The Crossroads of the Coagulation System and the Immune System: Interactions and Connections.

The coagulation and immune systems, two vital systems in the human body, share intimate connections that fundamentally determine patient health. These systems work together through several common regulatory pathways, including the Tissue Factor (TF) Pathway. Immune cells expressing TF and producing pro-inflammatory cytokines can influence coagulation, while coagulation factors and processes reciprocally impact immune responses by activating immune cells and controlling their functions. These shared pathways contribute to maintaining health and are also involved in various pathological conditions. Dysregulated coagulation, triggered by infection, inflammation, or tissue damage, can result in conditions such as disseminated intravascular coagulation (DIC). Concurrently, immune dysregulation may lead to coagulation disorders and thrombotic complications. This review elucidates these intricate interactions, emphasizing their roles in the pathogenesis of autoimmune diseases and cancer. Understanding the complex interplay between these systems is critical for disease management and the development of effective treatments. By exploring these common regulatory mechanisms, we can uncover innovative therapeutic strategies targeting these intricate disorders. Thus, this paper presents a comprehensive overview of the mutual interaction between the coagulation and immune systems, highlighting its significance in health maintenance and disease pathology.

Extracellular Vesicle Mediated Vascular Pathology in Glioblastoma.

Glioblastoma (GBM) is an incurable, infiltrative high-grade brain tumour associated with dramatic vascular responses observed both locally (angiogenesis, vascular cooption, angiocrine effects, microthrombosis) and systemically (venous thromboembolism). GBM-associated vascular pathology is diagnostically relevant and constitutes a source of morbidity, mortality and progressive changes in tumour biology. Extracellular vesicles (EVs) have emerged as unique mediators of vascular effects in brain tumours acting as vehicles for intercellular transfer of oncoproteins (e.g. EGFRvIII), RNA, DNA and molecular effectors of angiogenesis and thrombosis. Vascular effects of GBM EVs are regulated by cancer cell genome, epigenome and microenvironment and differ between subtypes of cancer cells and stem cells. Understanding and targeting EV-driven vascular processes in GBM may offer new approaches to diagnose and treat these intractable tumours.

Quantitative In-Depth Transcriptome Analysis Implicates Peritoneal Macrophages as Important Players in the Complement and Coagulation Systems.

To obtain a more detailed picture of macrophage (MΦ) biology, in the current study, we analyzed the transcriptome of mouse peritoneal MΦs by RNA-seq and PCR-based transcriptomics. The results show that peritoneal MΦs, based on mRNA content, under non-inflammatory conditions produce large amounts of a number of antimicrobial proteins such as lysozyme and several complement components. They were also found to be potent producers of several chemokines, including platelet factor 4 (PF4), Ccl6, Ccl9, Cxcl13, and Ccl24, and to express high levels of both TGF-ß1 and TGF-ß2. The liver is considered to be the main producer of most complement and coagulation components. However, we can now show that MΦs are also important sources of such compounds including C1qA, C1qB, C1qC, properdin, C4a, factor H, ficolin, and coagulation factor FV. In addition, FX, FVII, and complement factor B were expressed by the MΦs, altogether indicating that MΦs are important local players in both the complement and coagulation systems. For comparison, we analyzed human peripheral blood monocytes. We show that the human monocytes shared many characteristics with the mouse peritoneal MΦs but that there were also many major differences. Similar to the mouse peritoneal MΦs, the most highly expressed transcript in the monocytes was lysozyme, and high levels of both properdin and ficolin were observed. However, with regard to connective tissue components, such as fibronectin, lubricin, syndecan 3, and extracellular matrix protein 1, which were highly expressed by the peritoneal MΦs, the monocytes almost totally lacked transcripts. In contrast, monocytes expressed high levels of MHC Class II, whereas the peritoneal MΦs showed very low levels of these antigen-presenting molecules. Altogether, the present study provides a novel view of the phenotype of the major MΦ subpopulation in the mouse peritoneum and the large peritoneal MΦs and places the transcriptome profile of the peritoneal MΦs in a broader context, including a comparison of the peritoneal MΦ transcriptome with that of human peripheral blood monocytes and the liver.

Anticoagulation therapy in COVID-19 patients with chronic kidney disease.

