Coagulation Changes Research Articles

PERSISTENT COAGULATION ABNORMALITIES IN RECOVERED COVID-19 PATIENTS FOLLOWING VACCINATION: A RETROSPECTIVE ANALYSIS

This retrospective observational study assessed persistent coagulation abnormalities in individuals who recovered from COVID-19 and subsequently received two doses of COVID-19 vaccination. The study enrolled 250 individuals, aged 20–50 years, and evaluated four primary coagulation markers: prothrombin time, activated partial thromboplastin time, D-dimer, and fibrinogen. Blood samples were analyzed using the STA-R coagulation analyzer. Results indicated that 10% of participants exhibited elevated D-dimer levels, 34% had elevated prothrombin times, and 85% displayed prolonged activated partial thromboplastin times, while 7.2% showed increased fibrinogen levels. Statistical analysis revealed significant deviations in D-dimer, activated partial thromboplastin time, and fibrinogen from standard reference ranges. These abnormalities suggest a possible hypercoagulable state post-vaccination, potentially due to vaccine-induced mechanisms that activate coagulation pathways. Findings align with reports of vaccine-induced thrombotic complications, especially in adenovirus-vectored vaccines. This study underscores the importance of monitoring coagulation parameters in vaccinated individuals with prior COVID-19 infection to ensure vaccine safety and efficacy. Future studies should investigate the underlying mechanisms of these coagulation changes and their clinical implications.

Comparative Study of the Effectiveness of Pulsed and Continuous 450 nm Laser Radiation on Tissue for Layered Removal of Pigmented Nevi

Benign pigmented skin lesions, including congenital giant pigmented nevi (CGPN), are pathological formations located in various skin layers and consisting of melanocyte clusters. CGPN represent a serious psychological and medical problem associated with extensive unaesthetic changes in the patient’s skin appearance. These lesions are currently treated by various methods, including laser radiation. However, such methods often render ineffective and lead to unsatisfactory clinical and aesthetic results, with the incidence of complications in the form of scarring and recurrence sometimes reaching 41%. Therefore, the problem of effective and appropriate treatment of this pathology is relevant, deserving further research. In this work, we conduct an experimental biomedical study into the effect of blue laser radiation with a wavelength (λ) of 450 nm on the tissues of laboratory animals in order to determine its prospects in the treatment of pigmented nevi, including CGPN. Blue laser radiation (λ — 450 nm) was generated by an Lasermed 10-03 device (Russian Engineering Club, LLC, Tula, Russia). An experimental biomedical in vitro research was performed on chilled samples of the liver and muscles of mini-pigs and in vivo on the pigmented skin of live laboratory rats. The dynamics of the regenerative wound process in the exposure areas was studied at different periods, i.e., immediately after exposure and following up to 90 days. A morphometric assessment of the exposure areas was carried out in terms of penetration depth and coagulation changes. The results obtained allowed determination of optimal parameters of 450 nm blue laser radiation for a precision removal of various pigmented skin formations. Laser radiation with a wavelength of 450 nm is a promising treatment approach for pigmented skin lesions, including CGPN.

Recycling of Surface-Functionalized Nanoparticles—A Short Review

The present manuscript provides a comprehensive overview and partial analysis of both advanced and innovative recycling techniques for functionalized nanoparticles. Such methods are sieving techniques including filtration in different forms (e.g., ultrafiltration, diafiltration), centrifugation, and chromatography. Further microfluidics, solvent extraction, and evaporation as well as magnetic and electric field-assisted methods are presented followed by more conventional methods such as precipitation, coagulation, and ζ-potential changes. To facilitate future progress in nanotechnology recycling, it is necessary to provide improved and innovative production techniques across the whole life cycle of nanotechnology. This is analogous to any other methodology that is conceptualized during the initial phases. Furthermore, a diverse array of preparation methods for functionalized nanoparticles may be developed and implemented using various approaches depending on the evident use of the material. Further, the investigation of waste products containing nanoparticles is not yet possible to achieve an in-depth knowledge of this subject. Moreover, advanced technologies have the capacity to enable a more substantial future implementation of NM recycling for commercial use.

