Complement-Mediated Thrombotic Microangiopathy Related to COVID-19 or SARS-CoV-2 Vaccination.

Introduction: Infectious diseases and vaccinations are trigger factors for thrombotic microangiopathy. Consequently, the COVID-19 pandemic could have an effect on disease manifestation or relapse in patients with atypical hemolytic syndrome/complement-mediated thrombotic microangiopathy (aHUS/cTMA). Methods: We employed the Vienna TMA cohort database to examine the incidence of COVID-19 related and of SARS-CoV-2 vaccination-related relapse of aHUS/cTMA among patients previously diagnosed with aHUS/cTMA during the first 2.5 years of the COVID-19 pandemic. We calculated incidence rates, including respective confidence intervals (CIs) and used Cox proportional hazard models for comparison of aHUS/cTMA episodes following infection or vaccination. Results: Among 27 patients with aHUS/cTMA, 13 infections triggered 3 (23%) TMA episodes, whereas 70 vaccinations triggered 1 TMA episode (1%; odds ratio 0.04; 95% CI 0.003-0.37, P = 0.01). In total, the incidence of TMA after COVID-19 or SARS-CoV-2 vaccination was 6 cases per 100 patient years (95% CI 0.017-0.164) (4.5/100 patient years for COVID-19 and 1.5/100 patient years for SARS-CoV-2 vaccination). The mean follow-up time was 2.31 ± 0.26 years (total amount: 22,118 days; 62.5 years) to either the end of the follow-up or TMA relapse (outcome). Between 2012 and 2022 we did not find a significant increase in the incidence of aHUS/cTMA. Conclusion: COVID-19 is associated with a higher risk for aHUS/cTMA recurrence when compared to SARS-CoV-2 vaccination. Overall, the incidence of aHUS/cTMA after COVID-19 infection or SARS-CoV-2 vaccination is low and comparable to that described in the literature.

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review.

Thrombotic microangiopathy can present itself in the form of several clinical entities, representing a real challenge for diagnosis and treatment in pediatric practice. Our article aims to explore the evolution of two rare cases of pediatric thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with extremely similar clinical pictures, which, coincidentally, presented at approximately the same time in our hospital. These cases and our literature review demonstrate the multiple facets of thrombotic microangiopathy, which can produce various determinations and salient manifestations even among the pediatric population. TTP and aHUS may represent genuine diagnostic pitfalls through the overlap of their clinical and biological findings, although they develop through fundamentally different mechanisms that require different therapeutic approaches. As a novelty, we underline that COVID-19 infection cannot be excluded as potential trigger for TTP and aHUS in our patients and we predict that other reports of such an association will follow, raising a complex question of COVID-19's implication in the occurrence and evolution of thrombotic microangiopathies. On this matter, we conducted literature research that resulted in 15 cases of COVID-19 pediatric infections associated with either TTP or aHUS. Taking into consideration the morbidity associated with TTP and aHUS, an elaborate differential diagnosis and prompt intervention are of the essence.

Changing Trends of Pregnancy Related Acute Kidney Injury - a Single Centre Prospective Observational Study from Southern India

