other aspects of the hemostatic system than blood platelets. [Display omitted] • Anabolic steroids are associated with an increased risk of cardiovascular diseases. • It has been hypothesized that anabolic steroids might have a prothrombotic effect. • The prothrombotic effects of anabolic androgenic steroids are still unclear. • We found an increased activation of coagulation and fibrinolysis. • No increase of blood platelet activation was observed. [ABSTRACT FROM AUTHOR]

Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis. • Recombinant VIII (rFVIII) does not affect thrombus formation on normal intima. • rFVIII enhances platelet-fibrin thrombus on smooth muscle cell-rich neointima. • Enhanced thrombosis under elevated FVIII is neutrophil-independent. [ABSTRACT FROM AUTHOR]

Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0–10 d). As an in vitro hematoma model, anticoagulated human blood samples (200 mL) were recalcified at different temperatures. In one set of samples, the shear modulus was measured by shear wave elastography during blood clotting at 10℃, 22℃ and 37℃, and then daily during further aging. The ultrastructure of the samples was analyzed daily with scanning electron microscopy (SEM). Another set of blood samples (50–200 mL) were recalcified at 37℃ for density and retraction measurements over aging and exposed to histotripsy at varying time points. Boiling histotripsy (2.5 ms pulses) and hybrid histotripsy (0.2 ms pulses) exposures (2 MHz, 1% dc, P +/ P –/ A s = 182/–27/207 MPa in situ) were used to produce either individual cigar-shaped or volumetric (0.8–3 mL) lesions in samples incubated for 3 h, 5 d and 10 d. The obtained lesions were sized, then the lysate aspirated under B-mode guidance was analyzed ultrastructurally and diluted in distilled water for sizing of residual fragments. It was found that clotting time decreased from 113 to 25 min with the increase in blood temperature from 10℃ to 37℃. The shear modulus increased to 0.53 ± 0.17 kPa during clotting and remained constant within 8 d of incubation at 2℃. Sample volumes decreased by 57% because of retraction within 10 d. SEM revealed significant echinocytosis but unchanged ultrastructure of the fibrin meshwork. Liquefaction rate and lesion dimensions produced with the same histotripsy protocols correlated with the increase in the degree of retraction and were lower in retracted samples versus freshly clotted samples. More than 80% of residual fibrin fragments after histotripsy treatment were shorter than 150 µm; the maximum length was 208 µm, allowing for unobstructed aspiration of the lysate with most clinically used needles. The results indicate that hematoma susceptibility to histotripsy liquefaction is not entirely determined by its stiffness, and correlates with the retraction degree. [ABSTRACT FROM AUTHOR]

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO 2 nanospheres with Cu 2 O nanoblocks. The resulting CaO 2 –Cu 2 O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO 2 –Cu 2 O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g. , Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g. , Prevotellaceae and Helicobacter). Our gas-driven CaO 2 –Cu 2 O offers a promising therapeutic platform for robust treatment of UC via the rectal route. A versatile gas-propelled nanomotor (CaO 2 –Cu 2 O) was facilely produced to overcome rectal drug delivery barriers and achieve effective synergistic treatment outcomes against ulcerative colitis. [Display omitted] [ABSTRACT FROM AUTHOR]

Cascade-reaction containers generating reactive oxygen species (ROS) as an alternative for antibiotic-based strategies for bacterial infection control, require endogenous oxygen-sources and ROS-generation close to or preferably inside target bacteria. Here, this is achieved by cetyltrimethylammonium-chloride (CTAC) assisted in situ metabolic labeling and incorporation of mesoporous SiO 2 -nanoparticles, dual-loaded with glucose-oxidase and Fe 3 O 4 -nanoparticles as cascade-reaction containers, inside bacterial cell walls. First, azide-functionalized d-alanine (D-Ala-N 3) was inserted in cell wall peptidoglycan layers of growing Gram-positive pathogens. In Gram-negatives, this could only be achieved after outer lipid-membrane permeabilization, using a low concentration of CTAC. Low concentrations of CTAC had no adverse effect on in vitro blood clotting or hemolysis nor on the health of mice when blood-injected. Next, dibenzocyclooctyne-polyethylene-glycol modified, SiO 2 -nanoparticles were in situ click-reacted with d-Ala-N 3 in bacterial cell wall peptidoglycan layers. Herewith, a two-step cascade-reaction is facilitated inside bacteria, in which glucose-oxidase generates H 2 O 2 at endogenously-available glucose concentrations, while subsequently Fe 3 O 4 -nanoparticles catalyze generation of •OH from the H 2 O 2 generated. Generation of •OH inside bacterial cell walls by dual-loaded mesoporous SiO 2 -nanoparticles yielded more effective in vitro killing of both planktonic Gram-positive and Gram-negative bacteria suspended in 10 % plasma than SiO 2 -nanoparticles solely loaded with glucose-oxidase. Gram-positive or Gram-negative bacterially induced sepsis in mice could be effectively treated by in situ pre-treatment with tail-vein injected CTAC and d-Ala-N 3 , followed by injection of dual-loaded cascade-reaction containers without using antibiotics. This makes in situ metabolic incorporation of cascade-reaction containers as described attractive for further investigation with respect to the control of other types of infections comprising planktonic bacteria. In situ metabolic-incorporation of cascade-reaction-containers loaded with glucose-oxidase and Fe 3 O 4 nanoparticles into bacterial cell-wall peptidoglycan is described, yielding ROS-generation from endogenous glucose, non-antibiotically killing bacteria before ROS inactivates. Hitherto, only Gram-positives could be metabolically-labeled, because Gram-negatives possess two lipid-membranes. The outer membrane impedes direct access to the peptidoglycan. This problem was solved by outer-membrane permeabilization using a quaternary-ammonium compound. Several studies on metabolic-labeling perform crucial labeling steps during bacterial-culturing that in real-life should be part of a treatment. In situ metabolic-incorporation as described, can be applied in well-plates during in vitro experiments or in the body as during in vivo animal experiments. Surprisingly, metabolic-incorporation proceeded unhampered in blood and a murine, bacterially-induced sepsis could be well treated. [Display omitted] [ABSTRACT FROM AUTHOR]

