Right heart thrombi (RHT) are a rare entity with high morbidity and mortality. There are no societal guidelines on the management of intracardiac thrombi. In an effort to understand the clinical elements associated with...Right heart thrombi (RHT) are a rare entity with high morbidity and mortality. There are no societal guidelines on the management of intracardiac thrombi. In an effort to understand the clinical elements associated with treatment decisions for RHT, this retrospective multi-center cohort study evaluated a real-world diverse patient population treated at two academic medical centers with PE response team (PERT) programs who presented with RHT, with and without PE, and evaluated the associated treatment strategies and outcomes. This study examined the clinical features and outcomes among patients presenting with RHT who were treated with anticoagulation monotherapy, systemic thrombolysis, and advanced intervention. Outcomes of interest included 30-day mortality, duration of hospitalization, need for ICU admission, bleeding complications, and in-hospital mortality. A total of 48 adult patients with RHT identified by transthoracic echocardiography (TTE) between January 2010 and December 2022 were included. Most patients with RHT presented with intermediate-high or high risk PE with right heart dysfunction. Mortality at 30 days was higher in the anticoagulation monotherapy group when compared to the systemic thrombolysis and advanced intervention groups, though not reaching statistical significance (25 % vs 11 % and 5.6 %, respectively). Other outcomes were not significantly different between groups. Although it is not clear that advanced therapy offers a benefit in this population overall, there are likely patients who will benefit; identifying that subpopulation remains a key question.
Cancer-associated thrombotic microangiopathy (CA-TMA) is a rare condition with high mortality. The mainstay treatment is anti-cancer treatment. We conducted a retrospective cohort study of all adults hospitalized with CA...Cancer-associated thrombotic microangiopathy (CA-TMA) is a rare condition with high mortality. The mainstay treatment is anti-cancer treatment. We conducted a retrospective cohort study of all adults hospitalized with CA-TMA in a Canadian province between 2008 and 2023 to examine treatment patterns, quality of care, and outcomes. Eighteen patients were included, with a median age of 57.4 years. At presentation, nine (50 %) patients were newly diagnosed with malignancy, seven (39 %) had progressive or relapsed disease, and two (11 %) had stable disease. CA-TMA treatment included therapeutic plasma exchange (TPE, 13; 72 %), anti-cancer therapy (6; 33 %), and supportive transfusions (4; 22 %). Fifteen (83 %) patients died within three months. Anti-cancer therapy, but not TPE, was associated with higher TMA response (67 % vs 8 %) and longer survival (median 85 vs 9 days), although findings are limited by small sample size and generalizability. We identified suboptimal management including prolonged exposure to TPE, low rates of oncology consultation within 30 days of discharge, and low rates of initiation of cancer-directed therapies, especially in newly diagnosed cancers. Earlier recognition of CA-TMA is crucial, as prompt oncology consultation and initiation of cancer-directed therapy may improve outcomes.
Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality, with pregnancy increasing the risk of VTE four- to five-fold compared with the non-pregnant state and up to 60-fold in the postpar...Venous thromboembolism (VTE) remains a leading cause of maternal morbidity and mortality, with pregnancy increasing the risk of VTE four- to five-fold compared with the non-pregnant state and up to 60-fold in the postpartum period. The incidence of pregnancy-related VTE ranges from 0.5 to 2.0 per 1000 pregnancies, with deep vein thrombosis (DVT) and pulmonary embolism (PE) accounting for most cases. The heightened thrombotic risk during pregnancy and postpartum stems from physiological adaptations in hemostasis, creating a hypercoagulable state to mitigate hemorrhage risk at delivery. These changes involve increased coagulation activation, reduced fibrinolysis, and venous stasis, fulfilling Virchow's triad. The risk rises as pregnancy progresses, peaking in the third trimester and postpartum period, with both hormonal fluctuations and mechanical factors playing key roles. Estrogen and progesterone contribute to early pregnancy risk by enhancing clotting factor synthesis, while later stages involve uterine compression of venous structures, impairing venous return. The postpartum period presents the highest risk, driven by endothelial injury during delivery, inflammatory responses, and hemodynamic shifts. Evolving obstetric practices, such as early ambulation and compression therapy, may have influenced the temporal distribution of VTE events. This review aims to clarify how pregnancy-specific hemostatic adaptations influence thrombotic risk and to identify strategies for improved, individualized prevention. Despite updated international guidelines, major discrepancies persist in risk scoring and prophylaxis thresholds, underscoring the limitations of current empirical approaches. Functional biomarkers such as thrombin generation and the Endogenous thrombin potential (ETP)-based activated protein C (APC) resistance assay, could represent promising tools to bridge the gap between mechanistic understanding and clinical application.
