BACKGROUND: Trauma-induced coagulopathy (TIC) worsens patient outcomes and increases transfusion requirements. Resuscitation strategies following injury have evolved to improve clinical outcomes. However, the mechanisms...BACKGROUND: Trauma-induced coagulopathy (TIC) worsens patient outcomes and increases transfusion requirements. Resuscitation strategies following injury have evolved to improve clinical outcomes. However, the mechanisms by which these strategies impact coagulation and whether they restore native coagulation in the presence of TIC are poorly understood. METHODS: We compared coagulation parameters and vital signs of patients who did (n = 26) and did not (n = 37) receive transfusion following injury. Transfusion products administered to patients were recreated in vitro, and their influence on a simulated model of TIC was measured. Optical turbidity, rheology, thromboelastography, and confocal microscopy were used to evaluate the clotting properties of platelet-poor plasma and whole blood models of hypocoagulable and hypercoagulable TIC. Transfusion models were supplemented with Saline, Plasma, Fibrinogen Concentrate, or Red Blood Cells (RBC). RESULTS: Transfused patients exhibited faster time to mortality, clot stiffness, and fibrinogen concentration compared to non-transfused patients. In the simulated transfusion model, saline reduced clot stiffness, increased fibrinolytic rate, and affected network structure. Plasma increased clot stiffness and density, and reduced fibrinolysis. Fibrinogen concentrate enhanced clot stiffness in plasma-based models but also increased fibrinolytic rate. RBC supplementation had variable impacts, causing weaker blood clots and accelerated fibrinolysis in hypocoagulable models, but delayed fibrinolysis in hypercoagulable models. DISCUSSION: Resuscitation products exert context-dependent effects on clot formation and breakdown that may not restore hemostasis during TIC. Saline induced dilutional hypocoagulability and increased clot failure risk, plasma enhanced clot stability, fibrinogen improved clot formation, and RBCs exerted endogenous coagulation-specific effects. These results support coagulation phenotyping to guide targeted transfusion strategies.
Simurda T, Ceznerova E, Kolkova Z
… +9 more, Loderer D, Drotarova M, Brunclikova M, Skornova I, Agouba SM, Gemelova VV, Belakova KM, Stasko J, Kotlin R
Fibrinogen is a key determinant of clot formation and stability in the final phase of coagulation. Genetic variants in the fibrinogen γ-chain gene (FGG) are a frequent cause of congenital fibrinogen disorders (CFDs) and...Fibrinogen is a key determinant of clot formation and stability in the final phase of coagulation. Genetic variants in the fibrinogen γ-chain gene (FGG) are a frequent cause of congenital fibrinogen disorders (CFDs) and are associated with marked heterogeneity of clinical presentation, including thrombosis. Increasing evidence indicates that genetic findings alone are insufficient to predict thrombotic risk. We performed a comprehensive molecular, functional, and ultrastructural characterization of 20 patients from Czechia and Slovakia carrying FGG variants. Genetic analysis was combined with fibrin polymerization and fibrinolysis assays, fibrinopeptide release measurements, and scanning electron microscopy of fibrin clots. Five previously unreported pathogenic fibrinogen variants γp.T60A, γp.Y237H, γp.Y306C, γp.G310E, and γp.H333Y were identified. Although 60% of patients were clinically asymptomatic, 30% developed thrombotic manifestations in the absence of established thrombotic risk factors. Functional studies demonstrated delayed fibrin polymerization, reduced clot optical density, and prolonged fibrinolysis despite residual fibrin formation. Ultrastructural analysis revealed markedly altered fibrin clot architecture, characterized by abnormal fiber diameters and increased fiber density compared with controls, consistent with a dense, poorly lysable fibrin network. These findings indicate that FGG variants may promote thrombosis through qualitative alterations of fibrin structure and impaired fibrinolysis rather than fibrinogen deficiency alone. Integration of genetic, functional, and structural analyses is therefore essential for accurate assessment of thrombotic risk in patients with CFDs.
