Fibrin Monomer Research Articles

Efficacy and Safety of Rivaroxaban, Apixaban, and Edoxaban for Nonvalvular Atrial Fibrillation Based on Blood Coagulation Activity and Drug Plasma Concentration: SETtsu and North Osaka Multicenter Direct Oral AntiCoagulant (SET DOAC) Registry

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.

Establishing Expectancy Values for Fibrin Monomer in Uncomplicated Pregnancy.

Background During pregnancy, a physiological increase of molecular activation markers (MAM) of hemostasis such as prothrombin fragments 1 + 2, thrombin-antithrombin complex, and D-dimers (DD) occurs. Therefore, monitoring MAM levels during pregnancy to evaluate the risk of venous thromboembolism (VTE) may be unreliable; nevertheless, DD analysis in pregnancy is widely performed. In contrast to DD, fibrin monomer (FM) levels have been reported to remain stable during pregnancy. Objectives The main aim of this study was to define the expected range for FM levels in pregnant outpatients. In addition, we examined the impact of the individual VTE risk, as calculated by the pregnancy risk score of the Royal College of Obstetricians and Gynaecologists (RCOG), as well as that of antithrombotic treatment on FM levels. Methods A total of 342 pregnant women seen at our hemostasis unit were included throughout 350 pregnancies in 899 samples. Results Low-risk thrombophilia, but not the RCOG score itself, was found to influence all MAM levels, whereas antithrombotic treatment had only an impact on DD. For FM, a reference range could be calculated irrespective of the pregnancy term, in contrast to other MAMs, which fluctuated throughout pregnancy. Conclusions Our findings suggest a stronger impact of inherited thrombophilia on hemostasis activity during pregnancy as compared with acquired or other predisposing thrombophilic risk factors. FM levels showed a marginal increase during pregnancy in contrast to other MAM and remain a potential candidate to improve the laboratory assessment of VTE risk during pregnancy. Further prospective studies in pregnant patients with suspicion of VTE are needed.

MACE prediction in patients with STEMI and NSTEMI: from classic to novel markers in the estimation of coronary microcirculation disorder

Evaluation of classic and novel markers of coronary microcirculatory disorder (CMD) which have a predictive value on the risk of major cardiovascular event (MACE) in patients with STEMI and NSTEMI. Material and methods. The research included the retrospective analysis of a prospective observational study carried out on 600 patients, of which have been formed equal 4 groups of 80 patients (STEMI+MACE; STEMI-MACE; NSTEMI+MACE; NSTEMI-MACE) in which the collected blood on the 5-th day after angioplasty, the circulating level of 16 markers referring to CMD in the field of estimating endothelial dysfunction and hemostasis was determined: 8 classic markers (hsCRP, IL-6, TNF-α, IL-10, myeloperoxidase, NO , angiopoietin 2, fibrin monomers) and 8 new markers (neopteirn, endocan, syndecan 1, L-Arginine/ADMA, Ang 1-7/Ang II, endothelial microparticles, platelet microparticles, von Willebrand/ADAMTS13). In order to assess the prediction of MACE (cardiac death, re-infarction, stroke) at 1-st year, the relative risk of markers that had significant differences in patients with MACE versus without MACE in both groups (STEMI and NSTEMI) was assessed. The control group consisted of 40 apparently healthy people. Results. The MACE rate in STEMI and NSTEMI patients at 1 year was similar, 29% and 28%, respectively. All markers of endothelial dysfunction explored had significant deviations from control. Of these, however, only 4 markers had significant different values in patients (STEMI and NSTEMI) with MACE vs without MACE: neopterin, endocan, L-Arginine/ADMA and Ang 1-7/Ang II. Remarkably, all 3 markers of hemostasis explored had circulating levels in patients who developed MACE significantly higher than patients without MACE, which significantly exceeded the control marker. The assessment of the relative risk value has allowed the delineation of markers regarding the prediction of MACE such as: von Willebrand/ADAMTS13, platelet microparticles, fibrin monomers, endocan, neopterin, Ang 1-7/ Ang II, L-Arginine/ADAMTS13. Conclusions. 1. Endothelial dysfunction and compromised hemostasis are pathophysiological pillars of CMD which influences the MACE risk, and thus new markers such as von Willebrand/ADAMTS13 ratio, platelet microparticles, endocan, the ratio Ang 1-7/Ang II and L/Arginine/ ADMAs have notable predictive value on MACE.2. Since CMD may be a key mechanism of cardiac ischemia in chronic non-obstructive coronary artery disease (<50%) its evaluation, including through the identified predictors, has a conclusive diagnostic and prognostic relevance.

