Postpartum Renal Cortical Necrosis: A Case Series.

Rationale & Objective: Postpartum renal cortical necrosis (postpartum RCN) is a severe form of obstetric acute kidney injury. This study aimed to identify clinicopathologic features in Chinese postpartum RCN cases to determine how pathologic findings may contribute to the treatment and prognosis. Study Design: Single-center, case series. Setting & Participants: Twelve patients with postpartum RCN had kidney biopsies at Peking University First Hospital between 2014 and 2021. The diagnosis of postpartum RCN was made according to typical magnetic resonance imaging or pathologic features. Clinical, laboratory, and pathologic data were compared between patients with estimated glomerular filtration rate <30 (poor outcome) and ≥30 mL/min/1.73 m2 after 6 months. Observations: All patients with postpartum RCN presented with stage 3 acute kidney injury attributed to a probable atypical hemolytic uremic syndrome. Pregnancy terminations occurred at a median gestational age of 35.5 weeks. Kidney biopsy was performed from 18 days to 4 months from delivery. On biopsy, hemoglobin, platelet count, and lactate dehydrogenase levels had been restored to 137 g/L, 214 × 109/L, and 231.50 ± 65.01 U/L, respectively. Four patients exhibited poor outcome, demonstrating higher schistocyte count, serum creatinine, and mean arterial pressure at onset. Pathologically, glomerular segmental sclerosis was prevalent. The "not otherwise specified" variant was the most common type, followed by collapsing variant, cellular variant, and tip variant. Patients with poor kidney outcome had more glomerular coagulative necrosis, capillary thrombosis, extensive cortical coagulative necrosis, and pronounced arteriole/artery lesions including increased interlobular arteriole intimal edema and fibrin thrombosis, but a lower occurrence of segmental sclerosis. Limitations: Limited sample size and retrospective design. Conclusions: We identified key pathologic features in patients with postpartum RCN and atypical hemolytic uremic syndrome, highlighting the necessity for more effective therapeutic options. There is a clear demand for noninvasive biomarkers that can accurately track disease progression and inform treatment duration for long-term outcomes improvement.

Our study investigated postpartum renal cortical necrosis (RCN) in 12 Chinese women, a severe form of kidney injury that occurs after childbirth, often linked to atypical hemolytic uremic syndrome (aHUS). We aimed to identify clinical and pathologic features to improve treatment and predict patient outcomes. The women experienced stage 3 acute kidney injury, with kidney biopsies revealing various degrees of glomerular and vascular damage. Key findings included segmental glomerular sclerosis and arteriole lesions, which were more pronounced in patients with poor outcomes. The study, though limited by its small and retrospective design, underscores the importance of recognizing aHUS in postpartum RCN for better management and highlights the urgent need for noninvasive biomarkers to monitor disease progression and improve long-term prognosis.

Atypical Hemolytic Uremic Syndrome Following Influenza B: A Case Report.

Background: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy that presents with a triad of hemolytic anemia, thrombocytopenia, and acute kidney impairment. It can be attributed to mutations in an array of different complement proteins leading to the overactivation of the complement system, the most impacted being the alternative pathway. Though rare, influenza B has been documented as a potential trigger to the development of aHUS. Case Presentation: We discuss a 10-year-old girl with a history of aHUS who was found to have a repeat episode of aHUS following an influenza B infection. There have only been a few reports of aHUS triggered by influenza B, making this a unique case. Given the recurrence and atypical features present in this case, a genetic workup was obtained, which showed a heterozygous mutation of complement protein CD46. The presence of mutations in CD46 is a known predisposing factor to aHUS, but influenza B infection is rarely implicated as a trigger to aHUS. The prognosis of aHUS varies and is dependent on the complement mutation specific to the individual. Conclusion: Patients with CD46 mutations have been shown to have high rates of relapse but less long-term kidney damage, as seen in this case. Clinicians should be aware of the association between influenza B and aHUS to improve patient outcomes.

