BACKGROUND: Obstetric disseminated intravascular coagulation (DIC) is a life-threatening coagulopathy triggered by placental abruption, amniotic fluid embolism, HELLP syndrome, and postpartum hemorrhage. Although rapid h...BACKGROUND: Obstetric disseminated intravascular coagulation (DIC) is a life-threatening coagulopathy triggered by placental abruption, amniotic fluid embolism, HELLP syndrome, and postpartum hemorrhage. Although rapid hemostasis and transfusion are central to management, growing evidence implicates endothelial injury, particularly endothelial glycocalyx (eGCX) degradation, in amplifying coagulopathy and organ dysfunction. This review integrates endothelial pathophysiology into modern diagnostic and therapeutic frameworks for obstetric DIC. METHODS: We conducted a narrative synthesis of studies and guidelines published through 2025, examining (1) the pathophysiologic interplay among coagulation, fibrinolysis, and endothelial injury; (2) clinical utility of endothelial biomarkers; and (3) diagnostic criteria updates, including the 2024 revised Japanese obstetric DIC score. RESULTS: eGCX degradation, indicated by elevated syndecan-1, heparan sulfate, and hyaluronic acid levels, has been associated with disease severity and may reflect early endothelial dysfunction in obstetric DIC. Crystalloid overload, ischemia-reperfusion injury, and inflammatory cytokines promote glycocalyx shedding, exacerbating vascular permeability and consumption coagulopathy. The 2024 revised Japanese obstetric DIC criteria showed high sensitivity for pregnancy-specific coagulopathy and highlighted fibrinogen decline and fibrin-related markers as key diagnostic variables. Integrating endothelial biomarkers with these laboratory parameters may enhance early risk stratification and inform personalized resuscitation strategies addressing hemostasis and endothelial protection. CONCLUSIONS: Preservation of endothelial integrity represents a new therapeutic paradigm in obstetric DIC. Alongside optimized transfusion practices, timely fibrinogen replacement, and interventional hemostasis, targeting eGCX protection and endothelial recovery may redefine management goals. The 2024 Japanese obstetric DIC score provides a foundation for this integrative, endothelium-centered approach to improving maternal outcomes.
Venous thrombo-embolism (VTE) occurs in 10-15% of pediatric patients with acute lymphoblastic leukemia (ALL), yet the optimal duration of anticoagulation remains unclear. In this retrospective multi-center cohort study,...Venous thrombo-embolism (VTE) occurs in 10-15% of pediatric patients with acute lymphoblastic leukemia (ALL), yet the optimal duration of anticoagulation remains unclear. In this retrospective multi-center cohort study, we reported the clinical outcomes of pediatric patients treated for ALL with a history of central venous catheter (CVC)-related VTE and compared outcomes based on duration of anticoagulation. Patients aged 1-21 years old with newly-diagnosed ALL (2010-2023), receiving asparaginase-containing chemotherapy, experiencing a radiologically-proven CVC-related VTE requiring medical intervention, were included. Cumulative incidence and 95% confidence interval (CI) were estimated for VTE progression/recurrence and clinically relevant bleeding. Cox proportional hazard models were performed to compare clinical outcomes based on anticoagulation duration, categorized as a) asparaginase-based (following a 6-week course of anticoagulation, until the end of asparaginase' expected effects or earlier) or extended (later than asparaginase's expected effects), and b) before vs. after CVC removal. We included 106 patients (median age: 10 years, 59% male). Overall, 22 patients sustained a VTE progression/recurrence (cumulative incidence: 22%, 95% CI: 14-30%). Most progression/recurrences occurred while patients were still on anticoagulation, at a median of 54 days after index VTE. Duration of anticoagulation was not associated with VTE progression/recurrence (extended vs. asparaginase-based: HR = 1.49, 95%CI: 0.60-3.69, p = 0.392; after vs. before CVC removal: HR = 1.36, 95% CI: 0.49-3.74, p = 0.552). Clinically relevant bleeding occurred in 11/106 patients (cumulative incidence: 12%, 95% CI: 6-19%) and was not associated with anticoagulation duration. In summary, VTE progression/recurrence was common in pediatric patients with ALL. Further investigation into alternative approaches to reduce VTE progression/recurrence is warranted.
