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An increase in the frequency of patients with arterial hypertension (AH) seeking medical care and its more severe course after a novel coronavirus infection (NCI), COVID-19, determines the need to study possible pathogenetic mechanisms of disease progression. Aim of the study was to investigate some features of lipid metabolism and changes in hemostasis in patients with AH after NCI COVID-19. Material and methods. An analysis of the most informative indicators of lipid metabolism and hemostasis was carried out in 104 patients with AH underwent (more than 2 months ago) NCI, in comparison with 117 patients with AH, with no history of COVID-19. The study included men and women aged from 30 to 75 years. Determination of the concentration of lipids in blood serum was carried out using the photometric method on a biochemical analyzer AU 480 (Beckman Coulter, США). Hemostatic parameters were determined by the chromogenic method using an automatic hemostasis analyzer Technology Solution 190 (USA). Results and discussion. It was found that patients with AH underwent NCI had significantly higher serum levels of total cholesterol, LDL cho- lesterol, triglycerides, D-dimers, platelets and lower activated partial thromboplastin and thrombin time compared with patients without COVID-19. Conclusions. The data obtained indicate a tendency to atherogenic changes in the blood lipid profile and increased coagulation processes in patients with AH in the long-term period (more than 2 months) after suffering a NCI COVID-19.

Thrombocytopenia is a condition in which the level of platelets in the blood decreases and becomes less than 150×109/L. This can lead to an increased risk of bleeding. One of the causes of thrombocytopenia may be medication; its association with the use of more than 300 drugs has now been documented. The pathogenesis of such, drug-induced thrombocytopenia (DITP), is described as a consequence of direct cytotoxic effects of drug on megakaryocytes, which leads to increased platelet destruction in the bloodstream or dysfunctional thrombopoiesis. In the diagnosis of DITP the leading role belongs to the clinical approach: first of all, it is carried out on the basis of data of drug history and a minimum set of laboratory tests, including counting the number of platelets in the blood and determining the clotting time. Since thrombocytopenia may be associated with the risk of serious bleeding, its timely diagnosis is of key importance for determining the tactics of therapeutic intervention. We present a clinical case of DITP, after the combined use of drugs of different groups – statin, xanthine oxidase inhibitor, cytostatic drug of antimetabolite group, non-selective beta- adrenoblocker and two non-steroidal anti-inflammatory drugs with different mechanism of action. The described case showed that to avoid polypharmacy in patients with DITP it is necessary to assess hemostatic potential by low-frequency piezotromboelastography, because even in conditions of insufficient platelet count they can provide preserved functional ability to maintain hemostasis.

Background : Delayed post-polypectomy bleeding (DPPB) is a serious complication of polypectomy that is poorly understood. The aim of this study was to evaluate the effectiveness of endoscopic hemostasis in managing DPPB and to identify associated risk factors. Methods : We retrospectively analyzed 289 patients who experienced DPPB (≥ 24 hours after polypectomy) and underwent endoscopic hemostasis at five university hospitals between 2005 and 2018. Patient characteristics, polyp size, technical factors, rebleeding, complications, and length of hospitalization were assessed. Results : Endoscopic hemostasis was successful in all 289 cases of DPPB. The techniques and devices employed included epinephrine injection (24.9%), argon plasma coagulation (18.0%), hemostatic forceps (10.7%), and hemoclips (87.9%). Rebleeding occurred in 15 cases (5.2%) after initial endoscopic hemostasis. The incidence of rebleeding was significantly associated with polyp size (< 10 mm: 2.8%, 10 mm-19 mm: 5.6%, ≥ 20 mm: 13.5%, P = 0.030) and sedation status (yes: 1.8%, no: 7.3%, P = 0.040). However, hemostasis method, bleeding characteristics, and polyp location were not significantly linked to rebleeding. Multivariate analysis revealed that polyp size (odds ratio, 5.02; 95% confidence interval, 1.25-20.13; P = 0.023) was significantly associated with rebleeding after endoscopic hemostasis for DPPB. In all 15 cases of rebleeding, a second endoscopic hemostasis was successfully performed without the need for embolization or surgical intervention. No perforations occurred during the first or second endoscopic hemostatic procedures. Conclusion : Polyp size and sedation status were associated with rebleeding after endoscopic hemostasis for DPPB. As an intervention for DPPB, endoscopic hemostasis appears safe and effective.

Aim. To investigate the state of the platelet and plasma components of hemostasis in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).Material and methods. The study included 42 patients with non-ST-segment elevation myocardial infarction (NSTEMI): MINOCA (n=24) and MI-CAD (n=18). Platelet aggregation ability in response to activation was evaluated using Solar AP2110 and LASCA aggregometers. Platelet functional activity and calcium signaling were assessed using flow cytometry methods. The plasma component of hemostasis, in addition to routine coagulation tests was evaluated using the global coagulation test "Thrombodynamics". The control groups for tests consisted of healthy volunteers.Results. When analyzing the ability of platelets to form aggregates by the aggregometry tests, it was found that platelets in the MINOCA group formed aggregates significantly worse upon ADP stimulation at various concentrations compared to the MI-CAD group. However, when platelets were stimulated with collagen, the opposite effect was observed: in the MI-CAD group, there was a noticeable decrease in aggregate formation in terms of light scattering amplitude compared to the MINOCA group. Flow cytometry using the functional platelet activity test protocol revealed that both groups showed a significantly increased platelet size after activation, reduced platelet granularity) both at rest and upon activation, significantly decreased number of procoagulant phosphatidylserine-positive platelets, and reduced dense granule release upon activation compared to healthy volunteers. The calcium signaling test showed a weakened calcium release in response to ADP in the MINOCA group compared to the MI-CAD group. In the study of the plasma component, no significant differences between the groups or deviations were found according to both routine tests and the "Thrombodynamics" test.Conclusion. Platelet activity did not differ significantly between the MINOCA and MI-CAD groups; however, in the MINOCA group, platelet activity was lower in some tests compared to the MI-CAD group. In the study of the plasma hemostasis component, normocoagulation was recorded in both groups.

Nanan Miao,1,&ast; Tao Jiang,1,&ast; Yuanchao Li,1 Sihong Xue,1 Shilei Hao,2 Chunli Zhou,1 Yujie Gu,1 Ran Li,1 Bo Yu,1 Xiaoqu Duan,1 Wenchao Xu,1 Rupeng Wang,1 Lei Ran1 1Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China; 2College of Bioengineering, University of Chongqing, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rupeng Wang; Lei Ran, Department of Rheumatology and Dermatology, The Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 23 68755739, Email Wrp71@tmmu.edu.cn; ranlei1010@tmmu.edu.cnBackground: Wound healing is a complex physiological process that can be roughly divided into four stages: hemostasis, inflammation, proliferation, and remodeling. Conventional wound dressings often fail to meet the diverse needs of these healing stages due to their limited functionality. Cryogels, however, possess several attractive properties, such as large, interconnected pores, good mechanical strength, and ease of modification, making them suitable for developing advanced dressings with multiple functions. In this study, we developed a multifunctional cryogel dressing, with biocompatible polysaccharides as the main component, designed to provide a breathable, moist, and antibacterial microenvironment for chronic infected wounds, thereby promoting wound healing.Methods: Recombinant keratin 31 (RK31) was combined with chitosan (CS) to produce a CS/RK31 cryogel, referred to as CK. Gallic acid-reduced silver nanoparticles (GA/Ag NPs) were incorporated as the active antibacterial component to create the CS/K31@GA/Ag cryogel, known as CKGA. The cryogel was characterized using scanning electron microscopy (SEM) and a universal testing machine, and its biocompatibility was assessed in vitro. The dynamic hemostatic performance of the cryogel was evaluated with a rat tail amputation bleeding model. Additionally, the antibacterial effects of the cryogel against Staphylococcus aureus and Escherichia coli were tested using agar diffusion assays and turbidimetry. The antioxidant capacity of the CKGA cryogel was also measured in vitro. Finally, the cryogel’s ability to promote wound healing was tested in an SD rat model of infected wounds.Results: Characterization results showed that the CKGA cryogel features an interpenetrating porous network structure and exhibits excellent mechanical properties, with a swelling rate of up to 1800%. Both in vitro and in vivo experiments confirmed that the cryogel has good biocompatibility, effectively absorbs exudates, and rapidly stops bleeding. The addition of GA/Ag NPs provided significant antibacterial effects, achieving an inhibition rate of over 99.9% against both S. aureus and E. coli. Furthermore, CKGA cryogels demonstrated a strong scavenging capacity for ROS in a dose-dependent manner. Studies using the SD rat infected wound model showed that the cryogel effectively inhibited bacterial proliferation on wound surfaces, reduced local tissue inflammation, and promoted the healing of infected wounds.Conclusion: The multifunctional cryogel, with its rapid hemostatic, antibacterial, and antioxidant properties, as well as its ability to promote cell proliferation, could be widely used as a wound dressing for the healing of bacterial infections. Keywords: nanocomposite cryogel, hemostasis, antioxidant, antibacterial, wound healing

Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma, manifest in diverse types and locations. Although numerous wound dressings are available for various wound scenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse wound situations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties and capacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantages in wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecular-weight hyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging that could synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy in three distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively, these findings underscore the potential of the sHA-CA patch as a promising candidate for the next-generation wound dressing.

Purpose of the study. Development of a method for preventing hemorrhages during stereotactic biopsy of a brain tumor using liquid hemostatic matrices on the example of the drug "Floseal®".Patients and methods. The target of the biopsy is the most representative area of tumor tissue according to the data of various modalities of MRI neuroimaging, including contrast-enhanced ones. Out of 133 patients, 60 patients with signs of intraoperative bleeding along the biopsy needle cannula were included in the study group. Further, patients with signs of intraoperative bleeding along the cannula of the biopsy needle were divided into 2 subgroups by independent sequential randomization. Control subgroup (n = 45): cases with signs of intraoperative bleeding of varying severity were operated on, according to the standard technique, without the use of the liquid hemostatic drug Floseal®. The main subgroup (n = 15): in case of intraoperative signs of bleeding, the hemostatic fluid drug Floseal® was injected into the area of tumor material removal.Results. In 6.7 % of patients of the control subgroup, the formation of massive intracerebral hemorrhages was noted in the postoperative period. In 53.3 % of the observations of the control subgroup according to X-ray computer examinations of the brain, there were signs of minor hemorrhages at the point of tumor material collection, which did not require repeated surgical interventions. Postoperative hemorrhages after injection of the Floseal® liquid hemostatic matrix into the biopsy needle in the study subgroup were not detected according to neuroimaging X-ray CT.Conclusion. A method of hemostasis has been developed to prevent hemorrhages using liquid hemostatic matrices. If signs of bleeding from the biopsy needle appeare, the introduction of a hemostatic matrix in the volume of 2 ml helps to manage bleeding intraoperatively, as well as to prevent the occurrence of hemorrhage in the early postoperative period.

Background. Current treatment of patients with myocardial infarction is based on the strategy of early invasive coronary intervention in combination with dual antiplatelet therapy - with acetylsalicylic acid and a P2Y12 blocker of platelet adenosine diphosphate receptors. In patients with thrombosis of the infarct-related artery, the phenomenon of “slow/ no reflow” (slowing of blood flow due to distal embolization of the artery), inhibitors of glycoprotein IIb/IIIa platelet receptors are administered as additional disaggregant therapy. In patients undergoing standard antiplatelet therapy in combination with glycoprotein IIb/IIIa inhibitors, there is a risk of hemorrhagic complications, therefore, monitoring of hemostasis parameters is necessary. Currently, there are no standard approaches to monitor the antiplatelet therapy.Objective. To study the dynamics of hemostatic system parameters in patients with acute myocardial infarction during antiplatelet therapy.Material and methods. We assessed platelet aggregation with 10 µmol of adenosine phosphate as an inducer in patients with ST-segment elevation myocardial infarction with different options of standard antiplatelet therapy in combination with GPIIb/IIIa inhibitors. Group 1 included 20 patients on dual antiplatelet therapy (clopidogrel 75 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor (tirofiban). Group 2 included 15 patients on dual antiplatelet therapy (ticagrelor 180 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor.Results. While on antiplatelet therapy the patients in both groups 1 and 2 demonstrated a decrease in platelet aggregation ability under the impact of adenosine phosphate, relative to the norm: 38 (21;43) % and 14 (11;15) %, respectively, the norm being 79 (73;84) % (p

BACKGROUND. The development of new samples of local hemostatic agents is an intensively developing area of the modern industrial biotechnology due to a high need of clinical bases for such products. In addition to constant search for optimal substances used as a basis (collagen, cellulose and its derivatives, gelatin, etc.) for local hemostatic agents, methods for their comprehensive testing are also being developed. AIM OF THE STUDY. To evaluate the hemostatic activity of multicomponent polymer sponge implants using the coagulometer method developed by the authors in an in vitro experiment. MATERIAL AND METHODS. As research materials, new samples of multicomponent polymer sponge implants developed within the Laboratory of Experimental Surgery and Oncology of the Kursk State Medical University were used. The samples were based on marine collagen made from deep-sea squid in different ratios by weight with carboxymethylcellulose sodium salt (15/85, 25/75, 50/50). The hemostatic activity of these products was evaluated in the in vitro experiment using our method based on coagulometric measurement of blood clotting time of volunteer donors. Statistical processing of the data was carried out using methods of descriptive and variation statistics (Me [25; 75]). The validity of the difference was determined using the Mann–Whitney test (p ≤ 0,05). RESULTS. The blood clotting time in experimental group No. 2 turned out to be 2.12 s less than in the control group (the tested samples of hemostatic agents were not added). Statistically significant differences were found when comparing the values of coagulation time in experimental groups No. 3 (2.98 s less) and No. 4 (2.37 s less) with the values of the control group (No. 1). A decrease in the blood clotting time indirectly proves the effectiveness of the products used, due to the formation of the blood clot in a shorter period of time. This suggests that when the hemostatic agents are used in bleeding conditions, the products will reduce the time and volume of bleeding due to their hemostatic activity. CONCLUSION. Within the framework of the completed study, it was established that our method for assessing the hemostatic activity of local hemostatic agents, based on the evaluation of blood clotting time using electrocoagulometry, after grinding the tested samples, is easy to perform, accessible to most laboratories, and allows researchers to investigate the effectiveness of various forms of multicomponent polymer sponge implants. The development of multicomponent polymer sponge implants based on carboxymethylcellulose sodium salt and collagen seems to be a promising direction, since these products accelerate blood clotting time in the in vitro experiment.

Objective To demonstrate the noninferiority of the novel hemostatic agent, Hemofence (BMI Korea Co., Ltd., thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety. Methods This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For noninferiority test, a 97.5% one-sided confidence interval (CI) was used; the test group was deemed noninferior if the lower limit exceeded -10%. Results This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% CI (-4.90% to 7.44%) confirmed the test drug’s noninferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.000, p=0.243, and p=0.966, respectively). Conclusion A novel hemostatic agent, Hemofence, demonstrated an efficacy and safety profile comparable to that of Floseal.