• NXT007 is a bispecific IgG engineered from emicizumab to potentiate the activity. • The natural anticoagulant function of AT is unaffected by the presence of emicizumab. • NXT007 was here found not to affect the AT-function despite its enhanced FX-binding. • The results suggest that NXT007 would not increase the AT-related thrombotic risk. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) in sepsis patients increases patient mortality. Endothelial cells are important players in the pathophysiology of sepsis-associated AKI (SA-AKI), yet knowledge regarding their spatiotemporal involvement in coagulation disbalance and leukocyte recruitment is lacking. This study investigated the identity and kinetics of responses of different microvascular compartments in kidney cortex in response to SA-AKI. Laser microdissected arterioles, glomeruli, peritubular capillaries, and postcapillary venules from kidneys of mice subjected to cecal ligation and puncture (CLP) were analyzed using RNA sequencing. Differential expression and pathway enrichment analyses identified genes involved in coagulation and inflammation. A selection of these genes was evaluated by RT-qPCR in microvascular compartments of renal biopsies from patients with SA-AKI. The role of two identified genes in lipopolysaccharide-induced endothelial coagulation and inflammatory activation were determined in vitro in HUVEC using siRNA-based gene silencing. CLP-sepsis in mice induced altered expression of approximately 400 genes in the renal microvasculature, with microvascular compartments exhibiting unique spatiotemporal responses. In mice, changes in gene expression related to coagulation and inflammation were most extensive in glomeruli at early and intermediate time points, with high induction of Plat , Serpine1 , Thbd , Icam1 , Stat3 , and Ifitm3. In human SA-AKI, PROCR and STAT3 were induced in postcapillary venules, while SERPINE1 expression was diminished. IFITM3 was increased in arterioles and glomeruli. In vitro studies revealed that STAT3 and IFITM3 partly control endothelial coagulation and inflammatory activation. Renal microvascular compartments in mice and humans exhibited heterogeneous changes in coagulation- and inflammation-related gene expression in response to SA-AKI. Additional research should aim at understanding the functional consequences of the here described heterogeneous microvascular responses to establish the usefulness of identified genes as therapeutic targets in SA-AKI. [Display omitted] • Laser microdissection combined with RNA-seq enabled identification of unique renal microvascular transcriptome profiles. • Sepsis induced microvascular compartment-specific spatiotemporal coagulation- & inflammation-related gene expression changes. • Renal microvascular responses to sepsis partially overlapped between mice and patients. • STAT3 and IFITM3 were identified as novel endothelial therapeutic targets for sepsis. [ABSTRACT FROM AUTHOR]

Sepsis is a common and critical condition encountered in clinical practice that can lead to multi-organ dysfunction. Sepsis-induced coagulopathy (SIC) significantly affects patient outcomes. However, the precise mechanisms remain unclear, making the identification of effective prognostic and therapeutic targets imperative. The analysis of transcriptome data from the whole blood of sepsis patients, facilitated the identification of key genes implicated in coagulation. Then we developed a prognostic model and a nomogram to predict patient survival. Consensus clustering classified sepsis patients into three subgroups for comparative analysis of immune function and immune cell infiltration. Single-cell sequencing elucidated alterations in intercellular communication between platelets and immune cells in sepsis, as well as the role of the coagulation-related gene FYN. Real-time quantitative PCR determined the mRNA levels of critical coagulation genes in septic rats' blood. Finally, administration of a FYN agonist to septic rats was observed for its effects on coagulation functions and survival. This study identified four pivotal genes—CFD, FYN, ITGAM, and VSIG4—as significant predictors of survival in patients with sepsis. Among them, CFD, FYN, and ITGAM were underexpressed, while VSIG4 was upregulated in patients with sepsis. Moreover, a nomogram that incorporates the coagulation-related genes (CoRGs) risk score with clinical features of patients accurately predicted survival probabilities. Subgroup analysis of CoRGs expression delineated three molecular sepsis subtypes, each with distinct prognoses and immune profiles. Single-cell sequencing shed light on heightened communication between platelets and monocytes, T cells, and plasmacytoid dendritic cells, alongside reduced interactions with neutrophils in sepsis. The collagen signaling pathway was found to be essential in this dynamic. FYN may affect platelet function by modulating factors such as ELF1, PTCRA, and RASGRP2. The administration of the FYN agonist can effectively improve coagulation dysfunction and survival in septic rats. The research identifies CoRGs as crucial prognostic markers for sepsis, highlighting the FYN gene's central role in coagulation disorders associated with the condition and suggesting novel therapeutic intervention strategies. [Display omitted] • Found four key genes for sepsis prognosis linked to coagulation. • Created sepsis survival nomogram combining gene scores and clinical data. • Unveiled three sepsis subtypes with unique prognoses and immune traits. • Showed potential of FYN agonist in treating sepsis-induced coagulopathy. [ABSTRACT FROM AUTHOR]

In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes. Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models. Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI] =1.14, 1.77, P =0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P =0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P <0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P =0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95% CI=1.24, 4.73, P =0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P <0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P <0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P <0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P =<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P =< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P =<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P =<0.00001) were predictive of complications. Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history. [ABSTRACT FROM AUTHOR]

