Blood Coagulation & Fibrinolysis最新文献

One of the complications of chronic kidney disease (CKD) is venous thromboembolism (VTE). Currently, the D-dimer test is used for the diagnosis of VTE. This test has low diagnostic value and specificity. Circulating microRNAs are present in plasma, serum, and other body fluids and have recently been shown to be valuable biomarkers in numerous illnesses. Therefore, this study aimed to evaluate the diagnostic potential of serum microRNAs as noninvasive biomarkers for VTE diagnosis in hemodialysis patients. Serum samples were collected from 42 hemodialysis patients with thrombosis, 42 hemodialysis patients without thrombosis, and 42 healthy individuals. After the synthesis of cDNA from serum, the expression of miR-24-3P and miR-1277-5P was measured by qRT-PCR. The data were analyzed using SPSS 20 and GraphPad Prism7 software. The expression level of miR-24-3P in the thrombotic and nonthrombotic hemodialysis groups was significantly greater than that in the healthy groups after adjustment for hyperglycemia ( P  = 0.003, P  = 0.04). Receiver-operating characteristic (ROC) analysis revealed that the area under the curve (AUC) values were 0.769 and 0.649, respectively. However, in the thrombotic group compared with the nonthrombotic group after adjustment for hyperglycemia, no significant difference was detected ( P  = 0.063), and the AUC was 0.62. After adjustment for age, sex, and BMI, there was a significant difference between the thrombotic group and the nonthrombotic group ( P  = 0.002), and the AUC was 0.71. Compared with that in the control group, the odds ratio (OR) of increased miR-1277-5P expression was greater in the thrombotic group ( P  = 0.05, OR = 1.618). There was no significant difference between the nonthrombotic group and the control group ( P  = 0.73, OR = 0.914). Our results indicated that miR-24-3P is not a reliable marker for examining thrombosis in the studied samples, while miR-1277-5P has a positive association with VAT and could be considered a diagnostic and therapeutic marker.

This study aims to examine the impact of intrauterine growth restriction (IUGR) on coagulation in preterm newborns and assess the administration of fresh frozen plasma. The study involved 30 preterm infants with IUGR and 32 preterm infants without it. Blood samples were collected within 4 h after birth to analyze blood gases, complete blood counts, renal and liver function tests, and coagulation factors. Differences between the two groups were assessed using SPSS version 15. IUGR significantly impacts coagulation in infants born before the 32nd week of gestation. Preterm infants with IUGR, specifically those born before 32 weeks, show notably lower levels of coagulation factors V, VII, XIII, and antithrombin III. Additionally, they have higher levels of factor VIII and longer thromboplastin times. The coagulation effects are less pronounced in infants born at or after 32 weeks of gestation than those born before 32 weeks. Moreover, factor XII levels are significantly higher in all preterm infants with IUGR. Preterm infants with intraventricular hemorrhage have prolonged prothrombin time and activated partial thromboplastin time, and their coagulation factor levels differ significantly. Conventional coagulation tests may not reliably predict bleeding tendencies in preterm infants with IUGR. However, these tests help assess the risk of intraventricular hemorrhage in preterm babies. Infants born before 32 weeks of gestation often have lower levels of coagulation factors because of growth restriction, which makes the administration of fresh frozen plasma a reasonable option in cases of bleeding for this population. Additionally, factor XII levels may provide insight into conditions related to hypoxia and inflammation, including IUGR.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by clinical features including oculocutaneous albinism (OCA) and bleeding diathesis due to platelet storage pool deficiency. In this article, we report a 12-year-old boy with recurrent epistaxis who was referred to the Iranian Blood Transfusion Organization (IBTO) reference coagulation laboratory for platelet function analysis. Based on the laboratory diagnostic tests in this study and the patient's clinical presentation, the probability of HPS type 2 is more likely.