Background/Aims Advanced pancreatic and biliary tract cancers can invade the duodenum and cause duodenal hemorrhagic stenosis. This study aimed to evaluate the efficacy of covered self-expandable metal stents in the treatment of cancer-related duodenal hemorrhage with stenosis. Methods Between January 2014 and December 2016, metal stents were placed in 51 patients with duodenal stenosis. Among these patients, a self-expandable covered metal stent was endoscopically placed in 10 patients with hemorrhagic duodenal stenosis caused by pancreatobiliary cancer progression. We retrospectively analyzed the therapeutic efficacy of the stents by evaluating the technical and clinical success rates based on successful stent placement, degree of oral intake, hemostasis, stent patency, and overall survival. Results The technical and clinical success rates were 100%. All 10 patients achieved a gastric outlet obstruction scoring system score of three within two weeks after the procedure and had no recurrence of melena. The median stent patency duration and overall survival after stent placement were 52 days (range, 20–220 days) and 66.5 days (range, 31–220 days), respectively. Conclusions Endoscopic placement of a covered metal stent for hemorrhagic duodenal stenosis associated with pancreatic or biliary tract cancer resulted in duodenal hemostasis, recanalization, and improved quality of life.

Abstract Background Fibrin sealants are increasingly used in head and neck surgery to aid hemostasis, but individual studies lack conclusive evidence. This systematic review investigates their effectiveness compared to placebo or usual care in head and neck surgery. Methods Studies comparing fibrin sealant to placebo or usual care in patients 18 years or older who have undergone soft tissue surgery of the head and neck with drain placement were included. Primary outcomes include wound complications and time to surgical drain removal postoperatively. Secondary outcomes include length of hospital stay, drain volume output, surgical management of hematoma, blood transfusion rates, and adverse reactions. Electronic databases were searched on October 2023 for randomized controlled and quasi-experimental studies. Studies underwent independent screening, review, and appraisal by two reviewers using JBI appraisal tools. Certainty was assessed with GRADE, and meta-analysis was conducted using JBI SUMARI, presenting effect sizes as relative risk ratios or mean differences with 95% confidence intervals. Results Fourteen studies were included examining 904 patients. The fibrin sealant group exhibited reduced postoperative wound complications (hematoma, seroma, wound dehiscence, wound infection) (RR = 0.64, 95% CI = 0.45–0.92), shorter drain removal times (MD = − 0.49 days, 95% CI = − 0.68 to − 0.29), decreased drain output (MD = − 16.52 mL, 95% CI = − 18.56 to − 14.52), and shorter hospital stay (MD = − 0.84 days, 95% CI = − 1.11 to − 0.57) compared to controls. There was no statistically significant difference on the rate of intervention for postoperative hematoma and the rate of adverse reactions. Discussion Evidence demonstrates with low certainty that fibrin sealant use is associated with a modest reduction in the rate of wound complications, drain duration, and length of stay, and a small reduction in drain volume output. Methodological weaknesses and clinical heterogeneity limit these findings. Further research should focus on enhancing methodological quality and exploring the cost-effectiveness of fibrin sealant use in surgery. Systematic review registration CRD42023412820. Funding Nil.

AbstractFabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV–visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.

Introduction. As a result of portal hypertension (sequestration of platelets in an enlarged spleen) and liver failure (decreased production of thrombopoietin in the liver) in liver cirrhosis, thrombocytopenia develops, which is associated with the risk of periprocedural/perioperative bleeding complications. There are still unresolved questions regarding risk stratification of bleeding complications, the prognostic role of thrombocytopenia, as well as the need for treatment of thrombocytopenia and its methods.Materials and methods. The Russian Scientific Liver Society selected a panel of experts in the field of therapeutic and surgical hepatology, hematology, transfusion medicine to make reasoned statements and recommendations on the issue of treatment of thrombocytopenia before elective surgery / invasive procedures in patients with liver cirrhosis.Results. Relevant clinical issues were determined based on the PICO principle (patient or population, intervention, comparison, outcome). The Delphi panel made five questions and gave reasoned answers, framed as ‘clinical practice recommendations and statements’ with evidence-based comments. The questions and statements were based on the results of search and critical analysis of medical literature using keywords in English- and Russian-language databases. The formulated questions could be combined into four categories: bleeding risk stratification, the prognostic value of thrombocytopenia, the necessity and methods of thrombocytopenia drug correction, and bleeding risk reduction.Conclusions. The results of experts' work are directly related to high-quality management of patients with liver cirrhosis and thrombocytopenia, who have scheduled invasive procedures/surgery. Thus, this recommendations and statements can be used in clinical practice.

Abstract Background Excessive intraoperative bleeding remains a challenge in limb surgeries. The exsanguination tourniquet ring has emerged as a potential solution for effective exsanguination and hemostasis. This study aims to evaluate its efficacy and safety compared to the conventional exsanguination and hemostasis approach (pneumatic tourniquet combined with Esmarch bandage). Methods This randomized controlled trial evaluates the exsanguination tourniquet ring’s effectiveness and safety versus the conventional approach in 220 participants undergoing various limb surgeries. Allocation included experimental and control groups, assesses through efficacy (including intraoperative and total blood loss, hemoglobin levels, and exsanguination and hemostasis effectiveness) and safety (adverse event occurrence) indicators. Results The experimental group (n = 110) utilizes the exsanguination tourniquet ring, while the control group (n = 110) employs the conventional approach. As for intraoperative blood loss, the experimental group is non-inferior to the control group (p-value

Abstract To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P

Background. It is known that COVID-19 can be followed by a shift in the hemostatic system towards hypercoagulation, which is more pronounced in the presence of diabetes mellitus (DM). Tuberculosis process is often accompanied with hypercoagulation syndrome. Of great interest is the study of the state of hemostatic systems in patients with pulmonary tuberculosis (TB) with concomitant DM who have had COVID-19.The aim. To study the relationship between the state of the hemostatic and fibrinolysis systems and moderate and severe COVID-19 in patients with pulmonary tuberculosis and diabetes mellitus.Methods. 32 patients with TB and DM were divided into two groups. Group 1 included 16 patients with TB and DM who have previously had COVID-19 (TB-DM-COVID). Group 2 included 16 patients with TB and DM who did not have COVID-19 (TB-DM).Results. It was found that TB-DM-COVID patients were more likely to develop a hypercoagulable shift compared to TB-DM patients. This was evidenced by a more frequent shortening of such indicator as activated partial thromboplastin time (43.7 % and 25.0 % of cases, respectively; χ2 = 7.22; p = 0.01), an increase in fibrinogen levels (43.7 % and 25.0%, respectively; χ2 = 7.22; p = 0.01) and D-dimer (43.7 % and 18.7 %, respectively; χ2 = 14.74; p = 0.0001). These changes were closely associated with the systemic inflammatory response, as strong and positive correlations were found between fibrinogen and C-reactive protein levels (r = 0.420; p = 0.01), and erythrocyte sedimentation rate (r = 0.433; p = 0.01) in TB-DM-COVID patients.Conclusion. In patients with pulmonary tuberculosis and diabetes mellitus after moderate and severe COVID-19, compared to patients who have not had COV ID-19, a hypercoagulable shift associated with the development of more pronounced systemic inflammation develops more often.

随着人口老龄化，长期接受抗血小板治疗的患者在神经外科手术治疗人群中的比例不断增加。抗血小板药物导致的潜在血小板功能低下会影响术中止血效果，并增加术中大出血和术后出血并发症风险。因此，如何在术前快速准确地评估血小板功能，对于全面评估患者止血功能具有重要意义。本文通过总结相关文献，结合血小板功能检测在神经外科的使用现状，分析目前常用血小板功能检测方法的优缺点，介绍改善血小板功能的相关疗法，以期提高神经外科医师对血小板功能的认识。 Abstract: With the aging of the population, the proportion of patients receiving long-term antiplatelet therapy among those undergoing surgical treatment is increasing. Potential platelet hypofunction caused by antiplatelet drugs can affect intraoperative hemostasis and increase the risks of massive intraoperative hemorrhage and postoperative bleeding complications. Therefore, a quick and accurate assessment of platelet function before surgery is of great significance in comprehensively evaluating a patient’s hemostatic function. Based on the summary of relevant literature and the current status of the application of platelet function tests in neurosurgery, this paper analyzed the advantages and disadvantages of the currently commonly used platelet function tests, and introduced relevant therapies to improve platelet function, with the aim of improving the understanding of platelet function among neurosurgeons.

