Search Results (74)

Viper envenomation in dogs represents a significant medical emergency in regions where vipers are endemic. Despite its clinical relevance, detailed data on the haematological and biochemical alterations in canine viper envenomation remain limited. This study aimed to evaluate the clinical presentation and haematological, biochemical and coagulative changes occurring in dogs following bites from the Vipera aspis species, and to assess their diagnostic and prognostic significance. Twelve dogs with suspected Vipera aspis envenomation were encompassed in the study. Clinical data were gathered and blood samples were collected at hospital admission (T1), 24 h (T2) and 48 h later (T3). Complete blood counts, biochemical profiles and coagulation parameters were analysed using standard automated systems. Common clinical signs included local pain and swelling, depression, fever, haematuria and melena. Haematological evaluation revealed progressive anaemia, leucocytosis and thrombocytopenia. Biochemical findings showed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and creatine kinas (CK), indicating hepatic and muscular injury; however, no consistent evidence of renal failure was found. Coagulation analysis revealed a significant shortening of activated partial thromboplastin time (aPTT) and prothrombin time (PT) over time, alongside marked increases in fibrinogen and antithrombin III. This indicates an inflammatory rather than consumptive coagulopathy. Viper envenomation in dogs induces complex haematological and biochemical alterations, reflecting both direct venom toxicity and systemic inflammatory responses. Early recognition, supportive care and continuous laboratory monitoring are essential for improving prognosis. Full article

Background/Objectives: Combat trauma involving large joints is associated with a high risk of thromboinflammatory complications. Early identification of laboratory markers for hypercoagulability is essential to optimise perioperative management. This study aimed to evaluate the dynamics of inflammation and haemostasis indicators in patients with combat-related joint trauma and to identify the most informative markers for preoperative risk assessment. Methods: A total of 29 patients with combat injuries to the hip, knee, elbow, or ankle joints were examined. Blood samples were taken 1–3 days prior to surgery and again on the first postoperative day. Parameters of coagulation (e.g., PT, INR, fibrinogen, D-dimer, soluble fibrin complexes, antithrombin III), fibrinolysis, and inflammation (e.g., CRP, haptoglobin, sialic acid, ESR, LSI, LII) were analysed and compared to those of 30 healthy controls. Statistical analysis included Student’s t-test and Pearson’s correlation. Results: At baseline, patients demonstrated significant increases in inflammatory markers (CRP 64.2 ± 7.3 mg/L, ↑738.9%; haptoglobin 3.25 ± 0.4 g/L, ↑164.3%; ESR 46.8 ± 5.2 mm/h, ↑313.8%) and procoagulant activity (D-dimer 1.42 ± 0.18 µg/mL, ↑136.6%; fibrinogen 6.12 ± 0.51 g/L, ↑102.4%; soluble fibrin complexes 38.7 ± 4.9 mg/L, ↑597.3%), together with a reduction in antithrombin III activity (63.5 ± 6.2%, ↓39.5%) and prolonged fibrinolysis time (increase by 197%). Postoperatively, these abnormalities intensified, indicating a sustained thromboinflammatory response. Strong correlations were found between inflammatory and haemostatic markers. Conclusions: Combat trauma of large joints is associated with preoperative thromboinflammatory dysregulation, which is exacerbated by surgery. Monitoring specific biochemical and haematological markers—such as CRP, fibrinogen, D-dimer, and soluble fibrin complexes—may support preoperative risk assessment and postoperative monitoring strategies for hypercoagulable states in this high-risk group. These findings lay the groundwork for future prospective studies aimed at developing stratified therapeutic protocols and predictive models for thromboinflammatory complications in orthopaedic trauma care. Full article

