Routine Coagulation.

The term 'routine coagulation' typically applies to hemostasis tests routinely performed in hematology laboratories, often available 24/7, and potentially ordered urgently. These tests would comprise of the prothrombin time (PT), the PT converted to an international normalized ratio, the activated partial thromboplastin time (often called partial thromboplastin time in North American laboratories) and potentially the thrombin time, the D-dimer assay, and fibrinogen assays. Although other tests could feasibly be offered (testing feasible), there are good reasons for not including all of these other tests in all routine coagulation laboratories.

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).

BACKGROUND: Despite 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. METHODS: The 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. DISCUSSION: This 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 REGISTRATION: EudraCT: 2020-005405-10; ClinicalTrial.gov: NCT05507983 (retrospectively registered in August 2022, inclusion started in December 2021).

Histon activities in the extracellular environment: regulation and prothrombotic implications.

PURPOSE OF REVIEW: Thromboembolic complications are a major contributor to global mortality. The relationship between inflammation and coagulation pathways has become an emerging research topic where the role of the innate immune response, and specifically neutrophils in "immunothrombosis" are receiving much attention. This review aims to dissect the intricate interplay between histones (from neutrophils or cellular damage) and the haemostatic pathway, and to explore mechanisms that may counteract the potentially procoagulant effects of those histones that have escaped their nuclear localization. RECENT FINDINGS: Extracellular histones exert procoagulant effects via endothelial damage, platelet activation, and direct interaction with coagulation proteins. Neutralization of histone activities can be achieved by complexation with physiological molecules, through pharmacological compounds, or via proteolytic degradation. Details of neutralization of extracellular histones are still being studied. SUMMARY: Leveraging the understanding of extracellular histone neutralization will pave the way for development of novel pharmacological interventions to treat and prevent complications, including thromboembolism, in patients in whom extracellular histones contribute to their overall clinical status.

Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation.

The coronavirus disease 2019 (COVID-19) pandemic has not only challenged global health systems but also spurred intense scientific inquiry into its pathophysiology. Among the multifaceted aspects of the disease, coagulation abnormalities have emerged as a significant contributor to morbidity and mortality. From endothelial dysfunction to dysregulated immune responses, various factors contribute to the hypercoagulable state seen in severe COVID-19 cases. The dysregulation of coagulation in COVID-19 extends beyond traditional thromboembolic events, encompassing a spectrum of abnormalities ranging from microvascular thrombosis to disseminated intravascular coagulation (DIC). Endothelial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers a cascade of events involving platelet activation, coagulation factor consumption, and fibrinolysis impairment. Moreover, the virus direct effects on immune cells and the cytokine storm further exacerbate the prothrombotic milieu. Unraveling this intricate web of interactions between viral pathogenesis and host responses is essential for elucidating novel therapeutic targets and refining existing management strategies for COVID-19-associated coagulopathy. In the quest to unravel the complex interplay between coagulation and COVID-19, numerous clinical and laboratory studies have yielded invaluable insights into potential biomarkers, prognostic indicators, and therapeutic avenues. Anticoagulation therapy has emerged as a cornerstone in the management of severe COVID-19, although optimal dosing regimens and patient selection criteria remain subjects of ongoing investigation. Additionally, innovative approaches such as targeting specific components of the coagulation cascade or modulating endothelial function hold promise for future therapeutic development.

[Coagulation and complement crosstalk: molecular mechanisms of complement-mediated diseases].

The complement and coagulation systems are ancestrally related mechanisms of serine protease-induced protein activation. Recent studies have shown that the complement system enhances platelet aggregation by activating platelets and vascular endothelial cells. This system is also involved in the expression of tissue factor, which induces the coagulation reaction. Activated platelets and coagulation factors are also known to activate the complement system. In diseases involving the complement system, such as paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, and atypical hemolytic uremic syndrome, excessive activation of this system contributes to complement-mediated thrombosis. The anti-C5 antibody eculizumab has shown a remarkable thromboprophylactic effect in these complement diseases. The recent surge in development of new anti-complement agents has raised expectations for the advancement of treatments and preventive measures for thrombosis associated with complement disorders. This review outlines the crosstalk between these two systems, and describes the mechanisms of several diseases featuring both thrombosis and complement activation.

In vivo effects of balanced, low molecular 6% and 10% hydroxyethyl starch compared with crystalloid volume replacement on the coagulation system in major pancreatic surgery-a sub-analysis of a prospective double-blinded, randomized controlled trial.