La coagulation intravasculaire disséminée est un syndrome biologique responsable d'anomalies majeures de la coagulation. Sa physiopathologie est mieux connue aujourd'hui avec la description d'anomalies touchant les différentes étapes de l'hémostase étroitement intriquées avec les voies de l'inflammation. Ce processus de déséquilibre induit une coagulation qui n'est plus maitrisée dans le temps ni dans l'espace. On décrit classiquement des formes de CIVD symptomatiques, secondaires à un facteur déclenchant aigu, et des formes dites biologiques, responsables de tableaux cliniques plus insidieux. Les CIVD secondaires à un sepsis ou à un traumatisme sont les mieux décrites à ce jour mais de nombreux autres facteurs déclenchants sont retrouvés dans la littérature. Le diagnostic de ce syndrome nécessite un faisceau d'arguments reposant sur un facteur déclenchant et des anomalies biologiques répondant au score ISTH auxquels peuvent s'ajouter des signes cliniques évocateurs. La CIVD a une influence notable sur le pronostic des patients avec des manifestations hémorragiques ou thrombotiques pouvant mener à une défaillance viscérale et à des séquelles non négligeables chez les survivants. Le traitement repose sur la prise en charge du facteur étiologique ainsi que sur le traitement symptomatique. À ce jour, aucun autre traitement n'a fait preuve d'une efficacité formelle. Devant un pronostic sombre, ainsi il est ainsi nécessaire que l'ensemble des spécialités médicales maîtrise cette entité clinico-biologique pour la prendre en charge le plus rapidement possible. [ABSTRACT FROM AUTHOR]

Strenuous exercise may occasionally cause coronary thrombosis with myocardial infarction and sudden cardiac death. Patients with stable coronary artery disease (CAD) (n = 164) and healthy individuals (n = 25) performed strenuous exercise on a bicycle ergometer. Blood was drawn at baseline, immediately after exercise and 2 h later. Platelet aggregation was measured with Multiplate® Analyzer. Thrombin generation was determined using a thrombogram and by measuring prothrombin fragment 1 + 2 (F1 + 2). A clot lysis assay was used to investigate fibrinolysis. From baseline to immediately after exercise, thrombin receptor activating peptide (TRAP)-induced platelet aggregation increased in CAD patients (Δ77 AU × min, 95 % confidence interval (CI): 46;107) and in healthy individuals (Δ153 AU × min, 95%CI: 75;232). Endogenous thrombin potential (ETP) was unaffected by exercise, whilst F1 + 2 increased (Δ17%, 95%CI: 11;24) in CAD patients. Fibrin clot lysis time increased by 9 % (95%CI: 1–17) in CAD patients and by 26 % (95%CI: 8;45) in healthy individuals. When comparing baseline to 2 h post-exercise, TRAP-induced platelet aggregation remained slightly elevated in both CAD patients (Δ53 AU × min, 95%CI: 22;84) and healthy individuals (Δ140 AU × min, 95%CI: 62;219). In contrast, ETP and F1 + 2 decreased in CAD patients (Δ-6 %, 95%CI: −10;-1 and Δ-8 %, 95%CI: -14;-2). Moreover, clot lysis time decreased (Δ-19 %, 95%CI: −27;-11) in patients with CAD and returned to baseline in healthy individuals. All p -values were <0.05. Platelet aggregation and F1 + 2 were substantially elevated immediately after exercise in CAD patients, indicating a pro-thrombotic state. After 2 h of recovery, they exhibited a markedly increase in fibrinolysis. Similar results were observed in healthy individuals. • Acute strenuous exercise may occasionally induce coronary thrombosis. • Immediately after strenuous exercise, CAD patients were in a pro-thrombotic state. • Two hours after strenuous exercise, CAD patients were in a pro-fibrinolytic state. [ABSTRACT FROM AUTHOR]

Hormone replacement therapy is associated with an increased thromboembolic risk. The effects of testosterone (T) on coagulation markers in people assigned female at birth (AFAB) under gender affirming hormone therapy (GAHT) are not well described. Systematic review and meta-analysis on English-language articles retrieved from PubMed, Scopus and Cochrane Library up to April 2023 investigating T therapy in AFAB people. Coagulation parameters included international normalized ratio (INR), fibrinogen, activated partial thromboplastin clotting time (aPTT), plasminogen activator inhibitor-1 (PAI-1); hematological variables included hemoglobin (Hb) and hematocrit (HCT). We also reported the rate of thromboembolic events. Data were combined as mean differences (MD) with a 95 % confidence interval (CI) of pre- vs post-follow-up values, using random-effects models. We included 7 studies (6 prospective and 1 retrospective) providing information on 312 subjects (mean age: 23 to 30 years) who underwent GAHT with variable T preparation. T therapy was associated with a significant increase in INR values [MD: 0.02, 95 % confidence interval (CI): 0.01–0.03; p = 0.0001], with negligible heterogeneity (I2 = 4 %). T therapy was associated with increased Hb (MD: 1.48 g/dL, 95%CI: 1.17 to 1.78; I2 = 9 %) and HCT (4.39 %, 95%CI: 3.52 to 5.26; I2 = 23 %) values. No effect on fibrinogen, aPTT and PAI-1 was found. None of the study reported thromboembolic events during the follow-up. Therapy with T increased blood viscosity in AFAB men. A slight increase in INR values was also found, but the clinical relevance and mechanism(s) of this finding needs to be clarified. • Testosterone therapy in AFAB people is associated with pro-coagulant effects, such as increased HCT and Hb values. • Studies show lengthening of INR of uncertain clinical value. • No apparent thrombotic risk is present during testosterone-based affirming therapy in AFAB people. [ABSTRACT FROM AUTHOR]