BACKGROUND: Ischemic stroke (IS) incidence increases in cold periods, implicating cold exposure as a key environmental risk factor. However, the underlying biological mechanisms remain unclear. METHODS: We performed a cr...BACKGROUND: Ischemic stroke (IS) incidence increases in cold periods, implicating cold exposure as a key environmental risk factor. However, the underlying biological mechanisms remain unclear. METHODS: We performed a cross-sectional study in acute IS patients (n = 623) to compare platelet and coagulation profiles between cold- and non-cold-season admissions, analyzing temperature associations using Generalized Additive Models and age-cold interactions via additive measures. Parallel rat experiments examined cold effects on platelet function, hemostasis, cerebral ischemia, and the cGAS-STING pathway. RESULTS: Patients in cold periods exhibited significantly elevated platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), ADP-induced aggregation, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, and D-dimer. Lower daily temperature correlated with increased ADP-aggregation and PDW. A significant positive additive interaction existed between cold exposure and older age (≥65 years) for PLT, MPV, PDW, ADP-aggregation, APTT and FIB. In rats, cold shortened bleeding time, enhanced platelet aggregation, spreading, clot retraction, and microvesicle release, increasing cerebral infarct volume. Mechanistically, cold upregulated platelet cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING), effects blunted by the cGAS inhibitor RU.521. CONCLUSION: Cold exposure acts as an independent risk factor and exerts a synergistic effect with aging to promote a prothrombotic state in elderly stroke patients. Our findings suggest that activation of the platelet cGAS-STING pathway may serve as a potential mechanistic link. Importantly, pharmacological inhibition of this pathway was associated with attenuated pro-thrombotic phenotype and brain injury in cold-exposed animals. These findings support the platelet cGAS-STING axis as a candidate therapeutic target for mitigating seasonal stroke risk.
Central venous catheters (CVCs) are frequently used in the management of acute leukemia, providing safe and convenient access for the safe delivery of chemotherapy, transfusions, and supportive care. However, these devic...Central venous catheters (CVCs) are frequently used in the management of acute leukemia, providing safe and convenient access for the safe delivery of chemotherapy, transfusions, and supportive care. However, these devices are associated with a high risk of complications, including CVC-related thrombosis (CRT) and CVC-related infection (CRI). These complications can occur concomitantly, highlighting the challenging dilemma of which comes first and which leads to the other. This review explores the complex, intricately intertwined pathophysiological mechanisms underlying this relationship in patients with acute leukemia. Catheter bacterial colonization, frequently reinforced by biofilm formation, and bloodstream infections provoke immunothrombosis, playing a part in local infection management. Platelets and the coagulation process may amplify the inflammatory responses via their interactions with the endothelium, immune cells, and the complement system. Conversely, thrombosis creates a nidus for bacterial adhesion, thereby perpetuating infection. In patients with acute leukemia, Virchow's triad- vessel wall injury, stasis, and hypercoagulability -is exacerbated by chemotherapy-induced toxicity, malignancy-related hypercoagulability, and immunosuppression. Management requires balancing infection control and thrombosis prevention. Future studies should focus on exploring the mechanistic bidirectional links between CRT and CRI as well as developing targeted preventive strategies to improve outcomes.
BACKGROUND: A considerable number of pregnant individuals are prescribed anticoagulants in pregnancy. OBJECTIVE(S): To obtain and compare preference values for combined maternal-fetal health states arising from anticoagu...BACKGROUND: A considerable number of pregnant individuals are prescribed anticoagulants in pregnancy. OBJECTIVE(S): To obtain and compare preference values for combined maternal-fetal health states arising from anticoagulant use in pregnancy from pregnant individuals and their family members. STUDY DESIGN: We conducted a cross-sectional study at a tertiary referral centre in Toronto, Canada from July to October 2015. A diverse group of pregnant individuals receiving anticoagulants and family members involved in medical decision-making were interviewed individually and together. Participants assigned values to seven maternal-fetal health states using the visual analogue scale (VAS), time trade-off (TTO), and standard gamble (SG) instruments on a 0-100 scale, where 0 represented maternal-fetal death and 100 perfect maternal-fetal health. RESULTS: We recruited 57 pregnant individuals and 43 family members, of which 40 pairs completed all interviews. There were significant differences between preferences based on instruments, scenarios, and respondents. Across interviews and instruments, participants assigned lowest preference values to health states involving major fetal malformations and fetal death. Preferences obtained through shared interviews showed a significant shift away from those obtained from pregnant individuals and towards those of family members. Participants better understood and preferred the VAS and SG over the TTO. CONCLUSION(S): This study in addition to generating patient-preference values to inform decision analysis and economic evaluation studies, also highlights the importance families attribute to fetal complications while making clinical decisions during pregnancy. The role of shared interviews and the use of SG in eliciting preferences for pregnancy health states needs further exploration.