Introduction: Pregnancy-related acute kidney injury (PR-AKI) in India is largely showing a declining trend due to improved and accessible obstetric care. Nevertheless, PR-AKI continues to cause significant maternal and fetal morbidity and mortality. This study was taken up with the intention to study the incidence and clinical spectrum of AKI in pregnancy in recent times and assess maternal and neonatal outcomes Methods: All pregnant women admitted in the Department of Obstetrics and Gynecology at St John's Medical College Hospital, Bengaluru between January 2018 to June 2020 were screened for AKI with the following criteria 1. Increase in serum creatinine to >0.8mg/dL and/or a sudden increase in serum creatinine by more than 50% when prior renal function was normal. 2. Oligo-anuria 3. Need for renal replacement therapy Women with preexisting CKD were excluded. Patient's clinical and laboratory details recorded. Dialysis support was provided if indicated. The clinical profile and renal outcome of the mother and fetal outcome was assessed at the time of discharge. Mothers' were also followed up at the end of 3 months of postpartum period. Recovery was categorized as Complete recovery- normal serum creatinine (<0.8 mg/dL) or a previously known baseline and no proteinuria /hypertension at the end of 3 months Partial recovery- renal function improved but serum creatinine did not return to normal range and patient was dialysis independent. No recovery- patient continued to require dialysis at the end of 3months. Result(s): Of the 2650 deliveries in the study period 42 women (Mean age 26.9 +/-3.6 years) were diagnosed AKI during pregnancy (1.58%). Baseline characteristics and outcomes are depicted in table 1. Majority of women (n=37) were referred from peripheral hospitals. Hypertension and decreased fetal movements were the common reasons for referral. Third trimester was the most common time of presentation (76.1%). Severe Preeclampsia and HELLP syndrome was the leading cause of AKI (59.5%).ATN secondary to obstetric complications, sepsis and hemolytic uremic syndrome were the other causes. One case each of cortical necrosis, acute fatty liver of pregnancy and COVID 19 associated AKI was seen. Mean duration of hospital stay was 12.1+/-6.9 days. More than one third patients' required ICU stay (35.7%).12 patients (28.5%) required renal replacement therapy. Of them, 3 were dialysis dependent at the end of 3 months and 4 had partial renal recovery. 3 patients expired during hospital stay. Fetal survival was 69.04%.13 babies' required NICU care (44.8%). Neonatal outcomes are summarized in table 2. Close to one third of the pregnancies with AKI were associated with intrauterine fetal demise (28.5%). Low birth weight and prematurity were the common reasons for NICU admission with mean NICU stay of 8.2 +/-2.3 days [Formula presented] [Formula presented] Conclusion(s): Severe preeclampsia was the most common cause of AKI in our study. PR-AKI continues to be a significant problem in the peripheries of developing countries where availability of health care facilities is meager, with late referral to tertiary care centers. One third of the patients required ICU stay & dialytic support. Women who required dialysis had poorer renal prognosis. There was 30% fetal loss seen in PR-AKI and also a higher incidence of low birth weight and prematurity. No conflict of interestCopyright © 2023

Secondary thrombotic microangiopathy or secondary HUS: drugs or malignant hypertension to blame? Case report and review of the literature

Currently, thrombotic microangiopathy (TMA) is a common finding in the histological examination of kidney biopsy specimens, while verification of the nosological diagnosis is difficult due to the many etiological factors and the variety of clinical phenotypes. Today, along with primary TMAs, which include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), a large group of secondary TMAs associated with a variety of diseases and conditions, considered secondary HUS, is attracting more and more attention. The article presents a clinical case of the development of thrombotic microangiopathy in a 48-year-old man with a history of intravenous drug user who suffered from severe arterial hypertension for a long time. A feature of the disease was clinically – the almost complete absence of hematological manifestations with a progressive nature of nephropathy with an outcome in end-stage kidney disease, morphologically – mainly chronic changes in small extraglomerular vessels (arteries and arterioles), which led to severe ischemic damage to the glomeruli. Considering the predominantly chronic nature of the morphological manifestations of TMA, the absence of signs of acute TMA, and hematological syndrome, the patient did not undergo plasma therapy. In connection with the development of end-stage kidney disease, hemodialysis was initiated. The presented observation illustrates the complex genesis of secondary TMA in a patient with a history of drug addiction and severe arterial hypertension approaching malignant downstream. The presence in the anamnesis of such complement-activating conditions as intravenous drug use, severe arterial hypertension, as well as vaccination against a new coronavirus infection preceding the clinical manifestation, allowed us to interpret this condition as secondary HUS, which, however, does not exclude the presence of protein gene mutations, regulators of the alternative pathway of complement activation, which could act as a predisposing factor, which requires a genetic study of the complement system, since the information obtained will determine the tactics of management in case of kidney transplantation. In addition, this clinical observation demonstrates the importance of a thorough history taking in such patients, the analysis of which will help to identify complement-activating conditions and thereby accelerate the verification of the diagnosis. © 2022 Authors. All rights reserved.

Outbreak of Hemolytic-Uremic Syndrome in Children in Belarus: Epidemiology, Features of Clinical Course and Laboratory Changes, and Outcomes.