INTRODUCTION & OBJECTIVES: Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) are Philadelphia-negative myeloproliferative neoplasms (MPN) associated with gain-of-function mutations in...INTRODUCTION & OBJECTIVES: Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) are Philadelphia-negative myeloproliferative neoplasms (MPN) associated with gain-of-function mutations in JAK2, CALR, and MPL genes. Chronic inflammation is a central hallmark of MPN, significantly contributing to disease pathogenesis and progression and severe complications such as thrombosis. Alterations in platelet immunophenotype and gene expression may influence the thromboinflammatory state observed in MPN patients. We aimed to characterize platelet immunophenotype, ex vivo activation, and transcriptomic signatures in MPN patients compared to healthy controls. METHODS: Inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), were assessed to determine the thromboinflammatory status. Platelet immunophenotyping was performed at baseline and following stimulation with calcium ionophore A23187 or thrombin. Control platelets were exposed to MPN plasma to evaluate inflammatory activation. Transcriptomic data were analyzed in silico to identify dysregulated platelet-related pathways. RESULTS: MPN patients exhibited elevated NLR, PLR, and SII, consistent with systemic inflammation. Their platelets showed a pre-activated phenotype, with increased baseline expression of CD62P, CD36, CD63, and CD154. Compared to controls, MPN platelets were less responsive to thrombin stimulation, whereas control platelets exposed to MPN plasma acquired an activated phenotype. Transcriptomic profiling revealed downregulation of genes associated with cytoskeleton organization, integrin signaling, adhesion, metabolism, and trafficking. CONCLUSION: MPN platelets are intrinsically activated and transcriptionally dysregulated, even in treated patients. These findings underscore the critical role of platelets in MPN-associated thromboinflammation, highlighting platelet contribution to hemostatic and thrombotic complications.
BACKGROUND: Patients who survive a pulmonary embolism (PE) often suffer several negative long-term physical and mental consequences, limiting their ability to stay physically- and socially active ultimately deteriorating...BACKGROUND: Patients who survive a pulmonary embolism (PE) often suffer several negative long-term physical and mental consequences, limiting their ability to stay physically- and socially active ultimately deteriorating their quality of life. Patients with PE therefore need evidence-based rehabilitation, targeting what is important to each individual patient. Valid and reliable patient-reported outcome measures (PROMs) are crucial to help clinicians plan and track rehabilitation outcomes in a reliable manner. PURPOSE: A systematic review to generate an overview over psychometric properties (reliability, validity, responsiveness, floor/ceiling effect and accessibility) of 34 PROMs used to assess PE, identified in a previous review by the research group. METHODS: A literature search was performed in PUBMED, CINAHL and EMBASE from inception to September 2024 and included psychometric studies of 34 specific PROMs. The evidence for each psychometric property was evaluated according to the COSMIN criteria for good measurement properties and graded according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for systematic reviews. Methodological quality was assessed using the COSMIN Risk of Bias checklist for PROMs. RESULTS: The literature search yielded 3.801 records after removal of duplicates; 3.778 records were excluded based on title and abstract and further 10 articles were excluded during full-text reading leaving 13 articles evaluating the psychometric properties of PROMs. The Pulmonary Embolism Quality of life Questionnaire (PEmb-QoL) was assessed in 10 studies, showing very good internal consistency, reliability, criterion validity, construct validity, responsiveness and floor/ceiling effects. Structural validity for the PEmb-QoL was considered inadequate. One study found moderate evidence for the EQ-5D-5l showing adequate convergent construct validity. EQ-5D-5L also showed very good divergent construct validity, as well as good floor/ceiling effects and acceptability but inadequate structural validity. Low evidence for Perception of anticoagulation treatment questionnaire (PACT-Q) showed very good construct validity and internal consistency as well as adequate structural validity. Structural validity for the PACT-Q was acceptable, while content validity was doubtful and poor floor/ceiling effects. Finally moderate to high evidence for the Post-VTE functional status scale (PVFS) showing very good construct validity but inadequate structural validity and doubtful content validity. CONCLUSION: Some aspects of psychometric properties has been assessed in four out of the 34 PROMs used to assess patients with PE. Future studies should strive towards assessing all psychometric properties of PROMs used both clinically and in research. IMPLICATIONS: The results from this review put the reliability of tracking patients with PE into question, possibly skewing results from previous studies and more importantly showing an incomplete picture of rehabilitation following PE.