A-155 Development of drop-of-blood QATT heparinase and functional fibrinogen assays

Abstract Background Monitoring the blood coagulation status of patients with coagulopathy or on anticoagulant therapy is important for informed treatment decisions. Quasi-static acoustic tweezing thromboelastometry (QATT) can monitor changes in blood coagulation using a small blood drop. Here, we develop the heparinase and functional fibrinogen QATT assays. Methods Citrated whole blood (WB) samples were collected from 20 healthy volunteers using IRB-approved protocols No. 520566 and 944474. Half of the samples were used for fibrinogen, platelet count tests and the others were used for QATT measurements. For developing heparinase assay, WB samples from 4 healthy volunteers were randomly selected. For each volunteer sample, QATT experiments were performed for a WB sample, a WB sample spiked with 0.5 IU/mL heparin, and a WB sample spiked with heparin and then heparinase. For developing functional fibrinogen assay, QATT experiments were performed for a WB sample and a WB sample spiked with Cytochalasin-D (4 μM). Coagulation was triggered via intrinsic pathway. Pearson correlation coefficient (rp) or the Spearman rank correlation coefficient (rs) was used for correlation analysis. We focused on the following QATT parameters: CIT, MCF, and MCE. Results The heparinase assay effectively reversed heparinized samples (Fig. 1a). CIT of normal and heparinized samples treated with heparinase were within reference range (Fig. 1b). The effect of Cytochalasin-D was shown in Fig 1c. Strong correlation was found between MCE of Cyto-treated WB and fibrinogen level (rp = 0.75). MCE of the difference between normal and Cyto-treated WB, referred to as MCEplatelet, was also strongly correlated with platelet count test (rs = 0.76). The normal range for MCF of the functional fibrinogen assay is efficient in ruling out abnormal fibrinogen level (Fig. 1d). Conclusions QATT accurately predicted the inhibition of heparin by heparinase. QATT functional fibrinogen assay detected the contribution of both fibrinogen and platelets to the clot strength.

Toward Fine Horizontal Resolution Global Simulations of Aerosol Sectional Microphysics: Advances Enabled by GCHP‐TOMAS

AbstractGlobal modeling of aerosol‐particle number and size is important for understanding aerosol effects on Earth's climate and air quality. Fine‐resolution global models are desirable for representing nonlinear aerosol‐microphysical processes, their nonlinear interactions with dynamics and chemistry, and spatial heterogeneity. However, aerosol‐microphysical simulations are computationally demanding, which can limit the achievable global horizontal resolution. Here, we present the first coupling of the TwO‐Moment Aerosol Sectional (TOMAS) microphysics scheme with the High‐Performance configuration of the GEOS‐Chem model of atmospheric composition (GCHP), a coupling termed GCHP‐TOMAS. GCHP's architecture allows massively parallel GCHP‐TOMAS simulations including on the cloud, using hundreds of computing cores, faster runtimes, more memory, and finer global horizontal resolution (e.g., 25 km × 25 km, 7.8 × 105 model columns) versus the previous single‐node capability of GEOS‐Chem‐TOMAS (tens of cores, 200 km × 250 km, 1.3 × 104 model columns). GCHP‐TOMAS runtimes have near‐ideal scalability with computing‐core number. Simulated global‐mean number concentrations increase (dominated by free‐tropospheric over‐ocean sub‐10‐nm‐diameter particles) toward finer GCHP‐TOMAS horizontal resolution. Increasing the horizontal resolution from 200 km × 200–50 km × 50 km increases the global monthly mean free‐tropospheric total particle number by 18.5%, and over‐ocean sub‐10‐nm‐diameter particles by 39.8% at 4‐km altitude. With a cascade of contributing factors, free‐tropospheric particle‐precursor concentrations increase (32.6% at 4‐km altitude) with resolution, promoting new‐particle formation and growth that outweigh coagulation changes. These nonlinear effects have the potential to revise current understanding of processes controlling global aerosol number and aerosol impacts on Earth's climate and air quality.