Venous thromboembolism (VTE) is a complex condition influenced by genetic and acquired factors. While genetic variations in proteins like S, C, and antithrombin are known to play a role in VTE, some cases remain unexplained. This study aims to investigate other genetic variations, including Protein Z (rs3024731), FV (rs1800595), and FGA (rs6050), to understand their potential association with VTE risk. The study included 118 VTE patients and 118 healthy individuals with no history of thromboembolic disorders. Blood samples were collected from the patients for DNA extraction, and genotyping was carried out using the amplification refractory mutation system-PCR (ARMS-PCR) technique. The results were validated through DNA sequencing. Data analysis was done using SPSS 27 software. Analysis has revealed significant differences in the genotypic and allelic frequencies of the rs1800595 polymorphism between the control and case groups. It was found that individuals with the AG genotype had a 2.22 times higher likelihood of experiencing thrombophilia events [odds ratio (OR) = 2.229, P  = 0.039, confidence interval (CI) = 95%], while the G allele increased the risk by 2.103 times (OR = 2.103, P  = 0.047, CI = 95%). No significant correlation was observed between VTE and the rs3024731 and rs6050 polymorphisms. The rs1800595 polymorphism in the FV gene may be associated with an increased risk of thrombophilia in VTE patients.

Background: Protein C (PROC) deficiency is a rare hematological disorder caused by mutations in the PROC gene, leading to severe coagulopathy in homozygous cases. This report highlights the hematological challenges in managing homozygous protein C deficiency, particularly its association with intracerebral hemorrhage and thrombosis.

Case report: We describe two sisters with a homozygous PROC gene mutation (c.797A>G, p.Tyr266Cys), presenting with protein C activity <10%. The older sister (born 2020) developed neonatal intracerebral hemorrhage, followed by recurrent hemorrhage and deep vein thrombosis by 2025, managed with heparin, warfarin, and rivaroxaban. The younger sister (born 2022) also experienced neonatal hemorrhage and required anticoagulant therapy with heparin and warfarin. Both developed neurological complications, including epilepsy.

Conclusion: Homozygous protein C deficiency can lead to severe neonatal coagulopathy, necessitating early diagnosis and aggressive anticoagulant therapy. This case underscores the importance of multidisciplinary management and genetic screening in affected families.

Congenital hypofibrinogenemia presents not only with bleeding, but also paradoxically with thrombosis. This heterogeneity of clinical phenotype complicates both diagnosis and management. The thrombotic phenotype is thought to arise from alterations in fibrin structure and stability, leading to abnormal clot formation and an increased risk of thrombosis. Coagulation assays, gene analysis, and protein modeling were utilized to elucidate the pathogenic variant. We highlight the pathophysiology of the novel missense variant in the FGG gene (c.823G/A, p.Glu275Lys ), which causes mild hypofibrinogenemia and clinically manifests as an ischemic stroke. Protein modeling displays that the amino-acid substitution of glutamine with lysine at position 275 in mentioned missense variant causes local changes in the fibrinogen structure. The structural changes are mainly minor surface alterations and changes in physicochemical properties, which could potentially affect the recruitment of other proteins or lead to abnormal fibrin polymerization. This study provides novel insights into the pathophysiological mechanism, emphasizing the importance of molecular and structural analyses in understanding and managing atypical presentations of fibrinogen disorders.

Background: Venous thromboembolism (VTE) has a genetic component that can differ significantly among populations. The genetic landscape of VTE in China, where incidence is rising, may harbor unique susceptibilities. This study aimed to examine the factor XI (FXI) c.539A>G polymorphism's role in VTE risk and its correlation with FXI levels among central Chinese VTE patients.

Methods: We included 1748 VTE patients and 1819 matched controls, and extracted genomic DNA. Direct sequencing identified the FXI c.539A>G mutation in 50 patient samples. FXI antigen levels were quantified using ELISA, and bioinformatics evaluated the mutation's biological significance.

Results: The FXI c.539A>G mutation occurred in three heterozygous individuals. It was more prevalent in VTE patients (2.26%) than controls (1.37%), with a significant odds ratio of 1.66 (95% CI: 1.16-2.37, P  = 5.03 × 10 -3 ). Patients with the mutation showed increased FXI antigen levels (16.76 ± 5.78 ng/ml) versus the wild-type (10.77 ± 4.98 ng/ml, P  = 1.20 × 10 -3 ), without affecting FXI activity ( P  = 0.57).

