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Catecholamine infusion elicits an increase in clotting factors and this increase has been attributed to stimulation of [beta].sub.2 -adrenorecptors ([beta]2AR). Accordingly, we tested the hypothesis that inhalation of a short-acting selective [beta]2AR agonist can induce a procoagulant state in healthy individuals. We recruited 23 healthy volunteers (nine females; mean age: 26±0.8 years; body mass index: 24.7±0.5 kg/m.sup.2) and randomly allocated them into two groups, the [beta]2AR arm (seventeen subjects) and the saline arm (six subjects). Hemodynamics, plasma norepinephrine concentration, and procoagulant, anticoagulant, and fibrinolytic profiles of each participant were determined using specific assays before and after inhalation of either 2 mL nebulized normal saline or a mixture of 1 mL saline and 1 mL of salbutamol (5 mg salbutamol sulfate), a selective [beta]2AR agonist, which were delivered by a nebulizer over ten minutes. Saline inhalation had no effect on the procoagulant, anticoagulant and fibrinolytic profiles of the six healthy volunteer in the study's saline arm. Salbutamol inhalation caused (a) a significant increase in the activity or levels of the procoagulant factors; FVIII increased by 11±3% (p = 0.04), von Willebrand factor increased by 7±1% (p = 0.03), and (b) a significant decrease in the activated partial prothrombin time from 27.4±0.4 seconds to 25.5 ±0.5 seconds (p<0.001) in the 17 volunteers in the study's [beta]2AR arm. D-dimer and prothrombin fragments F1+2 were elevated by 200 ±90% and 505.0 ±300.0%, respectively. In addition, the activity of the anticoagulant protein C pathway (demonstrated by the protein C Global assay) decreased from 1.0±0.08 to 0.82±0.06 (p<0.001). Although plasma levels of tissue plasminogen activator decreased, all other indices of the fibrinolytic system did not change following salbutamol inhalation. We found that a single inhalation of salbutamol, a short-acting [beta]2AR agonist, activates the clotting system without affecting the fibrinolytic system. This induction of a procoagulant state in healthy subjects warrants further investigation in patients treated with these agents.

Numerous types of cancer have been shown to be associated with either ischemic or hemorrhagic stroke. In this review, the epidemiology and pathophysiology of stroke in cancer patients is discussed, while providing vital information on the diagnosis and management of patients with cancer and stroke. Cancer may mediate stroke pathophysiology either directly or via coagulation disorders that establish a state of hypercoagulation, as well as via infections. Cancer treatment options, such as chemotherapy, radiotherapy and surgery have all been shown to aggravate the risk of stroke as well. The clinical manifestation varies greatly depending upon the underlying cause; however, in general, cancer-associated strokes tend to appear as multifocal in neuroimaging. Furthermore, several serum markers have been identified, such as high D-Dimer levels and fibrin degradation products. Managing cancer patients with stroke is a delicate matter. The cancer should not be considered a contraindication in applying thrombolysis and recombinant tissue plasminogen activator (rTPA) administration, since the risk of hemorrhage in cancer patients has not been reported to be higher than that in the general population. Anticoagulation, on the contrary, should be carefully examined. Clinicians should weigh the benefits and risks of anticoagulation treatment for each patient individually; the new oral anticoagulants appear promising; however, low-molecular-weight heparin remains the first choice. On the whole, stroke is a serious and not a rare complication of malignancy. Clinicians should be adequately trained to handle these patients efficiently.

In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.

Occlusions in the blood vessels caused by blood clots, referred to as thrombosis, and the subsequent outcomes are leading causes of morbidity and mortality worldwide. In vitro and in vivo models of thrombosis have advanced our understanding of the complex pathways involved in its development and allowed the evaluation of different therapeutic approaches for its management. This review summarizes different commonly used approaches to induce thrombosis in vivo and in vitro, without detailing the protocols for each technique or the mechanism of thrombus development. For ease of flow, a schematic illustration of the models mentioned in the review is shown below. Considering the number of available approaches, we emphasize the importance of standardizing thrombosis models in research per study aim and application, as different pathophysiological mechanisms are involved in each model, and they exert varying responses to the same carried tests. For the time being, the selection of the appropriate model depends on several factors, including the available settings and research facilities, the aim of the research and its application, and the researchers’ experience and ability to perform surgical interventions if needed.