A Deployable Viscoelastic Coagulation Monitor Enables Point-of-Care Assessment of Coagulopathy in Swine With Polytrauma.

Absence of pre-hospital coagulation tests challenges prompt management of hemostasis after trauma. The Viscoelastic Coagulation Monitor (VCM, Entegrion, Durham, NC) is a hand-held coagulation test for point-of-care. We evaluated VCM in a translational swine polytrauma model, hypothesizing that VCM correlates with a laboratory reference method, the TEG 5000 (Haemonetics, Boston, MA), and can identify coagulopathic phenotypes relevant to trauma. Our secondary hypothesis was that pre-warming of VCM disposable test cartridges using a heating plate versus pre-warming of cartridges by carrying the cartridge in the user's pocket does not significantly alter results. This study was conducted in tandem with a parent study involving anesthetized, mechanically ventilated swine (n = 20; 54 ± 5 kg) that encountered traumatic brain injury, pulmonary contusion and hemorrhage, or combination/polytrauma injury. Blood was collected at baseline, post-injury, post-shock, post-transfusion, and 6-, 24-, and 48 h post-injury to perform VCM at point-of-care. Within-group effect of time was assessed. Spearman correlation examined linear relations between VCM and standard laboratory-based coagulation tests; as well as lactate, ionized calcium, and body temperature. Logistic regression examined predictiveness of VCM to identify coagulopathic phenotypes, with receiver operator characteristic curves generated to assess diagnostic capability. At a subset of timepoints, necessity of pre-warming the VCM test cartridge using a heating plate versus pre-warming the cartridge by placement in the user's pocket was assessed by conducting simultaneous tests on two separate instruments, with results analyzed by paired t-test with crossover design. VCM revealed time-dependent changes in clotting time, clot formation time (CFT), alpha, maximum clot firmness (MCF), and lysis index (LI30). All VCM metrics correlated with the respective TEG 5000 metrics, with strongest correlation for VCM MCF with TEG MA (rhos = 0.77, P < .0001) and VCM LI30 with TEG LY30 (rhos = -0.76, P < .0001). VCM demonstrated good (area under the curve >0.70) to excellent (area under the curve >0.90) diagnostic accuracy in detection of low platelet count (MCF), low hematocrit (clotting time, clot formation time, alpha, and MCF), low fibrinogen (MCF), and high fibrinogen (alpha, MCF). There was no statistically or clinically relevant effect of cartridge warming method on results. In a trauma model, VCM detected significant changes in coagulation at point-of-care in a simplified portable form factor. VCM could enable informed hemostasis management in pre-hospital settings where coagulations tests are unavailable, pending further validation in clinical trials.

Efficacy and safety of tranexamic acid use in elderly patients undergoing anterior cervical discectomy and fusion: a retrospective study.

To evaluate the safety and efficacy of intravenous tranexamic acid (TXA) administration in anterior cervical discectomy fusion (ACDF) for the treatment of cervical spondylosis in the elderly. Data from elderly patients who underwent ACDF between January 2020 and January 2023 were retrospectively reviewed. Patients who received 1 g intravenous TXA administration before skin incision (TXA group) were compared with patients who did not receive TXA (controls). Total and hidden blood loss were calculated, and the following outcomes were recorded: haemoglobin and haematocrit drop, operation time, drainage duration, drain volume, length of hospitalization, coagulation changes, and incidence of complications. A total of 114 patients were included (TXA group, n = 53 and controls, n = 61). Total blood loss, hidden blood loss, and postoperative drainage volume, haemoglobin and haematocrit drop were significantly lower in the TXA group than the control group. There were no significant differences in operation time, intraoperative blood loss, drainage duration, length of hospitalization, or coagulation function between the two groups. The incidence of complications did not differ significantly between the two groups during 3 months of follow-up. Intravenous TXA is effective in reducing perioperative blood loss in elderly patients undergoing ACDF without changing the coagulation function or increasing the risk of complications.