BACKGROUND: The outcome of patients undergoing major surgery treated with HES for hemodynamic optimization is unclear. This post-hoc analysis of a randomized clinical pilot trial investigated the impact of low-molecular balanced HES solutions on the coagulation system, blood loss and transfusion requirements. METHODS: The Trial was registered: EudraCT 2008-004175-22 and ethical approval was provided by the ethics committee of Berlin. Patients were randomized into three groups receiving either a 10% HES 130/0.42 solution, a 6% HES 130/0.42 solution or a crystalloid following a goal-directed hemodynamic algorithm. Endpoints were parameters of standard and viscoelastic coagulation laboratory, blood loss and transfusion requirements at baseline, at the end of surgery (EOS) and the first postoperative day (POD 1). RESULTS: Fifty-two patients were included in the analysis (HES 10% (n = 15), HES 6% (n = 17) and crystalloid (n = 20)). Fibrinogen decreased in all groups at EOS (HES 10% 338 [298;378] to 192 [163;234] mg dl-1, p<0.01, HES 6% 385 [302;442] to 174 [163;224] mg dl-1, p<0.01, crystalloids 408 [325;458] to 313 [248;370] mg dl-1, p = 0.01). MCF FIBTEM was decreased for both HES groups at EOS (HES 10%: 20.5 [16.0;24.8] to 6.5 [5.0;10.8] mm, p = <0.01; HES 6% 27.0 [18.8;35.2] to 7.0 [5.0;19.0] mm, p = <0.01). These changes did not persist on POD 1 for HES 10% (rise to 16.0 [13.0;24.0] mm, p = 0.88). Blood loss was not different in the groups nor transfusion requirements. CONCLUSION: Our data suggest a stronger but transient effect of balanced, low-molecular HES on the coagulation system. Despite the decline of the use of artificial colloids in clinical practice, these results may help to inform clinicians who use HES solutions.

New Findings Regarding the Effects of Selected Blue Food Colorants (Genipin, Patent Blue V, and Brilliant Blue FCF) on the Hemostatic Properties of Blood Components In Vitro.

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

Antithrombotic Effect of Oil from the Pulp of Bocaiúva-Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae).

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 µg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

Intravenous lipid emulsion interference in coagulation testing: an ex vivo analysis.

INTRODUCTION: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable. METHODS: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer. RESULTS: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range. DISCUSSION: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers. CONCLUSIONS: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

Analysis of coagulation alteration and its correlation with ß2-microglobulin in 371 patients with newly diagnosed multiple myeloma.

OBJECTIVES: To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and ß2-microglobulin (ß2-MG). METHODS: A total of 371 Patients with newly diagnosed MM (n = 371) and healthy controls (n = 48) were selected from January 2016 to December 2022. Baseline data, ß2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and ß2-MG was analyzed. RESULTS: Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all P < 0.001). ß2-MG was positively correlated with PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < 0.05), and negatively correlated with FIB (r = -0.220, P < 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all P < 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group. CONCLUSIONS: The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to ß2-MG.

NanoGraphene Clot: A New Fibrinogen-Mimic Hemostatic Material.

Trauma is the leading cause of death for adults under the age of 44. Internal bleeding remains a significant challenge in medical emergencies, necessitating the development of effective hemostatic materials that could be administered by paramedics before a patient is in the hospital and treated by surgeons. In this study, we introduce a graphene oxide (GO)-based PEGylated synthetic hemostatic nanomaterial with an average size of 211 ± 83 nm designed to target internal bleeding by mimicking the role of fibrinogen. Functionalization of GO-g-PEG with peptides derived from the α-chain of fibrinogen, such as GRGDS, or the γ-chain of fibrinogen, such as HHLGGAKQAGDV:H12, was achieved with peptide loadings of 72 ± 6 and 68 ± 15 µM, respectively. In vitro studies with platelet-rich plasma (PRP) under confinement demonstrated aggregation enhancement of 39 and 24% for GO-g-PEG-GRGDS and GO-g-PEG-H12, respectively, compared to buffer, while adenosine diphosphate (ADP) alone induced a 5% aggregation. Compared to the same materials in the absence of ADP, GO-g-PEG-GRGDS achieved a 47% aggregation enhancement, while GO-g-PEG-H12 a 25% enhancement. This is particularly important for injectable hemostats and highlights the fact that our nanographene-based materials can only act as hemostats in the presence of agonists, reducing the possibility of unwanted clotting during circulation. Further studies on collagen-coated wells under dynamic flow revealed statistically significant augmentation of PRP fluorescence signal using GRGDS- or H12-coated GO-g-PEG compared to controls. Hemolysis studies showed <1% lysis of red blood cells (RBCs) at the highest PEGylated nanographene concentration. Finally, whole human blood coagulation studies reveal faster and more pronounced clotting using our nanohemostats vs PBS control from 3 min and below (blood is clotted with 10% CaCl2 within 4-5 min), with the biggest differences to be shown at 2 and 1 min. At 1 min, the clot weight was found to be ∼45% of that between 4 and 5 min, while no clot was formed in PBS-treated blood. Reduction of CaCl2 to 5 and 3%, or utilization of prostaglandin E1, an anticoagulant, still leads to clots but of smaller weight. The findings highlight the potential of our fibrinogen-mimic PEGylated nanographene as a promising non-hemolytic injectable scaffold for targeting internal bleeding, offering insights into its platelet aggregation capabilities under confinement and under dynamic flow as well as its pronounced coagulation abilities.

Effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia: protocol for a randomized, double-blind, controlled study.

BACKGROUND: Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. METHODS: Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The "study drug" will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. DISCUSSION: Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. RESULTS: Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0-1, 2-3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0-1 (20.0%) than those with score 2-3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0-1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2-3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0-1 and 2-3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. CONCLUSION: Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0-1.

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition that is characterized by unresolved fatigue, post-exertion symptom exacerbation (PESE), cognitive dysfunction, orthostatic intolerance, and other symptoms. ME/CFS lacks established clinical biomarkers and requires further elucidation of disease mechanisms. A growing number of studies demonstrate signs of hematological and cardiovascular pathology in ME/CFS cohorts, including hyperactivated platelets, endothelial dysfunction, vascular dysregulation, and anomalous clotting processes. To build on these findings, and to identify potential biomarkers that can be related to pathophysiology, we measured differences in protein expression in platelet-poor plasma (PPP) samples from 15 ME/CFS study participants and 10 controls not previously infected with SARS-CoV-2, using DIA LC-MS/MS. We identified 24 proteins that are significantly increased in the ME/CFS group compared to the controls, and 21 proteins that are significantly downregulated. Proteins related to clotting processes - thrombospondin-1 (important in platelet activation), platelet factor 4, and protein S - were differentially expressed in the ME/CFS group, suggestive of a dysregulated coagulation system and abnormal endothelial function. Complement machinery was also significantly downregulated, including C9 which forms part of the membrane attack complex. Additionally, we identified a significant upregulation of lactotransferrin, protein S100-A9, and an immunoglobulin variant. The findings from this experiment further implicate the coagulation and immune system in ME/CFS, and bring to attention the pathology of or imposed on the endothelium. This study highlights potential systems and proteins that require further research with regards to their contribution to the pathogenesis of ME/CFS, symptom manifestation, and biomarker potential, and also gives insight into the hematological and cardiovascular risk for ME/CFS individuals affected by diabetes mellitus.

The coagulation status in women of endometriosis with stage IV.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

Neutrophil-derived migrasomes are an essential part of the coagulation system.

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.

Multifunctional curcumin-based polymer coating: A promising platform against bacteria, inflammation and coagulation.

The extensive use of polymers in the medical field has facilitated the development of various devices and implants, contributing to the restoration of organ function. However, despite their advantages such as biocompatibility and robustness, these materials often face challenges like bacterial contamination and subsequent inflammation, leading to implant-associated infections (IAI). Integrating implants effectively is crucial to prevent bacterial colonization and reduce inflammatory responses. To overcome these major issues, surface chemical modifications have been extensively explored. Indeed, click chemistry, and particularly, copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has emerged as a promising approach for surface functionalization without affecting material bulk properties. Curcumin, known for its diverse biological activities, suffers from low solubility and stability. To enhance its bioavailability, bioconjugation strategy has garnered attention in recent years. This study represents pioneering work in immobilizing curcumin derivative onto polyethylene terephthalate (PET) surfaces, aiming to combat bacterial adhesion, inflammation and coagulation. Before curcumin derivative bioconjugation, a fluorophore, dansyl derivative, was employed in order to monitor and determine the efficiency of the proposed methodology. Previous surface chemical modifications were required for the immobilization of both dansyl and curcumin derivatives. Ultraviolet-Visible (UV-Vis) demonstrated the amidation functionalization of PET surface. Other surface characterization techniques including X-ray Photoelectron Spectroscopy (XPS), Attenuated Total Reflectance Fourier Transformed Infrared (ATR-FTIR), Scanning Electron Microscopy (SEM) and contact angle, among others, confirmed also the conjugation of both dansyl and curcumin derivatives. On the other hand, different biological assays corroborated that curcumin derivative immobilized PET surfaces do not exhibit cytotoxicity effect. Additionally, corresponding inflammation test were performed, indicating that these polymeric surfaces do not produce inflammation and, when curcumin derivative is immobilized, they decrease the inflammation marker level (IL-6). Moreover, the bacterial growth of both Gram positive and Gram negative bacteria were measured, demonstrating that the immobilization of curcumin derivative on PET provided antibacterial properties to the material. Finally, hemolysis rate analysis and whole blood clotting assay demonstrated the antithrombogenic effect of PET-Cur surfaces as well as no hemolysis concern in the fabricated functional surfaces.