Adaptive drug release can combat coagulation and inflammation activation at the blood-material interface with minimized side effects. For that purpose, poly(styrene- alt -maleic-anhydride) copolymers were conjugated to heparin via coagulation-responsive linker peptides and shown to tightly adsorb onto poly(ethersulfone) (PES)-surfaces from aqueous solutions as monolayers. Coagulation-responsive release of unfractionated as well as low molecular weight heparins from the respective coatings was demonstrated to be functionally beneficial in human plasma and whole blood incubation with faster release kinetics resulting in stronger anticoagulant effects. Coated poly(ethersulfone)/poly(vinylpyrrolidone) (PES/PVP) flat membranes proved the technology to offer an easy, effective and robust anticoagulant interfacial functionalization of hemodialysis membranes. In perspective, the modularity of the adaptive release system will be used for inhibiting multiple activation processes. [Display omitted] • conjugates of styrene-maleic anhydrate copolymers and heparin tightly adsorb as monolayers on hemodialysis membranes • conjugates containing thrombin-cleavable peptide linkers enable the adaptive release of heparin • adaptive release from the conjugates enhances the anticoagulant action of unfractionated and low molecular weight heparin [ABSTRACT FROM AUTHOR]

Hematoma of corpus callosum is a very rare phenomenon and is caused by severe trauma to head. Most common traumatic injury to corpus callosum is seen in diffuse axonal injury in form of small hemorrhagic foci and associated prolonged unconsciousness. Trivial trauma causing well defined corpus callosal hematoma in absence of coagulation defects or neurological deficits in conscious patient has not been reported in the literature. We present such a unique case and the review the corpus callosal hematoma due to trauma. [ABSTRACT FROM AUTHOR]

Current evidence on how the use of bromelain-based enzymatic debridement techniques (NexoBrid™) affect patient coagulation is limited. A single patient case report [1] suggests that a patient with 15% total body surface area (TBSA) burn developed decreased coagulation activity following debridement with NexoBrid™ enzymatic debridement (ED). Regional Burns Centres in the United Kingdom may be reluctant to use ED, particularly in larger burns, citing concerns regarding coagulation. At our centre we have routinely used ED on deep partial thickness burns since 2017 including on patients with burns over 15% TBSA. This study aims to investigate whether there is a significant disruption in coagulation in patients undergoing ED with burns > 15% TBSA or admitted to intensive care compared to the standard of care (SOC) which is surgical debridement in theatre. This single-centre retrospective study includes all patients with a burn treated with ED at Pinderfields General Hospital Regional Burns Centre intensive care unit (ITU) from 2017 to 2020. Patients were matched to those treated with SOC at the same centre by age, % TBSA burn and presence of inhalational injury. These parameters correlate with the Baux score [9]. Percentage of burn debrided was matched as closely as possible, with coagulation profiles and platelet count taken the day before, the day of and three days following surgery. Thirty-one patients were treated with ED in the intensive care unit between 2017 and 2020. Four patients were excluded due to insufficient records and one patient was anti-coagulated. Twenty-six patients were included and matched as described above. Average age of patients receiving ED was 44 years, the same in the matched group. Average TBSA burn is 35.5% (35.8% in matched group). No statistically significant difference in coagulation was seen between patients undergoing ED compared to SOC when considering prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count. Both groups slightly breached the upper limit of normal on day 2 post ED and SOC. There was a slight breach of the lower limit of the average platelet count on day 2 post-ED which was neither statistically nor clinically significant. Large burns are associated with coagulation abnormalities, therefore isolating a single variable in this cohort is challenging. However, this study found no significant change following ED use when compared to SOC and therefore no convincing evidence that ED is associated with coagulation abnormalities. This study represents one of the largest focusing on coagulation abnormalities following the use of ED, as the current literature is limited. Our study suggests that concerns regarding coagulation abnormalities should not prevent patients with large, deep partial thickness burns or full thickness burns being treated with ED. • Similar coagulation in burn patients for enzymatic vs. surgical debridement. • Prothrombin time, activated partial thromboplastin time and platelet count included. • Coagulation abnormalities are not associated with enzymatic debridement. [ABSTRACT FROM AUTHOR]

Sodium dehydroacetate (DHA-S), a potent antifungal and antibacterial agent, is widely used in food, feed and cosmetics. However, recent studies have shown that DHA-S could pose a risk for human and animal health. We had previously reported that DHA-S could cause coagulation disorders in rats and chicken. In the present study, we further confirmed that DHA-S induced blood coagulation via VKORC1 and VKORC1L1 in rats, and elucidated the role played by mTOR/ERK signaling. The in vivo studies demonstrated that PT, APTT, and DHA-S content and relative protein expressions in tissues rebounded after drug withdrawal. In BRL-3A cells, 1.0 mM DHA-S increased the expression levels of mTOR, p-mTOR and p-ERK and decreased the levels of VKORC1, VKORC1L1 and Vitamin K. Rapamycin significantly decreased the expression levels of p-mTOR and p-ERK, while FR180204 (p-ERK Inhibition) lead to a decrease in p-ERK level. Rapamycin and FR180202 attenuated the inhibitory effect of DHA-S on VKORC1, VKORC1L1 and vitamin K levels. In addition, DHA-S increased the expression levels of mTOR, p-mTOR and p-ERK in male and female rat livers and prolonged PT and APTT. In summary, this study indicated that DHA-S induced blood coagulation via the modulation of the mTOR/ERK pathway in rats. • The Mechanism of Blood Coagulation Induced by Sodium Dehydroacetate via the Regulation of the mTOR/ERK Pathway in Rats. • Sodium dehydroacetate induces blood coagulation disorder in rats. • Sodium dehydroacetate inhibits coagulation factor activation by inhibiting VKORC1L1 and VKORC1 expression. • mTOR/ERK pathway might play an important role in the modulation of VKORC1 and VKORC1L1 expression by DHA-S. [ABSTRACT FROM AUTHOR]

Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/μL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement. • Rotational Thromboelastometry (ROTEM) has been used to assess leukemia-associated coagulopathy in adult malignancies, with a paucity of similar studies in pediatric leukemia • Abnormal coagulation test (PT/aPTT) values in leukemia patients do not clearly predict the risk of bleeding • Pediatric leukemia patients had evidence of hypocoagulability during induction chemotherapy using ROTEM assays despite acquired hypofibrinogenemia and thrombocytopenia and a low bleeding risk in our cohort • Strategies adopting ROTEM as a point of care test along with conventional coagulation tests (CCTs) can better evaluate hemostatic function to guide non-erythrocyte hemostatic factor replacement in this patient population • Our study demonstrates the utility of CCTs and ROTEM in newly diagnosed pediatric leukemia patients, with fibrinogen and platelets as the main drivers of leukemia-associated coagulopathy. [ABSTRACT FROM AUTHOR]

Growing evidence supports the importance of factor (F) XI activation for thrombosis and hemostasis as well as inflammation and complement systems. In this study, we evaluated the effect of activated FXI (FXIa) on the detection of factor deficiencies by global hemostasis assays of thrombin generation (TG), plasmin generation (PG), and clot formation and lysis (CFL). An absorbance and fluorescence microplate assay was used to simultaneously observe TG, PG, and CFL in FV-, FVII-, FVIII-, and FIX-deficient plasmas supplemented with purified factors. Coagulation was initiated with tissue factor with or without FXIa in the presence of tissue plasminogen activator. Thrombin and plasmin peak heights (TPH and PPH), maximal clot density (MCD), times to clotting (CT), thrombin and plasmin peaks (TPT and PPT) and clot lysis (LyT) and a new parameter, clot lifetime (LiT), were evaluated. TG/CFL were elevated by the FXIa at low FV (below 0.1 IU/mL), and at FVIII and FIX above 0.01 IU/mL. FXIa affected PG only at low FV and FVII. At high factor concentrations, FXIa reduced MCD. Thrombin and plasmin substrates had effect on CT, LyT, LiT and MCD parameters. FXIa reveals new relationships between TG, PG and CFL parameters in factor deficiencies suggesting potential benefits for discrimination of bleeding phenotypes. • Similar to Tissue factor (TF), factor XIa (FXIa) can mediate thrombosis and hemostasis • Thrombin and plasmin generation (TG and PG), Clot Formation and Lysis (CFL) were studied after activation with TF and FXIa • Addition of FXIa to TF reveals new relationships between TG/PG and CFL parameters in coagulation factors deficient plasmas • CFL parameters differ between TG and PG assays [ABSTRACT FROM AUTHOR]

Thrombotic disease may be an underdiagnosed condition of prolonged exposure to microgravity and yet the underlying factors remain poorly defined. Recently, an internal jugular vein thrombosis was diagnosed in a low-risk female astronaut after an approximately 7-week space mission. Six of the additional 10 crew members demonstrated jugular venous flow risk factors, such as suspicious stagnation or retroversion. Fortunately, all were asymptomatic. Observations in space as well as clinical and in vitro microgravity studies on Earth, where experiments are designed to recapitulate the conditions of space, suggest effects on blood flow stasis, coagulation, and vascular function. In this article, the related literature on thrombotic disease in space is reviewed, with consideration of these elements of Virchow's triad. • Asymptomatic internal jugular vein thrombosis (IJV) was detected in an astronaut. • Exposure to microgravity may cause unforeseen risk during long-term spaceflight. • Studies on thrombosis risk in space and analogous models on Earth are limited. • Microgravity affects the blood flow stasis, coagulation, and endothelial triad. • Here, the pathophysiological and biomolecular evidence are examined. [ABSTRACT FROM AUTHOR]

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15 and 20 %, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECFs. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECFs. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECFs. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECFs. This research manuscript presents a groundbreaking INAH for treating ECFs. The INAH, composed of a synthetic nanosilicate and gelatin-dopamine conjugate, offers versatile implications in tissue regeneration and localized drug delivery. Acting as a scaffold, the shear-thinning hydrogel enables easy injection, forming a stable structure that supports tissue regeneration and integrates with surrounding tissues. By incorporating bioactive cues, it guides cell behavior and promotes functional tissue regeneration. The INAH also demonstrates potential for localized drug delivery, releasing therapeutic agents over time to enhance efficacy and minimize side effects. This research showcases INAH as a promising solution for ECFs, with applications in tissue engineering and regenerative medicine, marking a significant advancement in the field. [Display omitted] [ABSTRACT FROM AUTHOR]

The persistence or recurrence of symptoms after acute SARS-CoV-2 infection, termed 'long COVID', presents a formidable challenge to global healthcare systems. Recent research by Cervia-Hasler and colleagues delves into the intricate immunological landscape in patients with long COVID, demonstrating an interplay between complement and coagulation, driven by antiviral antibodies and tissue damage. [ABSTRACT FROM AUTHOR]

Severely burned patients suffer from both coagulopathy and hypothermia, with a lack of international consensus and appropriate treatment guidelines. This study examines recent developments and trends in coagulation and temperature management in European burn centers. A survey was sent to burn centers in Switzerland, Austria and Germany in 2016 and again in 2021. The analysis was performed using descriptive statistics, with categorical data reported in absolute numbers (n) and percentages (%) and numerical data reported as mean and standard deviation. The rate of completed questionnaires was 84 % (16 of 19 questionnaires) in 2016 and 91 % (21 of 22 questionnaires) in 2021. The number of global coagulation tests performed has decreased over the observation period in favor of single factor determination and bed-side point-of-care coagulation tests. This has also led to increased administration of single factor concentrates in therapy. Although many centers had a defined treatment protocol for hypothermia in 2016, coverage increased such that in 2021 all centers surveyed had such a protocol. The body temperature was measured more consistently in 2021; thus, hypothermia was more actively sought, detected and treated. A point-of-care guided, factor-based coagulation management and the maintenance of normothermia have gained importance in the care of burn patients in recent years. Severely burned patients are at particular risk of developing burn-induced coagulopathy or perioperative hypothermia. Clear guidelines regarding coagulation and temperature management are largely absent in the care of severely burned patients. In recent years, point-of-care guided, factor-based coagulation management has gained importance in European burn centers. The high rate of hypothermia management concepts in 2016 was further expanded in 2021. [ABSTRACT FROM AUTHOR]