Coagulation after paediatric miniaturised versus conventional cardiopulmonary bypass: Retrospective cohort study.

Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score-matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss.

Alterations in visible light exposure modulate platelet function and regulate thrombus formation

BackgroundVariations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous (VT) and arterial thrombosis is largely unexplored. ObjectivesTo investigate the impact of altering light spectrum on platelet function in thrombosis. MethodsWild type (WT) C57BL/6J mice were exposed to ambient (micewhite, 400lux), blue (miceblue, 442nm, 1,400lux), or red light (micered, 617nm, 1,400lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating NET formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light filtering cataract patients were evaluated over an 8-year period for rate of VTE with multivariable logistic regression clustered by hospital. ResultsExposure to long wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between micered and micewhite. However, there were global metabolomic changes in platelets from micered compared to micewhite. Releasate from activated platelets resulted in reduced NET formation. Micered also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer have lower lifetime risk of VTE after implantation with lenses that filter low wavelength light. ConclusionsLight therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation.

Efficacy of tranexamic acid versus placebo in reducing blood loss during burn excisional surgery: a multi-center, double-blind, parallel, randomized placebo-controlled clinical trial (TRANEX)

BackgroundDespite an increase in knowledge, blood loss during burn excisional surgery remains a major challenge and is an independent predictor of mortality. During burn surgery, limited measures are available to control the bleeding. Increased fibrinolysis could be one of the contributing factors of blood loss during burn excisional surgery. Tranexamic acid inhibits the fibrinolytic response, and a small body of evidence shows positive effects of tranexamic acid on the volume of blood loss.MethodsThe main objectives of this study are twofold, (1) to investigate whether tranexamic acid reduces blood loss and (2) to investigate the changes in coagulation after burn trauma and during burn excisional surgery. This study is a multicenter double-blind randomized clinical trial in patients scheduled for burn excisional surgery within the Dutch burn centers. All adult patients scheduled for burn surgery with an expected blood loss of ≥ 250 are eligible for inclusion in this study. The study is powered on a blood loss reduction of 25% in the intervention group. In total, 95 subjects will be included. The intervention group will receive 1500 mg tranexamic acid versus placebo in the other group. Primary endpoint is reduction of blood loss. Secondary endpoints include occurrence of fibrinolysis during surgery, graft take of the split skin graft, and differences in coagulation and blood clot formation.DiscussionThis protocol of a randomized controlled trial aims to investigate the efficacy of tranexamic acid in reducing blood loss during burn excisional surgery. Furthermore, this study aims to clarify the coagulation status after burn trauma and during the surgical process.Trial registrationEudraCT: 2020-005405-10; ClinicalTrial.gov: NCT05507983 (retrospectively registered in August 2022, inclusion started in December 2021).

Temporal changes in markers of coagulation and fibrinolysis in adults during extracorporeal membrane oxygenation.