Introduction. Outbreaks of hemolytic uremic syndrome (HUS) have been described in many countries around the world, but no such information is available for Eastern European countries. Purpose. To determine clinical and laboratory differences, and to evaluate morbidity and outcomes during and outside the outbreak of HUS in children in Belarus. Materials and methods. A total o f 80 children diagnosed with HUS in 2021 in Belarus were included in the study;64 of them were admitted to the pediatric dialysis center in Minsk and divided into 2 groups: group 1 (29 children) - outside the HUS outbreak, and group 2 (35 children) - during the outbreak. In addition to standard laboratory tests, 52 children underwent stool analysis for Shiga toxin-producing Escherichia coli by real-time PCR (TaqMan Array Card). Results. The incidence of HUS in 2021 was 5.0/100 000 children <15 years (80 cases) and 10.6/100 000 children <5 years (59 cases). Boys were 52%, children <5 years old were 74%, patients with atypical HUS were 2.5%. Between 27.09.2021 and 29.10.2021 an outbreak of HUS was registered in 45 children, mostly from three country's regions: Minsk city - 17, Minsk region - 16 and Vitebsk region - 11. Patients of groups 1 and 2 did not differ in terms of age, 2.5 (1.6;5.1) and 3.6 (2.2;5.1) years, respectively, incidence of hemocolitis: 62% and 69%, respectively, baseline hemoglobin levels, 85 (77;99) and 102 (90;105) g/L, respectively, and platelet counts, 45 (25;71)x109/L and 53 (29;78) x109/L, respectively, need for dialysis, 79% and 57%, respectively, duration of anuria, 13 (7;16) and 12 (8;15) days, respectively, mortality, 3.4% (aHUS) and 2.9% (on the background of COVID-19), respectively, incidence of Shigatoxin-producing E. coli in faecal samples, 33% and 37%, respectively. The cause of HUS outbreak remained undetermined. Conclusions. Thus, the incidence of HUS in children in Belarus remains one of the highest in Europe. A national algorithm should be developed to detect the source of infection and to indicate and identify the pathogen in STEC infections.Copyright © 2022, Professionalnye Izdaniya. All rights reserved.

Outbreak of Hemolytic-Uremic Syndrome in Children in Belarus: Epidemiology, Features of Clinical Course and Laboratory Changes, and Outcomes.

Introduction. Outbreaks of hemolytic uremic syndrome (HUS) have been described in many countries around the world, but no such information is available for Eastern European countries. Purpose. To determine clinical and laboratory differences, and to evaluate morbidity and outcomes during and outside the outbreak of HUS in children in Belarus. Materials and methods. A total o f 80 children diagnosed with HUS in 2021 in Belarus were included in the study;64 of them were admitted to the pediatric dialysis center in Minsk and divided into 2 groups: group 1 (29 children) - outside the HUS outbreak, and group 2 (35 children) - during the outbreak. In addition to standard laboratory tests, 52 children underwent stool analysis for Shiga toxin-producing Escherichia coli by real-time PCR (TaqMan Array Card). Results. The incidence of HUS in 2021 was 5.0/100 000 children <15 years (80 cases) and 10.6/100 000 children <5 years (59 cases). Boys were 52%, children <5 years old were 74%, patients with atypical HUS were 2.5%. Between 27.09.2021 and 29.10.2021 an outbreak of HUS was registered in 45 children, mostly from three country's regions: Minsk city - 17, Minsk region - 16 and Vitebsk region - 11. Patients of groups 1 and 2 did not differ in terms of age, 2.5 (1.6;5.1) and 3.6 (2.2;5.1) years, respectively, incidence of hemocolitis: 62% and 69%, respectively, baseline hemoglobin levels, 85 (77;99) and 102 (90;105) g/L, respectively, and platelet counts, 45 (25;71)x109/L and 53 (29;78) x109/L, respectively, need for dialysis, 79% and 57%, respectively, duration of anuria, 13 (7;16) and 12 (8;15) days, respectively, mortality, 3.4% (aHUS) and 2.9% (on the background of COVID-19), respectively, incidence of Shigatoxin-producing E. coli in faecal samples, 33% and 37%, respectively. The cause of HUS outbreak remained undetermined. Conclusions. Thus, the incidence of HUS in children in Belarus remains one of the highest in Europe. A national algorithm should be developed to detect the source of infection and to indicate and identify the pathogen in STEC infections.Copyright © 2022, Professionalnye Izdaniya. All rights reserved.

Diagnosis of Bone Marrow Necrosis following Severe Vaso-Occlusive Crisis in Patient with Compound Heterozygous Sickle Cell Disease

Introduction: Bone marrow necrosis is a rare entity that can develop in context of a sickle cell disease vaso-occlusive crisis. Its physiopathology is related to an endothelial dysfunction taking place in bone marrow microvasculature. Case Presentation: A 30-year-old patient with history of compound heterozygous sickle cell disease was admitted following SARS-CoV-2 infection with fever and diarrhea. After initial favorable evolution, he developed a severe vaso-occlusive crisis with intense hemolysis and multi-organ ischemic complications. Patient then developed high fever and hypoxemia. With the suspicion of acute thoracic syndrome, a red blood cell exchange was performed. Respiratory symptoms ceased but patient persisted febrile with very high levels of acute phase reactants, persistent pancytopenia, and leucoerythroblastic reaction. An infectious cause was ruled out. Afterward, bone marrow aspiration and bone marrow biopsy showed a picture of bone marrow necrosis, which is an extremely rare complication of vaso-occlusive crisis but, paradoxically, more frequent in milder heterozygote cases of sickle cell disease. Ultimately, large deposits of complement membrane attack complex (particles C5b-9) were demonstrated after incubation of laboratory endothelial cells with activated plasma from the patient. Discussion: The clinical presentation and findings are consistent with a case of bone marrow necrosis. In this setting, the demonstration of complement as a potential cause of the endothelial dysfunction mimics the pattern of atypical hemolytic uremic syndrome and other microangiopathic anemias. This dysregulation may be a potential therapeutic target for new complement activation blockers. [ FROM AUTHOR] Copyright of Transfusion Medicine & Hemotherapy is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