Coagulopathy and derangements in the coagulation parameters are significant features of COVID-19 infection, which increases the risk of disseminated intravascular coagulation, thrombosis, and hemorrhage in these patients, resulting in increased morbidity and mortality. In times of COVID-19, special consideration should be given to patients with concurrent chronic kidney disease (CKD) and COVID-19 (CKD/COVID-19 patients) as renal dysfunction increases their risk of thrombosis and hemorrhage, and falsely affects some of the coagulation factors, which are currently utilized to assess thrombosis risk in patients with COVID-19. Hence, we believe extra attention should be given to determining the risk of thrombosis and bleeding and optimizing the timing and dosage of anticoagulant therapy in this unique population of patients. CKD/COVID-19 patients are considered a high-risk population for thrombotic events and hemorrhage. Furthermore, effects of renal function on paraclinical and clinical data should be considered during the evaluation and interpretation of thrombosis risk stratification. Individualized evaluation of clinical status and kidney function is necessary to determine the best approach and management for anticoagulant therapy, whereas there is a lack of studies about the population of CKD/COVID-19 patients who need anticoagulant therapy now.

Surgical stress and cancer progression: the twisted tango.

Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.

Thromboelastometry: studying hemostatic profile in small for gestational age neonates-a pilot observational study.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.

Influence of Glycemic Control on Coagulation and Lipid Metabolism in Pregnancies Complicated by Pregestational and Gestational Diabetes Mellitus.

Hypercoagulability and altered lipid metabolism, which are observed in normal pregnancy, can be enhanced in diabetes mellitus. The aim of the study was to evaluate the influence of glycemic control on coagulation and lipid metabolism in women with pregestational (PGDM) and gestational (GDM) diabetes treated with insulin. There were 50 patients with PGDM and 101 patients with GDM enrolled into the study. Serum lipid and coagulation parameters were assessed at 18-22, 25-28, and 31-34 weeks of pregnancy and were compared within the diabetic groups with reference to the effectiveness of glycemia control. We found that poor glycemic control was associated with shortened activated partial thromboplastin time (APTT) and increased activity of antithrombin III (ATIII) in both diabetic groups and with a higher plasminogen activator inhibitor (PAI-1) content level in the GDM group. Poorly controlled PGDM was associated with higher levels of total cholesterol and high-density cholesterol (HDL) in the second trimester and triglycerides in the third trimester. In patients with poorly controlled GDM, a higher concentration of HDL was observed in third trimester, whereas a higher triglyceride level was found in both second and third trimesters. Positive correlations between total cholesterol and APTT and between triglyceride and APTT and ATIII were found in the poorly controlled PGDM group. We conclude that poor glycemic control of diabetic pregnancy impacts both lipid metabolism and the blood coagulation system.

A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity.

In this review article, we focus on activation of the soluble components of the innate immune system triggered by nonbiological compounds and stress variances in activation due to the difference in size between nanoparticles (NPs) and larger particles or bulk material of the same chemical and physical composition. We then discuss the impact of the so-called protein corona which is formed on the surface of NPs when they come in contact with blood or other body fluids. For example, NPs which bind inert proteins, proteins which are prone to activate the contact system (e.g., factor XII), which may lead to clotting and fibrin formation or the complement system (e.g., IgG or C3), which may result in inflammation and vascular damage. Furthermore, we describe a whole blood model which we have developed to monitor activation and interaction between different components of innate immunity: blood protein cascade systems, platelets, leukocytes, cytokine generation, which are induced by NPs. Finally, we describe our own studies on innate immunity system activation induced by three fundamentally different species of NPs (two types of engineered NPs and diesel NPs) as demonstrator of the utility of an initial determination of the composition of the protein corona formed on NPs exposed to ethylenediaminetetraacetic acid (EDTA) plasma and subsequent analysis in our whole blood model.

Transcriptional profiling of liver during the critical embryo-to-hatchling transition period in the chicken (Gallus gallus).