OBJECTIVE: Inherited thrombophilia is a recognized, albeit globally debated, risk factor for recurrent pregnancy loss (RPL). This study investigates the prevalence of inherited thrombophilia gene variants in Georgian wom...OBJECTIVE: Inherited thrombophilia is a recognized, albeit globally debated, risk factor for recurrent pregnancy loss (RPL). This study investigates the prevalence of inherited thrombophilia gene variants in Georgian women with unexplained RPL, comparing those with and without a personal or family history of thrombosis. MATERIALS AND METHODS: A cohort of 191 Georgian women with unexplained RPL (≥2 miscarriages) was divided into Group I (n = 130, with personal/family history of thrombosis) and Group II (n = 61, without history). A control group (n = 72) of women with ≥2 live births and no history of complications was included. Genetic analyses for Factor V Leiden (FVL G1691A), Prothrombin (FII G20210A), MTHFR (C677T) were performed. Differences were assessed using Fisher's exact test. RESULTS: Prevalence of FVL, FII, and MTHFR (677TT) was 10.8%, 6.15%, and 12.3% in Group I, 4.9%, 8.2%, and 11.5% in Group II, respectively. Statistical analyses confirmed MTHFR 677TT was significantly more prevalent in RPL cases than controls (p = 0.04). However, thrombotic history was a poor predictor of variant carriage for FII (p = 0.61) and MTHFR (p = 0.86). FVL demonstrated a trend toward significance in history-positive patients (p = 0.06). Hyperhomocysteinemia (>12 μmol/L) was present in 51.4% of MTHFR (677CT/TT) carriers. CONCLUSION: Inherited thrombophilia gene mutations and polymorphism prevalence is higher in Georgian women with unexplained RPL than in healthy controls, regardless of thrombotic history. While international guidelines for routine screening remain conservative, clinical history alone is insufficient predictor for suspected thrombophilia. Our findings support individualized thrombophilia screening as part of comprehensive diagnostic workup for unexplained RPL in this regional context.
INTRODUCTION: The increased risk for thrombotic events during pregnancy and the peripartum period is well established. Our goal was to analyze the incidence and extent of endogenous clotting potential during the peripart...INTRODUCTION: The increased risk for thrombotic events during pregnancy and the peripartum period is well established. Our goal was to analyze the incidence and extent of endogenous clotting potential during the peripartum period that may contribute to the underlying mechanisms. METHODS: A prospective longitudinal study enrolled women with uncomplicated pregnancies at 38-41 weeks gestation. Citrated platelet poor plasma was isolated at three visits (one 3rd trimester, and two postpartum). In this secondary retrospective analysis, aliquots were thawed and either centrifuged to remove sedimentable material or not, before being refrozen in advance of subsequent analysis. Exogenously and endogenously initiated coagulation assays were used to assess clot and thrombin formation (Thrombodynamics T2F analyzer and the calibrated automated thrombogram (CAT), respectively). Parameters describing exogenously initiated clot (Clot) and endogenously initiated clot (Clot) growth, and standard CAT parameters were collected. Comparisons were made across visits and between preparations using paired t-tests. Data are presented as mean ± standard deviation or Spearman correlation values. RESULTS: Clot growth was more robust at 18-48 h postpartum compared to the late third trimester. Centrifugation removed all detectable Clot growth and reduced the speed of Clot growth. In exogenously initiated CAT assays, there were no significant differences across the immediate peripartum period. Depleted preparations had slightly slower dynamics compared to control preparations. We observed a correlation between the rates of Clot and Clot growth. CONCLUSION: Through 18-48 h after delivery there is an increase in endogenous clotting potential compared to late pregnancy, centrifugation of this sedimentable material removes most of this endogenous activity.