Characteristics of fibrin/fibrinogen degradation products in multiple sclerosis following SARS-CoV-2 infection

Background. The purpose of this study was to investigate plasma levels of fibrinogen and products of its degradation in patients with multiple sclerosis (MS) with and without a history of coronavirus disease 2019 (COVID-19). Materials and methods. We examined 97 patients with MS. Based on the presence of COVID-19, all cases were divided into two groups. MS group included 56 patients who did not suffer from COVID-19 previously. MS + COVID group consisted of 41 cases who had a laboratory-verified diagnosis of COVID-19. The group of healthy controls included 30 healthy volunteers. Spectrophotometric techniques were used to measure the concentrations of fibrinogen, D-dimer, and soluble fibrin monomer complexes (SFMCs). Size-exclusion chromatography was applied to analyze the composition of SFMC fractions. Results. We found that concentrations of fibrinogen, D-dimer, and SFMCs were remarkably increased in plasma of all MS patients compared with healthy controls. The levels of D-dimer, and SFMCs did not differ between two MS groups, while plasma fibrinogen concentration was significantly increased in MS + COVID patients compared to MS group. Moreover, the development of MS was accompanied by the changes in both quantity and quality of SFMC composition compared to that of healthy controls. Our results demonstrated accumulation of high-molecular-weight SFMCs in plasma of MS patients. Conclusions. The findings indicated that MS patients had changed hemostasis characteristics; however, more research is required to determine the connection between particular hemostatic factors, namely fibrinogen, D-dimer, and SFMCs, and the pathophysiology of MS.

Factor XIII in major burns coagulation

BackgroundIn the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. ObjectiveTo determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. MethodsProspective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. ResultsFXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. ConclusionMBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

Tissue-Penetrating Ultrasound-Triggered Hydrogel for Promoting Microvascular Network Reconstruction.

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound-triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration.

The Role of Fibrin Monomer Compared to D-dimer and CRP in Determining COVID-19 Severity

Fibrin Monomer (FM), as a product of thrombin activity in cleaving fibrinogen, can be used as an early marker of thrombotic events in COVID-19 patients. D-dimer is a commonly used marker of hemostasis as a product of plasmin activity in cleaving polymeric fibrin. D-dimer is often used to help decide whether to initiate anticoagulant administration. This study aims to know whether FM can be used as a marker for thrombotic events such as D-dimer in COVID-19 patients; CRP levels were also examined to determine how inflammation affected the two hemostatic indicators. A total of 93 patients were confirmed with COVID-19 by PCR. The median (min-max) FM in the severe stage was 4.53 (2.26-58.20)ug/mL, whereas, in the mild-moderate stage, it was 4.21 (2.19-32.35 ug/mL. There are significant differences in median D-dimer levels in severe stages to mild-moderate, respectively 0.46 (0.14–7.58) and 0.7890, and ages. The level of FM that can be used to differentiate the severe stage is > 4.46 ug/mL (sensitivity 56.3%, specificity 58.0%) as in the D-dimer level is > 0.58 ug/mL ((sensitivity 75.0%, specificity 65.2%). There is a moderate positive correlation between fibrin monomer and D-dimer, a weak positive correlation between D-dimer and CRP, and no correlation between FM and CRP. This study concludes that the FM median level is higher in severe COVID-19 than in D-dimer. Fibrin monomer levels have a positive correlation with D-dimer. Fibrin Monomer levels are not affected by CRP.

The Prognostic Value of Extended Inflammation Parameters and Soluble Fibrin Monomer Complex in Covid-19 Patients in The Intensive Care Unit