Pregnancy places increased demands on the maternal haemostatic system where it must maintain a balance between bleeding and thrombosis. Platelets are crucial to this process. Platelets support placental development and s...Pregnancy places increased demands on the maternal haemostatic system where it must maintain a balance between bleeding and thrombosis. Platelets are crucial to this process. Platelets support placental development and secrete bioactive mediators that influence trophoblast invasion, vascular remodelling and innate immune crosstalk (platelet-leukocyte and complement interactions). Normal pregnancy is characterised by a gradual decrease in platelet count with advancing gestation. This mild thrombocytopenia toward term is driven by haemodilution, placental sequestration and platelet activation. However, excessive platelet activation can trigger thrombo-inflammatory response linked to the development of pre-eclampsia and foetal growth restriction. Platelet dysfunction and inherited thrombocytopenia may increase the risk of postpartum haemorrhage without directly affecting the pregnancy. Platelets therefore play a dual role in pregnancy where controlled activation is protective but uncontrolled stimulation leads to obstetric complications. An appreciation of this informs preventive strategies such as low-dose aspirin in high-risk pregnancies and individualised management of thrombocytopenia in selected cases.
BACKGROUND: Real-world data on the characteristics, interventions, and associated outcomes of patients hospitalized with factor Xa (FXa) inhibitor-associated major bleeds are limited. OBJECTIVE: The REVERXaL study was de...BACKGROUND: Real-world data on the characteristics, interventions, and associated outcomes of patients hospitalized with factor Xa (FXa) inhibitor-associated major bleeds are limited. OBJECTIVE: The REVERXaL study was designed to gain an understanding of patient characteristics, treatment approaches, and associated outcomes for FXa inhibitor-associated bleeds in real-world clinical practice. METHODS: REVERXaL was designed to include historical and prospective cohorts of patients with FXa inhibitor-associated major bleeds from the United States, Germany, the United Kingdom, and Japan. Results for the historical cohort, which included information from electronic case report forms from admission to discharge for patients hospitalized for FXa inhibitor-related bleeds, are presented here. Evaluated outcomes included patient characteristics, physician-reported hemostatic effectiveness, thromboembolic event occurrence, and mortality. RESULTS: The historical cohort included 2025 patients hospitalized with FXa inhibitor-associated major bleeds (intracranial hemorrhage [ICH], n = 1353; gastrointestinal bleeds, n = 357; other, n = 315) from 74 clinical sites (October 2021-November 2024). The mean (SD) age was 78.5 (10.4) years, and patients had a high comorbidity burden. The Glasgow Coma Scale rating was moderate to severe for 30.1% (407/1353) of patients with ICH. The majority of patients (70.4% [1425/2025]) received reversal/replacement therapy, administered a median (interquartile range) of 134.0 (232.0) min after admission. Among patients receiving reversal/replacement therapy, 71.1% (1013/1425) achieved physician-reported hemostasis. Thromboembolic events were reported in 6.1% (124/2025) of patients. The overall in-hospital mortality rate was 21.9% (443/2025). CONCLUSIONS: Given the high mortality rate, these findings suggest a need for improved treatment of FXa inhibitor-associated major bleeds. REGISTRATION: ClinicalTrials.gov identifier: NCT06147830.