BACKGROUND: Plasma levels of activated factor VII-antithrombin complexes (FVIIa-AT) reflect indirectly tissue factor (TF)-FVII interaction. We investigated FVIIa-AT in acute ischemic stroke (AIS) and its prognostic value...BACKGROUND: Plasma levels of activated factor VII-antithrombin complexes (FVIIa-AT) reflect indirectly tissue factor (TF)-FVII interaction. We investigated FVIIa-AT in acute ischemic stroke (AIS) and its prognostic value. METHODS: We prospectively studied 88 AIS patients (median age 75 years), of whom 67 (76.1 %) received thrombolysis. Plasma FVIIa-AT levels, fibrin clot properties, i.e. clot lysis time (CLT), fibrin clot permeability (Ks), and protein carbonyl (PC) levels were measured on admission, at 24 h, and at 3 months. Stroke-related mortality and functional outcomes (modified Rankin Scale, mRS) were assessed at 3 months. RESULTS: Baseline FVIIa-AT (median 134.7 (IQR, 118.2-149.8 pM)), correlated with age (r = 0.51; p < 0.001), NIHSS (r = 0.54; p < 0.001), Ks (r = 0.32; p = 0.002), CLT (r = 0.34; p = 0.001), PC (r = 0.36; p < 0.001), and mRS at 3 months (r = 0.51; p < 0.001). After 24 h, FVIIa-AT increased by 8.3 % (p < 0.001) and correlated with NIHSS (r = 0.52; p < 0.001), PC (r = 0.35; p = 0.001), and mRS (r = 0.59; p < 0.001). At 24 h, thrombolysis had no impact on FVIIa-AT. After 3 months, FVIIa-AT decreased by 20.9 % compared to baseline (p < 0.0001). Baseline and 24-hour FVIIa-AT levels increased the odds of hemorrhagic transformation at 48 h (OR = 1.62, 95 %CI 1.09-2.42 and OR = 1.46, 95 %CI 1.04-2.03) and mRS > 2 at 3 months (OR = 1.48, 95 %CI 1.12-1.95 and OR = 1.61, 95 %CI 1.23-2.10, respectively). Stroke-related mortality was associated with FVIIa-AT solely at 24 h (OR = 1.59, 95 %CI 1.18-2.14). CONCLUSIONS: FVIIa-AT levels are linked to acute stroke severity and worse clinical outcomes, in association with prothrombotic fibrin clot properties and enhanced protein carbonylation.