Background: Recurrent pregnancy loss (RPL) is a multifactorial condition in which genetic variants associated with thrombophilia may contribute to altered coagulation and adverse pregnancy outcomes. Objective: This study aimed to investigate the association between thrombophilia-related single nucleotide variants (SNVs) and coagulation-related metabolites in a cohort of Mexican women with RPL. Methods: A retrospective and descriptive design was conducted including 105 women with at least two consecutive miscarriages and with a multidisciplinary approach that included a thrombophilia-associated SNVs panel. Peripheral blood samples were collected after fasting for biochemical and molecular analyses. Genotyping of thrombophilia-associated SNVs was performed using real-time PCR with custom-designed TaqMan probes on a Rotor-Gene Q platform, including variants in AGT (rs4762, rs699), F7 (rs6046), FGB (rs1800790), MTR (rs1805087), MTRR (rs1801394), MTHFR (rs1801133, rs1801131), F2 (rs1799963), F5 (rs6025), SERPINE1 (rs1799889), F12 (rs1801020), and F13A1 (rs5985) genes. Coagulation parameters evaluated were folic acid, cobalamin, fibrinogen, D-dimer, homocysteine, antithrombin III activity, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and Factor XII activity. Results: Significant differences were found in INR values across F7-rs6046 genotypes (p = 0.006), with an additive model showing a mean difference of 0.05 (p = 0.0009). The F12-rs1801020 variant was strongly associated with Factor XII activity (p = 0.002) and aPTT (p = 0.045). Conclusions: These findings indicate that F7-rs6046 and F12-rs1801020 genotypes influence specific coagulation parameters, suggesting that certain thrombophilia-associated SNVs may modulate the hemostatic profile in Mexican women with RPL and contribute to personalized risk assessment in reproductive medicine. Full article

Background/Objectives: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of infancy, often complicated by Kasabach–Merritt phenomenon (KMP), a consumptive coagulopathy characterized by severe thrombocytopenia and hypofibrinogenemia. Airway involvement at birth is exceptionally rare and can be life-threatening. This study reports the clinical presentation and treatment course of a full-term male neonate with severe airway obstruction caused by KHE with KMP. Case Presentation: The patient had unremarkable prenatal imaging but presented at birth with severe respiratory distress requiring emergent intubation. Physical examination revealed firm violaceous swelling over the right cervicothoracic region. Laboratory tests showed profound thrombocytopenia (22,000/μL), hypofibrinogenemia (75 mg/dL), and coagulopathy. Imaging findings were consistent with KHE complicated by KMP. Due to bleeding risk, the biopsy was not performed. Initial treatment included platelet and plasma transfusions, intravenous immunoglobulin (IVIG), corticosteroids, and antithrombin III replacement. Vincristine was discontinued owing to gastrointestinal toxicity. Sirolimus therapy was initiated on day 14. Following sirolimus initiation, rapid platelet recovery was observed. At three months, marked tumor regression was documented. After mild recurrence, sirolimus was reintroduced, and the patient remained stable at 16-month follow-up. Conclusions: This case underscores the critical importance of prompt airway stabilization, early recognition of consumptive coagulopathy, and sirolimus-based therapy in managing neonatal KHE with airway involvement. Full article

Background and Objectives: Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. Methods: A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case–control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. Results: Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3–8.0), protein C deficiency 4.3% (17/400; 2.5–6.8), and antithrombin deficiency 1.5% (6/400; 0.6–3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. Conclusions: Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications. Full article

Encephalitozoon cuniculi causes both clinical and subclinical infections in rabbits, complicating a diagnosis due to the limitations of conventional tools like ELISA. This study analyzes serum proteomic profiles across clinical, subclinical, and healthy rabbits to identify discriminatory biomarkers. Serum from 90 pet rabbits (30 per group) was pooled (10 samples per pool, 3 pools per group) and analyzed using one-dimensional gel electrophoresis and mass spectrometry. The proteomic analysis revealed 109, 98, and 74 proteins expressed in healthy, subclinical, and clinical groups, respectively. Of these, 50, 40, and 33 proteins were unique to the healthy, subclinical, and clinical groups, respectively, with only 10 proteins shared across all. A total of 88 proteins were differentially expressed in infected groups compared to healthy controls. Importantly, 12 proteins were consistently upregulated in both subclinical and clinical infections. These include markers related to the immune response (beta-2-microglobulin, alpha-2-HS-glycoprotein), coagulation (antithrombin-III, alpha-1-antiproteinase S-1), vitamin A transport (retinol-binding proteins), lipid metabolism (apolipoprotein C-III), cytoskeletal regulation (actin-depolymerizing factor), extracellular matrix integrity (fibrillin 2), and oxidative stress (monooxygenase DBH-like 1). Additionally, Gc-globulin and ER lipid-raft-associated 1 were linked to immune modulation and signaling. These findings identify specific serum proteins as promising biomarkers for distinguishing subclinical from clinical encephalitozoonosis in rabbits, enabling an early diagnosis and effective disease monitoring. Full article