Abstract Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

Abstract Rapid and safe hemostasis is crucial for the survival of bleeding patients in prehospital care. It is urgent to develop high performance hemostatic material to control the massive hemorrhage in the military field and accidental trauma. In this work, an efficient protein hemostat of thrombin was immobilized onto commercial gauze, which was mediated by self-polymerization and anchoring of tannic acid (TA). Through TA treatment, the efficient immobilization of thrombin was achieved, preserving both the biological activity of thrombin and the physical properties of the dressing, including absorbency, breathability, and mechanical performance. Moreover, in the presence of TA coating and thrombin, Gau@TA/Thr could obviously shortened clotting time and enriched blood components such as plasma proteins, platelets, and red blood cells, thereby exhibiting an enhanced in vitro coagulation effect. In SD rat liver volume defect and artery transection hemorrhage models, Gau@TA/Thr still had outstanding hemostatic performance. Besides, the Gau@TA/Thr gauze had inherent antibacterial property and demonstrated excellent biocompatibility. All results suggested that Gau@TA/Thr would be a potential candidate for treating uncontrollable hemorrhage in prehospital care.

Kenta Hasumi,1,2 Yukihiro Yoshida,1 Masaya Yotsukura,1 Kazuo Nakagawa,1 Koichi Goto,2 Shun-ichi Watanabe1 1Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan; 2Department of Comprehensive Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanCorrespondence: Kenta Hasumi; Yukihiro Yoshida, Department of Thoracic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, Tel +81-3-3542-2511, Email khasumi@ncc.go.jp; yukiyosh@ncc.go.jpBackground: This study investigated perioperative clinical information, surgical findings, and postoperative courses of patients who underwent reoperation due to bleeding after the surgery for pulmonary malignancies.Methods: We identified patients who underwent reoperation due to postoperative bleeding from 6989 patients who had had operations for pulmonary malignancies between January 2007 and July 2019. Data were retrospectively collected from medical charts.Results: Twenty-two patients (0.3%) underwent reoperation for hemostasis. The reason for reoperation was a shock state with minimum systolic blood pressure < 90 mm Hg in 12 patients (55%), persistent bloody drainage of 100 mL/h or more in 15 patients (68%), and intrathoracic hematoma on a chest X-ray image in 14 patients (64%). All those three findings were observed in five patients (23%), two in nine patients (41%), and one in eight patients (36%). The source of bleeding could not be identified during reoperation in four patients (18%). In the regression analysis, the coefficient of determination between the amount of drainage from a chest drain and the volume of intrathoracic hematoma found during reoperation was 0.31, indicating poor correlation. Postoperative complications and death occurred in two (9%) and zero patients, respectively.Conclusion: Reoperation due to bleeding is required in certain cases. The amount of drainage from a chest drain does not necessarily reflect the volume of intrathoracic hematoma and it is hard to estimate the total amount of bleeding. The decision to perform reoperation for hemostasis should be comprehensively made on the basis of clinical signs and chest X-ray findings.Keywords: bleeding, hemostasis, lung neoplasms, thoracic surgery, intraoperative complications, reoperation

Worldwide, burns are the fourth most frequent type of injury. The treatment of burn wounds requires a lot of experience and an interdisciplinary approach including both surgical treatment and pharmacological wound care. The most common management of burn wounds is debridement and wound closure through the use of skin grafts. The purpose of the study was to evaluate the hemostatic and antibacterial effects of the commercially available Tromboguard® foam dressing with an active layer containing alginates and chitosan. The site of application of the product was the donor fields for skin grafts. Findings proved that a polyurethane foam dressing with an active chitosan-alginate layer is a useful option for achieving rapid hemostasis, antimicrobial protection and effective healing at split-thickness skin graft donor sites. Substances present in the active layer promote clot formation and the wound healing process.

Relevance. Modern surgery is characterized by the use of various technical means to perform classical surgical techniques - separation and connection of tissues, hemostasis. The study of the applicability of new surgical devices and the search for technological techniques are an important task.The aim of the study: to evaluate the capabilities of the developed device based on microwave energy for hemostatic coagula­tion of resection surfaces of parenchymal organs.Materials and methods. The method is based on the principle of converting microwave energy into heat when it is absorbed in biological tissue. The choice of the microwave range is due to the higher efficiency of power supply to the heat­ing area. Based on the prototype of a medical microwave complex developed in 2011 for thermal effects on biological tissues (RF Patent 2481080. 2011), a prototype of a microwave coagulator for working with parenchymal organs was created. The device was tested on the paren­chymal organs of large laboratory animals under conditions of preserved and switched off blood flow in various energy supply modes. Tissue samples from coagulated lesions were studied histologically.Results. At the site of exposure of the applicator-coagulator to the parenchymal organ, a zone of coagulation changes appears. A clear dependence of the size of coagulation necrosis on the time and power of exposure was noted. When the blood flow is turned off, the necessary stable hemostasis is achieved by shorter exposure time of the coagulator antenna on the surface of the organ.Conclusions. The most effective and reliable hemostasis is achieved on the liver parenchyma. The use of temporary vascular isolation, especially on the kidneys and spleen, involves a single use of microwave energy to stop bleeding. By changing the power and duration of exposure, it is possible to dose the thermal load on biological tissue with great precision. This adjustment allows you to select the operating mode for each specific case. The obtained results of the experiment of the described system during surgery for the purpose of hemostasis in parenchymal bleeding.

Abstract Background Platelets stored at 1–6 °C are hypothesized to be more hemostatically active than standard room temperature platelets (RTP) stored at 20–24 °C. Recent studies suggest converting RTP to cold-stored platelets (Delayed Cold-Stored Platelets, DCSP) may be an important way of extending platelet lifespan and increasing platelet supply while also activating and priming platelets for the treatment of acute bleeding. However, there is little clinical trial data supporting the efficacy and safety of DCSP compared to standard RTP. Methods This protocol details the design of a multicentre, two-arm, parallel-group, randomized, active-control, blinded, internal pilot trial to be conducted at two cardiac surgery centers in Canada. The study will randomize 50 adult (≥ 18 years old) patients undergoing at least moderately complex cardiac surgery with cardiopulmonary bypass and requiring platelet transfusion to receive either RTP as per standard of care (control group) or DCSP (intervention group). Patients randomized to the intervention group will receive ABO-identical, buffy-coat, pathogen-reduced, platelets in platelet additive solution maintained at 22 °C for up to 4 days then placed at 4 °C for a minimum of 24 h, with expiration at 14 days after collection. The duration of the intervention is from the termination of cardiopulmonary bypass to 24 h after, with a maximum of two doses of DCSP. Thereafter, all patients will receive RTP. The aim of this pilot is to assess the feasibility of a future RCT comparing the hemostatic effectiveness of DCSP to RTP (defined as the total number of allogeneic blood products transfused within 24 h after CPB) as well as safety. Specifically, the feasibility objectives of this pilot study are to determine (1) recruitment of ≥ 15% eligible patients per center per month); (2) appropriate platelet product available for ≥ 90% of patients randomized to the cold-stored platelet group; (3) Adherence to randomization assignment (> 90% of patients administered assigned product). Discussion DCSP represents a promising logistical solution to address platelet supply shortages and a potentially more efficacious option for the management of active bleeding. No prospective clinical studies on this topic have been conducted. This proposed internal pilot study will assess the feasibility of a larger definitive study. Trial registration NCT 06147531 (clinicaltrials.gov).