BACKGROUND: Radiologic signs of chronic thrombi are present in approximately 20 % of patients with acute pulmonary embolism (PE). We assessed the effectiveness of ultrasound-assisted catheter-directed thrombolysis (USAT)...BACKGROUND: Radiologic signs of chronic thrombi are present in approximately 20 % of patients with acute pulmonary embolism (PE). We assessed the effectiveness of ultrasound-assisted catheter-directed thrombolysis (USAT) in patients with acute PE with or without signs of chronic PE and the accuracy of radiologic parameters predicting chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Index CT scans of patients who underwent USAT for acute PE with right ventricular strain were reviewed by three radiologists blinded to clinical and hemodynamic outcomes. At least 3 validated radiological criteria of chronic thromboembolism defined acute-on-chronic PE. Changes in mean pulmonary arterial pressure (mPAP) 20 h after USAT and presence of post-PE impairment (PPEI) or CTEPH at 3-6 months were compared between patients with and without acute-on-chronic PE. RESULTS: Among 180 consecutive patients (median age 65 years), 31 (17 %) had acute-on-chronic PE. Absolute mPAP reduction was 11 (Q1-Q3: 5-17) mmHg in acute vs. 10 (Q1-Q3: 5-17) mmHg in acute-on-chronic PE from similar baseline mPAP. PPEI or CTEPH were recorded in 2.0 % of patients in the acute group vs. 13 % in the acute-on-chronic group (odds ratio 7.0, 95 %C.I. 1.4-40). Of 3 (1.7 %) patients diagnosed with CTEPH, all presented with ≥3 radiological criteria suggesting pre-existing CTEPH at index CT scan. CONCLUSIONS: CT signs of chronic thromboembolism at the time of acute PE did not appear to influence the immediate hemodynamic response to USAT in most patients but may raise the suspicion of pre-existing CTEPH if ≥3 validated radiological criteria are present.
BACKGROUND: Antiphospholipid syndrome (APS) is a multifaceted autoimmune disorder associated with thrombosis and pregnancy morbidity. Thrombocytopenia, a frequent manifestation of APS, presents unique clinical challenges...BACKGROUND: Antiphospholipid syndrome (APS) is a multifaceted autoimmune disorder associated with thrombosis and pregnancy morbidity. Thrombocytopenia, a frequent manifestation of APS, presents unique clinical challenges due to its dual association with thrombotic and hemorrhagic risks. This study investigates the incidence, characteristics, and predictors of thrombocytopenia in a large cohort of antiphospholipid antibodies (aPL)-positive patients and its association with other clinical manifestations. METHODS: We conducted a multicenter retrospective cohort study from 2014 to 2024 involving 211 aPL-positive patients at San Giovanni Bosco and San Luigi Gonzaga Hospital, Turin, Italy. Data on demographic, laboratory, and clinical features were collected every six months or at the occurrence of new clinical events. Thrombocytopenia definitions excluded other etiologies. Laboratory and clinical evaluations included thrombosis risk factors, autoantibody profiles, and treatment regimens. RESULTS: Thrombocytopenia occurred in 42 patients (20 %), with varying severity: mild (33 %), moderate (38 %), and severe (29 %). Severe cases primarily exhibited platelet counts below 20 × 10^9/L. Patients with thrombocytopenia demonstrated higher rates of thrombotic events, venous recurrences, deep vein thrombosis, pulmonary embolism, and catastrophic APS (CAPS). Renal involvement was more frequent, while inflammatory manifestations (pericarditis, pleuritis, and arthralgia) were less common. Patients with thrombocytopenia showed higher frequency of anti-β2 glycoprotein I antibodies IgG positivity and leukopenia. Therapeutic interventions included increased use of steroids, intravenous immunoglobulins, mycophenolate, and rituximab. Thrombocytopenia was more prevalent in systemic APS diagnoses (21 % vs. 3 %). CONCLUSION: Thrombocytopenia in APS patients, particularly in severe cases, correlates with heightened thrombotic risk and systemic manifestations. These findings highlight the importance of customized strategies that balance thrombosis prevention with bleeding risk, especially in complex cases.