Objective: This study aimed to investigate how extended inflammation markers (EIM) and soluble fibrin monomer complex (SFMC) affected the prognosis of COVID-19-infected patients in the intensive care unit (ICU). Methods: In this study, 73 adults with COVID-19 were included. Patients were divided into two groups: those who died (Group 1; n = 45) and those who survived (Group 2; n = 28). SFMC and EIM [neutrophil reactivity index (NEUT-RI) and neutrophil granularity index (NEUT-GI), reactive lymphocyte (RE-LYMPH), antibodies synthesizing lymphocyte (AS-LYMP), neutrophil/lymphocyte ratio (NLR) and immature granulocyte/lymphocyte ratio (IGLR)], were analyzed in the first 28 days of these patients' follow-up. Results: The median NLR during the first four weeks, IGLR in the first two weeks, RE-LYMPH in the first three weeks, NEUT-RI and NEUT-GI values in the second week, and AS-LYMP in the third week of follow-up were significantly higher in Group 1 than in Group 2 (p<0.05). The median D-Dimer level during the first three weeks and SFMC value in the first week of follow-up were significantly higher in Group 1 than in Group 2 (p<0.05). In patients with COVID-19, older age (≥65 years), nosocomial infection, blood product use, longer ICU stay (>7 days), high DIC (>5), and comorbidities (>3) scores were all risk factors for mortality. In ROC analysis, the cut-off values for NLR and SFMC to predict mortality were 6 and 6.5, respectively. Conclusion: Our data show that elevated NLR and SFMC values in the first week should alert physicians to the risk of life-threatening COVID-19 complications.

Abstract TP268: Markers of Coagulation and Hemostatic Activation in Ischemic Stroke Patients With Reduced Ejection Fraction on Antiplatelet Therapy

Introduction: Heart failure with reduced ejection fraction (HFrEF) is a risk factor for ischemic stroke. However, antithrombotic choice in a patient with HFrEF remains challenging. We set out to evaluate serum markers of coagulation and hemostatic activation (MOCHA) among ischemic stroke patients with HFrEF. Methods: We performed a retrospective analysis of ischemic stroke patients with HFrEF (<40%) from July 28, 2017-June 13, 2023 seen at the Emory Stroke Clinic who underwent a MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. We excluded patients who were on anticoagulation therapy at the initial visit. Results: Overall, 40 patients (mean age 60 +/- 13.1, 53% female, 85% nonwhite) met criteria; median EF was 25% (IQR 15%-30%). Frequency of abnormal MOCHA profile was 43% in EF ≥25% and 58% in EF <25% (p = 0.52). No MOCHA components were associated with reduced EF in multivariate linear regression analysis (R2 = 0.03, p = 0.28). Over mean follow-up of 2.3 years, recurrent stroke occurred in 5.3 / 100 patient-years and major adverse cardiac events (MACE) occurred at 7.4 / 100 patient-years. Compared to patients with EF <25%, patients with EF ≥25% had higher recurrent stroke rates (6.46 vs 3.07 per 100 patient-years) and MACE (9.69 and 3.07 per 100 patient-years) Patients on antiplatelet regimens and anticoagulant regimens experienced MACE events at a rate of 4.25 and 10.62 per 100 patient-years, respectively. Patients with abnormal MOCHA profiles (n=20) had no recurrent strokes, but experienced other MACE events at a rate of 3.86 per 100 patient years, while patients with normal MOCHA profiles (n=20) experienced 11.73 MACE events per 100 patient-years, all of which were recurrent strokes. Conclusion: In HFrEF patients with an ischemic stroke, the MOCHA profile was not associated with ejection fraction. No difference in recurrent stroke and MACE events was seen among patients with normal vs abnormal MOCHA profile.

Blood coagulation system in experimental acute lung injury and its treatment with dexamethasone

The effects of short- and long-term administrations of dexamethasone on survival, severity of pulmonary edema, and hemostasis on experimental lipopolysaccharide-induced acute lung injury in rats were analyzed. Acute lung injury in rats was modeled by the intratracheal injection of lipopolysaccharide from the Salmonella enterica cell wall. White male rats were randomly divided into nine groups: the intact group consisted of 10 animals; two control groups of 20 animals each, in which acute lung injury was simulated without further treatment and removed from the experiment on day 3 or 7; six comparison groups of 20 animals each, in which, 3 h after modeling of acute lung injury and then once a day for 3 days (short mode of administration) or 7 days (long mode of administration), dexamethasone solution was administered intraperitoneally in the following doses: 0. 52 (equivalent to 6 mg/day for humans), 1. 71 (20 mg/day for humans), and 8 mg/kg/day (94 mg/day, pulse therapy for humans). On days 3 and 7, the survival rate, coagulogram values (active partial thromboplastin time, prothrombin time, activity of antithrombin, and soluble fibrin monomer complexes), and low-frequency piezotromboelastography data were assessed in the surviving animals. The results revealed that dexamethasone reduces mortality in acute lung injury and has a dose-dependent effect on the hemostasis system: with an increase in the dose administered, blood clotting processes increase and fibrinolysis is inhibited. Low-frequency piezothromboelastography with a conventional coagulogram allows for a comprehensive assessment of the hemostasis system, identifying violations, and timely drug correction.