Global aHUS Registry Analysis of Patients Switching to Ravulizumab From Eculizumab.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a progressive rare disease that, if untreated, can result in severe organ damage and death. Ravulizumab, a next-generation terminal complement inhibitor, provides immediate, complete, and sustained complement C5 inhibition. Real-world data in patients with aHUS who switched to ravulizumab from eculizumab are lacking. Methods: The Global aHUS Registry is a multicenter study (NCT01522183) collecting data on adult or pediatric patients with an aHUS diagnosis, regardless of treatment. Patient characteristics, genetic data, hematological and renal parameters, clinical events (e.g., dialysis and kidney transplantation), and adverse events (AEs) were extracted from patients who switched to ravulizumab from eculizumab up to July 3, 2023. Results: Overall, 60 patients switched to ravulizumab (adult: n = 43; pediatric: n = 17); 11 patients were excluded from effectiveness and genetic analyses (N = 49; adult: n = 40; pediatric: n = 9) because they received <3 months ravulizumab treatment and/or had >1 month between eculizumab discontinuation and ravulizumab initiation. Pathogenic complement variants were identified in 11 of 49 patients (22%); the most common was a complement factor H variant (n = 5/49 [10%]). During ravulizumab treatment, 20 AEs occurred in 13 patients, with no unexpected AEs and only 3 treatment-related AEs (infusion reaction, headaches, and fatigue). No meningococcal infections or deaths were reported. No new events of dialysis, kidney transplantation, or thrombotic microangiopathy were reported. Renal and hematological parameters remained stable after switching to ravulizumab. Conclusion: This is the first real-world cohort analysis of data from patients treated with ravulizumab and reinforces the real-world safety and effectiveness data of ravulizumab in patients with aHUS who switched from eculizumab.

Unusual Presentation of Aggressive Atypical Hemolytic Uremic Syndrome With Brugada Syndrome.

Hemolytic uremic syndrome (HUS) is part of a spectrum of disorders known as thrombotic microangiopathies. These disorders are characterized by giving rise to platelet microthrombi, which subsequently develop hemolytic anemia and thrombocytopenia. In HUS, the kidneys are destroyed, mainly due to damage to the renal blood vessels. HUS can be typical or atypical, depending on the cause, and can lead to significant mortality rates. We herein report an unusual case of atypical HUS in a 15-year-old female who presented with fatigue, abdominal pain with nausea and vomiting, loss of appetite, and urine discoloration. Further tests showed low platelets with significant anemia. She was diagnosed with atypical HUS after discovering that she had no previous bloody diarrhea episode with a negative E. coli strain, O157:H7, alongside valid ADAMTS13 activity. The diagnosis was confirmed by genetic testing, and a variant of uncertain significance was found in the CFH gene. The patient, therefore, was started on eculizumab, and a follow-up was done once or twice a month through blood testing. She showed significant improvement. Due to non-compliance with the eculizumab treatment, the patient showed deterioration numerous times. A kidney biopsy was subsequently done, showing signs of acute to chronic thrombotic microangiopathy with moderate tubular atrophy and interstitial fibrosis. After many hemodialysis and plasma exchange sessions and being put on several treatments, such as prednisolone and rituximab, the patient faced death after one year.

Corrigendum: Genetic investigation of Nordic patients with complement-mediated kidney diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1254759.].

Complement system activation: bridging physiology, pathophysiology, and therapy.

The complement system is a set of over 50 proteins that constitutes an essential part of the innate immune system. Complement system activation involves an organized proteolytic cascade. Overactivation of complement system activation is the main pathogenic mechanism of several diseases and contributes to the manifestations of many other conditions. This review describes the normal complement system and the role for complement dysregulation in critical illnesses, notably sepsis and acute respiratory distress syndrome. Complement activation is involved in the immune system response to pathogens but, when excessive, can contribute to tissue damage, runaway inflammation, and capillary leakage syndrome. Complement overactivation may play a key role in severe forms of coronavirus disease 2019 (COVID-19). Two diseases whose manifestations are mainly caused by complement overactivation, namely, atypical hemolytic and uremic syndrome (aHUS) and myasthenia gravis, are discussed. A diagnostic algorithm for aHUS is provided. Early complement-inhibiting therapy has been proven effective. When renal transplantation is required, complement-inhibiting drugs can be used prophylactically to prevent aHUS recurrence. Similarly, acetylcholine-receptor autoantibody-positive generalized myasthenia gravis involves complement system overactivation and responds to complement inhibition. The two main complement inhibitors used in to date routine are eculizumab and ravulizumab. The main adverse event is Neisseria infection, which is rare and preventable, but can be fatal. The complement system is crucial to health but, when overactivated, can cause or contribute to disease. Effective complement inhibitors are now available, although additional data are required to determine optimal regimens. Further research is also needed to better understand the complement system, develop advanced diagnostic tools, and identify markers that allow the personalization of treatment strategies.