BACKGROUND: Absolute time-dependent risk of hospital-acquired venous thromboembolism (HA-VTE) is essential to evaluate the net clinical benefit of pharmacologic thromboprophylaxis. The multicenter Children's Hospital Acq...BACKGROUND: Absolute time-dependent risk of hospital-acquired venous thromboembolism (HA-VTE) is essential to evaluate the net clinical benefit of pharmacologic thromboprophylaxis. The multicenter Children's Hospital Acquired Thrombosis (CHAT) risk assessment model (RAM) identified risk factors for pediatric HA-VTE but was not designed to predict this risk. We aimed to predict the absolute time-dependent risk of HA-VTE in hospitalized children. METHODS: We conducted a single center case-cohort study of children ≤18 years old admitted from 2013 to 2022. Children with radiologically confirmed, symptomatic HA-VTE were considered cases. A 5 % random sample of eligible admissions formed the subcohort. Using Kaplan-Meier estimates and Cox regression with risk factors from the CHAT RAM and time to HA-VTE as outcome, we calculated the absolute time-dependent risk of HA-VTE of each child. Performance was assessed using area under the receiver operating characteristic curve (AUROC), calibration plot, and area under the precision-recall curve (AUPRC). RESULTS: We identified 81 children with HA-VTE from 23,287 admissions. Adolescent age, slightly limited mobility, and central venous catheter were associated with time to HA-VTE. Median absolute time-dependent risk of HA-VTE was 1.7 % (IQR: 1.0 %, 2.1 %) by day 12 of admission when the revised RAM performed best. AUROC by day 12 was 0.81 (95 % confidence interval, CI: 0.70, 0.93) with calibration slope of 1.13 (95 % CI: 0.38, 1.87), calibration intercept of 0.004 (95 % CI: -0.64, 0.65), and AUPRC of 0.04 (95 % CI: 0.004, 0.07). CONCLUSIONS: We accurately predicted the absolute time-dependent risk of HA-VTE. Similar predictions should be developed for bleeding.
BACKGROUND: Sepsis-induced coagulopathy (SIC) is an early phase of disseminated intravascular coagulation and a candidate marker for risk stratification. Although SIC is linked to higher mortality, its value for predicti...BACKGROUND: Sepsis-induced coagulopathy (SIC) is an early phase of disseminated intravascular coagulation and a candidate marker for risk stratification. Although SIC is linked to higher mortality, its value for predicting thrombotic and hemorrhagic events remains uncertain. We assessed the prevalence of SIC and its association with hemostatic complications and mortality in sepsis. METHODS: In a prospective cohort of 389 adults with sepsis admitted to an intermediate care unit, SIC was defined by International Society of Thrombosis and Haemostasis criteria (score ≥ 4). Primary outcomes were 30-day venous thromboembolism, arterial thrombosis, and bleeding; all-cause 30-day mortality was secondary. Predictive performance of the SIC score was evaluated with receiver operating characteristic analysis, bootstrap resampling, and Monte Carlo simulation. RESULTS: SIC was present in 33.4 % of patients. Thirty-day mortality was 27.1 % in SIC-positive patients versus 13.1 % in SIC-negative patients (p = 0.001), and SIC remained independently associated with death (adjusted OR 1.43; 95 % CI 1.13-1.80; p = 0.003). SIC positivity was not associated with overall thrombotic events: 42.9 % (12/28) of patients with thrombosis and 32.7 % (118/361) without thrombosis had SIC (p = 0.301). Discrimination for thrombotic and hemorrhagic events was poor (AUROC 0.573 and 0.576, respectively), with further decline after resampling; simulation analyses confirmed limited predictive capacity for either complication. CONCLUSIONS: In this cohort, SIC was associated with higher mortality but not with thrombotic or hemorrhagic events. This association likely reflects overall severity of illness rather than clinically overt vascular complications. These findings do not support using SIC alone to guide anticoagulation or transfusion decisions and support the development of outcome-specific risk models, potentially integrating dynamic clinical variables and serial laboratory trajectories.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an important intervention for severe respiratory failure, yet coagulation abnormalities and circuit thrombosis remain significant challenges. Circuit exchanges ar...BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an important intervention for severe respiratory failure, yet coagulation abnormalities and circuit thrombosis remain significant challenges. Circuit exchanges are frequently performed to restore oxygenator function and mitigate ECMO-related coagulopathies, but optimal criteria for their indication remain unclear. METHODS: This retrospective analysis included adult patients with coronavirus disease 2019 associated acute respiratory distress syndrome (ARDS) receiving venovenous (VV) ECMO at a tertiary hospital between January 2020 and April 2023. The primary endpoint was the change in d-dimer level on the third day after a circuit exchange compared to the last value before the circuit exchange. Secondary analyses included parameters such as fibrinogen, platelet count, LDH, post‑oxygenator pO and transmembrane pressure. Statistical comparisons were made using Wilcoxon-signed-rank tests and linear mixed models. RESULTS: Among 48 patients, 37 (77.1 %) underwent at least one coagulation-related circuit exchange, totalling 96 exchanges. D-dimer levels significantly decreased from 19 μg/ml (IQR 11-25) before exchange to 4 μg/ml (IQR 2-7) after exchange (p < 0.001). Platelet counts increased significantly (p = 0.024), while LDH levels decreased (p = 0.001). No significant changes were observed in fibrinogen levels. A sharp increase in d-dimer prior to exchange correlated with subsequent decreases post-exchange (R = -0.66, p < 0.001). CONCLUSIONS: ECMO circuit exchanges are associated with significant improvements in coagulation parameters, particularly d-dimer reduction, suggesting that d-dimer trends may serve as a key indicator for elective circuit replacement. Future prospective studies should refine exchange criteria to optimize patient outcomes while minimizing unnecessary interventions.