Objective To prepare FLIVIGSII peptide (FI peptide) and investigate its physicochemical properties and hemostatic effect in vivo and in vitro. Methods The self-assembling peptide-based hydrogels were prepared by the FI peptide mixed with water. After gross observation for the hydrogel state of the FI peptide, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used for its microstructure, and dynamic light scattering (DLS) was performed for its size. The hemostatic effect of FI peptide after being mixed with blood samples treated with 3.8% sodium citrate was observed, and the microstructure of the blood clot was observed with SEM. CCK-8 assay and hemolysis assay were performed to verify its biocompatibility. After a rat model of hepatic parenchymal perforation and hemorrhage was established, 15 female SD rats (6~8 weeks old, weighing 150 g) were randomly divided into control group, FI peptide group and fibrin sealant group. The hemostatic effect of FI peptide and prognosis was observed and analyzed after treatment in each group, and the hemostatic mechanism was also investigated. Results FI peptides were successfully prepared, and it could rapidly self-assemble into a nanofiber network hydrogel in water, and further cause formation of blood clots. SEM showed that FI peptides self-assembled to form fibrous hydrogels after mixing with water. TEM results verified that the FI peptide formed into nanofibers in a diameter of 13.70±2.31 nm after gelatinization in water, and DLS results verified that the FI peptide formed polydisperse and multi-size nanofibers in water (in a range of 148.2~208.0 nm or 575.0~807.0 nm). The fibrous hydrogel formed by the FI peptide mixed with the blood could envelop the red blood cells, thus form a physical hemostatic barrier to achieve blood clotting in seconds. FI peptide hydrogel had no cytotoxicity to normal hepatocytes (L-O2 cells) and did not cause hemolysis of red blood cells. In in vivo experiment, FI peptide quickly formed nanofiber hydrogel when in contact with blood, thus formed physical hemostasis barrier to achieve hemostasis within a few seconds (hemostasis time < 5 s). Conclusion The FI peptide exhibits a rapid and efficient hemostatic effect, indicating a promising clinical application in the hemostasia of hepatic parenchymal traumatic hemorrhage.

Factor XI is a zymogen with an important role in the coagulation cascade. It is activated by FXII, thrombin and or it can be autoactivated. It has a prothrombotic effect after being activated by thrombin, but also through its antifibrinolytic action, stabilizing the formed clot.

Background: Operative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery. Study design: This prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urologic surgery. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was noninferiority as compared with control via effective hemostasis at 7 min. Patients were monitored and followed daily in the postoperative period until time of discharge and again at 6 weeks. Overall survival was assessed in oncology patients at 24 months. Safety of PH vs. MPH was determined by comparing relative incidence of adverse events. Results: Across 19 centers, 324 (161 PH, 163 MPH) patients were randomized (48 % general surgery, 27 % cardiac surgery, and 25 % urologic surgery). PH was noninferior to MPH and met the primary endpoint of hemostatic success at 7 min at a non-inferiority margin of 10 %. No significant differences were found in adverse event rates. Six deaths were reported within the 6-week follow-up period. No difference in overall survival was observed at 2 years (76 % PH vs. 74 % MPH, P = .66) for patients undergoing cancer operations. Conclusion: Across three therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points with no safety concerns. PH is an effective alternative to MPH for hemostasis during surgery.ClinicalTrials.gov Identifier: NCT02359994

IntroductionThe development of de novo anti-HLA donor specific antibodies (DSAs) is associated with poor outcomes in kidney transplant recipients. It is surmised that an interaction between DSAs and the graft endothelium cause tissue injury, however, the exact underlying pathomechanism and optimal management of patients with DSAs remain undetermined.AimsWe hypothesized that in kidney transplant recipients the presence of DSAs induce hemostasis alterations, including hypercoagulability, as assessed by the thrombin generation assay (TGA). Patients and methods. In this observational cohort study, 27 kidney transplant recipients with DSAs (DSA+ group) and 16 without DSAs (DSA– group) were enrolled. Venous blood samples were obtained, and besides routine laboratory tests, von Willebrand factor antigen (VWF), FVIII activity, soluble E selectin (sEsel), soluble P selectin (sPsel), TGA, clot lysis assay (CLA), complement levels (C3, C4) were measured. To correlate results with potential changes in DSA status over time, patients were followed and reassessed 6 ± 1.5 months later.ResultsVWF and sPsel did not differ between groups, but both parameters were increased in the majority of patients. Endogenous thrombin potential (ETP) was significantly higher in the DSA+ group as compared to DSA– patients (median:1666; IQR:1438-2012 vs. 1230; IQR:1097-1659 nM*min, p=0.0019). Follow-up measurements indicated that the observed hemostasis alterations were not transient. CLA parameters, C3 and C4 did not differ between DSA+ and DSA– groups. The extent of anti-HLA II DSA positivity correlated positively with ETP, while tacrolimus levels negatively correlated with ETP and VWF/FVIII levels.ConclusionsIn patients with anti-HLA class II DSAs, thrombin generation was significantly increased as compared to DSA– kidney transplant recipients, suggesting that the presence of antibodies is associated with hypercoagulability. Tacrolimus levels were negatively associated with TGA parameters. Hypercoagulability, associated with the presence of DSAs, may potentially contribute to the pathomechanism of antibody-mediated graft injury, warranting future prospective studies.

Background: In healthy individuals, plasma levels of clotting proteins naturally vary within a range of 50% to 150% of their mean values. We do not know how these variations modify thrombin generation. Objectives: To assess the impact of protein level variations on simulated thrombin generation in normal and factor (F)VIII-, FIX-, or FXI-deficient blood. Methods: We used a mathematical model of flow-mediated coagulation to simulate thrombin generation with all possible combinations of clotting protein variations within the normal range and for various tissue factor levels. We selected, analyzed, and ranked combinations that enhanced thrombin generation compared with baseline. Results: Protein variations most strongly affected thrombin generation at intermediate tissue factor levels. Low tissue factor levels prevented coagulation initiation, while high tissue factor levels always triggered thrombin generation. At intermediate levels, we identified protein variations that substantially modified thrombin generation. Low-normal FV shortened lag times and increased thrombin generation, whereas high-normal FV lengthened lag times and reduced thrombin generation. With severe FVIII and FIX deficiencies, low-normal tissue factor pathway inhibitor α and antithrombin amplified the effect of low-normal FV. For moderate FVIII and FIX deficiencies, high-normal tissue factor pathway inhibitor α and antithrombin enhanced the impact of high-normal FV in reducing thrombin production. In normal and FXI-deficient blood, high-normal FVIII and FIX significantly boosted thrombin generation. Conclusion: Our mathematical model predicted how variations in clotting protein levels, within the normal range, could contribute to the variability of bleeding phenotypes observed with clotting factor deficiencies. Our study generated experimentally testable hypotheses that could aid in developing new therapies toward normal hemostasis.

Background: This was a noninferiority trial to evaluate blood loss during total knee arthroplasty (TKA) when using the unipolar electrocautery system compared to the saline coupled bipolar sealer system in primary TKA. Methods: One hundred sixty-four patients were randomly assigned by a 1:1 ratio to either the unipolar electrocautery system (N = 82) or bipolar sealer system (N = 82). Inclusion criteria included patients scheduled for primary unilateral TKA, preoperative hemoglobin ≥11 mg/dL, preoperative platelet count ≥150,000, age >18 years, and patient willing to complete all study-related procedures. The primary efficacy outcome was estimated blood loss on morning of postoperative day. Secondary efficacy outcomes were comparison between the preoperative hemoglobin and postoperative day 1 hemoglobin, and allogeneic blood transfusions. Additionally, the study collected objective and functional outcomes using the postoperative 2011 Knee Society Score. Results: The unipolar electrocautery system was not found to be less efficacious than the bipolar sealer system. Mean blood loss for the unipolar electrocautery system was 1062.0 cubic centimeters (cc) (95% confidence limit for the mean: 985.2, 1138.7), and for the bipolar sealer system was 929.4 cc (95% confidence limit for the mean: 841.9, 1016.8). The mean difference in blood loss was 132.6 cc, below the margin of inferiority set at 200 cc. Additionally, there was no difference in patient outcomes as measured by the Knee Society Score. Conclusions: The safety, efficacy, and outcomes profile of the unipolar electrocautery system compared to the bipolar sealer system were similar. Use of the bipolar sealer system significantly increases surgical cost without any added benefits.

