Ultrasound-assisted catheter-directed thrombolysis (USAT) with recombinant tissue-type plasminogen activator (rt-PA) is widely used as a reperfusion approach for acute pulmonary embolism (PE). The fibrinolytic effector protease plasmin is known to be a potent activator of the complement system. The aim of this study was to better characterize the extent of complement activation during USAT, and its relationship with the fibrinolytic system. In this single-center cohort study of USAT for PE, pulmonary-arterial hemodynamic measurements were performed, and plasma samples obtained from 35 patients before treatment start and at 6 h (during infusion of rt-PA). Hemostatic properties were evaluated with thromboelastometry and assessment of fibrinolytic markers. In addition, levels of the complement components C3a, C4a, C5a, soluble C5b-9 (sC5b-9), Ba, Bb, factor H and factor I at these time points were determined. Several complement components, including the anaphylatoxin C3a, showed a reduction during USAT. We found a positive correlation of the plasmin-antiplasmin complex (plap complex) with factor H, yet a negative correlation with both Ba and Bb, C5a and sC5b-9. The potent plasmin-inhibitor, α2-antiplasmin, displayed a positive correlation with Ba and Bb, factor I and factor H. In addition, the anaphylatoxin C5a negatively, and Ba positively predicted treatment responsiveness to USAT. In conclusion, in the setting of acute PE and reperfusion therapy with USAT, there appears to be a competing effect between plasmin-mediated complement activation and a reduction of the inflammatory trigger by resolution of obstruction and ischemia. Complement activation in PE is downregulated during USAT, an effect exceeding the complement-activating properties of plasmin.

Accurate coagulation parameter reference intervals are crucial for diagnosing bleeding disorders and thromboembolic diseases. However, reference intervals vary across populations due to genetic, environmental, and demographic factors. This study aimed to establish localized coagulation reference intervals for healthy adults of Debre Berhan, Northeast Ethiopia, addressing the current reliance on non-local values. A community-based cross-sectional study was conducted in Debre Berhan, Northeast Ethiopia, from October-December 2024. We recruited 240 healthy adults (120 of each gender) using convenience sampling. Participants were interviewed face-to-face using a pre-tested questionnaire on KoBoToolbox to collect demographic data. Aseptically drawn venous blood was analyzed for coagulation parameters using Sysmex CA-104 coagulation analyzer. Stata 17 was used for data analysis, with reference intervals determined by the 2.5th and 97.5th percentiles. Gender differences were assessed using the Mann-Whitney U test (p < 0.05 significance). The established 95% coagulation reference intervals (2.5th -97.5th percentile) were: Prothrombin time (8.5-13.0sec), international normalized ratio (0.7-1.1), and activated partial thromboplastin time (21.6-37.9sec). Males exhibited significantly higher median PT (10.4 Vs. 9.8sec, p = 0.0006) and INR (0.9 Vs. 0.84, p = 0.0006) values compared to females. This study's findings strongly support the adoption of population-specific reference intervals to ensure accurate diagnoses and improve patient safety within the Debre Berhan adult population. The observed gender-related differences in Prothrombin time and international normalized ratio values further highlight the need for gender-specific reference intervals to improve clinical decision-making and prevent potential misinterpretations of coagulation test results.

Rapid diagnosis and treatment of deep vein thrombosis (DVT) reduce morbidity and mortality. This study aimed to investigate the time to diagnostic imaging, time to treatment, and outcomes associated with the delayed treatment of DVT. We retrospectively investigated 110 patients who were diagnosed with proximal DVT in outpatient clinics in a single academic centre in Thailand from January 2019 to September 2020. We recorded demographic data, clinical presentations, time to diagnostic imaging (ultrasound of the legs), and time to treatment. We recorded outcomes, including death, pulmonary embolism (PE), recurrent DVT, and thrombus resolution 3 months after the diagnosis of DVT. Of all 110 patients, 42 (38.2%) were male. Median age (IQR) was 68.5 (58-80) years. The median (IQR) time to diagnostic imaging was 7 days (2-27). The median (IQR) interval from the first OPD visit to the initiation of treatment was 14 days (3-31). The delayed diagnosis (more than 7 days from the first clinic visit to diagnostic imaging) was observed in 54 (49%) patients with DVT. The delay in treatment (more than 7 days from the first clinic visit to treatment) was observed in 67 (60.9%) patients. The maximum time to treatment was 160 days. Death and PE occurred in 9% and 33% of patients with delayed treatment, while they occurred in 5% and 20% of those with early treatment, respectively. No recurrent DVT was observed. Among 25 patients who had follow-up imaging, residual thrombus occurred in 71% of patients with delayed treatment and 63% of those with early treatment. Half of the DVT patients had delays in diagnosis and treatment of proximal DVT. The routine request option was associated with a delayed diagnosis. The importance of early diagnosis and treatment of DVT should be raised among physicians, and improvement strategies are warranted.