Baratta F, Cocomello N, Carpino G
… +14 more, Colantoni A, Cammisotto V, Bartimoccia S, Castellani V, Overi D, Lucatelli P, Ettorre E, Carnevale R, Pignatelli P, Pastori D, Del Ben M, Gaudio E, Desideri G, Violi F
BACKGROUND AND AIMS: Experimental study demonstrated that platelet cyclooxygenase-1 (COX-1) activation is implicated in the pathogenesis of metabolic dysfunction-associated steatosis liver disease (MASLD). However, the r...BACKGROUND AND AIMS: Experimental study demonstrated that platelet cyclooxygenase-1 (COX-1) activation is implicated in the pathogenesis of metabolic dysfunction-associated steatosis liver disease (MASLD). However, the relationship between COX-1 activation and MASLD severity is still unclear. This study aimed to investigate platelet COX-1 activation in patients with MASLD. METHODS: This is a cross-sectional study involving patients with biopsy-proven MASLD. Serum Thromboxane B (TxB) levels was measured as a biomarker of ex vivo COX-1 activation potential and plasma sP-selectin as in vivo marker of platelet activation. Oxidative stress biomarkers included serum NOX2-derived peptide (sNOX2-dp) and hydrogen peroxide breakdown activity (HBA). RESULTS: TxB serum levels increased progressively from MASLD simple steatosis (MASLD-SS) to steatohepatitis (MASH) (p = 0.017) and cirrhosis (p = 0.012). Serum TxB (rS = 0.467, p < 0.001) and sNOX2-dp (rS = 0.476, p < 0.001) levels were positively correlated with fibrosis stage and inversely correlated with HBA (rS = -0.506, p < 0.001). In addition, serum TxB correlated with sP-selectin (rS = 0.428, p < 0.001). Multivariate linear regression analysis revealed that TxB associated with liver fibrosis stage (p = 0.007) and sNOX2-dp (p = 0.018). CONCLUSIONS: This study provides evidence of platelet TxB overproduction, which increases progressively from MASLD-SS to MASH and cirrhosis and is significantly associated with the degree of liver fibrosis. These findings support the hypothesis that platelet COX-1 activation is involved in the pathogenesis of MASLD.
