Gynecological bleeding in women with congenital bleeding disorders: A comprehensive cohort from Iran.

BACKGROUND: Gynecological bleeding including menorrhagia and postpartum hemorrhage (PPH) face women's quality of life constantly with difficulties, especially those suffering from inherited bleeding disorders. In this study, we aim to evaluate gynecological bleeding particularly menorrhagia among Iranian women patients with inherited bleeding disorders admitted to the Iranian Comprehensive Hemophilia Care Center (ICHCC). METHODS: This study was conducted on 156 females aged ≥ 12 diagnosed with an inherited bleeding disorder in ICHCC. Demographic and laboratory data were documented for all patients. Bleeding questionnaires (the International Society on Thrombosis and Hemostasis bleeding assessment tool (ISTH-BAT), Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand disease (MCMDM-1), and Pictorial blood loss assessment chart (PBAC)) were filled out for all patients. For comparing metric and categorical parameters, Mann-Whitney was performed. Spearman's rho test was used for analyzing correlation. RESULTS: The mean age of patients was 33. Von Willebrand disease (VWD), Factor (F) VII deficiency and combined factor deficiency were the most diagnosed disorders. The median of ISTH-BAT, MCMDM-1, and PBAC was 7,7, and 517, respectively. Menorrhagia was the most common reason for diagnosis. Menorrhagia and PPH domain scores ≥ 2 were recorded in 82 and 34 patients, respectively, and PBAC scores > 100 were seen in 118 patients. Significant positive correlations were observed between bleeding scores and menorrhagia and PPH scores. No significant correlations were recorded for VWF: Ag and VWF: RCo with menorrhagia and PPH scores; however, significant correlations were seen for VWF: Ag and VWF: RCo with bleeding score questionnaires. CONCLUSION: Menorrhagia is the most common problem in females affected by different types of inherited bleeding disorders, particularly VWD. Increased awareness among gynecologists and hematologists about bleeding disorders in cases with unexplained menorrhagia is an essential step for optimal management.

Neutrophil extracellular traps in influenza infection.

Despite recent progress in developing novel therapeutic approaches and vaccines, influenza is still considered a global health threat, with about half a million mortality worldwide. This disease is caused by Influenza viruses, which are known for their rapid evolution due to different genetical mechanisms that help them develop new strains with the ability to evade therapies and immunization. Neutrophils are one of the first immune effectors that act against pathogens. They use multiple mechanisms, including phagocytosis, releasing the reactive oxygen species, degranulation, and the production of neutrophil extracellular traps. Neutrophil extracellular traps are used to ensnare pathogens; however, their dysregulation is attributed to inflammatory and infectious diseases. Here, we discuss the effects of these extracellular traps in the clinical course of influenza infection and their ability to be a potential target in treating influenza infection.

Natural killer cells and their exosomes in viral infections and related therapeutic approaches: where are we?

Innate immunity is the first line of the host immune system to fight against infections. Natural killer cells are the innate immunity lymphocytes responsible for fighting against virus-infected and cancerous cells. They have various mechanisms to suppress viral infections. On the other hand, viruses have evolved to utilize different ways to evade NK cell-mediated responses. Viruses can balance the response by regulating the cytokine release pattern and changing the proportion of activating and inhibitory receptors on the surface of NK cells. Exosomes are a subtype of extracellular vesicles that are involved in intercellular communication. Most cell populations can release these nano-sized vesicles, and it was shown that these vesicles produce identical outcomes to the originating cell from which they are released. In recent years, the role of NK cell-derived exosomes in various diseases including viral infections has been highlighted, drawing attention to utilizing the therapeutic potential of these nanoparticles. In this article, the role of NK cells in various viral infections and the mechanisms used by viruses to evade these important immune system cells are initially examined. Subsequently, the role of NK cell exosomes in controlling various viral infections is discussed. Finally, the current position of these cells in the treatment of viral infections and the therapeutic potential of their exosomes are reviewed. Video Abstract.

Associations of multiple genetic variations with plasma levels of Von Willebrand Factor and clinical phenotype in Iranian patients with Von Willebrand disease type 1.