End-Stage Kidney Disease Resulting from Atypical Hemolytic Uremic Syndrome after Receiving AstraZeneca SARS-CoV-2 Vaccine: A Case Report.

Hemolytic uremic syndrome (HUS) is classically described as a triad of nonimmune hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical HUS (aHUS) is a rare variant of the disease, and it accounts for 5-10% of the cases. It has a poor prognosis, with a mortality rate exceeding 25% and a more than 50% chance of progressing into end-stage kidney disease (ESKD). Genetic or acquired dysregulation of the alternative complement pathway is highly implicated in the pathogenesis of aHUS. Multiple triggers for aHUS have been described in the literature, including pregnancy, transplantation, vaccination, and viral infections. Herein, we report a case of a previously healthy 38-year-old male who developed microangiopathic hemolytic anemia and severe kidney impairment one week after receiving the first dose of AstraZeneca SARS-CoV-2 vaccine. A diagnosis of aHUS was made after excluding other causes of thrombotic microangiopathies. Treatment with plasma exchange, prednisone, and rituximab (375 mg/m2) once weekly for four doses resulted in improvement of his hematological parameters. However, he progressed to ESKD.

Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.

Introduction: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality. Case report: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19. His condition quickly deteriorated and he developed oliguria, accompanied with diarrhea, vomiting and oral intake intolerance. HUS was suspected, supported with compelling laboratory findings, including decreased platelets count and C3 levels, elevated LDH, urea, serum creatinine and sC5b-9 and presence of schistocytes in peripheral blood, negative fecal Shiga toxin and normal ADAMTS13 metalloprotease activity. The patient was given C5 complement blocker Ravulizumab and started to display rapid improvement. Conclusion: Although reports of HUS in the setting of COVID-19 continue to pour in, the questions of exact mechanism and similarities to MIS-C remain. Our case for the first time accentuates the use of complement blockade as a valuable treatment option in this scenario. We sincerely believe that reporting on HUS as a complication of COVID-19 in children will give rise to improved diagnosis and treatment, as well as better understanding of both of these intricating diseases.

Atypical Hemolytic Uremic Syndrome Occurring After Receipt of mRNA-1273 COVID-19 Vaccine Booster: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.

Case report: Area of focus in a case of malignant hypertension.

Malignant hypertension (MH) is characterized by severe hypertension (usually grade 3) associated with fundoscopic changes (flame hemorrhages and/or papilledema), microangiopathy and disseminated intravascular coagulation. In addition encephalopathy, acute heart failure and acute deterioration in renal function may be present. The term "malignant" reflects the very poor prognosis for this condition if untreated. When severe hypertension is associated with hypertension-mediated organ damage (HMOD) a life-threatening situation that requires immediate but careful intervention occurs (hypertensive emergency). In the last few years an increase in the number of patients with malignant hypertension has been observed, especially among those patients with black ethnicity. Limited access to treatment and the poor adherence to anti-hypertensive therapy may contribute to the development of hypertensive emergencies. It is considered appropriate to study patients in order to rule out thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. In fact, the microvascular damage caused by malignant hypertension can favor intravascular hemolysis like Thrombotic Microangiopathies (TMs). TMs may present in three different clinical conditions: typical hemolytic uremic syndrome (HUS), atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). TMs can arise in the context of other pathological processes, including malignant hypertension.

Atypical hemolytic uremic syndrome in a patient with HIV treated with eculizumab: A case report.

Thrombotic microangiopathy defines a group of pathologies characterized by microvascular dysfunction with the concurrence of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. It represents the most frequent microvascular manifestation of human immunodeficiency virus (HIV) infection. We report the case of a man in the seventh decade of life with a recent diagnosis of infection by HIV, who develops hemolytic uremic syndrome, requiring continuous renal replacement therapy and plasma replacement therapy, without response, ADAMTS13 with preserved activity, ruling out other etiologies (infectious, metabolic, and genetic) with successful response to eculizumab.