Reference Value Fibrin Monomer in Healthy Children: A Cross-Sectional Study.

The objective of this study is to determine the fibrin monomer reference intervals in healthy children. This cross-sectional study was conducted in the Hematology Department at Vietnam National Children's Hospital (April 2023 to March 2024). Children without prior history of clotting disorders or anticoagulants use hospitalized in preparation for orthopedic surgery or inguinal hernia surgery were enrolled in the study. The fibrin monomer test method was the quantitative fibrin monomer test on the STA-R system (Diagnostica Stago™, France). Eighty-six children (58 males and 28 females) were enrolled in the study. The median (interquartile range, 2.5th-97.5th) fibrin monomer value of the study subjects was 2.56 (0.11-5.93) µg/mL, with no statistically significant difference in fibrin monomer values among the age groups of 1 month to 3 years, 3 years to 13 years, and 13 years to 18 years. This is the first study conducted in Vietnam to determine reference values of fibrin monomer in children. This information can help in the diagnosis and treatment of early hypercoagulation stage and disseminated intravascular coagulation in children.

Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching

To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM). Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin III (ATIII), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients. A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio (OR) = 1.165, 95% confidence interval (95%CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95%CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0. Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

Low factor XIII levels and altered fibrinolysis in patients with multiple myeloma

BackgroundAcquired factor FXIII (FXIII) deficiency can be immune- or non-immune mediated and may cause severe bleeding symptoms. The incidence of acquired FXIII deficiency and its etiology in patients with multiple myeloma (MM) are poorly understood. ObjectivesTo assess FXIII levels and the balance of fibrinolysis in newly diagnosed, untreated MM and monoclonal gammopathy of undetermined significance (MGUS) patients. MethodsFXIII activity, mixing studies, FXIII-A2B2 antigen, total FXIII-B antigen were measured in platelet-poor plasma from 17 untreated MM patients, 33 untreated MGUS patients, and 30 age and sex-matched healthy controls. Besides routine laboratory measurements, the balance of coagulation and fibrinolysis was evaluated using quantitative fibrin monomer (FM) test, thrombin-antithrombin assay, α2-antiplasmin activity, plasmin-α2-antiplasmin (PAP) complex, D-dimer, plasmin generation assay, clot lysis assay, and ClotPro-TPA test. ResultsFXIII-A2B2 levels were significantly lower in MM patients compared to controls [median (IQR):14.6 (11.2–19.4) vs. 21.8 (17.1–26.4) mg/L, p = 0.0015], whereas total FXIII-B did not differ between groups. Decrease in FXIII activity was parallel to the decrease in FXIII-A2B2. An immune-mediated inhibitory mechanism was ruled out. Free/total FXIII-B was significantly higher in MM patients compared to MGUS and healthy controls, suggesting an etiology of FXIII-A consumption. In MM and MGUS patients, FM, D-dimer, and PAP complex were significantly elevated compared to controls, indicating hypercoagulability and ongoing fibrinolysis. ConclusionsLow FXIII levels due to consumption were observed in MM patients at diagnosis. Hypercoagulability and ongoing fibrinolysis were detected in MM and MGUS, indicating that a disturbed hemostasis balance is already present in the latter benign condition.

Fluorescent peptide for detecting factor XIIIa activity and fibrin in whole blood clots forming under flow

BackgroundDuring clotting, thrombin generates fibrin monomers and activates plasma-derived transglutaminase factor (F) XIIIa; collagen and thrombin-activated platelets offer thrombin-independent cellular FXIIIa (cFXIIIa) for clotting. Detecting fibrin on collagen and tissue factor surfaces in whole blood clotting typically uses complex reagents like fluorescent fibrinogen or antifibrin antibody. ObjectivesWe want to test whether the peptide using the α2- antiplasmin crosslinking mechanism by FXIIIa is a useful tool in both monitoring FXIIIa activity, and visualize and monitor fibrin formation, deposition, and extent of crosslinking within fibrin structures in whole blood clots formed under flow. MethodsWe tested a fluorescent peptide derived from α2-antiplasmin sequence (Ac-GNQEQVSPLTLLKWC-fluorescein) to monitor the location of transglutaminase activity and fibrin during whole blood clotting under microfluidic flow (wall shear rate, 100 s−1). ResultsThe peptide rapidly colocated with accumulating fibrin due to transglutaminase activity, confirmed by Phe-Pro-Arg-chloromethylketone inhibiting fibrin and peptide labeling. The FXIIIa inhibitor T101 had no effect on fibrin generation but ablated the labeling of fibrin by the peptide. Similarly, Gly-Pro-Arg-Pro abated fibrin formation and thus strongly attenuated the peptide signal. At arterial wall shear rate (1000 s−1), less fibrin was formed, and consequently, less peptide labeling of fibrin was detected compared with venous conditions. The addition of tissue plasminogen activator caused a reduction of both fibrin and peptide signals. Also, the peptide strongly colocalized with fibrin (but not platelets) in clots from laser-injured mouse cremaster arterioles. For clotting under flow, FXIIIa activity was most likely plasma-derived since a RhoA inhibitor did not block α2-antiplasmin fragment cross-linking to fibrin. ConclusionUnder flow, the majority of FXIIIa-dependent fibrin labeling with peptide during clotting was distal of thrombin activity. The synthetic peptide provided a strong and sustained labeling of fibrin as it formed under flow.

CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples

AbstractThe hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next-generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex vivo hemostatic activity of rFVIIa and CT-001 in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery lag time and time to peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.

Abstract 17813: Markers of Cellular Damage, Inflammatory Response, Coagulation and Platelet Activity, and Apoptosis During Catheter Ablation for Atrial Fibrillation Using Radiofrequency and Pulsed-Field Energy

Introduction: Pulsed-field ablation (PFA) presents a new technology for the ablation of AF using non-thermal ablation energy. Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation cascade activation. The study aimed to compare markers of cell damage and platelet and coagulation activation in patients undergoing PVI using PF and radiofrequency (RF) energy. Hypothesis: PFA will be associated will more pronounced myocardial damage, but less pronounced activation of platelets and inflammation. Methods: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster, USA) or PF (Farapulse, Boston-Scientific, USA) energy. Markers of myocardial damage (high-sensitivity troponin I), apoptosis (Fas ligand, caspase-3), inflammation (interleukin-6), coagulation (D-dimers, Fibrin monomers, von Willebrand antigen and factor activity), platelet activation (P-selectin, activated Gp IIb/IIIa antigen and CD42b), and neuron axon damage (NGF-β) were measured before the procedure (T1), after transseptal puncture, (T2), after completing the ablation in the left atrium (T3), and one day after the procedure (T4). Results: Sixty-five patients were enrolled in the PFA (n=33) and RFA (n=32) groups. Both groups were similar in baseline characteristics (age 60.5±12.7 vs. 64.0±10.7 and 20 (60.6%) non-paroxysmal vs. 20 (62.5%) paroxysmal AF). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09±11:57 vs. 151:19±41:25 min, p< 0.001; 36:00±8:05 vs. 115:58±36:49 min, p<0.001). Troponin release (1 d after the procedure) was substantially higher in the PFA group (10,102, IQR 8,272-14,207 vs. 1,006, IQR 603-1,433) and was ten times higher in PFA patients. However, during the procedure, markers of platelet activation, coagulation activation, and inflammation were similar between groups. Conclusions: PF ablation was associated with substantially more myocardial damage compared to radiofrequency ablation. However, coagulation activation, platelet activation, and inflammatory responses were similar.

Myocardial Damage, Inflammation, Coagulation, and Platelet Activity During Catheter Ablation Using Radiofrequency and Pulsed-Field Energy

BackgroundPulsed-field ablation (PFA) represents a new, nonthermal ablation energy for the ablation of atrial fibrillation (AF). Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation activation. ObjectivesThis study aimed to compare the systemic response in patients undergoing pulmonary vein isolation (PVI) using pulsed-field and radiofrequency (RF) energy. MethodsPatients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or pulsed-field (Farapulse, Boston-Scientific) energy. Markers of myocardial damage (troponin I), inflammation (interleukin-6), coagulation (D-dimers, fibrin monomers, von Willebrand antigen and factor activity), and platelet activation (P-selectin, activated GpIIb/IIIa antigen) were measured before the procedure (T1), after trans-septal puncture (T2), after completing the ablation in the left atrium (T3), and 1 day after the procedure (T4). ResultsA total of 65 patients were enrolled in the pulsed-field ablation (n = 33) and RF ablation (n = 32) groups. Both groups were similar in baseline characteristics (age 60.5 ± 12.7 years vs 64.0 ± 10.7 years; paroxysmal AF: 60.6% vs 62.5% patients). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09 ± 11:57 min vs 151:19 ± 41:25 min; P < 0.001; 36:00 ± 8:05 min vs 115:58 ± 36:49 min; P < 0.001). Peak troponin release was substantially higher in the PFA group (10,102 ng/L [IQR: 8,272-14,207 ng/L] vs 1,006 ng/L [IQR: 603-1,433ng/L]). Both procedures were associated with similar extents (>50%) of platelet and coagulation activation. The proinflammatory response 24 h after the procedure was slightly but nonsignificantly higher in the RF group. ConclusionsDespite 10 times more myocardial damage, pulsed-field ablation was associated with a similar degree of platelet/coagulation activation, and slightly lower inflammatory response. (The Effect of Pulsed-Field and Radiofrequency Ablation on Platelet, Coagulation and Inflammation; NCT05603637)