The treatment of internal hemorrhage remains challenging due to the current limited antibacterial capability, hemostatic efficacy, and biocompatibility of hemostatic materials. The TEMPO-oxidized cellulose nanofibers/collagen/chitosan (TCNF/COL/CS) hemostatic aerogel was developed in this work by physically encasing COL in a sandwich structure and electrostatically self-assembling polyanionic TCNF with polycationic CS. In vitro coagulation experiments revealed the favorable procoagulant properties of TCNF/COL/CS along with high adhesion to erythrocytes and platelets. TCNF/COL/CS significantly increased the hemostatic efficacy by 59.8 % and decreased blood loss by 62.2 % in the liver injury model when compared to Surgicel®, the most frequently used hemostatic material. Furthermore, it demonstrated outstanding biodegradability both in vitro and in vivo, and a substantial increase in resistance (96.8 % against E. coli and 95.4 % against S. aureus) compared to TCNF. The significant hemostatic and biodegradable characteristics of TCNF/COL/CS can be ascribed to its interconnected porous structure, increased porosity, and efficient water absorption, along with the synergistic effect of the three constituents. The TCNF/COL/CS aerogel shows significant potential to control internal bleeding. A novel plant-derived nanocellulose composite aerogel has been described here for the first time; it has outstanding antibacterial characteristics, higher biocompatibility, and outstanding hemostatic characteristics in vivo.

BackgroundThe effect of acidemia on blood coagulation remains inadequately understood in veterinary medicine. Therefore, we assessed the effect of in vitro acidification of canine whole blood on coagulation and investigated whether acidemia-induced coagulopathy could be reversed by reversing acidemia.MethodsCitrated whole blood samples were taken from six healthy Beagle dogs and categorized, based on pH adjustment, into neutral, weak acidemia (WA), strong acidemia (SA), and reversal from SA. Then, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, conventional thromboelastography (TEG) parameters, and velocity curve (V-curve) variables of TEG were assessed.ResultsThe PT, aPTT, and most TEG parameters showed significant coagulopathy in the SA group compared to the neutral group, with additional significant changes in reaction time (R), clot kinetic (K), maximum amplitude (MA), split point (SP), elasticity (E), thrombodynamic potential index (TPI), and coagulation index (CI) between the SA and WA groups. Among V-curve variables, the maximum rate of thrombus generation (MRTG) and total thrombus generation were significantly inhibited in the SA group compared to the neutral group, with significant differences in the time to maximum rate of thrombus generation (TMRTG) between the WA and SA groups. In the reverse group, aPTT, R, K, α-angle, MRTG, TMRTG, SP, TPI, and CI exhibited significant recovery compared to the SA group.ConclusionThe in vitro induction of acidemia in canine whole blood leads to impairment of coagulation profiles, and pH correction can reverse most acidemia-induced coagulopathy.

Background: Gastric cancer has a high prevalence in Asia and may only be diagnosed in advanced stages. Therefore, patients with gastric cancer may experience fatal symptoms, such as bleeding or stenosis at the time of consultation. In this review, we aimed to describe the effectiveness and toxicity of hemostatic radiotherapy (RT). Methods: A total of 17 retrospective and 3 prospective studies were analyzed. The prescription dose, biologically effective dose, equivalent dose in 2 Gy fractions, response rate, survival prognosis, and toxicities were also reported. Results: Using 20 studies, the following observations were made the hemostatic effect was ∼ 80 %, the mean survival time after irradiation was about 3 months, and prescribed doses of 30 Gy/10 fractions and 20 Gy/5 fractions were considered suitable. Conclusion: In this review, studies on hemostatic irradiation have been summarized, and the most optimal treatment method has been proposed. 30 Gy/10 fractions and 20 Gy/5 fractions were ideal. However, because palliative RT is preferably completed within a short period of time, a randomized trial is needed to determine whether the 8 Gy/single fraction treatment is equivalent to fractionated RT. Therefore, more prospective studies are warranted to establish a standard of care for palliative RT in gastric cancer.

Aim: to assess adaptive hemostasis changes in multiple dichorionic pregnancy after in vitro fertilization (IVF). Materials and Methods. A prospective observational randomized controlled trial was conducted by examining 58 and 46 pregnant women with multiple dichorionic diamniotic twins resulting from applying assisted reproductive technologies (ART) and spontaneous delivery (comparison group), respectively. Hemostasis parameters were studied as follows: activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin, protein C, protein S, functions of protein С (РrоС Global test), D-dimer, platelet aggregation with adenosine-5-diphosphate (ADP), ristocetin, and collagen. Results. A high coagulation potential was revealed, more prominent after using ART (p < 0.05). Fibrinogen level gradually increased while gestation age increased, whereas APTT, PT and TT level decreased. In the group with natural conception, fibrinogen increased by 22 % in the second trimester, reaching 4.5 g/L (95 % CI = 4,2–4,8) and by 6 % in the third trimester, reaching 4.8 g/L (95 % CI = 4,3–5,4), whereas in the IVF group – by 26 %, reaching 5.3 g/L (95 % CI = 4,7–5,6) and by 21 %, reaching (6.5 g/L; 95 % CI = 5,2–6,8) in relevant trimester of pregnancy, respectively. Antithrombin level was lower in IVF patients – 76.8 % (95 % CI = 72.6 – 81.0) in the second trimester, reaching 70.6 % (95 % CI = 64.8–76.4) in the third trimester (p < 0.001). Protein C level did not differ significantly between groups and was low within the reference range. The aggregatogram demonstrated a high platelet hemostatic potential in IVF patients (p < 0.05) as early as in the first trimester: ADP-induced aggregation – 68.3 % (95 % CI = 62.9–73.7), ristocetin-induced aggregation – 53.1 % (95 % = CI 48.7–58.5), collagen-induced aggregation – 58.4 % (95 % CI = 52.1–64.7). In the third trimester, both platelet aggregation and functional activity (ADP-induced aggregation – 64.5 % [95 % CI = 59.3–69.7], ristocetin-induced aggregation – 68.4 % [95 % CI = 63.2–73.6], collagen-induced aggregation – 50.7 % [95 % CI = 44.3–57.1]; p < 0.05) and D-dimer level persistently increased, also more prominently in the IVF group (1.60 ± 0.46 ng/ml; p < 0.05). Conclusion. Gestational adaptation in induced multiple pregnancies is at high risk of breach in compensatory mechanisms and requires monitoring for timely detection of decompensation signs and their correction to prolong pregnancy till optimal delivery time frame.

Massive gastric mucosal ruptures during upper gastrointestinal endoscopy in patients with esophageal hiatal hernias are rare. However, tearing of the gastric mucosa alone, without tearing of the gastroesophageal junction, is even rarer. This study reports a case of a large mucosal rupture that occurred on the posterior wall of the upper body of the stomach during upper gastrointestinal endoscopy in an 83-year-old woman with an esophageal hiatal hernia while sedated. The patient was treated with endoclips for the rupture.

