Search Results (679)

Plant latex is a rich source of proteolytic enzymes with potential biomedical applications, particularly in hemostasis. Among them, thrombin-like enzymes (TLEs) have garnered interest in their ability to mimic thrombin by catalyzing the conversion of fibrinogen to fibrin, facilitating clot formation. While TLEs from snake venoms have been well-characterized and applied clinically, their plant-derived counterparts remain underexplored. This review critically examines the structural and functional characteristics of TLEs from plant latex, comparing them to animal-derived TLEs and evaluating their role in both procoagulant and fibrinolytic processes. Emphasis is placed on dual fibrinogenolytic and fibrinolytic activities exhibited by latex proteases, which often vary with concentration, incubation time, and protease type. In vitro coagulation assays and electrophoretic analyses are discussed as critical tools for characterizing their multifunctionality. By addressing the knowledge gaps and proposing future directions, this paper positions plant latex proteases as promising candidates for development in localized hemostatic and thrombolytic therapies. Full article

Patient blood management (PBM) is a multidisciplinary approach aimed at improving patient outcomes through targeted anemia treatment that minimizes allogeneic blood transfusions, employs blood conservation techniques, and avoids inappropriate use of blood product transfusions. Viscoelastic testing (VET) techniques, such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), have led to significant advancements in PBM. These techniques offer real-time whole-blood assessment of hemostatic function. This provides the clinician with a more complete hemostasis perspective compared to that provided by conventional coagulation tests (CCTs), such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT), which only assess plasma-based coagulation. VET does this by mapping the complex processes of clot formation, stability, and breakdown (i.e., fibrinolysis). As a result of real-time whole-blood coagulation assessment during hemorrhage, hemostasis can be achieved through targeted transfusion therapy. This approach helps fulfill an objective of PBM by helping to reduce unnecessary transfusions. However, challenges remain that limit broader adoption of VET, particularly in hospital settings. Of these, standardization and the high cost of the devices are those that are faced the most. This discussion highlights the potential of VET application in PBM to guide blood-clotting therapies and improve outcomes in patients with coagulopathies from various causes that result in hemorrhage. Another aim of this discussion is to highlight the limitations of implementing these technologies so that appropriate measures can be taken toward their wider integration into clinical use. Full article

Background and Objectives: Although cyanoacrylate–polylactic acid (CA + PLA) patches shorten the time to hemostasis after partial hepatectomy, their long-term biocompatibility remains uncertain. We compared the 5-month histopathological footprint of a novel CA + PLA patch (Study group) with a licensed fibrinogen/thrombin matrix (TachoSil^® group) and electrocautery (Control group). Methods: Thirty-three male Wistar rats underwent a 3 × 1.5 cm hepatic segment resection and were randomized to the Control (n = 5), Study (n = 14), or TachoSil^® (n = 14) group. The animals were sacrificed on postoperative day (POD) 50, 100, or 150. Blinded semiquantitative scoring (0–3) was used to capture inflammation intensity, and the number of neutrophils (PMNs), lymphocytes (Ly’s), isolated histiocytes, and foreign-body giant cells (FBGCs). Results: The proportions of animals in each group across the different sacrifice time points were homogeneous (χ² = 4.34, p = 0.36). The median inflammation remained mild (2 [IQR 1–2]) in the Control and Study groups but lower in the TachoSil^® group (1 [1–2], p = 0.47). The FBGC scores differed markedly (score ≥ 2: 64% in Study, 0% in Control, 14% in TachoSil^®; p < 0.001). Fibrosis occurred almost exclusively in the Study group (79% vs. 0%; χ² = 22.4, p < 0.001). Mature vessels were most frequently observed in the TachoSil^® group (50%, aOR = 5.1 vs. Study, p = 0.04). Abscesses only developed in the Study group (29%, p = 0.046). Within the TachoSil^® group, inflammation (ρ = −0.62, p = 0.019) and Ly infiltration (ρ = −0.76, p = 0.002) declined with time; no significant temporal trends emerged in the Study group. Conclusions: At the five-month follow-up, there was an exuberant foreign-body reaction, dense collagen deposition, and a higher abscess rate around the CA + PLA patch compared with both TachoSil^® and cautery. Conversely, TachoSil^® evolved toward a mature, well-vascularized scar with waning inflammation. These findings underscore the importance of chronic-phase evaluation before clinical adoption of new hemostatic biomaterials. Full article

Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article

Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals. Full article

Despite the prevalence of fucosylated IgG in plasma, specific IgGs with low core fucosylation sporadically emerge in response to virus infections and blood cell alloantigens. This low fucosylation of IgG is implicated in the pathogenesis of SARS-CoV-2 and dengue infections. In COVID-19, the presence of IgGs with low core fucosylation (afucosylated IgGs) targeting spike protein predicts disease progression to a severe form and actively mediates this progression. This study reveals that SARS-CoV-2 infection of megakaryocytes promotes the generation of pathogenic afucosylated anti-spike IgGs, leading to outcomes, such as pulmonary vascular thrombosis, acute lung injury, and mortality in FcγRIIa-transgenic mice. Platelets from mice injected with virus-infected human megakaryocytes express significant activation biomarkers, indicating a direct link between the immune response and platelet activation. Mice injected with virus-infected human megakaryocytes demonstrate an elevated rate of thrombus formation induced by FeCl₃ (4%) and a reduction in bleeding time, emphasizing the intricate interplay of viral infection, immune response, and hemostatic complications. Treatment with inhibitors targeting FcγRIIa, serotonin, or complement anaphylatoxins of mice injected with spike-expressing MKs successfully prevents observed platelet activation, thrombus formation, and bleeding abnormalities, offering potential therapeutic strategies for managing severe outcomes associated with afucosylated IgGs in COVID-19 and related disorders. Full article

The hemostatic system in the newborn is a complex entity, characterized by dynamism in its development; therefore, the correct measurement of its potential is challenging. In this narrative review, we analyzed the current knowledge of the “developmental hemostasis” of the newborn; we also studied the performance of routine coagulation tests in its evaluation, with considerations about the establishment of neonatal age-specific normal ranges and about the role of preanalytical variables, in particular, hematocrit (which could represent an important cause of error); we also focused on the increasing importance of viscoelastic coagulation tests, which are becoming increasingly widespread (especially in some settings such as intensive care unit) and are able to quickly provide information about the hemostatic function of the newborn, even if they lack adequate standardization in the neonatal period. Full article

Background and Objectives: Cyanoacrylate (CA) tissue adhesives have gained increasing attention as alternatives to sutures in oral surgery and periodontology. The objective of this scoping review is to assess their clinical applications and effectiveness in wound closure and postoperative management. Materials and Methods: The review was conducted following the JBI methodology and PRISMA-ScR guidelines. A comprehensive search was performed in PubMed, Scopus, and Web of Science to identify randomized controlled trials published between 2015 and 2025 evaluating the use of CAs in oral surgery and periodontal procedures. Results: A total of 19 studies were included. Cyanoacrylate adhesives demonstrated comparable or superior outcomes to other wound healing strategies in terms of operative time, postoperative pain reduction, and early wound healing. Their use was particularly beneficial in free gingival grafts and palatal donor site management. However, the findings across studies were not always consistent, and some trials did not report statistically significant differences. The use of long-chain CA formulations is associated with minimal toxicological risk, though these adhesives demonstrate intrinsic hemostatic and antimicrobial effects. Conclusions: Cyanoacrylate tissue adhesives represent a valid alternative to sutures in several dental surgical contexts, especially in procedures involving mucogingival grafts. Further high-quality clinical studies are needed to clarify their long-term outcomes and broaden their indications in dentistry. Full article