Bleeding and thrombotic events (BTE) are frequent during extracorporeal membrane oxygenation (ECMO). They occur at varying timepoints and may be affected by temporal changes in coagulation and fibrinolysis. We aimed to assess various coagulation and fibrinolytic markers over time and their relationship with BTE. A single-centre prospective study was performed in 17 patients with severe respiratory failure receiving veno-venous ECMO. Blood samples were collected before and during ECMO, and around circuit decannulation. Prior to ECMO, D-Dimer, Plasmin-Antiplasmin complexes (PAP), Plasminogen-Activator Inhibitor-1 (PAI-1) and fibrinogen were elevated. There was an increase in D-Dimer and Prothrombin Fragments 1+2 (PF1+2) (729 to 1305pmol/L, p = .034) by day 1 and PAP increased by day 2 from baseline levels (median 1022 to 1797µg/L, p = .023). There was a strong positive correlation in PAP, PF1+2 and thrombin-antithrombin complexes (TAT) to D-Dimer. BTE were frequent - 18% had major extracranial haemorrhage and 24% had intracranial haemorrhage. Over time, there was a progressive elevation PAP in patients developing subsequent extracranial haemorrhage, whereas D-Dimer, PAP and PF1+2 increased after intracranial haemorrhage. There were early changes in coagulation activity during ECMO by PF1+2 followed by subsequent fibrinolysis by PAP. Changes in PAP, PF1+2 and TAT were associated with major haemorrhage.

Identification of coagulation diagnostic biomarkers related to the severity of spinal cord injury

BackgroundBlood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels. MethodsHuman blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed. ResultsDECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered. ConclusionTherefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.

Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight

As spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated “spaceflight secretome profiles,” which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight. Moreover, these proteomic alterations correlated better with peripheral blood mononuclear cells than whole blood, suggesting that immune cells contribute more DAPs than erythrocytes. Finally, to discern possible mechanisms leading to brain-enriched protein detection and blood-brain barrier (BBB) disruption, we examined protein changes in dissected brains of spaceflight mice, which showed increases in PECAM-1, a marker of BBB integrity. These data highlight how even short-duration spaceflight can disrupt human and murine physiology and identify spaceflight biomarkers that can guide countermeasure development.

Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Abstract 137: Identification Of A Noncoding Genetic Variant In The Tissue Factor Locus That Reverses Lethal Thrombosis In Mice

Background: Thrombosis is initiated by tissue factor (TF, gene name F3 ) binding to coagulationFVII, with tissue factor pathway inhibitor (TFPI) inhibiting this complex. Alterations in TF orTFPI expression significantly affect thrombosis. Reducing TFPI expression by 50% ( Tfpi +/-) inmice results in a perinatal lethal phenotype on the Factor V Leiden homozygous( F5 L/L )prothrombotic background. We used the F5 L/L Tfpi +/- lethal phenotype to conduct a dominantsensitized whole genome ENU mutagenesis screen to suppress the F5 L/L Tfpi +/- lethality. Weidentified a Modifier of Factor 5 Leiden 6 (MF5L6) line with 72% penetrance and 85 F5 L/L Tfpi +/- offspring. A significant linkage peak (LOD=4.35),explaining half the suppressing effect andcontaining F3 (Chromosome 3) was identified. Goals/Hypothesis: To identify the genomic variant controlling F3 expression in the MF5L6 line. Methods: To quantify F3 expression in the surviving mice from MF5L6, quantitative PCR onliver, lung, and heart tissues from MF5L6 was performed. We used Sanger DNA and highthroughput sequencing to identify candidate TF regulatory variants in the F3 locus. Theprothrombin time assay was used to test the effects of reduced TF expression on in vitro bloodcoagulation. Results: Two distinct expression profiles in the lung and liver of the MF5L6 mice wereobserved, those that had a 50% reduction in F3 mRNA and those that did not. Heart tissuesexhibited one expression profile, suggesting that the variant regulates F3 expressiontissue-specifically. Sanger sequencing of the F3 coding region revealed no coding mutations inMF5L6 mice. Whole genome sequencing identified two novel candidate variants (in unknownF3 regulatory elements) in the 200 kilobase upstream region of F3 . The 50% reduction in F3 resulted in significant changes in coagulation by the prothrombin assay (n=18,p&lt;0.0009). Conclusion: We identified novel candidate variants for regulating F3 gene expression and aredetermining their mechanism of action. Investigation of these variants will provide new insightsinto the regulation of F3 and enable us to identify the variant(s) responsible for the remainder ofthe thrombosis suppressing effect in MF5L6. Our findings provide new insights into the geneticregulation of thrombosis.