BACKGROUND: Although hatching is perhaps the most abrupt and profound metabolic challenge that a chicken must undergo; there have been no attempts to functionally map the metabolic pathways induced in liver during the embryo-to-hatchling transition. Furthermore, we know very little about the metabolic and regulatory factors that regulate lipid metabolism in late embryos or newly-hatched chicks. In the present study, we examined hepatic transcriptomes of 12 embryos and 12 hatchling chicks during the peri-hatch period-or the metabolic switch from chorioallantoic to pulmonary respiration. RESULTS: Initial hierarchical clustering revealed two distinct, albeit opposing, patterns of hepatic gene expression. Cluster A genes are largely lipolytic and highly expressed in embryos. While, Cluster B genes are lipogenic/thermogenic and mainly controlled by the lipogenic transcription factor THRSPA. Using pairwise comparisons of embryo and hatchling ages, we found 1272 genes that were differentially expressed between embryos and hatchling chicks, including 24 transcription factors and 284 genes that regulate lipid metabolism. The three most differentially-expressed transcripts found in liver of embryos were MOGAT1, DIO3 and PDK4, whereas THRSPA, FASN and DIO2 were highest in hatchlings. An unusual finding was the "ectopic" and extremely high differentially expression of seven feather keratin transcripts in liver of 16 day embryos, which coincides with engorgement of liver with yolk lipids. Gene interaction networks show several transcription factors, transcriptional co-activators/co-inhibitors and their downstream genes that exert a 'ying-yang' action on lipid metabolism during the embryo-to-hatching transition. These upstream regulators include ligand-activated transcription factors, sirtuins and Kruppel-like factors. CONCLUSIONS: Our genome-wide transcriptional analysis has greatly expanded the hepatic repertoire of regulatory and metabolic genes involved in the embryo-to-hatchling transition. New knowledge was gained on interactive transcriptional networks and metabolic pathways that enable the abrupt switch from ectothermy (embryo) to endothermy (hatchling) in the chicken. Several transcription factors and their coactivators/co-inhibitors appear to exert opposing actions on lipid metabolism, leading to the predominance of lipolysis in embryos and lipogenesis in hatchlings. Our analysis of hepatic transcriptomes has enabled discovery of opposing, interconnected and interdependent transcriptional regulators that provide precise ying-yang or homeorhetic regulation of lipid metabolism during the critical embryo-to-hatchling transition.

Comparing coagulation activity of Selaginella tamariscina before and after stir-frying process and determining the possible active constituents based on compositional variation.

CONTEXT: Selaginella tamariscina (P. Beauv.) Spring (Selaginellaceae) (ST) has been widely used in China as a medicine for improving blood circulation. However, its processed product, S. tamariscina carbonisatus (STC), possesses opposite haemostatic activity. OBJECTIVE: To comprehensively evaluate the activity of ST and STC on physiological coagulation system of rats, and seek potential active substances accounting for the activity transformation of ST during processing. MATERIALS AND METHODS: The 75% methanol extracts of the whole grass (fine powder) of ST and STC were prepared, respectively. Male Sprague-Dawley rats were randomly divided into five groups: control group, model group, model + ST group, model + STC group and positive control group (model + Yunnanbaiyao). The duration of intragastric administration was 72 h at 12 h intervals. Haemorheology parameters were measured using an LB-2 A cone-plate viscometer and the existed classic methods, respectively. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of ST and STC extracts. RESULTS: STC shortened tail-bleeding time, increased whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR), reduced activated partial thromboplastin time (APTT) and increased the fibrinogen (FIB) content in the plasma of bleeding model rats. Although ST could shorten APTT and TT, the FIB content was significantly decreased by ST. Dihydrocaffeic acid with increased content in STC vs. ST showed haemostatic activity for promoting the platelet aggregation induced by collagen and trap-6, and reducing APTT and PT significantly with a concentration of 171.7 µM in vitro. Amentoflavone with reduced content in STC vs. ST inhibited ADP and AA-induced platelet aggregation significantly with a concentration of 40.7 µM. DISCUSSION AND CONCLUSIONS: As the processed product of ST, STC showed strong haemostatic activity on bleeding rat through regulating the parameters involved in haemorheology and plasma coagulation system. Two active compounds, dihydrocaffeic acid and amentoflavone, might be partially responsible for the haemostatic and anticoagulant activity of STC and ST, respectively.

Acute ischemic stroke in the setting of essential thrombocytemia (clinical cases).

This article describes several clinical cases of acute ischemic stroke among patients suffering from essential thrombocytemia. Ambiguity of etiological factors of stroke is demonstrated among patients with this pathology. Thrombocytosis and high allele load in the Jak2 gene play an important role (even with normal platelet count) in progression of cerebrovascular disease. Also the question of effectiveness of preventive and etiological therapy is considered.

[Inhibitory and mild forms of hemophilia: diagnostic difficulties, surgical complications]. / Trudnosti diagnostiki i khirurgicheskie oslozhneniia pri razlichnykh formakh gemofilii.