Gao T, Wang L, Wang B
… +18 more, Yin R, Qian L, Zhai A, Qureshi V, Yang C, Han F, Wang S, Wang D, Xu X, Wang X, Han K, Li P, Zhou X, Ye X, Shao R, Chen L, Wang W, Mao Y
BACKGROUND: Pneumonia-related sepsis is frequently complicated by coagulation disorders, which significantly increase mortality risk. The current ISTH criteria demonstrate limited sensitivity in diagnosing pneumonia-spec...BACKGROUND: Pneumonia-related sepsis is frequently complicated by coagulation disorders, which significantly increase mortality risk. The current ISTH criteria demonstrate limited sensitivity in diagnosing pneumonia-specific coagulopathy, and the mechanisms underlying clinical phenotypic heterogeneity remain poorly understood. There is a growing need to identify novel biomarkers that can enhance the early detection and stratification of disseminated intravascular coagulation (DIC), particularly in its non-overt stages. AIMS: The study aimed to evaluate the prognostic value of antithrombin (AT) and activated protein C (aPC) testing for predicting clinical deterioration and early DIC progression in adults with severe pneumonia-related sepsis. METHODS: We conducted a prospective observational cohort study of 86 adults with severe pneumonia-related sepsis admitted to the Intensive Care Unit (ICU). All patients underwent testing of AT and aPC upon enrollment. The predictive value of this biomarker combination was evaluated for the development of overt DIC within 72 h and 28-day all-cause mortality using receiver operating characteristic (ROC) analysis. RESULTS: Among 86 adults with severe pneumonia-related sepsis (median age 65 years; 56.9 % male), 18 (20.9 %) progressed to overt DIC within 72 h, and the 28-day mortality rate was 26.7 % (23/86). Compared with survivors, non-survivors exhibited significantly lower antithrombin activity (median 65 % vs. 78 %; P = 0.005) and higher activated protein C levels (median 127 pg/mL vs. 93.9 pg/mL; P < 0.001). Notably, the presence of overt DIC was the strongest predictor of mortality (OR = 144, 95 % CI: 18.66-1111.07). Similarly, patients with overt DIC exhibited markedly elevated aPC (P < 0.001). Among non-survivors, aPC was positively correlated with the 24-hour vasoactive-inotropic score (VIS; r = 0.567, P = 0.005). ROC analysis revealed that for predicting mortality, both aPC (AUC = 0.804, 95 % CI: 0.709-0.900) and the combined AT/aPC model (AUC = 0.814, 95 % CI: 0.714-0.913) significantly outperformed AT alone (AUC = 0.736, 95 % CI: 0.595-0.878).For predicting overt DIC, aPC (AUC = 0.859, 95 % CI: 0.778-0.939) and the combined model (AUC = 0.850, 95 % CI: 0.764-0.935) both demonstrated high accuracy. Notably, only the combined model effectively identified non-overt DIC (AUC = 0.850, 95 % CI: 0.768-0.932), whereas AT (AUC = 0.723) and aPC (AUC = 0.742) alone showed suboptimal performance. CONCLUSION: In conclusion, this preliminary study identifies a combined AT/aPC model as a promising early predictor of DIC progression and mortality in pneumonia-sepsis. If validated in larger, multicentre cohorts, this simple two-biomarker approach provides a potential biomarker foundation for future studies investigating personalised anticoagulation strategies by identifying high-risk patients in the non-overt DIC stage.
OBJECTIVES: This study aims to investigate the pathological mechanisms, clinical features, and prognostic differences between thrombotic thrombocytopenic purpura-like syndrome (TTP-like syndrome) and sepsis-induced coagu...OBJECTIVES: This study aims to investigate the pathological mechanisms, clinical features, and prognostic differences between thrombotic thrombocytopenic purpura-like syndrome (TTP-like syndrome) and sepsis-induced coagulopathy (SIC) in patients experiencing septic shock. The findings will provide a basis for subtype-guided diagnosis and treatment of coagulation disorders. METHODS: In this single-center retrospective cohort, 250 septic shock patients were divided into TTP-like syndrome (n = 101), SIC (n = 113), and control (n = 36) groups. Platelet count, vWF, FM, Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality were analyzed to compare coagulation phenotypes and outcomes. RESULTS: The TTP-like syndrome group was characterized by thrombocytopenia, with a median platelet (PLT) decline rate of 49.10 %. This group also exhibited markedly elevated vWF antigen levels, averaging 334.66 ± 80.04 %. Additionally, all patients in this group presented with multiple organ dysfunction syndrome (MODS) at a rate of 100 %. In contrast, the SIC group demonstrated more severe platelet consumption, with a median PLT of 42 × 10/L, elevated fibrinogen degradation product (FM) levels (median 9.22 μg/mL), and a significantly higher 28-day mortality rate (35.40 % vs. 11.88 % in the TTP-like group). The patterns of organ injury varied between the two groups; the SIC group displayed more pronounced liver (SOFA 1.43 ± 1.08) and renal (SOFA 1.41 ± 1.47) involvement, while the TTP-like syndrome group predominantly exhibited circulatory (SOFA 2.46 ± 1.45) and respiratory (SOFA 2.53 ± 0.76) dysfunction. vWF and FM had some predictive value for 28-day mortality, with area under the curve values of 0.59 and 0.60, respectively. CONCLUSION: TTP-like syndrome and SIC represent heterogeneous coagulation phenotypes in septic shock, with differences in biomarkers, organ injury, and prognosis. A vWF- and FM-guided subtype classification may improve individualized treatment strategies and prognostic management.