Thrombotic microangiopathy (TMA) associated with pregnancy: role of the clinical laboratory in differential diagnosis.

Objectives: Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia and target organ damage. Pregnancy is associated with several forms of TMA, including preeclampsia (PE), HELLP syndrome, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). When HUS is secondary to a deregulation of the alternative complement pathway, it is known as atypical HUS (aHUS). Differential diagnosis is challenging, as these forms share clinical characteristics. However, early diagnosis is crucial for a specific treatment to be established and improve prognosis. Case presentation: We present the case of a 43 year-old primiparous woman admitted to hospital for an urgent C-section at 33 gestational weeks due to a diagnosis of severe preeclampsia and fetal distress. In the immediate postpartum, the patient developed acute liver failure and anuric renal failure in the context of the HELLP syndrome, anemia, thrombocytopenia, arterial hypertension (HTN) and neurological deficit. TMA study and differential diagnosis confirmed pregnancy-associated aHUS. Treatment with eculizumab was initiated, with good response and progressive improvement of clinical and analytical parameters. Conclusions: aHUS is a rare multifactorial disease that used to be associated with high mortality rates before the advent of eculizumab. Due to challenging diagnosis, the clinical laboratory plays a major role in the differential diagnosis and management of the disease.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials.

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a C5i approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from 2 phase 3, single-arm studies. Setting & Participants: One study included C5i-naïve adults (NCT02949128), and the other included 2 cohorts of pediatric patients (C5i-naïve and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure: Patients received intravenous ravulizumab every 4-8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naïve patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine concentrations from baseline, at 2 consecutive assessments ≥4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naïve adults and pediatric patients, respectively. The median increase in estimated glomerular filtration rate from baseline was maintained over 2 years in C5i-naïve adults (35 mL/min/1.73 m2) and pediatric patients (82.5 mL/min/1.73 m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy - Fatigue score achieved by 26 weeks was maintained over 2 years. Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematologic and renal parameters and quality of life in adults and pediatric patients with aHUS.

This research tested a drug called ravulizumab for the treatment of atypical hemolytic uremic syndrome (aHUS). aHUS is a rare disease that causes clots in tiny blood vessels. This can damage the kidneys and other organs. We analyzed data from 2 clinical trials in which children and adults with aHUS received ravulizumab through a tube placed in a vein (intravenous line). They received ravulizumab every 4-8 weeks depending on their weight. We found that treating patients for 2 years with ravulizumab was associated with improved blood health, kidney function, and quality of life and was well tolerated. These results support ravulizumab as a long-term treatment for people with aHUS.

[Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension].

BACKGROUND: The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy. AIM: To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH. MATERIALS AND METHODS: 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome - exome) by next-generation sequencing technology (NGS). RESULTS: GD of CS were detected in a quarter of patients. Rare genetic variants classified as "likely pathogenic" including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3). CONCLUSION: Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy.

The efficacy and safety of eculizumab in patients and the role of C5 polymorphisms.

Eculizumab is an orphan drug with indications for extremely rare autoimmune disorders. It is primarily prescribed for use in patients with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome; but is also highly effective in the treatment of myasthenia gravis, among others. By binding to the C5 protein in the complement system, eculizumab effectively inhibits cellular hemolysis and autoimmune reactions. Despite this effective treatment, some patients reported no improvement in symptoms. Genetic sequencing revealed three distinct C5 mutations in the non-responders and these polymorphisms appeared to be most prevalent among Japanese, Korean and African populations. Here, we present an overview of the current and potential future applications of eculizumab, as well as the disadvantages of eculizumab treatment in patients with C5 polymorphisms.

[Coagulation and complement crosstalk: molecular mechanisms of complement-mediated diseases].

