Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of intravascular hemolysis caused by a somatic mutation in the gene responsible for glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins. This mutation leads to the production of abnormal blood cell clones lacking CD55 and CD59. PNH can result in renal damage. The challenge of early identification and diagnosis leads to misdiagnosis as other intravascular hemolytic conditions. This paper presents a case that began with fever, diarrhea, and acute renal failure, initially misdiagnosed as atypical hemolytic uremic syndrome (aHUS) but later confirmed as PNH through renal biopsy and related diagnostic tests. After treatment, the patient's renal function recovered, and anemia improved. Intravascular hemolysis is a prominent feature common to both PNH and HUS. They exhibit similar clinical manifestations, which pose a challenge for differential diagnosis. Unlike previous reports, the patient in this case denied any history of hematologic disorders, which made the diagnosis more challenging.

Pregnancy-associated hemolytic uremic syndrome (P-aHUS) is characterized by microvascular hemolytic anemia, thrombocytopenia, and acute organ damage, particularly acute kidney injury, occurring during pregnancy or in the postpartum period. This rare disease has been associated with mutations in genes that regulate the complement system in most reported cases. This article introduces a 38-year-old maternal, who gave birth again after 13 years. Approximately four days post-cesarean section, she developed severe anemia, thrombocytopenia, renal impairment, and abnormal liver function, prompting urgent symptomatic treatment by the doctor. Subsequent detections revealed decreased complement C3 levels, a negative result for the ADAMTS13 inhibitory antibody, and a negative stool culture for bacterial fungi. The diagnosis of P-aHUS was confirmed, and the condition was successfully managed with complement blockade therapy using Eculizumab. Genetic sequencing of the complement factor H (CFH) gene revealed the c.3643 C > T mutation (p.Arg1215*), indicating the presence of rare CFH gene variants that may contribute to the patient's condition. These findings elucidate the clinical manifestations and treatment responses associated with the rare disease P-aHUS in relation to specific gene mutations. We underscore the significance of genetic testing for accurate diagnosis and personalized treatment, offering new insights and evidence for the future clinical management and research of similar cases.

Atypical hemolytic uremic syndrome is a thrombotic microangiopathy caused by the abnormal activation of the alternative complement pathway. Mutations in complement-related genes and autoantibodies against complement regulators are involved in the pathogenesis of this condition; the frequency of, and prognosis of patients harbouring, each genetic mutation varies based on the region and race. Complement factor I (CFI) mutations have been observed in 4%-8% of cases in Europe; however, they have not yet been reported in Japan. We present the first Japanese case of atypical hemolytic uremic syndrome in a patient harbouring a CFI mutation. An 83-year-old female patient presented with severe acute kidney injury, thrombocytopenia, and hemolytic anaemia following a femoral neck fracture. Plasma exchange and haemodialysis were initiated, resulting in improved kidney function and platelet count. However, the platelet count decreased when plasma exchange was discontinued. Therefore, we administered ravulizumab, an anti-complement 5 monoclonal antibody, which led to the maintenance of stable kidney function and platelet count. Genetic analysis revealed a CFI mutation, and the patient was treated with ravulizumab for 2 years without relapse. Individuals diagnosed with atypical hemolytic uremic syndrome harbouring CFI mutations experience poor outcomes, including low rates of remission, high rates of mortality, and progression to end-stage kidney disease. Our case serves as a crucial example demonstrating how prompt identification and appropriate management can lead to better patient outcomes.

Eculizumab is a C5 complement inhibitor approved by the FDA for the targeted treatment of four rare diseases, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and aquaporin-4 immunoglobulin G-positive optic neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD). The current study was conducted to assess real-world adverse events (AEs) associated with eculizumab through data mining of the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses, including Reporting Ratio Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms were used to quantify the signals of eculizumab-associated AEs. A total of 46,316 eculizumab-related ADEs reports were identified by analyzing 19,418,776 reports in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. A total of 461 PTs were identified as satisfying by all four algorithms. These PTs reported adverse reactions consistent with the specifications, such as fatigue, nasopharyngitis, meningococcal infection, fever, and anemia. Some PTs, such as aplastic anemia, gene mutation, mastication disorder, kidney fibrosis, BK virus infection, abnormal neutrophil count, C3 glomerulopathy, neuroblastoma, and glomerulonephritis membranoproliferative, were also detected outside the instructions. The median time to onset of eculizumab adverse events was 159 days (interquartile range [IQR] 11∼738 days). In addition, at the PT level, 51 PTs were determined to have an imbalance in the occurrence of ADEs between the sexes. These findings provide valuable insights into the occurrence of ADEs following the use of eculizumab and could support clinical monitoring and risk identification efforts.

Posttransplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3% to 14% of kidney transplants (KTs), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first 3 months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA. We retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA. Kidney biopsy was performed in 91.1% of patients, and complement genetic study was performed in 64.4%. Of the kidney biopsies, 85.4% showed signs of TMA; genetic analysis revealed 1 pathogenetic variant, 2 variants of uncertain significance, 1 likely benign variant, 8 risk polymorphisms, and 27 risk haplotypes. After 2 weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After 6 months, 28.8% of patients had a complete renal recovery whereas 44.4% had a partial recovery. This is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.