Background With the increase of awareness of mycoplasma pneumoniae pneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis. Methods We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children’s Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes. Results Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3–1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough. Conclusions SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Background During sepsis-induced coagulopathy (SIC), the balance of coagulation, anticoagulation, and fibrinolysis is disrupted, and endothelial dysfunction plays a key role in the disease progression. Current studies have indicated that the Proviral integration site for Moloney murine leukemia virus 1 (Pim-1) can promote thrombosis and activate an autoimmune response. This study aimed to assess the relevance of inhibiting Pim-1 as a potential therapeutic target for SIC. Methods Wild-type, Pim-1-KO, and TLR4-KO mice were categorized into the sham and cecal ligation and puncture (CLP) groups. Human umbilical vein endothelial cells were classified into the control, lipopolysaccharide (LPS) stimulation, and intervention groups. Enzyme-linked immunosorbent assay was used to detect plasma coagulation index in mice. Western blotting and immunofluorescence were employed to examine protein expression in tissues or cells. Additionally, immunohistochemistry and hematoxylin and eosin staining were conducted to detect liver/lung tissue damage. Tissue factor (TF) promoter activity was detected using a dual-luciferase reporter assay. Results Pim-1 kinase inhibition decreased the coagulation response of sepsis mice and improved the survival rate. Pim-1 activated the LPS-induced HUVECs downstream mTOR/Sp1 pathway, promoted TF activity. Pim-1 is mediated by the upstream TLR4 pathway to promote TF activity in LPS-induced HUVECs. Conclusions Inhibiting the activity of Pim-1 kinase may be an effective way to improve the function of endothelial cells and treat SIC.

Protein C (PC) deficiency is a heritable or acquired risk factor for thrombophilia, with presentations varying from asymptomatic to venous thromboembolism to neonatal purpura fulminans, a life-threatening disorder. Hereditary PC deficiency is caused by mutation in the PC (PROC) gene located on chromosome 2q14.3. Heterozygous and acquired PC deficiencies are more common than homozygous deficiency. The recommended initial laboratory test measures PC activity using either clot-based or chromogenic methods. There are numerous potential interferences in PC activity testing that may result in either false-positive (falsely low activity) or false-negative (falsely normal or elevated activity) results. In the present review, we discuss common clinical presentations; laboratory testing, with a focus on potential assay interferences; treatment options; and prognosis in patients with PC deficiency.

Glioblastoma (GBM) is often complicated by venous thromboembolism (VTE), primarily driven by tissue factor (TF, F3 ) and podoplanin (PDPN). These factors promote local hypercoagulation and microthrombosis, thereby contributing to tumor progression by enhancing migration, invasion, and inflammation. Both TF and PDPN can be released via extracellular vesicles (EVs), which carry procoagulant and immunomodulatory cargo. We developed a translational workflow combining biobanked tumor samples, clinical data, ex vivo GBM cultures, and coagulation assays to investigate mechanisms of hypercoagulation. Intraoperative blood coagulation was profiled using ClotPro ® . Gene expression of coagulation-related markers was analyzed in tumor tissues and cell lines, complemented by RNAseq-based profiling of coagulation–inflammation links. Functional coagulation assays included clotting time, platelet aggregation, and EV-based analysis of prothrombotic and immunomodulatory activity. Peripheral coagulation in GBM patients was largely unaltered. However, tumor tissues consistently showed high F3 and PDPN expression and markedly low tissue factor pathway inhibitor ( TFPI ) levels ( p  < 0.001), indicating a shift toward a procoagulant phenotype. Patient-derived GBM cell lines showed variable TF and PDPN expression, which correlated with clotting potential. Distinct procoagulant mechanisms were observed, with some cells engaging both TF-mediated thrombin generation and PDPN-driven platelet activation. EVs isolated from GBM patient plasma and culture media showed similar procoagulant characteristics, with activity proportional to TF expression, and immune-modulating effects. Notably, GBM-derived EVs modulated microglial behavior, induced senescence, and triggered immune polarization in a cell line-dependent manner, likely contributing to tumor microenvironment remodeling. GBM-associated hypercoagulability is shaped by heterogeneous tumor-intrinsic pathways and EV-mediated mechanisms. The dual role of EVs in promoting coagulation and modulating immune responses provides a mechanistic framework for further studies investigating EVs as potential biomarkers and therapeutic targets relevant to future thromboprophylactic strategies in GBM patients.

P -selectin, a cell adhesion molecule of the selectin family, is expressed on the surface of activated endothelial cells (ECs) and platelets. Binding of P -selectin to P -selectin glycoprotein ligand-1 (PSGL-1) supports the leukocytes capture and rolling on stimulated ECs and increases the aggregation of leukocytes and activated platelets. Cancer cachexia is a systemic inflammation disorder characterized by metabolic disturbances, reduced body weight, loss of appetite, fat depletion, and progressive muscle atrophy. Cachexia status is associated with increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which activates ECs to release P -selectin. Single-nucleotide polymorphisms (SNPs) loci of P -selectin encoding gene SELP are associated with higher level of plasma P -selectin and increase the susceptibility to cachexia in cancer patients. Elevated P -selectin expression has been observed in the hypothalamus, liver, and gastrocnemius muscle in animal models with cancer cachexia. Increased P -selectin may cause excessive inflammatory processes, muscle atrophy, and blood hypercoagulation, thus facilitating the development of cancer cachexia. In this review, physiological functions of P -selectin and its potential roles in cancer cachexia have been summarized. We also discuss the therapeutic potential of P -selectin inhibitors for the treatment of cancer cachexia.