Conclusion: The FXI c.539A>G variant is associated with VTE in central China, marked by elevated FXI antigen levels but not altered activity. This finding suggests that FXI c.539A>G may serve as a genetic marker for VTE risk. Further studies are needed to explore its role in early screening of VTE and gene-environment interactions.

DOCK8 deficiency syndrome, formerly known as autosomal recessive hyper-IgE syndrome (AR-HIES), is a rare combined immunodeficiency disorder characterized by recurrent infections, eczema, eosinophilia, and elevated immunoglobulin E (IgE) levels. We present a case of a 6-year-old girl with DOCK8 deficiency syndrome, who experienced recurrent skin infections and molluscum contagiosum since infancy. Genetic testing confirmed the diagnosis. Due to the high morbidity and mortality associated with DOCK8 deficiency syndrome, she underwent hematopoietic stem cell transplantation (HSCT) from her father. Posttransplant, the patient's skin condition significantly improved, and she achieved full donor chimerism. This case highlights the importance of considering DOCK8 deficiency in patients with recurrent infections, eczema, eosinophilia, and high IgE levels, and the potential curative effect of HSCT for these patients.

Objective: This study aims to evaluate the hemostatic effects of combined extracts from Thymus vulgaris and Medicago sativa in an animal model, focusing on their impact on coagulation indices. We hypothesize that the combined extracts will modulate the extrinsic and intrinsic coagulation pathways, improving hemostasis.

Methods: Thirty-two male NMRI mice were randomly assigned to four groups ( n  = 8): negative control (distilled water), 300 mg/kg/day M. sativa (MS300), 100 mg/kg/day T. vulgaris extract (TV100), and combined extracts (TV100 + MS300). After 14 days of treatment, blood samples were collected to measure prothrombin time (PT) and activated partial thromboplastin time (aPTT). Chemical analysis identified active compounds, and molecular docking studies were performed to assess their interaction with coagulation factor VIIa (FVIIa).

Results: The treated groups showed significant changes in coagulation indices compared to the control. PT was significantly decreased ( P  < 0.05), and aPTT was significantly increased ( P  < 0.05) in the M. sativa , T. vulgaris , and combined extract groups. The combined extract showed the most significant effect. Computational analyses revealed that compounds like Scandenon and Vitamin E interacted with FVIIa, suggesting their role in modulating the extrinsic coagulation pathway. These compounds showed strong binding affinity to FVIIa.

Conclusion: Combined extracts of T. vulgaris and M. sativa significantly influence coagulation, especially the extrinsic pathway. The presence of aromatic, hydroxyl, alcoholic, and phenolic groups in these compounds likely contributes to their interaction with coagulation factors. These findings support the potential development of plant-based hemostatic agents for clinical use.

Objectives: Stroke is an injury occurring due to a sudden interruption of blood supply to the brain. It is the leading cause of disability worldwide and the second most prevalent cause of mortality. The objective of this study is whether momentous inflammatory and coagulation markers may have a correlation with each other in stroke patients.

Material and methods: Sixty stroke patients and twenty sex-age matched normal controls were sampled. Interleukin (IL)-6, IL-1β, sP-selectin, and high-sensitivity C-reactive protein (hsCRP), key inflammatory markers, were selected and measured by ELISA, and tissue factor gene expression level was evaluated by real-time PCR in peripheral blood mononuclear cells.

Results: The serum levels of sP-selectin, IL-1β, IL-6, and hsCRP increased significantly in patients ( P -value < 0.05). In the patient group, a significant correlation was observed between these inflammatory markers and coagulant tissue factor gene expression in peripheral blood mononuclear cells ( P -values < 0.05), while it was not significant in the control group.

Conclusion: This study proposed that the main inflammatory markers in connection with tissue factor may play a role in the occurrence of thrombosis in stroke patients. Therefore, targeting and inhibiting the key inflammatory factors along with existing anticoagulants may greatly reduce the complications associated with stroke.