The complement and coagulation systems are ancestrally related mechanisms of serine protease-induced protein activation. Recent studies have shown that the complement system enhances platelet aggregation by activating platelets and vascular endothelial cells. This system is also involved in the expression of tissue factor, which induces the coagulation reaction. Activated platelets and coagulation factors are also known to activate the complement system. In diseases involving the complement system, such as paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, and atypical hemolytic uremic syndrome, excessive activation of this system contributes to complement-mediated thrombosis. The anti-C5 antibody eculizumab has shown a remarkable thromboprophylactic effect in these complement diseases. The recent surge in development of new anti-complement agents has raised expectations for the advancement of treatments and preventive measures for thrombosis associated with complement disorders. This review outlines the crosstalk between these two systems, and describes the mechanisms of several diseases featuring both thrombosis and complement activation.

Atypical hemolytic-uremic syndrome after COVID-19 vaccine: A case report.

BACKGROUND: The emergence of new SARS-CoV-2 variants and the global COVID-19 pandemic spurred urgent vaccine development. While common vaccine side effects are well-documented, rare adverse events necessitate post-marketing surveillance. Recent research linked messenger RNA vaccines to thrombotic microangiopathy (TMA), a group of syndromes characterized by microvascular hemolytic anemia and thrombocytopenia. This report describes a new-onset atypical hemolytic-uremic syndrome (aHUS) occurring after COVID-19 vaccination and complements recent literature. CASE PRESENTATION: A previously healthy 25-year-old woman developed malaise, nausea, edema, and renal dysfunction 60 days postvaccination. Laboratory findings confirmed TMA diagnosis. Genetic testing for complement system mutations was negative. Kidney biopsy supported the diagnosis, and the patient required hemodialysis. CONCLUSION: This case illustrates the rare occurrence of aHUS following COVID-19 vaccination, with unique characteristics compared to previous reports. Despite the critical role of vaccination in pandemic control, emerging adverse events, such as vaccine-related TMA, must be recognized and investigated. Additional clinical trials are imperative to comprehend the clinical features and pathophysiological mechanisms underlying TMA associated with COVID-19 vaccination.

Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H (CFH) gene mutation, currently classified as a variant of uncertain significance (VUS). Now he is in disease remission after successful complement blockade therapy, thus highlighting a unique presentation of aHUS in a patient with newly diagnosed NB.

Living with Atypical Hemolytic Uremic Syndrome in the Netherlands: Patient and Family Perspective.

Introduction: Atypical hemolytic uremic syndrome (aHUS) poses a significant health challenge due to its rarity and severity within the spectrum of thrombotic microangiopathy. Despite efforts to optimize and personalize health care for patients with aHUS, understanding the individual experiences, needs, and desires of patients with aHUS and their relatives remains limited. Methods: Here, we present a nationwide, exploratory, qualitative interview study with a direct content analysis approach. In-depth interviews and a 6-week evaluation were audio-recorded and conducted using a semistructured topic guide, based on the Institute for Positive Health (IPH) model. Results: Analysis of 10 interviews involving 6 patients with aHUS and 13 relatives revealed the prevalence of long-term disease symptoms in adult patients, notably fatigue, which significantly impacted daily functioning. Moreover, the resilience demonstrated by patients and their relatives was noteworthy; however, the acute phase of aHUS and the unpredictable nature of disease recurrence could profoundly affect mental well-being. The emotional toll of aHUS is pervasive, with feelings of fear, guilt, and trauma persisting across disease phases in both patients and relatives. Challenges in medical care, including delays in diagnosis and the need for personalized and uniform protocols, were highlighted. Support was deemed crucial, indicating the necessity for enhancements in the accessibility to comprehensible disease information and psychological counseling. Finally, complexities surrounding genetic testing and carriership were discussed. Conclusion: This study underscores the profound, enduring, and multifaced impact of aHUS. The insights gleaned from the experiences and needs of patients with aHUS and their relatives could lay the foundation for development and implementation of more personalized innovations in aHUS health care.

Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.

BACKGROUND: No reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies. CASE PRESENTATION: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening. CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Clinical efficacy and safety of switching from eculizumab to ravulizumab in adult patients with aHUS- real-world data.

