BACKGROUND: Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors and formation of less compact fibrin clots prone to faster lysis predispose to this type of ICH.
METHODS: We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins.
RESULTS: ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001).
CONCLUSIONS: We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.

OBJECTIVE: This article summarizes the role of coagulation factors in the pathophysiology of heart failure including D-dimer, fibrinogen and fibrin, prothrombin, p-selectin, tissue factor, tissue plasminogen activator, von Willebrand factor, β-thromboglobulin, Factor XI, tissue thromboplastin, plasminogen activator inhibitor-1 (PAI-1), thrombomodulin, soluble urokinase-type plasminogen activator receptor (suPAR) and stuart-prower factor.
RESULTS: The D-dimer, P-selectin, prothrombin, von Willebrand factor, tissue plasminogen activator, fibrinogen, suPAR, tissue factor, thrombomodulin and Factor XI play significant roles the pathophysiology of heart failure. However, no associations were found between β-thromboglobulin, tissue thromboplastin, PAI-1 and stuart-prower factor in the context of heart failure. Coagulation factors play significant role in the pathophysiology of heart failure. Consequently, the underlying pathophysiological mechanisms that explain changes in the cascade are closely related to the diagnostic, prognostic and therapeutic roles of coagulation cascade factors, which help physicians identify and treat heart failure.

Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV-C2) by characterizing its membrane binding the specific lipid-protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2-25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1-3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid-protein interactions. Despite existing crystal structures representing presumed \"open\" and \"closed\" states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both \"open\" and \"closed\" states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1-3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures.

OBJECTIVE: Gliomas are associated with high rates of disability and mortality, and currently, there is a lack of specific and sensitive biomarkers for diagnosis. The ideal biomarkers should be detected early through noninvasive methods. Our research aims to develop a rapid, convenient, noninvasive diagnostic method for gliomas, as well as for grading and differentiation.
METHODS: We retrospectively collected data from patients who underwent surgery for glioma, trigeminal neuralgia/hemifacial spasmschwannoma, and those diagnosed with multiple sclerosis at our institution from January 2018 to December 2020. Inflammatory markers and coagulation factor levels were collected on admission, and neutrophil count (NLR), (WBC count minus neutrophil count) / lymphocyte count, platelet count / lymphocyte count, lymphocyte count / monocyte count, and albumin count [g/L] + total lymphocyte count × 5 were calculated for patients. Analyze the significance of biomarkers in the diagnosis and grading of gliomas, the diagnosis of MS, and the differential diagnosis of them.
RESULTS: We evaluated 155 healthy individuals, 64 trigeminal neuralgia/hemifacial spasm patients, 47 MS patients, 316 schwannoma patients, and 814 with glioma patients. Compared with healthy controls and MS group, the preoperative levels of NLR, (WBC count minus neutrophil count) / lymphocyte count, D-dimer, Fibrinogen, Antithrobin, and Factor VIII of glioma patients were significantly higher in glioma patients and positively correlated with the grade of glioma. Conversely, 0020 lymphocyte count / Monocyte count and albumin count [g/L] + total lymphocyte count × 5 were significantly lower and negatively correlated with glioma grading. ROC curves confirmed that for the diagnosis of glioma, NLR showed a maximum area under the curve value of 0.8616 (0.8322-0.8910), followed by D-dimer and Antithrombin, with area under the curve values of 0.8205 (0.7601-0.8809) and 0.8455 (0.8153-0.8758), respectively. NLR and d-dimer also showed great sensitivity in the diagnosis of MS and differential diagnosis with gliomas.
CONCLUSIONS: Our study demonstrated that multiple inflammatory markers and coagulation factors could be utilized as biomarkers for the glioma diagnosis, grading, and differential diagnosis of MS. Furthermore, the combination of these markers exhibited high sensitivity and specificity.

