Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematologic disorder characterized by complement-mediated intravascular hemolysis, pancytopenia, and thrombosis. NTQ5082 is a novel oral selective complement factor B (CFB) inhibitor that suppresses alternative pathway activity, thereby inhibiting intravascular hemolysis in PNH. We conducted a randomized, open-label Phase 2 study to investigate NTQ5082 monotherapy in adults with PNH who had not previously received complement inhibitors. Twenty-five patients were assigned to receive oral NTQ5082 once daily (QD) at 100 mg (group A) or 200 mg (group B) for 12 weeks. In both groups, lactate dehydrogenase (LDH) levels rapidly decreased, and hemoglobin (Hb) levels increased within 1 week after treatment initiation, with no further transfusions needed. At week 12, the mean LDH concentration was 239.4 ± 63.5 U/L in group A and 245.8 ± 72.6 U/L in group B. The Hb concentration increased to ≥ 20 g/L from baseline in 100% of patients, while 50% and 61.5% of patients in groups A and B, respectively, achieved Hb concentrations ≥ 120 g/L. The most frequently reported treatment-related adverse events (TRAEs) were headache (12%), upper respiratory tract infection (8%), and decreased neutrophil count (8%); no grade ≥ 3 adverse events (AEs) were reported. Oral NTQ5082 administered at 100 or 200 mg QD effectively controlled hemolysis, significantly increased Hb levels, and improved quality of life, with a satisfactory safety profile, suggesting that NTQ5082 may represent a promising therapeutic option for complement inhibitor-naïve patients with PNH.

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia characterized by the abrupt onset of hemoglobinuria and anemia, typically following exposure to cold temperatures. The pathogenesis of PCH is primarily associated with the presence of a unique autoantibody known as the Donath-Landsteiner antibody, a biphasic hemolysin (immunoglobulin G) with specificity for P blood group antigens. This rare clinical entity can manifest at any age; however, in children, it typically follows a viral upper respiratory tract infection or immunization. We hereby report a rare case of PCH in a 3-year-old boy who presented at our hospital with severe anemia along with liver and renal dysfunction.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disorder caused by mutations affecting the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. Recent advances in genetic analyses have shown that, in addition to PIGA mutations, rare mutations in PIGT, PIGB, and PIGV can also underlie PNH. Moreover, PNH may have an oligoclonal structure, and small PIGA-mutated clones can be detected even in healthy individuals. The expansion of PNH clones is thought to be driven not only by immune-mediated selective pressure but also, in some cases, by HMGA2 mutations and myeloid driver lesions, suggesting that PNH develops through multifactorial mechanisms that vary among patients. In addition, the genetic factors involved in progression to secondary myeloid neoplasms and response to complement inhibitors are becoming better understood. This article reviews the genetic findings relevant to PNH and discusses their clinical significance.

Iptacopan, an oral Factor B inhibitor, is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). In clinical trials it was safe and effective but real-world data, particularly in patients with associated bone marrow failure, remain limited. A retrospective, multicenter study was conducted in patients with PNH who received iptacopan monotherapy in the UK and France between July 2021 and July 2025. Patient demographics, prior treatment and indication for switch were collected, as were hematological parameters at baseline, 3, 12 and 24 months. Outcomes included breakthrough hemolysis, infections, thrombotic events, treatment discontinuation and death. A total of 151 patients were included with a median treatment duration of 238 days. Iptacopan produced significant increases in mean hemoglobin, from 104 g/L at baseline to 127 g/L at 3 months, with improvements sustained to 24 months. A total of 76% achieved a hemoglobin ≥ 120 g/L by 12 months, compared with 21.9% at baseline, with transfusion independency in 88%. There was no statistical difference in responses between patients with and without history of bone marrow failure. Breakthrough hemolysis occurred in 6.6% of patients, with a mean hemoglobin fall of 24 g/L. Suspected bacterial infections occurred at a rate of 0.18 per patient-year, but there were no meningococcal or pneumococcal infections. There were no thromboses, and no deaths related to iptacopan. This cohort demonstrates that iptacopan produces sustained improvements in patients with PNH, irrespective of prior complement inhibition or history of bone marrow failure. Longer follow-up is needed to characterize long-term efficacy and infection risk.