Ii K, Hisamune R, Ushio N
… +10 more, Nii M, Nishioka D, Oda T, Umemura Y, Okamoto K, Matsuoka T, Mochizuki K, Takasu A, Yamakawa K, Japanese Society on Thrombosis and Hemostasis LOCOMOCO (Landmark Of Clinical Observations in MicrOcirculation and Coagulation Outcomes) study group
BACKGROUND: Postpartum hemorrhage (PPH) remains a major cause of direct obstetric mortality. We aimed to predict pregnant women with severe PPH, defined as cases requiring hemostatic interventions-such as transcatheter a...BACKGROUND: Postpartum hemorrhage (PPH) remains a major cause of direct obstetric mortality. We aimed to predict pregnant women with severe PPH, defined as cases requiring hemostatic interventions-such as transcatheter arterial embolization, hysterectomy, bimanual uterine compression, or intrauterine balloon tamponade-or blood transfusions. METHODS: This retrospective observational study utilized a large-scale database covering approximately 600 hospitals in Japan from 2014 to 2023. Women of ≥18 years of age, emergency hospitalized for placental abruption, amniotic fluid embolism, or peripartum hemorrhage were included. Laboratory test (platelets, fibrinogen, fibrinogen/fibrin degradation product [FDP], and prothrombin time-internationalized ratio [PT-INR]) results at admission and perinatal parameters were collected. The primary outcome was receiving hemostatic intervention or blood transfusion. Risk factors were assessed by logistic regression and non-linear regression analyses. Decision curve analysis (DCA) was used to compare Japanese obstetric scores with platelet adjustment and three existing obstetric disseminated intravascular coagulation (DIC) scores. RESULTS: Among 902 obstetric inpatients meeting the inclusion criteria, 343 received hemostatic interventions or blood transfusions; 559 did not. Multivariate logistic regression revealed fibrinogen level (adjusted odds ratio [OR]: 0.994, 95% CI: 0.991-0.998), but not platelet count (adjusted OR: 0.980, 95% CI: 0.933-1.029) as a risk factor for the primary outcome. Non-linear regression using restricted cubic splines demonstrated that the predictive risk increased steeply when platelet count and fibrinogen fell below 10 × 10/μL and 200 mg/dL, respectively. DCA revealed that the platelet-adjusted obstetric DIC score developed in this study showed the highest net benefit across most threshold probabilities when compared with the pregnancy-modified ISTH DIC score, the JAAM-2 DIC score, and the new Japanese obstetric DIC score, although the advantage was modest. CONCLUSION: Platelet counts and fibrinogen levels may be useful for identifying women with severe PPH who are at risk of requiring hemostatic interventions and transfusions.
BACKGROUND: Diagnosis of antithrombin deficiency (ATD), the most severe inherited thrombophilia, commonly relies on functional assays despite their uncertain sensitivity. Moreover, routine characterization of ATD remains...BACKGROUND: Diagnosis of antithrombin deficiency (ATD), the most severe inherited thrombophilia, commonly relies on functional assays despite their uncertain sensitivity. Moreover, routine characterization of ATD remains uncommon due to limited supporting clinical data. OBJECTIVES: This study aimed to evaluate the diagnostic sensitivity of commercial antithrombin (AT) activity assays and assess clinical differences among ATD types to refine the current diagnostic approach. METHODS: Eighty-eight patients with decreased AT activity and 124 consecutive patients with unprovoked venous thromboembolism were included. AT activity was measured using six assays. Genetic analysis of SERPINC1 was performed by Sanger sequencing and multiplex ligation-dependent probe amplification; additionally, long-read whole-genome sequencing was conducted. RESULTS: Fifteen SERPINC1 variants were detected, including two novel ones. AT Padua I (p.Arg79His) was the most prevalent (49%). Sensitivity varied across AT activity assays, particularly for types IIRS and IIHBS, with variant-specific discrepancies. AT Dublin (p.Val30Glu), causing transient deficiency, was undetected by all assays. Two assays demonstrated very high sensitivity (93%; p < 0.001), while two others showed poor sensitivity (46%). Regardless of measured AT activity, characterization of ATD type enabled better risk stratification. Type I was associated with early-onset and recurrent venous thromboembolism, and type IIHBS was distinctly linked to arterial thrombosis. CONCLUSIONS: Assay sensitivity varies considerably, and only a few proved suitable as first-line tests. Genetic testing for common variants undetectable by even the most sensitive assays, along with ATD characterization, should be integrated into diagnostic algorithms. Our results also suggest that young patients with arterial thrombosis should be screened for ATD.