Bleeding diathesis’ diagnosis can be challenging due to the high number of disorders with hemorrhagic symptomatology. Sitosterolemia is a rare disease characterized by increased sterols plasma levels and cardiovascular, cutaneous, articular, and hematological manifestations, including anemia and macrothrombocytopenia. The disorder is caused by ABCG5 and ABCG8 mutations.We present a case of a patient with bleeding diathesis, macrothrombocytopenia, a moderate defect of primary hemostasis and a pathological platelet aggregation analysis, with an initial diagnosis of Bernard-Soulier variant syndrome. After performing a genetic study using an exome analysis, the patient had two ABCG8 gen variants, one pathogenic (NP_071882.1:p.Trp536Ter (NM_022437.2:c.1608G > A) variant, ClinVar ID: 499930) and the other one probably pathogenic (NP_071882.1:p.Leu465Arg (NM_022437.2:c.1394T > G) variant), changing the diagnosis to sitosterolemia, which has its own therapeutic approach.This case report shows the importance of the genetic analysis. Sitosterolemia should be suspected in the presence of macrothrombocytopenia, stomatocytes in the blood smear and hemolytic anemia, performing a genetic study including ABCG5 and ABCG8 gene variants.

BackgroundSeptic-induced coagulopathy (SIC) is a major cause of mortality in sepsis, closely associated with endothelial glycocalyx damage. Enolase 1 (Eno1), a key enzyme in glycolysis, plays a crucial role in sepsis-related systemic inflammation and the maintenance of glycocalyx integrity.ObjectiveThis study utilizes multi-omics analysis to investigate the Eno1-regulated network, providing a comprehensive understanding of its molecular mechanisms in SIC.MethodsWe used RNA-seq datasets to identify Eno1-related gene sets through weighted gene co-expression network analysis and validated their biological functions via gene set enrichment analysis.ResultsThrough RNA-seq analysis, we identified gene sets associated with Eno1 involved in immune regulation, endothelial cell apoptosis, coagulation, and glycosaminoglycan metabolism. Immune infiltration analysis revealed that Eno1 modulates SIC pathogenesis by influencing T cells and macrophages, with significant associations with endothelial dysfunction and inflammatory markers. Additionally, we observed that Eno1 regulation of glycolysis is linked to endothelial glycocalyx degradation, contributing to microcirculatory and vascular impairments in SIC. Furthermore, preliminary studies suggest that melatonin treatment may alleviate glycocalyx damage by inhibiting Eno1-mediated glycolytic pathways, offering a potential new therapeutic avenue for intervening in endothelial injury associated with SIC.ConclusionsThis study underscores the critical role of Eno1 in promoting SIC and its potential as both a diagnostic marker and therapeutic target for glycocalyx repair. The multi-omics approach provides valuable insights into the molecular networks regulating SIC, offering new avenues for targeted interventions in sepsis management.

BackgroundCystic adventitial disease (CAD) is a rare vascular condition that causes arterial stenosis due to the presence of a cyst in the adventitia (outer layer) of the artery. It is most commonly seen in young and middle-aged men, with an occurrence rate of around 0.1% among vascular diseases. Symptoms may include intermittent claudication, rest pain, and, in severe cases, ulcers or limb ischemia. CAD is often underdiagnosed due to its rarity and the broad range of differential diagnoses for arterial obstruction.Case presentationThis case describes a 36-year-old female who presented with sudden left lower limb soreness that worsened with activity over five days, but without symptoms such as intermittent claudication or rest pain, which are typically associated with other vascular diseases. The patient had no significant history of smoking or other risk factors for peripheral arterial disease. Imaging studies, including angiography, revealed a focal filling defect and luminal narrowing in the popliteal artery (PA), which suggested the presence of an abnormality in the vessel wall. Given the findings and the patient’s symptoms, surgical intervention was planned. The procedure involved the resection of the affected portion of the artery and replacement with an autologous vein graft. Pathological examination of the resected arterial segment confirmed the diagnosis of CAD, revealing a cyst in the adventitia filled with a gelatinous substance.ConclusionCAD is a rare but important cause of arterial obstruction and the etiology of CAD is still unclear. It should be considered in younger patients with symptoms of limb ischemia, especially without smoking history or traditional risk factors. Imaging techniques, such as ultrasound and CT/MRI angiography, are crucial for diagnosis. Surgical management, typically involving resection and autologous grafting, is often required to alleviate symptoms and prevent further vascular complications. However, it is worth mentioning that conservative treatments, such as avoiding triggering movements, are sometimes sufficient. Since CAD is rarely suspected, awareness of this condition can help in making an early diagnosis, potentially avoiding misdiagnosis and improving patient outcomes.