Glycosaminoglycans (GAGs) are key ligands for proteins involved in physiological and pathological processes. Specific GAG-binding patterns are rarely identified, with the heparin pentasaccharide as an Antithrombin-III ligand being the best characterized. Generating glycan-specific antibodies is difficult due to their size, pattern dispersion, and flexibility. Single-domain variable new antigen receptors (VNAR nanobodies) from nurse sharks are highly soluble, stable, and versatile. Their unique properties suggest advantages over conventional antibodies, particularly for challenging biotherapeutic targets. Here we have used VNAR semi-synthetic phage libraries to select high-affinity fondaparinux-binding VNARs that did not show cross-reactivity with other GAG species. Competition ELISA and surface plasmon resonance identified a single fondaparinux-selective VNAR clone. This VNAR exhibited an extraordinarily stable protein fold: the beta-strands are stabilized by a robust hydrophobic network, as revealed by heteronuclear NMR. Docking fondaparinux to the VNAR structure revealed a large contact surface area between the CDR3 loop of the antibody and the glycan. Fusing the VNAR with a human Fc domain resulted in a stable product with a high affinity for fondaparinux (Kd = 9.3 × 10⁻⁸ M) that could efficiently discriminate between fondaparinux and other glycosaminoglycans. This novel glycan-targeting screening technology represents a promising therapeutic strategy for addressing GAG-related diseases. Full article

Little is known about the effect of hepatic hemangiomas on protein induced by vitamin K absence or antagonist II (PIVKA-II). The aim of this study was to clarify the correlation of PIVKA-II levels with hepatic hemangiomas. In 335 consecutive patients with hepatic hemangiomas, ultrasonography (US), laboratory tests for liver function, serum levels of PIVKA-II and α-fetoprotein (AFP), and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin–antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDPs)) as indicators of coagulation disorders were examined. PIVKA-II levels were significantly higher in the hemangioma group than in the control group (p < 0.0001), and significantly higher in the large hemangioma group (p < 0.0001). PIVKA-II levels in the hemangioma increase group were higher with increases in tumor size and abnormal coagulation factors, and those in the hemangioma decrease group were lower with decreases in tumor size and abnormal coagulation factors. PIVKA-II levels were significantly correlated with tumor size (p < 0.0001) and all coagulation factors (p < 0.05) except prothrombin. Hepatic hemangiomas were associated with elevated serum PIVKA-II levels, showing significant correlations with tumor size and coagulation disorders. PIVKA-II elevation was attributed to the increased production of prothrombin precursors caused by accelerated coagulation–fibrinolysis within hemangiomas. Full article