BACKGROUND: The complement factor 5 (C5)-inhibitor eculizumab has been established as standard-of-care for the treatment of atypical hemolytic uremic syndrome (aHUS). In 2021, the long-acting C5-inhibitor ravulizumab was approved, extending intervals of intravenous treatment from two to eight weeks resulting in improvement of quality of life for patients and lowering direct and indirect therapy associated costs. METHODS: This multicenter, retrospective data analysis of 32 adult patients with aHUS (including 10 kidney transplant recipients) treated with eculizumab for at least three months and switched to ravulizumab aims to evaluate the safety and efficacy of switching medication in the real-world setting. Hematologic parameters, kidney function, concurrent therapy and aHUS associated events were evaluated three months before and until up to 12 months after switching to ravulizumab. RESULTS: Mean age (range) at ravulizumab initiation was 41 years (19-78 years) and 59% of the patients were female. Genetic analysis was available for all patients with 72% showing a pathogenic variant. Median time (range) on eculizumab before switching was 20 months (3-120 months). No new events of TMA or worsening of renal function were reported during up to 12 months of follow-up during ravulizumab treatment. CONCLUSIONS: This is the largest, non-industry derived, multi-center retrospective analysis of adult patients with aHUS switching C5-inhibitor treatment from eculizumab to ravulizumab in the real-world setting. Switching to ravulizumab was safe and efficient resulting in sustained hematological stability and preservation of renal function.

Plasma Exchange in Postpartum Hemorrhage (PPH)-Associated Thrombotic Microangiopathy (TMA): A Case Report.

Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features akin to TMA during the peripartum period such as eclampsia, preeclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and antiphospholipid syndrome. A 28-year-old woman with no significant past medical history developed TMA following a massive hemorrhage after an emergency cesarean section at 41 weeks of gestation. This case was finally diagnosed as postpartum hemorrhage (PPH)-associated TMA. The patient fully recovered after plasma exchange therapy. We posit the value of accumulating case reports, given that the documentation on the efficacy of plasma exchange in PPH-associated TMA is limited.

Anti-factor H Autoantibody-Associated Hemolytic Uremic Syndrome: A Rare Entity in a Pediatric Patient.

An 11-year-old patient presented with the primary complaint of hematuria and vomiting. On further investigation and a series of diagnostic tests, including a biopsy and thrombotic microangiopathy (TMA) profile, the patient was diagnosed with thrombotic microangiopathy. TMA is a pathological process involving endothelial cell injury, leading to thrombocytopenia and microangiopathic hemolytic anemia. This case highlights the importance of considering TMA in pediatric patients presenting with nonspecific symptoms, such as loss of appetite. Further research is needed to understand the pathophysiology and optimal management strategies for pediatric TMA. This case adds to the growing body of literature on pediatric TMA and underscores the need for a high index of suspicion in similar clinical scenarios.

Clinical presentation and management of atypical hemolytic uremic syndrome in Latin America: a narrative review of the literature.

INTRODUCTION: Comprehensive information about atypical hemolytic uremic syndrome (aHUS) is relatively scarce outside of Europe and North America. This narrative review assembles available published data about the clinical presentation and management of aHUS in Latin America. AREAS COVERED: A search conducted in February 2023 of the MEDLINE (from inception), Embase (from inception), and LILACS/IBECS (1950 to 2023) databases using search terms 'atypical hemolytic uremic syndrome' and 'Latin America' and their variations retrieved 51 records (full papers and conference abstracts) published in English, Spanish, or Portuguese. After de-duplication, manual screening of titles/abstracts and addition of author-known articles, 25 articles were included of which 17 (68%) are full papers. All articles were published during the years 2013-2022. Articles include cohort studies, a registry analysis, and case reports from Argentina, Brazil, Chile and Columbia. Overall, Latin American patients with aHUS present the classic epidemiological, clinical, and genetic characteristics associated with this condition as described in other world regions. Depending on the country and time of reporting, aHUS in Latin America was treated mainly with plasma therapy and/or eculizumab. Where reported, eculizumab substantially improved aHUS-related outcomes in almost all adult and pediatric patients. EXPERT OPINION: Eculizumab has dramatically altered the natural course of aHUS, improving prognosis and patient outcomes. Addressing economic challenges and investing in healthcare infrastructure will be essential to implement strategies for timely detection and early treatment of aHUS in Latin America.