Haemophilia A and B are X-linked inherited bleeding disorders caused by quantitative or qualitative deficiencies of coagulation factors VIII and IX, respectively. Understanding the underlying genetic pathogenesis and its variants is of paramount importance for current treatment targets, such as gene therapy. The current comprehensive review synthesizes the current evidence of molecular pathogenesis of haemophilia A and B, while it presents the therapeutic strategies, their limitations and future directions. Advances in molecular genetics have defined a highly heterogeneous mutational spectrum. Recurrent F8 inversions (intron 22 and 1) dominate severe phenotypes, while null mutations (nonsense, frameshift) are strongly associated with increased inhibitor risk. Conversely, missense variants predominantly underlie mild-to-moderate forms, and the identification of gain-of-function variants has directly informed next-generation therapeutic design. Clinically, strategies have transitioned from episodic replacement to individualized prophylaxis with ultra-long-acting concentrates and non-factor mimetics (emicizumab), which effectively prevent joint disease even in the presence of inhibitors. Furthermore, adeno-associated viral-mediated gene therapy offers a path toward a functional cure through sustained endogenous factor expression, although the long-term durability of FVIII expression and hepatic safety remain the primary current challenges. This review bridges the gap between the complex molecular landscape of haemophilia and the latest therapeutic breakthroughs. By linking specific genotypes to clinical outcomes and inhibitor risk, it provides a framework for precision management using factor, non-factor, and gene-based strategies in the current clinical landscape.
BACKGROUND Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in children, and splenectomy remains the standard treatment. However, postoperative thrombocytosis (PST) frequently occurs and may predispose patients to thromboembolic events. Despite its clinical relevance, the risk factors contributing to PST in children with HS remain inadequately defined, and reliable predictive tools are lacking. We hypothesized that specific clinical and hematological parameters could be integrated into a nomogram model to predict the occurrence of PST and thereby improve perioperative risk stratification and individualized management. AIM To identify risk factors for PST in children with HS after splenectomy and develop a predictive nomogram model. METHODS We retrospectively analyzed 230 children with HS who underwent total splenectomy at Anhui Provincial Children’s Hospital (2018 to 2025). Patients were classified into PST (n = 158) and normal platelet (n = 72) groups. Clinical features and preoperative hematological indices were collected, and postoperative platelet counts were monitored on days 6-10. Univariate and multivariate logistic regression identified independent predictors. A nomogram was constructed, and its discrimination, calibration, and clinical utility were evaluated using receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS Among 230 patients, 158 (68.7%) developed PST. Univariate analysis showed associations with preoperative hemoglobin < 90 g/L (P = 0.03), reticulocyte > 6% (P = 0.001), total bilirubin > 34 μmol/L (P = 0.04), preoperative platelet count < 150 × 109/L (P = 0.02), and transfusion ≥ 10 mL/kg (P = 0.01). Multivariate regression identified reticulocyte > 6% [odds ratios (OR) = 2.46, 95% confidence interval (CI): 1.35-4.48, P = 0.003], preoperative platelet count < 150 × 109/L (OR = 1.95, 95%CI: 1.12-3.39, P = 0.02), and transfusion ≥ 10 mL/kg (OR = 1.88, 95%CI: 1.09-3.24, P = 0.02) as independent predictors. The nomogram achieved an area under the curve of 0.92 (95%CI: 0.87-0.96), with good calibration and clinical net benefit across thresholds of 0.2-0.7. CONCLUSION PST is frequent after splenectomy in pediatric HS. The nomogram integrating reticulocyte percentage, platelet count, and transfusion volume provides an accurate and clinically useful tool for risk prediction and individualized perioperative management.
Haptoglobin, a protein primarily recognized for its role in sequestering free hemoglobin, has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases. This editorial explores the multifaceted roles of haptoglobin, highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes, cardiovascular disorders, and cancer. Through a synthesis of recent research findings, this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential. A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.
Haptoglobin (HP) is a liver glycoprotein that is actively synthesized during inflammatory and hemolytic processes. It also has pro-oxidant and proinflammatory properties, which are a function of its genotype. The genetic polymorphism of the chains leads to synthesis of three phenotypes/proteins, which are related to the number and type of chains and their molecular weight, namely HP1-1, HP1-2 and HP2-2. Patients with HP2-2 have more vascular complications, while those with HP1-1 have fewer. HP is involved in the worsening of diseases, such as HP2-2 in aggravation of vaso-occlusive crises in sickle cell disease, and worsening of the pathophysiology of other diseases. In contrast, HP1-1 confers better protection against diseases. All of this suggests that further studies should be conducted, including experimental and analytical studies focused on demonstrating the influence of different HP genotypes on individual clinical and hematological data. This would help in understanding the role played by this genetic polymorphism in the pathophysiology of diseases.