BACKGROUND: Genetic variations influence the Von Willebrand Factor plasma level and function. This study aims to evaluate the frequency and clinical phenotype effects of eight single nucleotide polymorphism candidates in four genes (VWF, STXBP5, CLEC4M, and ABO) in Iranian patients with VWD type 1. METHOD: The study recruited 50 patients with VWD type 1 and 100 healthy individuals. The demographic data from all participants were collected, and the High-Resolution Melting technique was used to determine the frequency of specific single nucleotide polymorphisms. Bleeding scores were also obtained from all patients to assess how these genetic variations might affect the severity of their bleeding symptoms. RESULTS: The study found notable variations in the occurrence of certain SNPs (rs7853989 and rs8176743 for ABO gene and rs1063856 and rs1063857 for VWF gene) between the control group and the patients. Additionally, the study discovered that two SNPs (rs868875 for CLEC4M gene and rs9390459 for STXBP5 gene) were significantly linked to the severity of bleeding, and two others (rs868875 for CLEC4M gene and rs8176746 for ABO gene) were associated with reduced levels of VWF antigen in the patients. CONCLUSION: According to this study, the above-selected SNPs can cause variations in VWF plasma levels in patients with VWD type 1. Furthermore, the effects of SNPs on bleeding phenotype prove the role of these SNPs in the severity of bleeding manifestations in patients.

Coagulopathy and thromboembolic events a pathogenic mechanism of COVID-19 associated with mortality: An updated review.

During 2019, the SARS-CoV-2 emerged from China, and during months, COVID-19 spread in many countries around the world. The expanding data about pathogenesis of this virus could elucidate the exact mechanism by which COVID-19 caused death in humans. One of the pathogenic mechanisms of this disease is coagulation. Coagulation disorders that affect both venous and arterial systems occur in patients with COVID-19. The possible mechanism involved in the coagulation could be excessive inflammation induced by SARS-CoV-2. However, it is not yet clear well how SARS-CoV-2 promotes coagulopathy. However, some factors, such as pulmonary endothelial cell damage and some anticoagulant system disorders, are assumed to have an important role. In this study, we assessed conducted studies about COVID-19-induced coagulopathy to obtain clearer vision of the wide range of manifestations and possible pathogenesis mechanisms.

Bleeding disorder of unknown cause: Results from Iranian study.

BACKGROUND: Definite diagnosis of patients with mild to moderate bleeding is challenging. Some studies reported that even more than 50% of their patients remained undiagnosed which is classified as a Bleeding disorder of unknown cause (BDUC). This study aims to document the clinical characteristics and proportion of patients with BDUC in the Iranian Comprehensive Hemophilia Care Center (ICHCC) one of the referral centers for diagnosis of congenital bleeding disorder in Iran. METHODS: This study was conducted on 397 patients who were referred with a bleeding manifestation to ICHCC from 2019 to 2022. Demographic and laboratory data were documented for all patients. Bleeding questionnaires including ISTH-Bleeding Assessment tool (ISTH-BAT) and the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 (MCMDM-1 (ISTH-BAT, MCMDM-1, and the Pictorial Bleeding Assessment Chart (PBLAC) were filled out for all patients. The data were analyzed by the statistical package for social science (SPSS version 22, SPSS, Chicago, Illinois, USA). RESULTS: BDUC was diagnosed in 200 patients and 197 patients reached the final diagnosis. Hemophilia, von Willebrand disease (VWD), factor (F) VII deficiency, and platelet functional disorders (PFDs) were confirmed in 54, 49, 34, and 15 of the patients, respectively. No significant difference was found in bleeding scores between patients with BDUC and those with confirmed disease. In contrast, after setting cut-off (ISTH-BAT for males ≥ 4 and females ≥ 6 and MCMDM-1 for males ≥ 3 and females ≥ 5) clinically significant difference was found. There was no association between having a positive consanguineous marriage and setting a diagnosis; however, significant associations were seen for having a positive family history of bleeding. Age (OR =0.977, 95% CI.965-0.989), gender (BDUC female, 151/200; final diagnosis female, 95/197) (OR=3.3, 95% CI 2.16-5.06), family history (OR = 3.19, 95% CI 1.99-5.11), and consanguineous marriage (OR=1.59, 95% CI 1.03-2.45) were considered as a risk factor for categorizing the patients with BDUC or final diagnosis. CONCLUSION: The findings are mainly in line with previous studies about BDUC patients. The large number of patients with BDUC underlines the incompleteness of available routine laboratory tests and shows the necessity of progress in the development of reliable diagnostic tools to identify underlying bleeding disorders.