Short-duration peripherally inserted central catheters do not alter viscoelastic parameters in healthy dogs.

Objective: To determine if short-duration peripherally inserted central catheters (PICCs) cause a hypercoagulable state in healthy dogs, based on point-of-care viscoelastic coagulation monitor (VCM). Animals: Ten beagle dogs were randomly and equally allocated into control and PICC groups. Procedure: Control dogs had VCM analysis on whole blood following direct venipuncture before sedation (T0) and 2 h after sedation (T2). In the experimental group, a PICC was placed (medial saphenous or femoral vein) under sedation and removed after 4 h, with measurements before placement (T0) and 2 and 6 h after placement (T2 and T6, respectively). Parametric data were analyzed using 1-way ANOVA with Holm-Sídák test for multiple comparisons and paired or unpaired Student's t-test. Nonparametric data were analyzed using Friedman test with Dunn multiple comparison test for Wilcoxon matched-pairs signed-rank test, and Mann-Whitney U test for PICC group, control group, and to compare PICC versus control groups, respectively. Results: Clot formation time was longer at T2 versus T6 (P = 0.0342, but not clinically relevant) in the PICC group, with no significant differences between the PICC and control groups. Conclusion and clinical relevance: Short-term placement of a PICC line did not alter viscoelastic endpoints in healthy beagles.

L'utilisation de courte durée d'un cathéter central inséré par voie périphérique n'affecte pas les paramètres viscoélastiques chez les chiens sains. Objectif: Déterminer si les cathéters centraux insérés par voie périphérique (CCIP) pour une courte durée provoque un état d'hypercoagulabilité chez des chiens en bonne santé sur la base des mesures du Viscoelastic Coagulation Monitor (VCM) au point de soins. Animaux: Dix chiens sains de race beagle ont été choisis et répartis de façon égale et aléatoire dans un groupe témoin et un groupe de CCIP. Procédure: Les chiens témoins ont eu une prise de sang et analyse par VCM avant sédation (T0) et 2 heures après la sédation (T2). Dans le groupe expérimental, un CCIP a été mis en place (veines saphènes ou fémorales médiales) sous sédation et retiré après 4 heures. Les mesures viscoélastiques sur le sang frais ont été effectuées avant la pose du CCIP (T0), 2 heures après la pose (T2) et 2 heures après le retrait/6 heures après la pose du cathéter (T6). L'analyse statistique des données paramétriques a été faite par le test ANOVA à un facteur avec un test de comparaisons multiples de Holm-Sídák pour le groupe CCIP, un test t de Student apparié pour le groupe témoin, et un test t de Student non apparié pour comparer les groupes CCIP et témoin. Les données non paramétriques ont été analysées à l'aide du test de Friedman avec un test de comparaison multiple de Dunn pour le groupe CCIP, du test de rang signé de Wilcoxon pour le groupe témoin et du test de Mann-Whitney U pour comparer les groupes CCIP et témoin. Résultats: Pour le groupe CCIP, le temps de formation du caillot à T2 était plus long mais non cliniquement pertinent. comparativement à T6 (P = 0,0342) et il n'y avait aucune différence significative entre les groupes CCIP et témoin. Conclusion et pertinence clinique: La pose d'un CCIP pour une courte durée n'a pas modifié les variables viscoélastiques chez les chiens beagle en bonne santé.(Traduit par les auteurs).