OBJECTIVE: Atrial fibrillation (AF), the most common cardiac arrhythmia favoring ischemic stroke and heart failure involves left atrial remodeling, fibrosis and a complex interplay between cardiovascular risk factors. This study examined whether activated factor X (FXa) induces pro-remodeling and pro-fibrotic responses in atrial endothelial cells (AECs) and human atrial tissues and determined the underlying mechanisms.
RESULTS: AECs were from porcine hearts and human right atrial appendages (RAA) from patients undergoing heart surgery. Protein expression levels were assessed by Western blot and immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and NO using fluorescent probes, thrombin and angiotensin II generation by specific assays, fibrosis by Sirius red staining and senescence by senescence-associated beta-galactosidase (SA-β-gal) activity.In AECs, FXa increased ROS formation, senescence (SA-β-gal activity, p53, p21), angiotensin II generation and the expression of pro-inflammatory (VCAM-1, MCP-1), pro-thrombotic (tissue factor), pro-fibrotic (TGF-β and collagen-1/3a) and pro-remodeling (MMP-2/9) markers whereas eNOS levels and NO formation were reduced. These effects were prevented by inhibitors of FXa but not thrombin, protease-activated receptors antagonists (PAR-1/2) and inhibitors of NADPH oxidases, ACE, AT1R, SGLT1/SGLT2. FXa also increased expression levels of ACE1, AT1R, SGLT1/2 proteins which was prevented by SGLT1/2 inhibitors. Human RAA showed tissue factor mRNA levels that correlated with markers of endothelial activation, pro-remodeling and pro-fibrotic responses and SGLT1/2 mRNA levels. They also showed protein expression levels of ACE1, AT1R, p22phox, SGLT1/2, and immunofluorescence signals of nitrotyrosine and SGLT1/2 colocalized with those of CD31. FXa increased oxidative stress levels which were prevented by inhibitors of the AT1R/NADPH oxidases/SGLT1/2 pathway.
CONCLUSIONS: FXa promotes oxidative stress triggering premature endothelial senescence and dysfunction associated with pro-thrombotic, pro-remodeling and pro-fibrotic responses in AECs and in human RAA involving the AT1R/NADPH oxidases/SGLT1/2 pro-oxidant pathway. Targeting this pathway may be of interest to prevent atrial remodeling and the progression of atrial fibrillation substrate.

Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm2. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.

UNASSIGNED: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis.
UNASSIGNED: A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves.
UNASSIGNED: Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively).
UNASSIGNED: The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient\'s condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.

BACKGROUND: Mathematical models of coagulation have been developed to mirror thrombin generation in plasma, with the aim of investigating how variation in coagulation factor levels regulates hemostasis. However, current models vary in the reactions they capture and the reaction rates used, and their validation is restricted by a lack of large coherent datasets, resulting in questioning of their utility.
OBJECTIVE: To address this debate, we systematically assessed current models against a large dataset, using plasma coagulation factor levels from 348 individuals with normal hemostasis to identify the causes of these variations.
METHODS: We compared model predictions with measured thrombin generation, quantifying and comparing the ability of each model to predict thrombin generation, the contributions of the individual reactions, and their dependence on reaction rates.
RESULTS: We found that no current model predicted the hemostatic response across the whole cohort and all produced thrombin generation curves that did not resemble those obtained experimentally. Our analysis has identified the key reactions that lead to differential model predictions, where experimental uncertainty leads to variability in predictions, and we determined reactions that have a high influence on measured thrombin generation, such as the contribution of factor XI.
CONCLUSIONS: This systematic assessment of models of coagulation, using large dataset inputs, points to ways in which these models can be improved. A model that accurately reflects the effects of the multiple subtle variations in an individual\'s hemostatic profile could be used for assessing antithrombotics or as a tool for precision medicine.

The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.

Age is a significant risk factor for ischemic stroke. However, the influence of aging on coagulation parameters in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) remains unclear. A total of 775 samples were collected from 224 NVAF patients receiving apixaban, edoxaban or rivaroxaban. The samples were categorized into three age groups: (i) ≤ 64 years, (ii) 65-74 years, and (iii) ≥ 75 years (apixaban: N = 48, 108, 119; edoxaban: N = 63, 68, 126; rivaroxaban: N = 115, 90, 38, respectively). Coagulation parameters including fibrinogen (Fbg), factor II, factor V, factor VII, factor X, and D-dimer, were compared between the three age groups for each drug. The slopes in the correlation between drug concentrations and modified diluted prothrombin time (mdPT) were also assessed. Fbg and factor V increased with age, while factor II and factor X decreased. Factor VII and D-dimer showed no significant differences across age categories. The slope in response to drug concentrations was similar between the age groups. In NVAF patients treated with apixaban, edoxaban and rivaroxaban, some coagulation parameters exhibited age-related variation. However, the response of mdPT to drug concentration was consistent across age categories.