Post-acute sequelae of COVID-19 have been associated with an elevated risk of thromboembolism and adverse cardiovascular events (CVEs). We aim to evaluate whether alterations in poorly studied hemostatic and endothelial proteins are associated with CVEs in patients previously admitted to the ICU and evaluated one year post-discharge. We carried out a cross-sectional study involving 63 COVID-19 patients previously admitted to the ICU one year post-discharge. Plasma levels of factor IX (coagulation factor), protein C, protein S (natural anticoagulant), and von Willebrand factor (VWF, an endothelial marker) were measured using a Luminex 200™ analyzer. Generalized linear models (GLMs) were used to assess the association of these coagulation proteins with CVEs and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We found that lower levels of factor IX (p = 0.011), protein C (p = 0.028), and protein S (p = 0.008) were associated with CVEs one year after ICU discharge. Additionally, at the one-year follow-up, we found lower levels of factor IX (p = 0.002) and higher levels of VWF (p = 0.006) associated with higher levels of NT-proBNP, underscoring the involvement of both hemostatic imbalance and persistent endothelial dysfunction. Our findings revealed a gender-specific pattern of associations with NT-proBNP levels. These findings highlight the significant role of persistent hemostatic imbalance and endothelial dysfunction in the development of cardiovascular abnormalities among COVID-19 survivors discharged from the ICU. Full article

Pulmonary hemorrhage (PH) is a life-threatening complication predominantly affecting preterm infants, particularly those with very low birth weight (VLBW) and fetal growth restriction (FGR). Typically occurring within the first 72 h of life, PH is characterized by acute respiratory deterioration and significant morbidity and mortality. This review synthesizes current evidence on the multifactorial pathogenesis of PH, highlighting the roles of immature pulmonary vasculature, surfactant-induced hemodynamic shifts, and left ventricular diastolic dysfunction. Key risk factors include respiratory distress syndrome (RDS), hemodynamically significant patent ductus arteriosus (hsPDA), sepsis, coagulopathies, and genetic predispositions. Diagnostic approaches incorporate clinical signs, chest imaging, lung ultrasound, and echocardiography. Management strategies are multifaceted and include ventilatory support—particularly high-frequency oscillatory ventilation (HFOV)—surfactant re-administration, blood product transfusion, and targeted hemostatic agents. Emerging therapies such as recombinant activated factor VII and antifibrinolytics show promise but require further investigation. Preventive measures like antenatal corticosteroids and early indomethacin prophylaxis may reduce incidence, particularly in high-risk populations. Despite advancements in neonatal care, PH remains a major contributor to neonatal mortality and long-term neurodevelopmental impairment. Future research should focus on individualized risk stratification, early diagnostic tools, and optimized treatment protocols to improve outcomes. Multidisciplinary collaboration and innovation are essential to advancing care for this vulnerable population. Full article

Postoperative adhesions are a prevalent complication following abdominal surgeries, often leading to significant clinical challenges. This study introduces an innovative solution utilizing a polyethylene glycol (PEG)-based triblock copolymer to form an injectable, self-healing hydrogel aimed at preventing these adhesions. The hydrogel, formulated with temperature-responsive and self-healing properties through the incorporation of poly (N-isopropyl acrylamide) (PNIPAM) and anion–pi interactions, was synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization. The hydrogel’s physical properties, biocompatibility, hemostatic effect, and anti-adhesive capabilities were rigorously tested through in vitro and in vivo experiments involving rat models. It demonstrated excellent biocompatibility, effective tissue adhesion, and robust hemostatic properties. Most notably, it exhibited significant anti-adhesive effects in a rat abdominal wall–cecum model, reducing adhesion formation effectively compared to controls. The PEG-based injectable hydrogel presents a promising approach for postoperative adhesion prevention. Its ability to gel in situ triggered by body heat, coupled with its self-healing properties, provides a substantial advantage in clinical settings, indicating its potential utility as a novel anti-adhesion material. Full article

Background/Objective: Laser therapy has gained attention in dental practice to minimize bleeding and enhance blood clot formation. This study aimed to explore the utilization and to compare the clinical efficacy of laser-mediated hemostasis for older patients receiving routine dental treatment. Methods: A prospective observational study was conducted across research networks between October 2023 and August 2024, involving 60 patients aged 50 years and older (average = 63.35 years) at risk of postoperative bleeding following dental treatments. Additionally, laser therapy for hemostasis was selected and provided among calibrated operators. A single researcher performed data collection. Before statistical analysis, data verification and clinical assessment were conducted by the operators and researcher. A clinical cut-off for hemostasis was set at 5 min. Two diode laser machines were used namely, an 810 nm and dual wavelengths of 635 nm and 980 nm. Results: There were 94 extraction sockets, 28 procedures of scaling and root planing and 18 procedures of minor oral surgery. Combining laser ablating sulcular fiber and photobiomodulation initiating blood clot formation was a preferable hemostatic technique for extraction socket, while photobiomodulation alone was a preferred technique for soft tissue hemostasis (p < 0.001). All operators confirmed that 97.86 percent of bleeding events achieved more rapid hemostasis. 61.43 percent of bleeding events clinically achieved hemostasis within 5 min by using laser-mediated hemostasis alone (p = 0.092). Full recovery of the extraction socket was significantly observed during the 2- to 4-week follow-up period (p = 0.005). No clinical complications were reported. Conclusions: Laser-mediated hemostasis effectively reduced hemostatic duration, prevented postoperative bleeding and promoted wound healing in older patients undergoing routine dental treatment. Full article