AIM: To identify patients with hemophilia who have a high risk of postoperative hemorrhagic complications. MATERIAL AND METHODS: Prospective trial included 69 patients aged 18-71 years (median 29) with congenital hemophilia A and B. They underwent elective and emergency treatment for abdominal and thoracic pathology at the National Medical Research Center for Hematology in 2011-2016. Patients with mild and inhibitory forms of hemophilia were compared with those with severe and moderate forms of hemophilia. There were 50 (73%) patients with severe and moderate forms of hemophilia, 8 (11%) with inhibitory and 11 (16%) patients with mild form. Emergency operations were performed in 18 cases, elective - in 51. RESULTS: Inhibitory form of hemophilia is associated with 1.5 times higher (95% CI, 1.1-3.0) risk of hemorrhagic postoperative complications and death and 3,5 times higher (95% CI 1.7-5.9) risk of redo surgery compared with severe and moderate forms (p<0.05). Risk of hemorrhagic postoperative complications is also higher in patients with mild form of hemophilia compared with severe and moderate forms (1/6 vs. 1/50; p=0.05). CONCLUSION: The risk of postoperative hemorrhagic complications is significantly higher in inhibitory and mild hemophilia compared with severe and moderate forms and associated with hemostatic therapy defects and inadequate assessment of hemostatic disorders. Long-standing haemorrhagic syndrome should be followed by blood clotting system analysis including evaluation of procoagulant activity, presence of inhibitor, and thromboelastography. Decreased levels of albumin (by 2.9-8.6% in our trial) and cholesterol (by 6.5-54.8%) reflects impaired liver function and is sign of unfavorable prognosis. This finding should be considered for surgery and therapy of hemorrhagic manifestations.

Coagulation factor II from rock bream (Oplegnathus fasciatus): First report on the molecular biological function and expression analysis in the teleost.

The rapid haemostasis of fish prevents bleeding or infection that could be caused by physical properties of the aquatic environment. Additionally, the innate immune system is the first line of defence against infection and is responsible for the recognition of pathogen-associated molecular patterns, which are important for the activation of acquired immune responses. Coagulation factor II (CFII) is an important factor in the coagulation system and is involved in recognition and interaction with various bacterial and extracellular proteins. In this study, we identified and characterised the gene encoding CFII in rock bream (Oplegnathus fasciatus) (RbCFII) and analysed its expression in various tissues after a pathogen challenge. The full-length RbCFII cDNA (2079 bp) contained an open reading frame of 1854 bp encoding 617 amino acids. Alignment analysis revealed that a gamma-carboxyglutamic acid-rich domain, two kringle domains, and a trypsin-like serine protease domain of the deduced protein were well conserved. RbCFII was ubiquitously expressed in all tissues examined but, predominantly detected in the liver and skin. RbCFII expression was dramatically up-regulated in the kidney, spleen and liver after infection with Edwardsiella tarda, Streptococcus iniae, or red seabream iridovirus. The recombinant protein RbCFII (rRbCFII) produced using an Escherichia coli expression system was able to bind all examined bacteria. Interestingly, rRbCFII has agglutination activities towards E. coli and E. tarda, while no agglutination was shown toward Vibrio ordalii and S. iniae. These findings indicate that rRbCFII performs an immunological function in the immune response, and might be involved in innate immunity as well as blood coagulation.

Esophageal perforation due to soft coagulation heat injury after right lower lobectomy: A case report.

INTRODUCTION: Soft coagulation is a hemostatic system of electrosurgical units that automatically regulates its output to avoid carbonization or incision. This system is widely used in invasive procedures, including thoracic surgery. Few reports exist on the harmful effects of these devices. Herein, we encountered a case of an esophagopleural fistula caused by soft coagulation. PRESENTATION OF CASE: A 74-year-old man with a history of bladder cancer was diagnosed with a tumor in the right lower lung lobe 2.5 cm in diameter. A thoracoscopic right lower lobectomy with lymph node dissection was performed. During surgery, hemostasis using soft coagulation was performed on the right wall of the lower esophagus. Eight days after surgery, thoracoscopic empyema curettage and drainage were performed. Three days after the second surgery, an esophageal fistula was identified. Suturing for the esophageal fistula and omentoplasty were performed. Suture failure occurred and an esophagobronchial fistula developed after the third surgery, which was reduced by drainage, antibiotics, and enteral nutrition. The fistula was finally addressed by fibrin glue filling in its cavity. DISCUSSION: Soft coagulation helps manage hemostasis and contributes to safe surgery. However, it may cause severe complications owing to the unpredictable spread of heat denaturation. It is suspected that delayed esophageal perforation was caused by an unnoticed heat injury to the deeper layer of the esophageal wall. CONCLUSION: There have been no reports of esophagus injury caused by soft coagulation exept for our experience. Although soft coagulation is a useful device owing to its excellent hemostatic capacity, the spread of heat denaturation may cause unpredictable tissue damage. Extra caution should be observed when using this device for hemostasis.