Renal cortical hemosiderosis is the accumulation of iron in the renal cortex. On MRI, this can be inferred by marked cortical T2 hypointensity and loss of signal on in-phase imaging relative to opposed-phase imaging. Although classically associated with paroxysmal nocturnal hemoglobinuria, renal hemosiderosis can be seen in a variety of pathologic conditions associated with acute or chronic renal injury. We present a case of a 59-year-old female that developed acute kidney injury while hospitalized for management of hydronephrosis and hepatic abscess with imaging features on MR angiography and renal parenchymal biopsy consistent with renal cortical hemosiderosis. Combined with other laboratory results, this finding supports the diagnosis of atypical hemolytic uremic syndrome, a condition with poor prognosis for which timely treatment is essential. Thus, recognition of renal cortical hemosiderosis on imaging may facilitate appropriate clinical workup and timely management.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic disorder with a nonspecific clinical presentation that often delays the diagnosis. We present the case of a 32-year-old female patient who presented with diffuse abdominal pain, fatigue, and anemia. An abdominal ultrasound was performed, revealing hepatosplenomegaly, and a subsequent abdominal magnetic resonance imaging (MRI) identified diffuse, symmetrical renal cortical hypointense signal, consistent with chronic iron deposits due to intravascular hemolysis, together with absent hepatic venous flow and lack of venous enhancement, indicating chronic hepatic venous outflow obstruction consistent with Budd-Chiari syndrome. The combination of renal hemosiderosis with venous thrombosis at an unusual site prompted a hematological evaluation, which confirmed the diagnosis. This case reinforces a well-recognized imaging pattern that helps radiologists suspect this entity, thereby enabling timely diagnosis and treatment.

To describe outcomes after haematopoietic stem cell transplantation (HSCT) and non-transplant treatment in patients with classical paroxysmal nocturnal haemoglobinuria (cPNH) without access to complement inhibitors, we analysed 227 patients with cPNH treated at 10 centres between January 1976 and April 2022. Among them, 51 underwent HSCT and 176 received non-transplant treatment without complement inhibitors. At 6 months post-treatment, 96.08% of HSCT patients achieved normal complete blood count, compared to 3.41% in the non-HSCT cohort (p < 0.001). Estimated 5-year overall survival (OS) did not differ significantly between HSCT and non-HSCT cohorts (92.16% vs. 98.83%, p = 0.097). Five-year failure-free survival (FFS) was 92.16% in the HSCT cohort and 0.57% in the non-HSCT cohort (p < 0.001). Delayed platelet engraftment-free, graft-versus-host disease-free, failure-free survival did not differ significantly between HSCT performed within 12 months after diagnosis and later transplantation (83.33% vs. 62.34%, p = 0.136). In addition, alternative donor HSCT achieved OS and FFS comparable to matched sibling donor HSCT. This study reports outcomes after HSCT and non-transplant treatment in a historical setting without access to complement inhibitors. However, further studies are needed to clarify the role and indications for HSCT in cPNH in the complement inhibitor era.

Ciprocopan ([®]) is a small molecule inhibitor of complement factor B, which is a key component of the alternative complement pathway. It is being developed by Haisco Pharmaceutical Group for the treatment of complement-mediated disorders. In July 2026, ciprocopan received its first approval for treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have not previously received treatment with a complement inhibitor therapy in China. This article summarizes the milestones in the development of ciprocopan leading to this first approval.

A 6-y-old postpartum Nubian crossbreed goat was submitted for postmortem examination following a clinical course of ataxia, lateral head tilt, and recumbency. The liver had a poorly defined, pale-yellow focally extensive lesion and focal thickening of bile ducts. Histologically, an area of extensive coagulative necrosis was surrounded by many viable and degranulated neutrophils and gram-positive bacilli, which were identified as Clostridium novyi by immunohistochemistry. Numerous neutrophilic infiltrates were observed in the brainstem. PCR on DNA extracted from hepatic tissue was positive for the fliC, tcna, and tcnb genes of C. novyi type B. Additionally, PCR testing of brainstem tissue was positive for the hlyA gene of Listeria monocytogenes. To our knowledge, infectious necrotic hepatitis (INH), confirmed by molecular testing and with concurrent listeriosis, has not been reported previously in a goat. Clostridial hepatitis in animals is typically triggered by anaerobic conditions within the liver parenchyma, which facilitate the germination of dormant spores and the subsequent release of potent toxins. Although flukes were not observed, the presumptive inciting hypoxic event leading to parenchymal necrosis in this case was Fasciola hepatica larval migration. Because the clinical and pathology features of INH caused by C. novyi type B and bacillary hemoglobinuria caused by C. haemolyticum are nearly identical, molecular differentiation is essential to establish an accurate etiologic diagnosis.