BACKGROUND: The association between C-reactive protein (CRP) and venous thromboembolism (VTE) is currently not well explained. AIMS: To determine whether the association between CRP and VTE can be explained by concurrent...BACKGROUND: The association between C-reactive protein (CRP) and venous thromboembolism (VTE) is currently not well explained. AIMS: To determine whether the association between CRP and VTE can be explained by concurrent presence of a procoagulant state, chronic diseases or obesity. METHODS: Using data from the Multiple Environmental and Genetic Assessment of multiple risk factors for venous thrombosis (MEGA) case-control study, data on high sensitivity CRP (hsCRP), factor VIII activity (FVIII) concentration, chronic diseases (i.e. rheumatic disease, cancer, history of arterial cardiovascular disease and chronic kidney diseases) and body mass index (BMI) were available in 2205 cases with VTE and 2777 controls. Logistic regression analysis was performed to estimate risk of VTE by categories of hsCRP (<25th, 25-50th, 50-75th, 75-97.5th and > 97.5th percentiles). The analyses were adjusted for confounding and done separately for FVIII levels, BMI and chronic diseases. We investigated whether chronic diseases could be related to concurrent high levels of hsCRP, BMI and FVIII levels by calculating the mean levels of these factors in individuals with and without the presence of chronic diseases. RESULTS: HsCRP levels were associated with BMI, FVIII levels and presence of chronic diseases. The risk of VTE was higher across hsCRP categories in a dose response manner, with individuals in the highest percentile (>13.13 mg/L) having a 3.3-fold higher risk (OR: 3.3, 95% CI: 2.48-4.5) than in the lowest percentile (<0.68 mg/L). This association was strongest for unprovoked VTE (OR: 5.3, 95% CI: 3.3-8.5). Upon adjustment for BMI, FVIII and chronic diseases, the association with the overall VTE attenuated (OR: 1.6, 95% CI: 1.1-2.2). CONCLUSIONS: Our findings suggest that the association between CRP and VTE risk is at least partly explained by FVIII, BMI and the presence of comorbidities. These results suggests that elevated CRP should not be considered an independent risk factor for VTE but rather as a marker of underlying inflammatory and prothrombotic states.
BACKGROUND: Apixaban prolongs the dilute Russell's viper venom time (dRVVT), which may serve as a rapid surrogate for identifying clinically relevant drug concentrations in urgent settings. OBJECTIVES: To evaluate the co...BACKGROUND: Apixaban prolongs the dilute Russell's viper venom time (dRVVT), which may serve as a rapid surrogate for identifying clinically relevant drug concentrations in urgent settings. OBJECTIVES: To evaluate the correlation between dRVVT and apixaban concentration, and to establish cut-off values for clinically relevant thresholds (≥ 30 and ≥ 50 ng/mL). METHODS: This cross-sectional study included 104 patients receiving apixaban. Normalized dRVVT screening and confirmation ratios were compared with chromogenic anti-factor Xa-based apixaban concentrations. Correlations were evaluated using Spearman's rank correlation coefficient (ρ). The ROC curve analysis with the Youden index was performed to identify optimal diagnostic cut-offs. RESULTS: The median apixaban concentration was 116.3 ng/mL (IQR, 78.9-177.2), with ≥ 30 ng/mL observed in 96.2%. Moderate correlations were observed between dRVVT ratios and apixaban concentrations for both screening and confirmatory assays (ρ = 0.675 [95% CI, 0.554-0.768] and 0.713 [95% CI, 0.604-0.797], respectively). Both dRVVT ratios showed comparable discriminative ability for detecting concentrations ≥ 50 ng/mL (AUC, 0.885 vs. 0.892; P = 0.690) and ≥ 30 ng/mL (AUC, 0.956 vs. 0.975; P = 0.446). Optimal cut-off values (screening/confirmation) for ≥ 50 ng/mL were 1.33/1.42, with sensitivities of 82.8%/84.9% and specificities of 90.9%. For ≥ 30 ng/mL, cut-offs of 1.12/1.16 provided sensitivities of 92.0%/96.0% and specificities of 100%. CONCLUSIONS: dRVVT assays correlate moderately with apixaban concentrations. dRVVT may support semi-quantitative assessment and rule-in of apixaban exposure; however, it cannot reliably exclude low drug levels. The low prevalence of subthreshold concentrations may limit specificity precision, warranting caution in borderline or high-risk clinical scenarios. TRIAL REGISTRATION: Thai Clinical Trials Registry: TCTR20250124009.