In the present study, the effectiveness of biomedical titanium (Ti) with plasma oxidation, polymerization, and albumin immobilization in producing a bioactive surface (Ti/rutile TiO 2 /NH 2 /protein) that promote hemocompatibility performance was investigated through scanning electron microscopy Raman spectrometry, X-ray photoemission spectroscopy, transmission electron microscopy, wettability examination, and blood clotting time assay. The results indicated that the bioactive surface with uniform island-like immobilized protein clusters was formed on the plasma-oxidized at 240 W specimen. This bioactive surface showed the significantly lowest contact angle as compared with the control (** p < 0.01) and other bioactive surfaces (plasma-oxidized at 80 W and 160 W) (* p < 0.05). In addition, the blood clotting time assay also demonstrated that the bioactive surface with 240 W exhibited the best red blood cell aggregation and adhesion performance. Thus, the fabricated bioactive surface not only increases wettability but also promotes hemocompatibility, thereby could potentially enhancing tissue healing at early-stage post-implantation. [ABSTRACT FROM AUTHOR]

Activated platelets provide phospholipid surface and secrete coagulation factors, enhancing blood clotting. We investigated the role of platelets in the regulation of blood coagulation spatial dynamics. We activated blood clotting with tissue factor-bearing (TF) surface in platelet-rich plasma (PRP) or platelet-free plasma (PFP). When blood coagulation was initiated by high TF density, clot growth rate (V) in PRP (2 × 105/μL platelets) was only 15 % greater than in PFP. Spatial distribution of thrombin in PRP had a peak-like shape in the area of the fibrin clot edge, while in PFP thrombin was distributed in the shape of descending plateau. Platelet inhibition with prostaglandin E1 or cytochalasin D made spatial thrombin distribution look like in the case of PFP. Inhibition of blood coagulation by natural endogenous inhibitor heparin was diminished in PRP, while the effect of the exogenous or artificial inhibitors (rivaroxaban, nitrophorin, hirudin) remained undisturbed in the presence of platelets. Ten times decrease of the TF surface density greatly depressed blood coagulation in PFP. In PRP only clotting initiation phase was, while the propagation phase remained intact. Coagulation factor deficiency greatly reduced amount of thrombin and decreased V in PFP rather than in PPR. Thus, platelets were redundant for clotting in normal plasma under physiological conditions but provided robustness of the coagulation system to the changes in initial conditions. • Platelets were redundant for clotting in normal plasma under physiological conditions. • Platelets provided robustness of the coagulation system to the changes in initial conditions. • Platelets were different from artificial lipids in effect on the thrombin generation. [ABSTRACT FROM AUTHOR]

Milk-clotting enzyme (MCE) is the essential active agents in dairy processing. The traditional MCE is mainly obtained from animal sources, in which calf rennet is the most widely used in cheese industry. Traditional MCE substitute is becoming necessary due to its limited production and increased cheese consumption. A novel traditional MCE substitute was produced from Bacillus velezensis DB219 in this study. The DB219 MCE exhibited a notable specific activity of 6,110 Soxhlet units/mg and 3.16-fold purification yield with 28.87% recovery through ammonium sulfate fractionation and DEAE-Sepharose Fast Flow. The purified DB219 MCE was a metalloprotease with a molecular weight of 36 kDa. The DB219 MCE was weak acid resistance and stable at pH 6.0 to 10.0 and temperature <45°C. The highest milk-clotting activity was observed in substrate at pH 5.5 added with 20 to 30 m M CaCl 2. The Michaelis constant and maximal velocity for casein were 0.31 g/L and 14.22 μmol/min. The DB219 MCE preferred to hydrolyze β-casein instead of α-casein. The DB219 MCE hydrolyzed α-casein, β-casein, and κ-casein to generate significantly different peptides in comparison with calf rennet and ES6023 MCE (fungal MCE) through SDS-PAGE and reversed-phase HPLC analysis. The DB219 MCE mainly cleaved Thr124-Ile125 and Ser104-Phe105 bonds in κ-casein and had unique casein cleavage sites and peptide composition through LC-MS/MS analysis. The DB219 MCE was potential to be a new milk coagulant and enriched kinds of traditional MCE substitute. [Display omitted] [ABSTRACT FROM AUTHOR]

The extreme factors associated with space flight influence pronouncedly various physiological systems of the human body. The current study focuses on the impact of factors associated with prolonged space missions lasting up to 6 months on cellular innate immunity, hormonalregulation, and hemostasis in Russian cosmonauts. Immune system adaptation to the conditions of long-term space flight was shown to be accompanied by a significant increase in the level of monocytes and granulocytes, along with a decreased number of cells expressing adhesion molecules. The coagulation cascade, main anticoagulant and fibrinolysis proteins were also evaluated. The early post-flight period was characterized by elevated D-dimer levels compared to baseline values, indicative of blood clotting and fibrinolysis activation caused by a damage of endothelium during landing. aAlterations in blood rheology during re-adaptation to Earth conditions was also observed. The blood concentrations of aldosterone, cortisol, estradiol, testosterone, osteocalcin, and erythropoietin were analyzed, and their correlation with the parameters of hemostasis was assessed. The summary findings indicate an adaptive physiological reaction in cosmonauts associated with 6 months duration of spaceflight. The observations may be related to endothelium damage, which manifested in the activation of certain components of the immune system, along with the activation of fibrin clot formation and subsequent fibrinolysis. • Long-term space missions significant affect innate immunity and hemostasis. • The hemostasis regulation correlates with hormones. [ABSTRACT FROM AUTHOR]