BACKGROUND: Lower extremity deep venous thrombosis (LEDVT) represents a critical vascular disorder with substantial clinical burden, where the mechanistic interplay between low-density lipoprotein receptor-related protei...BACKGROUND: Lower extremity deep venous thrombosis (LEDVT) represents a critical vascular disorder with substantial clinical burden, where the mechanistic interplay between low-density lipoprotein receptor-related protein 1 (LRP1) and plasminogen activator inhibitor-1 (PAI-1) remains incompletely defined despite their implicated roles in thrombogenesis. METHODS: This study employed integrated bioinformatic, cellular, and in vivo approaches. Protein interactions were predicted via STRING database, while co-expression patterns were analyzed using GTEx transcriptomic data. Functional validation involved: (i) ox-LDL-induced human endothelial injury models with LRP1 knockdown (shRNA lentivirus) and PAI-1 overexpression; (ii) rat LEDVT models with LRP1-targeting interventions. Molecular interactions were assessed through co-immunoprecipitation and immunofluorescence, while thrombotic phenotypes were evaluated via histopathology, ELISA, and Western blotting. RESULTS: LRP1 and PAI-1 demonstrated significant physical interaction and co-expression in thrombotic microenvironments. LRP1 suppression markedly reduced PAI-1 expression and attenuated pro-thrombotic mediator release (endothelin-1, thromboxane B2, von Willebrand factor), while enhancing nitric oxide production. In vivo, LRP1 knockdown diminished thrombus formation severity, concurrently reducing inflammatory cytokines and restoring fibrinolytic markers. Crucially, PAI-1 restoration reversed the anti-thrombotic effects of LRP1 suppression, confirming its downstream effector role. CONCLUSION: These findings establish LRP1 as an upstream regulator of PAI-1-driven thrombogenesis, revealing the LRP1-PAI-1 axis as a pivotal mechanistic pathway and potential therapeutic target for LEDVT.
INTRODUCTION: Sepsis remains a leading cause of morbidity and mortality among critically ill patients and is frequently complicated by coagulopathy and thrombocytopenia. The study aimed to evaluate the impact of uremia o...INTRODUCTION: Sepsis remains a leading cause of morbidity and mortality among critically ill patients and is frequently complicated by coagulopathy and thrombocytopenia. The study aimed to evaluate the impact of uremia on platelet contribution to clot strength in septic patients using rotational thromboelastometry (ROTEM) and determine whether platelet contribution to clot strength is associated with short-term mortality. MATERIAL AND METHODS: This retrospective cohort study was carried out in an intensive care unit (ICU). Clinical, biochemical, hematological, and coagulation parameters were retrieved. Patients receiving antiplatelet agents or oral anticoagulants were excluded. RESULTS: There were 107 adult patients diagnosed with sepsis or septic shock in whom ROTEM was performed upon ICU admission. ROTEM-derived platelet contribution in patients without sepsis-induced coagulopathy (SIC) showed a significant inverse correlation with blood urea nitrogen and urea concentrations, but not with creatinine, estimated glomerular filtration rate, or creatinine clearance. ICU mortality in the cohort was 34.6%, exceeding the predicted mortality rate. Platelet contribution was independently associated with ICU mortality after adjustment for age, sex, presence of SIC, and SOFA score. CONCLUSIONS: Uremia is associated with impaired platelet contribution to clot strength in patients without SIC. This impairment independently predicts ICU mortality. These findings underscore the importance of a multifaceted approach to renal assessment and support the integration of viscoelastic testing into the diagnostic and prognostic framework for sepsis.