Emerging roles of protease-activated receptors in cardiometabolic disorders.

Cardiometabolic disorders, including obesity-related insulin resistance and atherosclerosis, share sterile chronic inflammation as a major cause; however, the precise underlying mechanisms of chronic inflammation in cardiometabolic disorders are not fully understood. Accumulating evidence suggests that several coagulation proteases, including thrombin and activated factor X (FXa), play an important role not only in the coagulation cascade but also in the proinflammatory responses through protease-activated receptors (PARs) in many cell types. Four members of the PAR family have been cloned (PAR 1-4). For instance, thrombin activates PAR-1, PAR-3, and PAR-4. FXa activates both PAR-1 and PAR-2, while it has no effect on PAR-3 or PAR-4. Previous studies demonstrated that PAR-1 and PAR-2 activated by thrombin or FXa promote gene expression of inflammatory molecules mainly via the NF-κB and ERK1/2 pathways. In obese adipose tissue and atherosclerotic vascular tissue, various stresses increase the expression of tissue factor and procoagulant activity. Recent studies indicated that the activation of PARs in adipocytes and vascular cells by coagulation proteases promotes inflammation in these tissues, which leads to the development of cardiometabolic diseases. This review briefly summarizes the role of PARs and coagulation proteases in the pathogenesis of inflammatory diseases and describes recent findings (including ours) on the potential participation of this system in the development of cardiometabolic disorders. New insights into PARs may ensure a better understanding of cardiometabolic disorders and suggest new therapeutic options for these major health threats.

A sealant with a hemostatic mechanism independent of the blood coagulation function was effective in both elective and emergency surgery for thoracic aorta.

OBJECTIVES: Matsudaito is a unique surgical sealant with a powerful hemostatic effect that works independent of a patient's blood coagulation function. Because of its mechanism, this sealant is expected to be particularly useful in patients with a poor blood coagulation function, such as in cases of acute aortic syndrome requiring emergency surgery. We, therefore, evaluated the hemostatic static effect of the sealant in both emergency and elective surgery of the thoracic aorta. METHODS: We used data obtained from post-marketing surveillance of the sealant. Patients who underwent replacement of the thoracic aorta were enrolled. The hemostatic effect was evaluated as effective if a further hemostatic procedure was not performed after applying the sealant. RESULTS: From 46 hospitals in Japan, a total of 542 patients (327 elective and 215 emergency cases) were enrolled. Hospital mortality was 4.0% and 11.6% in elective and emergency cases, respectively (p < 0.05). Among the 1039 anastomoses (609 elective and 430 emergency cases), effective hemostasis was confirmed in 436 (71.6%) elective and 259 (60.2%) emergency cases. The data from the clinical trial of the sealant showed a hemostatic rate of 44.4% in elective control cases without the sealant. CONCLUSION: Given that the hemostatic rate in emergency surgery with the sealant seemed to be better than that in elective surgery without the sealant (determined from the clinical trial), we concluded that the sealant was effective in both emergency and elective thoracic surgery of the aorta.

Cerebrospinal fluid proteomics in recent-onset Narcolepsy type 1 reveals activation of the complement system.

Introduction: Narcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes. Methods: To gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer. Results and discussion: Our study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system.

Dysregulated coagulation system links to inflammation in diabetic kidney disease.

Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting that these systems could serve as promising therapeutic targets for DKD. This review aims to shed light on the underlying connections between coagulation and complement systems and their involvement in the advancement of DKD.

Surgical technique of laparoscopic ureterocalicostomy using the VIO soft-coagulation system.

One of the most crucial issues while performing ureterocalicostomy (UC) in patients with well-functioning thick renal parenchyma is controlling bleeding from the anastomotic site. In general, renorrhaphy is necessary for hemostasis because conventional coagulation remains unreliable in cases of an incised thick renal parenchyma. Instead of the parenchymal renorrhaphy, the VIO soft-coagulation system is used for hemostasis. Sutureless hemostasis using soft coagulation is a safe, feasible, and minimally invasive technique for laparoscopic UC.