Role of Fibrin Monomer Complex in Coronavirus Disease 2019 for Venous Thromboembolism and the Prognosis.

Objective Venous thromboembolism (VTE) is a common complication of severe coronavirus disease 2019 (COVID-19) and is associated with its prognosis. The fibrin monomer complex (FMC), a marker of thrombin generation, is reportedly useful in diagnosing acute thrombosis. To date, there has been only one report on FMC in COVID-19, and the usefulness of FMC in COVID-19 is unknown. We therefore evaluated the frequency of VTE in non-intensive-care unit COVID-19 patients in Japan and determine the clinical utility of FMC in COVID-19. Methods This was a single-center retrospective study. Laboratory test results and outcomes (thrombosis and severe progression of COVID-19) were obtained via medical record review. We assessed the relationship between FMC and VTE incidence and evaluated the association between elevated FMC levels and severe progression of COVID-19. Patients/Materials This study included 247 patients with COVID-19 who were hospitalized between December 2020 and September 2021 and had had their levels of D-dimer and FMC measured. Results Of the 247 included patients, 3 (1.2%) developed VTE. All three had elevated FMC levels on admission; however, the D-dimer level was not elevated in one case on admission. The FMC level was significantly higher in the group with severe COVID-19 progression than in the group without severe progression. A multivariate analysis showed that severe progression was associated with elevated FMC levels (odds ratio, 7.40; 95% confidence interval, 2.63-22.98; p<0.001). Conclusion FMC can be useful for diagnosing VTE in the acute phase of COVID-19. Elevated FMC was found to be associated with severity on admission and severe progression.

Morphological determinants for the local hemostatic effect of exogenous fibrin monomer in its systemic administration after injury with inhibition of platelet aggregation in the experiment

Background. In our previously published studies, we demonstrated a high hemostatic activity of a low dose of exogenous fibrin monomer during its systemic administration in a model of dosed liver injury with preliminary inhibition of platelet aggregation. However, the analysis of platelet involvement in the mechanisms of local fibrin formation has not been analyzed. The aim of the study. To conduct a comparative analysis of the cellular composition of venous and wound blood, as well as blood in the wound vessels to assess the contribution of platelets to the hemostatic effect of exogenously administered fibrin monomers in dosed liver injury under conditions of pharmacologically determined thrombocytopathy. Methods. In a model of dosed liver injury in rabbits after inhibition of platelet aggregation by acetylsalicylic acid in combination with clopidogrel, the effect of the administration of fibrin monomer was evaluated in comparison with the use of tranexamic acid. We studied the number of platelets in venous and wound blood smears, as well as in the contents of wound vessels. Results. It has been established that with the systemic administration of exogenous fibrin monomer, the number of platelets in wound blood smears decreases by 17.2 % in comparison with free circulating venous blood. Platelets in wound blood form aggregates and are in an activated state. In the wound vessels, the number of these cells was maximum (150 per lower field) compared with the number of platelets in the placebo and tranexamic acid groups (55 and 84 per lower field, respectively). Also in the wound blood, erythrocytes with altered forms (echinocytes, schistocytes, stomatocytes and ovalocytes) were found. Conclusion. Systemic administration of exogenous fibrin monomer affects the redistribution of platelets between the systemic circulation, wound vessels and wound blood, determining its hemostatic effect and local wound fibrin formation in dosed liver injury. The presence of receptor-mediated platelets recruitment due to fibrin monomer in the wound vessels with the participation of damaged erythrocytes is assumed.

PB0091 Fibrin Monomers Positivity During Hospitalization is a Good Predictive Marker of In-Hospital Mortality during COVID-19

PB0091 Fibrin Monomers Positivity During Hospitalization is a Good Predictive Marker of In-Hospital Mortality during COVID-19