INTRODUCTION: Inherited antithrombin (AT) deficiency, mainly caused by variants in the SERPINC1 gene, is a high-risk inherited thrombophilia. OBJECTIVES: We sought to characterize the molecular mechanisms underlying AT d...INTRODUCTION: Inherited antithrombin (AT) deficiency, mainly caused by variants in the SERPINC1 gene, is a high-risk inherited thrombophilia. OBJECTIVES: We sought to characterize the molecular mechanisms underlying AT deficiency in a series of Polish patients including long-term follow-up data. PATIENTS AND METHODS: Twenty-nine unrelated probands (13 women [44.8%], mean [SD] age, 44.2 [13.0] years) with type I AT deficiency (n = 21, 72.4%) and type II AT deficiency (n = 8, 27.6%) who mostly had prior venous thromboembolism (n = 21, 72.4%) were screened for mutations using next-generation sequencing (NGS), long-read whole-genome sequencing or multiplex ligation-dependent probe amplification (MLPA). Hypoglycosylation was evaluated by Western blot and HPLC. RESULTS: NGS sequencing and MLPA of SERPINC1 detected variants in 22 probands (75.9%): 13 missense (44.8%, including a new AT Kraków III: c.457T>C); 6 small deletions/insertions (20.7%, including 2 new: AT Ostrowiec: c.962dup and AT Poznań: c.[400_401insG;402_403del;406_408 + 1del]), 2 nonsense (6.9%, one new: AT Tychy: c.81G>A) and one new deletion covering exons 1 and 2 (AT Częstochowa). The nanopore sequencing revealed a new insertion of 2940 bp (a SINE-VNTR-Alu element) in intron 3 of SERPINC1 (AT Tkaczew). Congenital disorders of glycosylation were detected in two patients (7%) without any other variants. During a median follow-up of 27 (12-39) months, 21 (72.4%) patients with prior VTE receiving oral anticoagulants and no thrombotic events were recorded. CONCLUSION: Our findings indicate the need for advanced genomic analyses to detect complex structural variants in subjects with AT deficiency including retrotransposon insertions and intronic variants.
BACKGROUND: Direct oral anticoagulant (DOAC) use in children is increasing, supported by multi-center randomized controlled trials (RCTs) and registry data. This study describes real-world experience using DOACs in a pae...BACKGROUND: Direct oral anticoagulant (DOAC) use in children is increasing, supported by multi-center randomized controlled trials (RCTs) and registry data. This study describes real-world experience using DOACs in a paediatric population. METHODS: We performed a retrospective case series at a single Australian paediatric tertiary hospital, including children aged 0-18 years treated with a DOAC for thrombosis prophylaxis or treatment between January 1st 2021 to May 1st 2025. Data was obtained through retrospective review of patient medical records. Patients were excluded if their medical records lacked sufficient documentation to allow for our analysis. Primary outcomes measured were thrombus resolution, recurrence, extension or development. Principal safety outcomes measured were major or clinically relevant non-major bleeding (CRNMB) and adverse events. Qualitative data on quality of life (QoL) was also obtained if available. FINDINGS: Out of 69 patients prescribed a DOAC, 67 met inclusion criteria creating 74 treatment episodes. Two patients were excluded due to insufficient documentation. Indications for treatment included therapeutic (n = 49), primary prophylaxis (n = 4), secondary prophylaxis (n = 10), central venous line (CVL) prophylaxis for patients on longterm total parenteral nutrition (TPN) (n = 5) and localized intravascular coagulopathy (LIC) secondary to venous malformation (n = 6). Treatment failure occurred in four episodes (5%), with one episode in each of the therapeutic, primary prophylaxis, secondary prophylaxis, and LIC groups. There were no episodes of fatal thromboembolism. There were no major bleeding events or treatment-related deaths, three (4%) CRNMB events and four (5%) DOAC related side effects. INTERPRETATION: We confirm the effectiveness of DOACs for the prophylaxis and treatment of paediatric thromboembolism and report acceptable risk of bleeding and side effects.
BACKGROUND: Neutrophils can eject out neutrophil extracellular trap (NET)-enclosed extracellular vesicle (NET-EVs) in response to stimuli such as Staphylococcus aureus. Though enhanced thrombosis associated with NET is d...BACKGROUND: Neutrophils can eject out neutrophil extracellular trap (NET)-enclosed extracellular vesicle (NET-EVs) in response to stimuli such as Staphylococcus aureus. Though enhanced thrombosis associated with NET is documented, the thrombotic potential of NET-EVs is not known. AIM: After confirming the presence of NET-EVs in vivo in diabetes-induced BALB/c mouse, this study analysed thrombosis associated with NET-EV release. METHODS: Two sets of experiments were designed to check the procoagulant activity connected to the release of NET-EVs. In the first set, to the diabetic mice, either aspirin, Cl-amidine or aspirin + Cl-amidine were administered orally. Bleeding time, spontaneous platelet aggregation, and clot lysis were analysed after 10 days. Histopathological analyses of heart, liver, lung, and kidney tissues were also performed. As Cl-amidine increased bleeding time effectively, it was used for a second experiment. Here, diabetic mice were triggered by an intraperitoneal injection of Staphylococcus aureus culture supernatant (SCS) to trigger NET formation. Presence of NET-EV was confirmed in them using anti-citrullinated histone-H4 and anti-CD63. Cl-amidine was given to one group of these mice and all the tests were performed as before. RESULTS: Citrullinated histone-H4 in the cells and NET-EV was reduced after Cl-amidine treatment. Both Cl-amidine and aspirin increased bleeding time. Cl-amidine reduced spontaneous platelet aggregation and enhanced clot lysis more efficiently even after SCS-treatment. While no tissue alteration was seen in the Cl-amidine-treated mice, aspirin-treated mice showed haemorrhage and oedema in the heart and lung tissues. CONCLUSION: Cl-amidine showed the ability to reduce procoagulant activity associated with NET-EV release.