BACKGROUND: Atrial fibrillation/flutter (AF/AFL) is associated with an increased stroke risk, for which oral anticoagulation (OAC) is often indicated. Bleeding risk assessment is crucial in these patients to mitigate ble...BACKGROUND: Atrial fibrillation/flutter (AF/AFL) is associated with an increased stroke risk, for which oral anticoagulation (OAC) is often indicated. Bleeding risk assessment is crucial in these patients to mitigate bleeding complications, yet AF guidelines do not recommend the use of any bleeding risk score (e.g., HAS-BLED) due to concerns about predictive accuracy. The AF-adapted VTE-BLEED (AF-BLEED) score was developed to predict major bleeding (MB) post-OAC initiation. AIMS: Evaluate the incidence of clinically relevant bleeding, and externally validate the AF-BLEED score in new-onset AF/AFL patients. METHODS: Patients enrolled in the DUTCH-AF registry, who started OAC at diagnosis were studied. AF-BLEED categorized patients as low-risk (score ≤ 3) or high-risk (score > 3) for bleeding. Outcomes were first (i) MB and (ii) composite MB and clinically relevant non-major bleeding (CRNMB), with death and OAC discontinuation as competing events. Discrimination (cumulative AUC [AUCt]) was evaluated at 180 days and 2 years. RESULTS: 4647 patients (AF-BLEED low-risk: 94.0 %) were included. Cumulative MB incidences for low- and high-risk patients were 0.58 % (95 %CI 0.34-0.82 %) and 1.65 % (0.04-3.26 %) at 180 days (p 0.04), and 1.82 % (1.39-2.26 %) and 5.07 % (2.26-7.87 %) at 2 years (p < 0.001), respectively. Cumulative CRNMB/MB incidences for low- and high-risk patients were 1.81 % (1.39-2.24 %) and 4.13 % (1.62-6.65 %) at 180 days (p 0.01), and 6.37 % (5.58-7.16 %) and 9.68 % (5.91-13.45 %) at 2 years (p 0.04), respectively. Discrimination was poor to moderate for both outcomes at both time windows, ranging between 0.51 and 0.62. CONCLUSION: Although AF-BLEED was associated with subsequent risk of clinically relevant bleeding, its discriminative ability was poor, limiting the practical utility in its current form.
The management of severe haemophilia A (SHA) in China has evolved significantly from on-demand treatment to low-dose prophylaxis, substantially reducing bleeding rates. The Chinese Haemophilia Individualized Prophylaxis...The management of severe haemophilia A (SHA) in China has evolved significantly from on-demand treatment to low-dose prophylaxis, substantially reducing bleeding rates. The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS) protocol was developed as a standardized, cost-effective framework to pursue zero joint bleeding and long-term joint health preservation. This review provides a comprehensive overview of the CHIPS protocol, synthesizing evidence from three interrelated studies that demonstrate the efficacy of a structured, individualized approach incorporating pharmacokinetic-guided dosing and multimodal joint assessment. The results indicate that this strategy achieves near-zero bleeding rates, improves quality of life, and maintains joint health while optimizing factor consumption. Furthermore, the review discusses the expanding role of the CHIPS framework in the current treatment landscape, highlighting its utility as a practical platform for monitoring patients transitioning to non-factor therapies, such as emicizumab, in resource-conscious settings. The CHIPS protocol represents a timely and scalable prophylaxis framework that optimizes factor replacement therapy and adapts to novel agents. Its structured monitoring and individualized dosing offer a critical solution for protecting joint health in boys with SHA until non-factor and gene therapies become widely accessible in China.