Although studies have identified deep intronic variants associated with hemophilia B in patients undiagnosed by conventional genetic testing, knowledge in this field remains limited. Long range-PCR of entire F9 gene was...Although studies have identified deep intronic variants associated with hemophilia B in patients undiagnosed by conventional genetic testing, knowledge in this field remains limited. Long range-PCR of entire F9 gene was used to screen variants of three unrelated genetically unresolved severe hemophilia B patients. In silico analysis and minigene assay with two minigene plasmid construction methods were conducted to explore the effects of candidate deep intronic variants on splicing. Three novel putative pathogenic deep intronic variants (c.278-765_278-764ins6.1kb, c.392-903A>G and c.724-751T>G) and one variant of uncertain significance (c.723+2708del) in F9 were identified in three patients. All the three putative pathogenic variants created de novo donor splice site and utilized cryptic acceptor splice site to generate pseudoexon. We successfully developed antisense oligonucleotide-mediated exon-skipping correction strategies for the three identified putative pathogenic variants and the previously reported c.392-864T>G. However, the results obtained from minigene assay revealed certain discrepancies with the clinical phenotype. It is still challenging to accurately characterize the pathogenicity of deep intronic variants in vitro. Overall, our results highlight the complementary role of whole-gene sequencing of F9 to conventional genetic diagnosis. Furthermore, we provide insight into a potential therapeutic approach based on antisense oligonucleotide technology-mediated exon-skipping.
BACKGROUND: COVID-19 is associated with increased thromboembolic risk, but population-level trends in pulmonary embolism (PE) incidence and outcomes across the pandemic remain incompletely characterized. METHODS: Serial...BACKGROUND: COVID-19 is associated with increased thromboembolic risk, but population-level trends in pulmonary embolism (PE) incidence and outcomes across the pandemic remain incompletely characterized. METHODS: Serial cross-sectional analysis of the National Inpatient Sample (2017-2022) including adult hospitalizations. Acute PE was identified using ICD-10-CM codes I26.0 and I26.9. Survey-weighted logistic regression assessed predictors of in-hospital mortality. Analyses were stratified by COVID-19 status (ICD-10-CM U07.1). RESULTS: Acute PE incidence increased from 1232 per 100,000 adult discharges (2017) to 1814 per 100,000 (2021), declining to 1640 per 100,000 (2022). PE without COVID rose from 1232 to 1444 per 100,000 (2017-2021). PE with COVID emerged in 2020 (169 per 100,000), peaked in 2021 (370 per 100,000), and declined in 2022 (215 per 100,000). Unadjusted in-hospital mortality among PE admissions increased from 6.4% (2017) to 10.0% (2021), improving to 8.7% (2022). Mortality was substantially higher for PE with COVID (16-21%) versus PE without COVID (6-8%). In pooled models, COVID-19 was associated with 2.47-fold higher mortality odds (95% CI 2.32-2.63), corresponding to adjusted absolute mortality increases of 11.2% (2020), 14.7% (2021), and 7.0% (2022). Older age, higher comorbidity burden, and lower income quartile independently predicted mortality. CONCLUSIONS: The COVID-19 pandemic was associated with substantially increased PE incidence and mortality. Although outcomes improved by 2022, mortality remained elevated compared to pre-pandemic levels, reflecting the overall severity of illness and comorbidity burden in patients with concurrent COVID-19 and PE rather than mortality directly attributable to PE itself.