The recent study by Ryu et al. demonstrates that the SARS-CoV-2 Spike protein binds fibrin(ogen), impacting coagulation and immune responses in mice. In this spotlight article we focus on the described effects on natural killer (NK) cell responses as well as the suggested translation into potential new therapeutic targets against COVID-19. [ABSTRACT FROM AUTHOR]

E x vivo viscoelastic testing can be used to assess the concentration responses to tranexamic acid in blood samples obtained from pregnant women across the three trimesters and in non-pregnant controls. Minor variations in fibrinolysis across pregnancy suggest a target tranexamic acid blood concentration of 12.5 mg L−1 for complete inhibition of fibrinolysis. Although the data support the potential utility of viscoelastic testing using the ClotPro® TPA test in maintaining therapeutic tranexamic acid concentrations during postpartum haemorrhage, it might obscure potentially crucial endogenous fibrinolysis inhibitor interactions essential to the microcirculation. [ABSTRACT FROM AUTHOR]

This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various prothrombin complex concentrate (PCC) products in a battery of tests. In static coagulation assays, andexanet alpha outperformed PCCs except for activated PCC being more effective in standard coagulation times. However, in a flow chamber model mimicking arterial shear, both andexanet alpha and high-concentration PCC restored fibrin formation, but not platelet adhesion. In the Russell's viper venom test and anti-Xa assay, only andexanet alpha could be tested for efficacy. The antidote effects of andexanet alpha and PCCs in restoring coagulation can be qualitatively or selectively demonstrated using in vitro coagulation tests. [ABSTRACT FROM AUTHOR]

The present study illustrates the doping of Zn and Mg in the HAp matrix synthesized using sol-gel process. The addition of two vital metal ions in HAp enhances both mechanical and biocompatibility of the HAp. The present investigation focuses on how ZnMg doping affects the phase, its morphology, shifting of the functional groups, mechanical, corrosion resistance, and dielectric properties. The Ca/P ratio was maintained between 1.60 and 1.63 as confirmed from EDS analysis. The clotting behaviour was studied using whole blood clotting assay method. The XRD and Raman spectra were used to determine different compound formation. The grain size increases after adding the Zn/Mg as observed from FESEM. However, the crystallite size decreases as calculated from XRD. Therefore, hardness increases after the addition of ZnMg in HAp. The ECA study in Ringer solution showed that addition of two different metals Zn & Mg in HAp improves the corrosion resistance. The impedance studies showed doped sample ZnMg/HAp has more polarization resistance compared to pure HAp and hence has more corrosion resistance. Moderate clotting behaviour was observed for this doped sample as well. [ABSTRACT FROM AUTHOR]

Patients with acute myeloid leukemia (AML) are at increased risk of thrombohemorrhagic complications. Overexpressed tissue factor (TF) on AML blasts contributes to systemic coagulation activation. We have recently shown that the heme enzyme myeloperoxidase (MPO) negatively regulates TF procoagulant activity (PCA) on myelomonocytic cells in vitro. We now aimed to further characterize the functional interaction of MPO and TF in AML in vivo. We prospectively recruited 66 patients with newly diagnosed AML. TF PCA of isolated peripheral blood mononuclear cells (PBMC) was assessed by single-stage clotting assay in the presence or absence of inhibitors against MPO catalytic activity (ABAH) or against MPO-binding integrins (anti-CD18). MPO in plasma and in AML blasts was measured by ELISA, and plasma D-dimers and prothrombin fragment F1+2 were quantified by automated immunoturbidimetric and chemiluminescence assays, respectively. Patients with AML had significantly higher MPO plasma levels compared to healthy controls and exhibited increased levels of D-dimers and F1+2. In vivo thrombin generation was mediated by TF PCA on circulating PBMC. Ex vivo incubation of isolated PBMC with ABAH or anti-CD18 antibody resulted in either increased or decreased TF PCA. The strong and robust correlation of F1+2 with TF PCA of circulating PBMC was abrogated at MPO plasma levels higher than 150 ng/mL, indicating a modulatory role for MPO on TF-mediated in vivo thrombin generation above this threshold. Our study indicates that catalytically active MPO released by circulating myeloblasts regulates TF-dependent coagulation in patients with newly diagnosed AML in a CD18-dependent manner. [ABSTRACT FROM AUTHOR]

HIV-infected individuals are known to be at higher risk for thrombotic cardiovascular disease (CVD), which may also be differentially affected by components of anti-HIV drugs. To identify the effects of a series of FDA-approved anti-HIV drugs on platelet aggregation in humans, focusing on the novel pharmacological effects of rilpivirine (RPV), a reverse transcriptase inhibitor, on platelet function both in vitro and in vivo and the mechanisms involved. In vitro studies showed that RPV was the only anti-HIV reagent that consistently and efficiently inhibited aggregation elicited by different agonists, exocytosis, morphological extension on fibrinogen, and clot retraction. Treatment of mice with RPV significantly prevented thrombus formation in FeCl 3 -injured mesenteric vessels, postcava with stenosis surgery, and ADP -induced pulmonary embolism models without defects in platelet viability, tail bleeding, and coagulation activities. RPV also improved cardiac performance in mice with post-ischemic reperfusion. A mechanistic study revealed that RPV preferentially attenuated fibrinogen-stimulated Tyr773 phosphorylation of β3-integrin by inhibiting Tyr419 autophosphorylation of c-Src. Molecular docking and surface plasmon resonance analyses showed that RPV can bind directly to c-Src. Further mutational analysis showed that the Phe427 residue of c-Src is critical for RPV interaction, suggesting a novel interaction site for targeting c-Src to block β3-integrin outside-in signaling. These results demonstrated that RPV was able to prevent the progression of thrombotic CVDs by interrupting β3-integrin-mediated outside-in signaling via inhibiting c-Src activation without hemorrhagic side effects, highlighting RPV as a promising reagent for the prevention and therapy of thrombotic CVDs. [Display omitted] • Efficient medications with combination antiretroviral therapies (cARTs) make AIDS no longer an acute life-threaten for HIV-patients, but components of that can differently affect thrombotic cardiovascular outcomes • Potent and safe anti-platelet abilities uncover a pharmacological rationale for less cardiovascular implications in HIV-infected individuals receiving RPV • RPV is identified as a novel c-Src inhibitor to control β3 Integrin outside-in signaling pathway [ABSTRACT FROM AUTHOR]