Cap-assisted endoscopy refers to a procedure in which a short tube made of a polymer (mostly transparent) is attached to the distal tip of the endoscope to enhance its diagnostic and therapeutic capabilities. It is reported to be particularly useful in: (1) minimizing blind spots during screening colonoscopy, (2) providing a constant distance from a lesion for clear visualization during magnifying endoscopy, (3) accurately assessing the size of various gastrointestinal lesions, (4) preventing mucosal injury during foreign body removal, (5) securing adequate workspace in the submucosal space during endoscopic submucosal dissection or third space endoscopy, (6) providing an optimal approach angle to a target, and (7) suctioning mucosal and submucosal tissue with negative pressure for resection or approximation. Here, we review various applications of attachable caps in diagnostic and therapeutic endoscopy and their future implications.

Abstract Background Thromboinflammation is caused by mutual activation of platelets and neutrophils. The site of thromboinflammation is determined by chemoattracting agents release by endothelium, immune cells, and platelets. Impaired neutrophil chemotaxis contributes to the pathogenesis of Shwachman-Diamond syndrome (SDS). In this hereditary disorder, neutrophils are known to have aberrant chemoattractant-induced F-actin properties. Here, we aim to determine whether neutrophil chemotaxis could be analyzed using our previously developed ex vivo assay of the neutrophils crawling among the growing thrombi. Methods Adult and pediatric healthy donors, alongside with pediatric patients with SDS, were recruited for the study. Thrombus formation and granulocyte movement in hirudinated whole blood were visualized by fluorescent microscopy in fibrillar collagen-coated parallel-plate flow chambers. Alternatively, fibrinogen, fibronectin, vWF, or single tumor cells immobilized on coverslips were used. A computational model of chemokine distribution in flow chamber with a virtual neutrophil moving in it was used to analyze the observed data. Results The movement of healthy donor neutrophils predominantly occurred in the direction and vicinity of thrombi grown on collagen or around tumor cells. For SDS patients or on coatings other than collagen, the movement was characterized by randomness and significantly reduced velocities. Increase in wall shear rates to 300–500 1/s led to an increase in the proportion of rolling neutrophils. A stochastic algorithm simulating leucocyte chemotaxis movement in the calculated chemoattractant field could reproduce the experimental trajectories of moving neutrophils for 72% of cells. Conclusions In samples from healthy donors, but not SDS patients, neutrophils move in the direction of large, chemoattractant-releasing platelet thrombi growing on collagen.

We aimed to investigate the differences in renal function between patients who underwent single inner-layer renorrhaphy (SILR) or double-layer renorrhaphy (DLR) among those with renal tumors who underwent robot-assisted partial nephrectomy (RAPN). This retrospective multicenter cohort study was conducted between November 2018 and October 2023 at two institutions and included patients who underwent RAPN. In total, 93 eligible patients who underwent RAPN were analyzed. Preoperative renal function and prevalence of chronic kidney disease were not significantly different between the two groups. Although urinary leakage was observed in three patients (5.9%) in the SILR group, there was no significant difference between the two groups regarding surgical outcomes (p = 0.249). Serum creatinine levels after RAPN were significantly lower in the SILR group than in the DLR group on postoperative days 1 and 365 following RAPN (p = 0.04). The estimated glomerular filtration rate (eGFR) was significantly lower in the DLR group than in the SILR group only on postoperative day 1; however, there was no significant difference between the two groups thereafter. Multivariate analysis showed that the method of renorrhaphy was not a predictor for maintaining renal function after RAPN even though it was associated with eGFR on postoperative day 1.

During cellular stress, the master regulators of intrinsic self-death (apoptosis) are BCL-2 family proteins. The BCL-2 family proteins play a key role in apoptosis and are tightly regulated via other BCL-2 family proteins, non-BCL-2 protein suppressors, and epigenetic modifications. As the name implies, these proteins possess one or two of the four BCL-2 homology domains (BH1–BH4). According to their roles, they are classified as pro-apoptotic or pro-survival proteins. BH-3-only proteins possess a single BH3 domain and are specific/key effector proteins for intracellular death commitment, particularly in the context of cell survival and programmed cell death. This delicate interplay among the BCL-2 family members is essential for maintaining the primary hemostasis, or balance, of cell fate. The anti-apoptotic proteins, such as BCL-2 and BCL-XL, promote cell survival by inhibiting apoptosis. On the other hand, the pro-apoptotic proteins, such as BAX and BAK, drive apoptosis. It ensures that cells are able to respond appropriately to various internal and external signals, ultimately determining whether a cell survives or undergoes programmed cell death. Understanding and targeting this delicate balance is a promising avenue for developing therapeutic strategies to modulate cell fate and treat various diseases. The molecular pathogenesis of BCL-2 family proteins in blood disorders involves differential expression of these components resulting in the dysregulation of the pathway contributing to cell survival and resistance to apoptosis as observed in follicular lymphoma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, and acute myeloid leukemia. Such dysregulation is a major impediment to standard therapies and aids in chemo resistance. Studies show some promising clinical outcomes with antineoplastic agent venetoclax either as a monotherapy or in combination with other agents. This review discusses recent studies on the regulation of BCL-2 family proteins which might provide a molecular landscape for their clinical implications in blood disorders.

Abstract Background The immature platelet fraction (IPF), a parameter obtained by the Sysmex XN‐1000V analyzer, is used in humans to differentiate between central (CEN) and peripheral (PER) thrombocytopenia (TP) but has not been evaluated in small animals. Objectives Compare IPF between healthy, clinical non‐TP and TP dogs and cats, study IPF in different causes of TP in dogs and cats and, establish IPF reference intervals (RIs), and study the effect of age and sex on IPF in healthy dogs and cats. Animals A total of 3281 dogs and 726 cats. Methods Retrospective review of medical records. Animals were classified as nonthrombocytopenic (healthy group and group of clinical patients without TP [NTP]) or TP. These latter animals were subclassified as pseudothrombocytopenia (PSE), CEN and PER, based on evaluation of platelet clumps, estimated platelet count in blood smears and final diagnosis. Blood samples were evaluated using a Sysmex XN‐1000V with a specific platelet channel (PLT‐F). Results The IPF was significantly different between each subtype of TP in both species. Immature platelet fractions

Abstract Background REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. Methods A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. Results Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). Conclusion This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. Level of evidence Therapeutic study, Level III.

Abstract A nanofiber-based composite nonwoven fabric was fabricated for hemostatic wound dressing, integrating polyvinyl alcohol (PVA), kaolin, and γ-chitosan extracted from three type of insects. The γ-chitosan extracted from Protaetia brevitarsis seulensis exhibited the highest yield at 21.5%, and demonstrated the highest moisture-binding capacity at 535.6%. In the fabrication process of PVA/kaolin/γ-chitosan nonwoven fabrics, an electrospinning technique with needle-less and mobile spinneret was utilized, producing nanofibers with average diameters ranging from 172 to 277 nm. The PVA/kaolin/γ-chitosan nonwoven fabrics demonstrated enhanced biocompatibility, with cell survival rates under certain compositions reaching up to 86.9% (compared to 74.2% for PVA). Furthermore, the optimized fabric compositions reduced blood coagulation time by approximately 2.5-fold compared to PVA alone, highlighting their efficacy in hemostasis. In other words, the produced PVA/kaolin/γ-chitosan nonwoven fabrics offer potential applications as hemostatic wound dressings with excellent biocompatibility and improved hemostatic performance. Graphical abstract

Dieulafoy’s lesion is a rare cause of gastrointestinal bleeding, accounting for approximately 1–2% of all cases of gastrointestinal bleeding. Dieulafoy’s lesion usually occurs in the lesser curvature of the stomach within six centimeters of the gastroesophageal junction. On the other hand, extragastric Dieulafoy’s lesions are uncommon. Diagnosing an extragastric Dieulafoy’s lesion by endoscopy can be challenging because of its small size and obscure location. The key elements for an accurate diagnosis include heightened awareness and a careful early endoscopic evaluation following a bleeding episode. Various endoscopic hemostatic techniques can be used for treatment. This paper presents a case of successful hemostasis using argon plasma coagulation for a life-threatening duodenal Dieulafoy’s lesion.