Global epidemiology of HBV infection among hemodialysis patients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Hemodialysis (HD) is a life-saving procedure that purifies the blood in patients with end-stage renal disease (ESRD). Among all major complications, blood-borne diseases like hepatitis B virus (HBV) may be exposed as serious side effects of hemodialysis. A comprehensive review of the global burden of HBV among HD patients has not been written so far. The aim of the current systematic review and meta-analysis was to determine the globally epidemiology of HBV infection among HD patients. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, articles that investigated the prevalence of HBV among HD patients were searched from the major databases such as EMBASE, PubMed, Web of Science collection, and Scopus. Pooled prevalence with 95% CI and identification of heterogeneity were obtained using the random effects model and Cochran's Q-test, respectively, and quantification was evaluated using the I2 statistics. All statistical analyses were performed by STATA 14.1 statistical software. RESULTS: among 322 datasets (795,623 cases) that included in this study, the pooled prevalence of HBV infection among HD patients was 7.32% (95% CI: 6.53-8.15%; I2 = 97.91%), including 7.57% (95% CI: 6.69-8.48%) for HBsAg and 6.09% (95% CI: 4.05-8.49%) for DNA, respectively. In addition, based on geographic area, the prevalence was 7.44% (95% CI: 6.35-8.61%) in Asia, 4.32% (95% CI: 2.21-7.04%) in North America, 7.07% (95% CI: 6.35-8.61%) in Europe, 5.52% (95% CI: 3.60-7.78%) in Africa, 8.45% (95% CI: 5.81-11.78%) in Oceania, and 9.73% (95% CI: 7.11-12.70%) in South America. CONCLUSIONS: Our analysis indicates a relatively high prevalence of HBV infection in HD patients, even in some developed countries. Considering that ESRD patients are not able to properly respond to the vaccination strategies in order to develop an acceptable immunity, vaccination of healthy individuals is highly recommended to arm their bodies for possible immunocompromise conditions in the future. Moreover, donated blood in blood transfusion centers should be checked for possible hepatitis B virus infection using sensitive molecular tests.

Natural killer cells in COVID-19: from infection, to vaccination and therapy.

Natural killer (NK) cells are among the most important innate immunity members, which are the first cells that fight against infected cells. The function of these cells is impaired in patients with COVID-19 and they are not able to prevent the spread of the disease or destroy the infected cells. Few studies have evaluated the effects of COVID-19 vaccines on NK cells, though it has been demonstrated that DNA vaccines and BNT162b2 can affect NK cell response. In the present paper, the effects of SARS-CoV-2 on the NK cells during infection, the effect of vaccination on NK cells, and the NK cell-based therapies were reviewed.

The Role of NK Cells and Their Exosomes in Graft Versus Host Disease and Graft Versus Leukemia.

Natural killer (NK) cells are one of the innate immune cells that play an important role in preventing and controlling tumors and viral diseases, but their role in hematopoietic stem cell transplantation (HCT) is not yet fully understood. However, according to some research, these cells can prevent infections and tumor relapse without causing graft versus host disease (GVHD). In addition to NK cells, several studies are about the anti-leukemia effects of NK cell-derived exosomes that can highlight their roles in graft-versus-leukemia (GVL). In this paper, we intend to investigate the results of various articles on the role of NK cells in allogeneic hematopoietic cell transplantation and also their exosomes in GVL. Also, we have discussed the antiviral effects of these cells in post-HCT cytomegalovirus infection.