Hemophilia B is an X-linked bleeding disorder caused by a functional deficiency of coagulation factor IX (FIX). Adeno-associated virus (AAV) mediated gene therapy based on vector serotypes 5 and 8, has shown promising cl...Hemophilia B is an X-linked bleeding disorder caused by a functional deficiency of coagulation factor IX (FIX). Adeno-associated virus (AAV) mediated gene therapy based on vector serotypes 5 and 8, has shown promising clinical outcomes. Nonetheless, a high prevalence of neutralizing antibodies in the general population to these serotypes requires the use of an alternate gene transfer system. AAVrh10, a non-human primate-derived serotype, has low pre-existing immunity in humans, making it a promising alternative for hemophilia gene therapy. We reasoned that further rational engineering, particularly at post-translational modification (PTM) sites of AAVrh10 capsid and codon optimization of the Factor 9 (F9) transgene, can enhance therapeutic efficiency. Initially, we evaluated three rationally engineered AAVrh10 capsid mutants (S157A, K169Q, and K709Q) encoding a F9 transgene, regulated by Kozak sequence and liver-specific promoter (LP1) by systemic gene transfer. In the initial screening, AAVrh10K169Q vectors demonstrated a ~ 4.6-fold (p < 0.001) improved FIX clotting activity in hemophilia B mice in comparison to the AAVrh10WT vector, one year after hepatic gene transfer. Subsequently, we performed codon optimization of the hyperactive F9 Padua transgene (CoF9 Padua) to enhance its translational potential. The hepatic gene transfer of AAVrh10WT and AAVrh10K169Q vectors carrying CoF9 Padua transgene exhibited supraphysiological FIX clotting activity (~529.4%-1435.6%) with no immunological complications, ~18 months post gene transfer. Our study highlights the translational potential of optimized AAVrh10-CoF9 vectors for gene therapy in patients with hemophilia B.
Venous thromboembolism (VTE) is a complex multifactorial disorder in which the contribution of genetic and non-genetic risk factors is well recognized, yet standard thrombophilia testing is unable to explain a substantia...Venous thromboembolism (VTE) is a complex multifactorial disorder in which the contribution of genetic and non-genetic risk factors is well recognized, yet standard thrombophilia testing is unable to explain a substantial proportion of cases. To explore additional genetic contributors, we performed whole-exome sequencing (WES) in 35 patients with recurrent and/or severe VTE in whom routine diagnostic evaluation failed to identify risk factors. Variants were first screened against established thrombophilia-associated loci using clinical classification tools, while the remaining variants were prioritized through machine learning-based algorithms and Bayesian statistical methods combined with pathway enrichment and network analysis. Pathogenic or likely pathogenic variants were identified in PROC (c.70 + 1G > A, p.Ala43Thr, p.Pro321Leu), PROS1 (p.Tyr234Cys), and ADAMTS13 (p.Val832AlafsTer12). Additional candidate variants were detected in F5 (p.Arg376Ser, two patients) and F7 (p.Arg88Trp, p.Ala354Val), the latter previously associated with bleeding disorders. In the remaining patients, prioritized variants were predominantly enriched in pathways related to blood coagulation, including processes involving FVIII/von Willebrand factor (vWF) interactions and platelet biology. These included variants in STAB2, LRP1, ARSA, THBS1, SVEP1, LRP5, TLN1, MYH9, FERMT3, and PLCG1. Our findings indicate that, in addition to established thrombophilia genes, variants affecting auxiliary pathways, particularly those involving vWF and platelet biology, may contribute to unexplained VTE.