Venous thromboembolism (VTE) represents a significant complication of cancer immunotherapy, with emerging evidence suggesting distinct pathophysiological mechanisms compared to traditional chemotherapy-associated thrombosis. This narrative review examines the epidemiology and pathogenesis of VTE in patients receiving immunotherapies for cancer including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, bispecific T-cell engagers (BiTEs), among others. Real-world studies demonstrate a wide range of VTE incidence rates in ICI recipients, with potential mechanisms including exacerbated underlying interleukin-8-mediated inflammatory pathways and consequent neutrophil extracellular trap (NET) formation. CAR T-cell therapy is associated with unique hemostatic challenges, including concurrent thrombotic and bleeding risks related to cytokine release syndrome. Current risk assessment tools show limited predictive utility in patients receiving immunotherapies for cancer, highlighting the need for novel stratification models. Future research priorities include developing immunotherapy-specific risk prediction tools, elucidating mechanistic pathways linking immune activation to thrombosis, and establishing evidence-based and tailored thromboprophylaxis strategies. As cancer immunotherapy continues to evolve, understanding and mitigating thrombotic complications remains crucial for optimizing patient outcomes. Full article

As a synthetic analogue of vasopressin, desmopressin or DDAVP has well established hemostatic properties. We present a review of DDAVP and summarize the clinical and laboratory evidence for its use in hemophilia A, von Willebrand disease (VWD), platelet function disorders, uremia, liver cirrhosis, and pregnancy, followed by illustrative examples of its broad efficacy from our local practice. In brief, DDAVP acts to release von Willebrand factor (VWF) and factor VIII from endogenously stored reserves, thereby correcting plasma deficiencies present in mild to moderately affected patients with hemophilia A and VWD. Thus, DDAVP represents a non-transfusional therapy for these disorders. Typically, a trial of DDAVP is arranged to assess individual responsiveness before employing DDAVP clinically, since there is individual variation in responsiveness. Thereafter, DDAVP can be utilized in responsive patients for clinical use and provides a factor replacement sparing strategy in these patients for some clinical situations. Nevertheless, DDAVP is best applied as a factor replacement sparing strategy, especially for minor procedures or short-term use. Full article

Platelets are attributed an increasing role in the post-traumatic immune response. The exact mechanisms, particularly the link between immune response and hemostasis, have not been conclusively established. This study aimed to investigate the activity marker CD63 on platelets after polytrauma and its significance for hemostasis. A non-interventional, prospective clinical study was conducted, in which the blood of 20 polytraumatized patients was analyzed at nine time points within 10 days following trauma. Peripheral blood platelets were analyzed using flow cytometry to determine CD63 expression and rotational thromboelastometry (ROTEM^®) for hemostatic platelet function. Additionally, the clinical parameters of age, gender, and injury severity were correlated to the experimental outcomes. During the observation period, an increase in platelet count and CD63 expression was observed. Simultaneously, a hemostasiological dysfunction with reduced platelet maximum clot firmness (MCF) was observed. The factors of age, gender, and injury severity showed no significant influence on immunological activation or coagulation function. These results suggest that polytrauma induces a platelet response and CD63 activation while simultaneously impairing hemostasis. This reveals a novel perspective on post-traumatic coagulation disorders, indicating that immunologically active platelets may lose their ability to contribute effectively to blood clotting. Consequently, these findings emphasize the critical role of platelet immunology in hemostatic regulation. Full article