Introduction: Precut fistulotomy is of interest as one of the salvage techniques for selective bile duct cannulation using endoscopic retrograde cholangiopancreatography. Of the various endoscopic treatments reported to date for bleeding associated with papillotomy incision, endoscopic hemostasis treatment with a novel self-assembling peptide (SAP) matrix-forming gel (TDM-621) (3-D Matrix Ltd., Tokyo, Japan) remains only insufficiently reported in the literature. Case Presentation: We herein report 6 cases of precut fistulotomy-related bleeding successfully treated with endoscopic hemostasis treatment with TDM-621, i.e., 5 and 1 cases during and after precut fistulotomy, respectively, in 2 males and 4 females aged 68–96 years (mean age, 85 years), 3 of whom had been on antithrombotic drugs. Types of bleeding treated included oozing bleeding (n = 5) and oozing bleeding from a visible vessel (n = 1). In all cases, complete hemostasis was achieved with TDM-621 without causing rebleeding. Conclusion: Endoscopic hemostasis with TDM-621 may prove effective for precut fistulotomy-related bleeding and represent a potential modality of first choice in hemostasis. In addition, endoscopic hemostasis with combined modality therapy using TDM-621 and endoscopic hemoclips may prove effective for bleeding from visible vessels.

Platelet-derived extracellular vesicles (PEVs) are released by platelets in the blood circulation, which carry a rich bio-molecular cargo influential in intercellular communications. PEVs can enter the lymph, bone marrow, and synovial fluid as nano-sized particles, while platelets cannot cross tissue barriers. Considering the advantages of PEVs such as low immunogenicity, high regulation of signal transduction, and easy obtainment, PEVs may be promising therapeutic tools for medical applications. The exceptional functional roles played by PEVs explain the recent interest in exploring new cell-free therapies that could address needs in angiogenesis, regenerative medicine, and targeted drug delivery. The review takes a critical look at the main advances of PEVs in the treatment of diseases by presenting the latest knowledge from the performed studies, in order to enhance the further translation of the PEVs research into feasible therapeutic applications.

Receptor-induced tyrosine phosphorylation of spleen tyrosine kinase (Syk) has been studied extensively in hematopoietic cells. Metabolic mapping and high-resolution mass spectrometry, however, indicate that one of the most frequently detected phosphorylation sites encompassed S297 (S291 in mice) located within the linker B region of Syk. It has been reported that Protein kinase C (PKC) phosphorylates Syk S297, thus influencing Syk activity. However, conflicting studies suggest that this phosphorylation enhances as well as reduces Syk activity. To clarify the function of this site, we generated Syk S291A knock-in mice. We used platelets as a model system as they possess Glycoprotein VI (GPVI), a receptor containing an immunoreceptor tyrosine-based activation motif (ITAM) which transduces signals through Syk. Our analysis of the homozygous mice indicated that the knock-in platelets express only one isoform of Syk, while the wild-type expresses two isoforms at 69 and 66 kDa. When the GPVI receptor was activated with collagen-related peptide (CRP), we observed an increase in functional responses and phosphorylations in Syk S291A platelets. This potentiation did not occur with AYPGKF or 2-MeSADP, although they also activate PKC isoforms. Although there was potentiation of platelet functional responses, there was no difference in tail bleeding times. However, the time to occlusion in the FeCl3 injury model was enhanced. These data indicate that the effects of Syk S291 phosphorylation represent a significant outcome on platelet activation and signaling in vitro but also reveals its multifaceted nature demonstrated by the differential effects on physiological responses in vivo.

A novel bioresorbable agent on the market is PuraGel® (3‐D Matrix, Tokyo, Japan), a RADA‐16 product that acts as a synthetic hemostatic and space‐filling gel that promotes wound healing and prevents adhesion formation. Given the reported benefits of accelerated wound healing and scar tissue prevention, there are multiple otolaryngologic applications where RADA‐16 might improve outcomes. Our study highlights current utilization and associated post‐operative complications with this product.

Chitosan (CS) has been extensively studied in wound care for its intrinsic hemostatic and antibacterial properties. However, CS has limiting hemostasis applications on account of its drawbacks such as poor adhesion in humid environments and water solubility at neutral pH. CS-based biomaterials, inspired by mussel-adhesive proteins, serve as a suggested platform by biomedical science. The reports show that the mussel-inspired CS-based hemostatic structure has negligible toxicity and excellent adhesiveness. Biomedicine has witnessed significant progress in the development of these hemostatic materials. This review summarizes the methods for the modification of CS by mussel-inspired chemistry. Moreover, the general method for preparation of mussel-inspired CS-based biomaterials is briefly discussed in this review. This work is expected to give a better understanding of opportunities and challenges of the mussel-inspired strategy for the functionalization of CS-based biomaterials in hemostasis and wound healing. This review is hoped to provide an important perspective on the preparation of mussel-inspired CS-based hemostatic materials.

In recent years, the development of biodegradable hydrogels as an alternative over the traditional wound dressing has become increasingly significant. These specific hydrogels are able to offer suitable microenvironments to further aid the process of tissue or organ regeneration. However, application of biodegradable hydrogels in clinical medicine remains uncommon due to most biodegradable hydrogels struggle with achieving satisfactory adhesiveness property, high mechanical support and cell compatibility simultaneously. In order to overcome these constraints and enhance the applicability of biodegradable hydrogels, methods have been employed in this study.By reacting gellan gum with methacrylic anhydride and incorporating a biodegradable protein, keratin, we endowed the hydrogels with high pliability via photo-polymerization chain extension, thereby obtaining a biodegradable hydrogel with exceptional properties. Through a series of in vitro tests, GGMA/keratin hydrogels exhibited great cell compatibility via providing an appropriate environment for cell proliferation. Furthermore, this hydrogel not only exhibits extraordinary adhesive ability on visceral tissues but also extends to scenarios involving skin or organ damage, offering valuable assistance in wound healing. Our design provides a suitable platform for cell proliferation and tissue regeneration, which shows prospects for future medical research and clinical applications.

Background: Platelet function is driven by the expression of specialized surface markers. The concept of distinct circulating subpopulations of platelets has emerged in recent years, but their exact nature remains debatable. Objectives: To design a spectral flow cytometry–based phenotyping workflow to provide a more comprehensive characterization, at a global and individual level, of surface markers in resting and activated healthy platelets, and to apply this workflow to investigate how responses differ according to platelet age. Methods: A 14-marker flow cytometry panel was developed and applied to vehicle- or agonist-stimulated platelet-rich plasma and whole blood samples obtained from healthy volunteers, or to platelets sorted according to SYTO-13 (Thermo Fisher Scientific) staining intensity as an indicator of platelet age. Data were analyzed using both user-led and independent approaches incorporating novel machine learning–based algorithms. Results: The assay detected differences in marker expression in healthy platelets, at rest and on agonist activation, in both platelet-rich plasma and whole blood samples, that are consistent with the literature. Machine learning identified stimulated populations of platelets with high accuracy (>80%). Similarly, machine learning differentiation between young and old platelet populations achieved 76% accuracy, primarily weighted by forward scatter, cluster of differentiation (CD) 41, side scatter, glycoprotein VI, CD61, and CD42b expression patterns. Conclusion: Our approach provides a powerful phenotypic assay coupled with robust bioinformatic and machine learning workflows for deep analysis of platelet subpopulations. Cleavable receptors, glycoprotein VI and CD42b, contribute to defining shared and unique subpopulations. This adoptable, low-volume approach will be valuable in deep characterization of platelets in disease.