BACKGROUND: Guidelines recommend systemic thrombolysis (ST) as first-line reperfusion therapy for highrisk pulmonary embolism (PE), however, clinical concerns regarding bleeding risk frequently limit its use in clinical...BACKGROUND: Guidelines recommend systemic thrombolysis (ST) as first-line reperfusion therapy for highrisk pulmonary embolism (PE), however, clinical concerns regarding bleeding risk frequently limit its use in clinical practice. Catheter-directed therapy (CDT) should be considered when ST is contraindicated or has failed but is increasingly used outside these recommendations despite limited guideline support. Prospective data on short- and long-term outcomes after CDT, particularly in relation to a concurrent ST-treated population, remain scarce. PE-NORDIC aims to evaluate short- and long-term outcomes after CDT and ST for PE in the Nordic countries. METHODS: In this multicenter prospective observational study conducted in the Nordics, 244 adult patients with confirmed acute PE treated with CDT or ST will be enrolled and followed for up to 1 year. The primary outcome is a composite of all-cause mortality or severe bleeding within 30 days. Secondary outcomes include the individual components of the primary composite, need for rescue treatment, recurrent PE, length of stay in intensive care unit and hospital, right ventricular function, functional capacity, dyspnea, health-related quality of life, health economics, and PE complications. Analyses will be performed using multivariable regression models adjusted for relevant clinical confounders, with complementary propensity score-based methods.
BACKGROUND: Clot waveform analysis (CWA) provides enhanced coagulation monitoring from routine coagulation tests. Patients with systemic lupus erythematosus (SLE) who progress to antiphospholipid syndrome (APS) are at hi...BACKGROUND: Clot waveform analysis (CWA) provides enhanced coagulation monitoring from routine coagulation tests. Patients with systemic lupus erythematosus (SLE) who progress to antiphospholipid syndrome (APS) are at higher risk of thrombosis. METHODS: 291 healthy individuals were collected as control group (CTL) and 129 SLE patients as the case group. The PT, aPTT, TT-based CWA parameters, including maximum coagulation velocity (Min1), maximum coagulation acceleration (Min2); maximum coagulation deceleration (Max2) were obtained. RESULTS: The SLE-aPTT normal group exhibited elevated aPTT-Min1 levels than this in controls (P = 0.019), whereas aPTT-Min1 and aPTT-Min2 were lower but aPTT-Max2 higher in the SLE-aPTT prolonged group (all P < 0.001); As the number of positive antiphospholipid antibodies categories increased, APTT-Min1 and APTT-Min gradually decreased, whereas APTT-Max2 showed a progressive increase, with statistically significant differences observed between the groups (P < 0.001); The difference between aPTT-Min1, aPTT-Max2 for mild (n = 43), moderate (n = 33) and severe (n = 53) SLE was statistically significant (P < 0.05); The thrombosis group of SLE patients exhibited elevated aPTT-Max2 and reduced aPTT-Min1, aPTT-Min2 levels compared to non-thrombosis group (P < 0.01). Receiver operating characteristic curve analysis demonstrated that aPTT-Max2 exhibited superior discriminative capability for thrombotic events compared to other aPTT-based CWA parameters, with an area under curve of 0.727 (95% CI: 0.615-0.840). The cut-off value was -352.36 with a 74.10% sensitivity and 64.60% specificity. Multivariable analysis confirmed aPTT-Max2 as an independent association with thrombotic events (adjusted odds ratio = 1.009, 95% CI:1.001-1.017, P = 0.037). CONCLUSION: The aPTT-CWA serves as a valuable tool for assessing disease severity in SLE patients, with aPTT-Max2 demonstrating an independent association with thrombotic events.
Wieruszewski PM, Eder TH, Johnson EC
… +7 more, Cole KC, Barreto JN, Hernandez BN, Kashani KB, Rule AD, Barreto EF, Cystatin C in Acute Care (CCAC) study