BACKGROUND: Data on bleeding risk from combining prophylactic anticoagulation with drugs that have antiplatelet properties (antiplatelet agents or nonsteroidal anti-inflammatory drugs (NSAIDs)) in patients with active ca...BACKGROUND: Data on bleeding risk from combining prophylactic anticoagulation with drugs that have antiplatelet properties (antiplatelet agents or nonsteroidal anti-inflammatory drugs (NSAIDs)) in patients with active cancer are limited. We evaluated the impact of concurrent antiplatelet/NSAID use on the safety and efficacy of apixaban thromboprophylaxis in ambulatory cancer patients. METHODS: This post-hoc analysis of the AVERT trial assessed clinically relevant bleeding (major plus clinically relevant non-major bleeding [CRNMB]) as the primary outcome. Secondary outcomes included major VTE, major bleeding, CRNMB, and all-cause mortality. Hazard ratios (HRs) were estimated using Cox models adjusted for age, sex, and center. Subgroup analyses examined antiplatelet agents (aspirin or clopidogrel) and NSAIDs separately. RESULTS: Among 563 included patients, 184 used drugs with antiplatelet properties (apixaban n = 99; placebo n = 85) and 379 did not. In the apixaban arm, concurrent use of these drugs increased clinically relevant bleeding (HR 1.80; 95% CI 1.15-2.82) and CRNMB (HR 2.01; 95% CI 1.21-3.34) without reducing VTE (HR 0.61; 95% CI 0.26-1.45). Among antiplatelet users (n = 61), risks of clinically relevant bleeding (HR 2.02; 95% CI 1.29-3.18) and CRNMB (HR 2.63; 95% CI 1.59-4.35) were higher. NSAID users (n = 42) showed no significant differences in bleeding outcomes. In the placebo arm, concurrent use was not associated with increased clinically relevant bleeding but was linked to more CRNMB (HR 1.88; 95% CI 1.00-3.55). No impact on all-cause mortality was observed. CONCLUSIONS: Concurrent use of antiplatelet drugs during apixaban thromboprophylaxis in cancer patients increases clinically relevant bleeding without reducing VTE.
Splenectomy remains a common operation performed in the setting of trauma, haematological disease, malignancy and diagnostic purposes. Contemporary evidence indicates an increased risk of thromboembolism after splenectom...Splenectomy remains a common operation performed in the setting of trauma, haematological disease, malignancy and diagnostic purposes. Contemporary evidence indicates an increased risk of thromboembolism after splenectomy. This includes both systemic venous thromboembolism (deep vein thrombosis and pulmonary embolism) and splanchnic thrombosis involving the portal-splenic-mesenteric axis. Comparator-based population studies demonstrate a pronounced early postoperative risk and disease-matched cohorts suggest that risk can persist beyond the immediate perioperative period. This suggests a durable post-splenectomy prothrombotic phenotype. Mechanistically, this phenotype may reflect the loss of splenic functions that are intrinsically antithrombotic, including clearance of procoagulant cellular substrates and microparticles, sequestration and regulation of platelet mass, modulation of portal haemodynamics, and facilitation of thrombus remodelling and resolution. Splenectomy as a risk factor is over-represented among patients with chronic thromboembolic pulmonary hypertension (CTEPH) with evidence for biological links between thrombotic risk and impaired thrombus resolution. Anticoagulation strategies in splenectomised patients remain heterogeneous and evidence for its use is largely based on observational studies. Most guidance supports routine perioperative pharmacologic thromboprophylaxis and consideration of extended prophylaxis in selected cases. When post-splenectomy thrombosis occurs, therapeutic anticoagulation is the mainstay for the first three to six months. Extended therapy is reserved for persistent risk factors and those who develop CTEPH.
INTRODUCTION: Isolated subsegmental pulmonary embolism (iSSPE) is being diagnosed with increasing frequency, but its optimal treatment remains uncertain. OBJECTIVES: This systematic review and meta-analysis aimed to inve...INTRODUCTION: Isolated subsegmental pulmonary embolism (iSSPE) is being diagnosed with increasing frequency, but its optimal treatment remains uncertain. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the efficacy and safety of anticoagulation versus clinical surveillance for the management of iSSPE. METHODS: The Medline and EMBASE databases were searched up to April 2025 for all studies that compared anticoagulation therapy against clinical surveillance in patients with iSSPE. Clinical outcomes included venous thromboembolism (VTE) recurrence, bleeding complications and all-cause mortality. Pooled risk ratios (RRs) and 95% Confidence Intervals (CI) were estimated by random-effects model. RESULTS: Eight observational studies reported data on VTE recurrence, encompassing 674 patients. The risk of VTE recurrence did not differ statistically significantly between anticoagulated and non-anticoagulated patients (RR 0.61, 95% CI 0.28-1.35, I = 0%). Conversely, nine studies reported data on safety outcomes, encompassing 862 patients. The incidence of any bleeding complication was higher in anticoagulated patients compared with those managed by clinical surveillance (RR 3.10, 95% CI 1.39-6.88, I = 0%). A similar association was observed when the analysis was restricted to major bleeding events. Finally, all-cause mortality did not differ statistically significantly between the two groups (RR 0.70, 95% CI 0.44-1.12, I = 45%). CONCLUSIONS: Available evidence does not support a net clinical benefit from routine anticoagulation in patients with iSSPE.