Thermocoagulation of resection surfaces of parenchymal organs using a new source of ultrahigh frequency energy (experimental study)

Relevance. Modern surgery is characterized by the use of various technical means to perform classical surgical techniques - separation and connection of tissues, hemostasis. The study of the applicability of new surgical devices and the search for technological techniques are an important task.The aim of the study: to evaluate the capabilities of the developed device based on microwave energy for hemostatic coagula­tion of resection surfaces of parenchymal organs.Materials and methods. The method is based on the principle of converting microwave energy into heat when it is absorbed in biological tissue. The choice of the microwave range is due to the higher efficiency of power supply to the heat­ing area. Based on the prototype of a medical microwave complex developed in 2011 for thermal effects on biological tissues (RF Patent 2481080. 2011), a prototype of a microwave coagulator for working with parenchymal organs was created. The device was tested on the paren­chymal organs of large laboratory animals under conditions of preserved and switched off blood flow in various energy supply modes. Tissue samples from coagulated lesions were studied histologically.Results. At the site of exposure of the applicator-coagulator to the parenchymal organ, a zone of coagulation changes appears. A clear dependence of the size of coagulation necrosis on the time and power of exposure was noted. When the blood flow is turned off, the necessary stable hemostasis is achieved by shorter exposure time of the coagulator antenna on the surface of the organ.Conclusions. The most effective and reliable hemostasis is achieved on the liver parenchyma. The use of temporary vascular isolation, especially on the kidneys and spleen, involves a single use of microwave energy to stop bleeding. By changing the power and duration of exposure, it is possible to dose the thermal load on biological tissue with great precision. This adjustment allows you to select the operating mode for each specific case. The obtained results of the experiment of the described system during surgery for the purpose of hemostasis in parenchymal bleeding.

Whole blood storage duration alters fibrinogen levels and thrombin formation.

Whole blood resuscitation for hemorrhagic shock in trauma represents an opportunity to correct coagulopathy in trauma while also supplying red blood cells. The production of microvesicles in stored whole blood and their effect on its hemostatic parameters have not been described in previous literature. We hypothesized that microvesicles in aged stored whole blood are procoagulant and increase thrombin production via phosphatidylserine. Whole blood was obtained from male C57BL/6 male mice and stored in anticoagulant solution for up to 10 days. At intervals, stored whole blood underwent examination with rotational thromboelastography, and platelet-poor plasma was prepared for analysis of thrombin generation. Microvesicles were prepared from 10-day-old whole blood aliquots and added to fresh whole blood or platelet-poor plasma to assess changes in coagulation and thrombin generation. Microvesicles were treated with recombinant mouse lactadherin prior to addition to plasma to inhibit phosphatidylserine's role in thrombin generation. Aged murine whole blood had decreased fibrin clot formation compared with fresh samples with decreased plasma fibrinogen levels. Thrombin generation in plasma from aged blood increased over time of storage. The addition of microvesicles to fresh plasma resulted in increased thrombin generation compared with controls. When phosphatidylserine on microvesicles was blocked with lactadherin, there was no difference in the endogenous thrombin potential, but the generation of thrombin was blunted with lower peak thrombin levels. Cold storage of murine whole blood results in decreased fibrinogen levels and fibrin clot formation. Aged whole blood demonstrates increased thrombin generation, and this is due in part to microvesicle production in stored whole blood. One mechanism by which microvesicles are procoagulant is by phosphatidylserine expression on their membranes.

Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.

Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10days, 11-15days, 16-20days, 21-25days, and 26-30days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.

Sepsis induces heterogeneous transcription of coagulation- and inflammation-associated genes in renal microvasculature

BackgroundAcute 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. MethodsLaser 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. ResultsCLP-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. ConclusionRenal 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.

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.