Background/Objectives: The recommendations for antithrombotic therapy after transcatheter edge-to-edge mitral valve repair (TEER) are empirical, and the benefit of antiplatelet (APT) or anticoagulation therapy (ACT) remains undetermined. The study sought to investigate the degree and the timing of coagulation and platelet marker activation after TEER. Methods: This was a prospective study including 46 patients undergoing TEER. The markers of coagulation activation, namely prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III (TAT), and the markers of platelet activation, namely soluble P-Selectin and soluble CD-40 ligand (sCD40L), were measured at baseline, 24 h, 1 month, and 1 year after TEER. Results: At discharge, 20 (43%) patients received APT (single: 16, dual: 4), 24 (52%) received ACT, and 2 (4%) had both single APT and ACT. Levels of F1 + 2 and TAT significantly increased at 24 h post TEER (both p < 0.001), rapidly returning to baseline levels at 1 month. However, levels of F1 + 2 and TAT remained higher at 1 month in patients without ACT compared to patients with ACT (respectively, 303.1 vs. 148.1 pmol/L; p < 0.001 and 4.6 vs. 3.0 µg/L; p = 0.020), with a similar trend at 1 year. Levels of soluble P-selectin and sCD40L remained stable at all times after TEER (respectively, p = 0.071 and p = 0.056), regardless of the APT. Conclusions: TEER is associated with an acute activation of the coagulation system, with no increase in platelet activation markers. Hence, the use of dual APT is questionable in this population. Our results raise the hypothesis that the optimal antithrombotic therapy after TEER could be short-term ACT over APT. Further larger studies are warranted. Full article

Paradoxical embolism occurs when a clot originates in the venous system and traverses through a pulmonary or intracardiac shunt into the systemic circulation, with a mortality rate of around 18%. The risk factors for arterial embolism and venous thrombosis are similar, but different disease entities can lead to a hypercoagulable state of the blood, including antithrombin III (AT III) deficiency. We report the case of a 43-year-old man with a massive central pulmonary embolism with a rider embolus and concomitant aortic arch embolism with involvement of the brachiocephalic trunk, bilateral subclavian and axillary arteries, and the right vertebral artery, followed by a secondary ischaemic stroke. The Pulmonary Embolism Response Team (PERT) consulted the patient on several occasions; he was treated initially with an intravenous infusion of unfractionated heparin under activation partial thromboplastin time (APTT) and AT III substitution. After several days of hospitalisation and the conversion of pharmacotherapy to oral anticoagulants, the patient was discharged home in a stable condition with recommendations for further follow-up in appropriate clinics. This case highlights the role of in-depth diagnostics for coagulation disorders in patients after pulmonary embolism, especially without known risk factors. Full article

Various inflammatory and renal biomarkers have already been assessed for monitoring the response to anti-leishmanial therapy in canine leishmaniosis. This study assessed the parasite load, various inflammatory and renal biomarkers pre- and post-treatment, and any association between the studied variables and the degree of disease severity at diagnosis. This is a prospective cohort study of 30 client-owned dogs with leishmaniosis, classified according to LeishVet’s guidelines as stage I (n = 2), stage IIa (n = 7), stage IIb (n = 6), stage III (n = 8), and stage IV (n = 7). In addition to Leishmania real-time PCR in the bone marrow, blood and urine, previously studied biomarkers, and several inflammatory and renal markers never investigated in canine leishmaniosis, such as fibrinogen, antithrombin, urinary fractional excretion of sodium, and urinary amylase-to-creatinine ratio were measured pre- and post-treatment (meglumine antimoniate or miltefosine + allopurinol). A positive Leishmania real-time PCR in the blood at diagnosis predicted a positive Leishmania real-time PCR in the bone marrow post-treatment (p = 0.003). Following treatment, antithrombin and urinary amylase-to-creatinine ratio were significantly changed (p < 0.001, respectively). Urinary amylase-to-creatinine ratio, total iron-binding capacity, and antithrombin were the variables most strongly associated with disease severity (p < 0.005, respectively). Urinary amylase-to-creatinine ratio can be a useful marker to monitor treatment response and to classify the degree of disease severity. Full article