BACKGROUND: Cerebral venous thrombosis (CVT) in children is rare and may complicate head and neck infections, particularly mastoiditis. Optimal anticoagulation strategies in this setting remain uncertain. METHODS: We con...BACKGROUND: Cerebral venous thrombosis (CVT) in children is rare and may complicate head and neck infections, particularly mastoiditis. Optimal anticoagulation strategies in this setting remain uncertain. METHODS: We conducted a multicenter retrospective study across four Italian pediatric referral centers, including consecutive children hospitalized for infections-related CVT and treated with Direct Oral Anticoagulants from July 2023 to December 2024. RESULTS: Thirty-four children (median age 63 months; 67.6% males) met the inclusion criteria and were included in the study. Mastoiditis was the most frequently reported infection (85.3%). The most common site of CVT was the sigmoid sinus (91.1%), followed by the transverse sinus (67.6%). All patients initially received heparin, followed by rivaroxaban. Twenty patients (58.8%) required additional medical therapy for intracranial hypertension. Eight patients (23.5%) underwent therapeutic lumbar puncture, and four (11.8%) required ventriculoperitoneal shunt placement. At three months, 61.8% of patients achieved complete recanalization and 85.3% showed thrombus improvement. Female sex, younger age, internal jugular vein involvement, papilledema, and surgical treatment for intracranial hypertension were associated with lower recanalization rates. No major bleeding events occurred; minor bleeding (epistaxis) was observed in 8.8% of patients. At a median follow-up of 12 months, no recurrences or new thromboembolic events were observed. CONCLUSION: Our findings suggest that rivaroxaban is safe and effective for the treatment of pediatric infections-related CVT and support an individualized duration of anticoagulation based on thrombotic burden and clinical complexity.
BACKGROUND: Growing evidence suggests that thrombus composition may influences embolic stroke severity, treatment response, and patient outcomes. While previous studies have characterized histopathological differences be...BACKGROUND: Growing evidence suggests that thrombus composition may influences embolic stroke severity, treatment response, and patient outcomes. While previous studies have characterized histopathological differences between cardioembolic stroke (CES) and atheroembolic stroke (AES), less is known about embolic strokes of undetermined source (ESUS). This study examines the relationship between embolic stroke etiology, thrombus composition, and clinical outcomes to improve classification and guide therapeutic strategies. METHODS: This retrospective study included 323 patients with acute embolic ischemic stroke treated with mechanical thrombectomy. Stroke etiology was classified as CES (n = 151), AES (n = 71), or ESUS (n = 81). Histopathological examination was performed on 127 retrieved thrombi, assessing fibrin architecture, platelet distribution, neutrophil content, and red blood cell integrity. Clinical parameters, including National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), length of hospital stay, and in-hospital mortality, were analyzed. Statistical models examined associations between thrombus characteristics, stroke etiology, and functional recovery. RESULTS: CES thrombi exhibited higher platelet and neutrophil content, with a dense, centrally concentrated platelet distribution consistent with fibrin-rich, compact thrombi. In contrast, AES thrombi showed a more diffuse, net-like distribution of platelets, aligning with high-shear conditions in stenotic arteries. ESUS thrombi closely resembled AES but contained a heterogeneous fibrin profile, including the highest proportion of compact fibrin, suggesting alternative thrombus maturation mechanisms. Patients with AES exhibited the poorest functional recovery (lowest NIHSS and mRS improvement), despite successful recanalization. ESUS had the highest in-hospital mortality. Stroke mechanism was significantly associated with both thrombus composition and patient outcomes in this study. CONCLUSIONS: Thrombus histopathology varies significantly by stroke etiology, with platelet distribution emerging as a strong classifier. ESUS thrombi exhibit hybrid features, emphasizing the need for improved classification. Clinical outcomes differed across etiologies, with AES patients experiencing the slowest recovery and ESUS patients exhibiting the highest in-hospital mortality. Integrating thrombus characteristics into risk stratification models, secondary prevention strategies, and artificial intelligence-driven classification may enhance acute stroke management.