Bromelain-based enzymatic debridement has emerged as a valuable option to the standard surgical intervention for debridement in burn injuries. Adverse effects on coagulation parameters after enzymatic debridement have been described. The purpose of this study was to compare the effect of enzymatic and surgical debridement on coagulation. Between 03/2017 and 02/2021 patients with burn injuries with a total body surface area (TBSA) ≥ 1% were included in the study. Patients were categorized into two groups: the surgically debrided group and the enzymatically debrided group. Coagulation parameters were assessed daily for the first seven days of hospitalization. In total 132 patients with a mean TBSA of 17% were included in this study, of which 66 received enzymatic debridement and 66 received regular surgical-debridement. Patients receiving enzymatic debridement presented significantly higher factor-V concentration values over the first seven days after admission (p = <0.01). Regarding coagulation parameters, we found no difference in INR-, aPTT-, fibrinogen-, factor-XIII- and thrombocyte-concentrations over the first seven days (p = >0.05). Enzymatic debridement in burned patients does not appear to increase the risk of coagulation abnormalities compared with the regular surgical approach. • Enzymatic debridement (ED) in burned patients does not increase the risk of coagulation. • ED emerges are safe and an alternative to standard treatment without significant effect of the coagulation. • This is the first analysis of coagulation-specific laboratory markers including coagulation factor-V and factor-XIII concentrations in ED. [ABSTRACT FROM AUTHOR]

The protein tyrosine phosphatase SHP2 (PTPN11) is a negative regulator of glycoprotein VI (GPVI)-induced platelet signal under certain conditions. Clinical trials with derivatives of the allosteric drug SHP099, inhibiting SHP2, are ongoing as potential therapy for solid cancers. Gain-of-function mutations of the PTPN11 gene are observed in part of the patients with the Noonan syndrome, associated with a mild bleeding disorder. Assessment of the effects of SHP2 inhibition in platelets from controls and Noonan syndrome patients. Washed human platelets were incubated with SHP099 and stimulated with collagen-related peptide (CRP) for stirred aggregation and flow cytometric measurements. Whole-blood microfluidics assays using a dosed collagen and tissue factor coating were performed to assess shear-dependent thrombus and fibrin formation. Effects on clot formation were evaluated by thromboelastometry. Pharmacological inhibition of SHP2 did not alter GPVI-dependent platelet aggregation under stirring, but it enhanced integrin αIIbβ3 activation in response to CRP. Using whole-blood microfluidics, SHP099 increased the thrombus buildup on collagen surfaces. In the presence of tissue factor and coagulation, SHP099 increased thrombus size and reduced time to fibrin formation. Blood from PTPN11 -mutated Noonan syndrome patients, with low platelet responsiveness, after ex vivo treatment with SHP099 showed a normalized platelet function. In thromboelastometry, SHP2 inhibition tended to increase tissue factor-induced blood clotting profiles with tranexamic acid, preventing fibrinolysis. Pharmacological inhibition of SHP2 by the allosteric drug SHP099 enhances GPVI-induced platelet activation under shear conditions with a potential to improve platelet functions of Noonan syndrome patients. [Display omitted] • The PTPN11 inhibitor SHP099 was used to study effects in platelets. • SHP099 increased collagen-induced thrombus build-up in whole blood microfluidics. • SHP099 enhanced platelet- and shear-dependent coagulation. • SHP099 restored thrombus formation in Noonan syndrome patients with mutated PTPN11. [ABSTRACT FROM AUTHOR]

This study was aimed at using hot water extracts of pod (KP), seed (KS), leaf (KL) and seed shell (KSS) of Cola nitida (kola nut) for the synthesis of nano-sized magnesium oxide and evaluation for biomedical applications. The nano-sized MgO were biosynthesized for the first time using kola nut extracts and characterized by UV–visible spectroscopy, Fourier transform infra-red spectroscopy (FTIR), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and energy-dispersive X-ray (EDX). The antimicrobial, antioxidant, larvicidal, anticoagulant and thrombolytic activities of the nano-sized MgO were evaluated. The crystalline polygonal-shaped nano-sized MgO absorbed maximally in the range of 270–280 nm and FTIR spectra indicated the involvement of phenolic compounds and proteins in their biosynthesis. At 40 µg/ml, nano-sized MgO showed growth inhibition of 41.2–79.3% against eight multi-drug resistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella granulomatis , and inhibition of 60.2–88.4% on Rhizopus stolonifer, Trichoderma longibrachiatum, Aspergillus flavus and Aspergillus fumigatus. DPPH scavenging activities of 26.1–90.4% were obtained for 1–40 µg/ml of MgO nanostructures, while mortality of 13.33–100% against anopheline larvae was achieved at 30 µg/ml. The nanostructures also prevented blood coagulation and completely dissolved preformed blood clots within 10 min which is herein reported for the first time. This report has shown that Cola nitida can be employed for sustainable synthesis of nano-sized MgO with potent biomedical applications. [Display omitted] • First report of MgO nanostructure synthesis by Cola nitida. • MgO nanostructures displayed SPR at 270–280 nm. • MgO nanostructures inhibited growth of multi-drug resistant bacteria the particles had antifungal, DPPH scavenging and larvicidal activities. • MgO nanostructures prevented blood coagulation and lysed blood clots. [ABSTRACT FROM AUTHOR]