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient’s plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent assays. These analyses showed low PS activity and clotting time associated with the missense mutation in the PROS1 gene. During the COVID-19 pandemic, the patient received her first Pfizer vaccination dose in 2021, followed by a booster dose in 2022. The plasma samples were collected 8 weeks post-immunization, after which her clotting parameters had improved for up to 6 months following vaccination. The patient’s plasma showed a significant reduction in thrombin generation and an improved aPTT clotting time. Mass spectrometry analysis revealed that her antithrombin-III level was significantly higher post-vaccination, and both thrombin and FXII levels were significantly lowered compared with her father. To our knowledge, this is the first report to document that COVID-19 vaccination can lower the risk of thrombosis in a patient with inherited thrombophilia. Although the effect was observed on a single mutation, it would be interesting to investigate the effect of COVID-19 vaccinations on other thrombophilia. Full article

Antithrombin III (ATIII) is a potent endogenous anticoagulant that binds to heparan sulfate proteoglycans (HSPGs) on endothelial cells’ surfaces. Among these HSPGs, syndecans (SDCs) are crucial as transmembrane receptors bridging extracellular ligands with intracellular signaling pathways. Specifically, syndecan-4 (SDC4) has been identified as a key receptor on endothelial cells for transmitting the signaling effects of ATIII. Meanwhile, SDCs have been implicated in facilitating the cellular internalization of SARS-CoV-2. Given the complex interactions between ATIII and SDC4, our study analyzed the impact of ATIII on the virus entry into host cells. While ATIII binds to all SDC isoforms, it shows the strongest affinity for SDC4. SDCs’ heparan sulfate chains primarily influence ATIII’s SDC attachment, although other parts might also play a role in ATIII’s dominant affinity toward SDC4. ATIII significantly reduces SARS-CoV-2′s cellular entry into cell lines expressing SDCs, suggesting a competitive inhibition mechanism at the SDC binding sites, particularly SDC4. Conversely, the virus or its spike protein decreases the availability of SDCs on the cell surface, reducing ATIII’s cellular attachment and hence contributing to a procoagulant environment characteristic of COVID-19. Full article

Background: Phosphorylcholine has emerged as a potential adjunctive agent in cardiopulmonary bypass (CPB) circuits. Phosphorylcholine serves as a coating for the CPB circuit, potentially enhancing biocompatibility and reducing thrombotic events. However, its impact on specific patient populations and procedural outcomes remains underexplored. Materials and Methods: In this retrospective study, we analyzed data from 60 patients who underwent cardiac surgery with CPB, comprising 20 cases each of coronary artery bypass grafting (CABG), mitral valve repair, and aortic valve replacement. The patient cohort was divided into two groups—30 patients whose CPB circuits were coated with phosphorylcholine (phosphorylcholine-coated group) and 30 patients who did not receive phosphorylcholine supplementation or circuit coating. Both groups underwent surgery with identical CPB circuit designs. We assessed the absence of adverse events, safety, and efficacy parameters, including blood loss, clotting, and the structural integrity of the CPB circuit. Additionally, we measured changes in mean albumin levels (g/dL), mean platelet counts (×10⁹/L), and antithrombin III (ATIII) levels before and after CPB. Results: The retrospective analysis revealed an absence of adverse events in both groups. In the phosphorylcholine-coated group compared to the non-phosphorylcholine-coated group, there was a notable difference in the delta change in mean albumin levels (0.87 ± 0.1 vs. 1.65 ± 0.2 g/dL, p-value 0.021), mean platelet counts (42.251 ± 0.121 vs. 54.21 ± 0.194 × 10⁹/L, p-value 0.049), and ATIII levels (16.85 ± 0.2 vs. 31.21 ± 0.3 p-value 0.017). There was a notable reduction in the perioperative consumption of human complex units after CPB (3 vs. 12, p-value 0.019). Conclusions: Both groups, phosphorylcholine and non-phosphorylcholine, demonstrated the absence of adverse events and that the systems are safe for iatrogenic complication. Our findings suggest that the use of phosphorylcholine coating on the CPB circuit, in the absence of supplementary phosphorylcholine, in cardiac surgery is associated with favorable changes in mean albumin levels, mean platelet counts, and ATIII levels. Further research is warranted to elucidate the full extent of phosphorylcholine’s impact on patient outcomes and CPB circuit performance. Full article