Normal Reference Values Evaluation of Rapid Chemiluminescent Adamts 13 Activity Assay

Introduction: Acquired thrombotic thrombocytopenic purpura (TTP) is a severe, rare, thrombotic microangiopathy (TMA). A diagnosis of acquired TTP is confirmed by a severe deficiency (< 10%) of ADAMTS13 activity. Recently, maybe because of Sars-COV2 Pandemic, in our laboratory we had the impression that normal reference ranges of our ADAMT13 activity assay HemosiL Acustar ADAMTS13 rapid immunoassay, could be larger than manufacturer's. The objective of this study was to evaluate whether manufacturer's are suitable normal reference values for this assay in our laboratory Methods: To evaluate manufacturer's reference limits (60-130.6%) in our laboratory we decided to assay with HemosIL Acustar ADAMTS13 activity test 30 plasma samples from normal subjects. Result(s): 3 out of 20 normal subjects tested showed ADAMTS13 activity outside manufacturer's limits (1 below 60.6% and 2 above 130.6%), therefore even if calculated in a small number of subjects (30 individuals) we decide to try to calculate in house ADAMTS13 reference values. They ranged from 47.5 (10th perc.), 72.5 (25th perc.) and 41.6 (mean- 2sd) to 150.0 (99th perce.), 119,6 (75th perc.) and 152.7 (mean+2sd). To investigate the analytical performance of manufacturer's and calculated cut-offs limits, we re-evaluate one year of ADAMTS13 activity results (95 subjects). ADAMTS13 activity was severely reduced (< 0.7%) in 10 acute TTPs;20 patients with Hemolytic Uremic Syndrome showed ADAMTS13 activity above manufacturer's and in all calculated cut-offs;21/45 patients with TTPs in remission phase showed ADAMTS activity below all in house calculated cut off and 24/45 showed ADAMTS activity below manufacturer's;12/20 other patients showed ADAMTS activity below all in house calculated and manufacturer's cut offs, all of them were Sars COV2 positive subjects Conclusion(s): In conclusion HemosiL Acustar ADAMTS13 activity calculated cut-offs in our laboratory were larger than manufacturer's reference range. By the analysis of one year ADAMTS13 activity dosages both manufacturer's and calculated cut-offs showed similar performances but our calculated reference ranges even if obtained by the analysis of a small number of normal subjects were found to be more similar to literature ELISA (40-130%) and FRET (45-147%) ADAMTS13 activity normal values.

Hemolysis and COVID-19 infection: A fatal combination - An interesting series of three cases

COVID-19 has wreaked havoc ever since its inception and with the protean manifestations of the disease, it is imperative that progressively data are added to the literature. COVID-19 infection is a multisystem disorder with a wide range of clinical symptomatology. Recent information garnered has laid emphasis on pathological changes at microvascular level causing thrombotic/hemostatic defects, leading to the assorted clinical presentation. We present a consortium of three confirmed COVID-19 cases whose hospital course got convoluted with grave hematological complications in the form of hemolytic uremic syndrome and autoimmune hemolytic anemia. Regrettably, all three patients succumbed to their illness.

Outbreak of Hemolytic-Uremic Syndrome in Children in Belarus: Epidemiology, Features of Clinical Course and Laboratory Changes, and Outcomes

Introduction. Outbreaks of hemolytic uremic syndrome (HUS) have been described in many countries around the world, but no such information is available for Eastern European countries. Purpose. To determine clinical and laboratory differences, and to evaluate morbidity and outcomes during and outside the outbreak of HUS in children in Belarus. Materials and methods. A total o f 80 children diagnosed with HUS in 2021 in Belarus were included in the study;64 of them were admitted to the pediatric dialysis center in Minsk and divided into 2 groups: group 1 (29 children) – outside the HUS outbreak, and group 2 (35 children) – during the outbreak. In addition to standard laboratory tests, 52 children underwent stool analysis for Shiga toxin-producing Escherichia coli by real-time PCR (TaqMan Array Card). Results. The incidence of HUS in 2021 was 5.0/100 000 children <15 years (80 cases) and 10.6/100 000 children <5 years (59 cases). Boys were 52%, children <5 years old were 74%, patients with atypical HUS were 2.5%. Between 27.09.2021 and 29.10.2021 an outbreak of HUS was registered in 45 children, mostly from three country’s regions: Minsk city – 17, Minsk region – 16 and Vitebsk region – 11. Patients of groups 1 and 2 did not differ in terms of age, 2.5 (1.6;5.1) and 3.6 (2.2;5.1) years, respectively, incidence of hemocolitis: 62% and 69%, respectively, baseline hemoglobin levels, 85 (77;99) and 102 (90;105) g/L, respectively, and platelet counts, 45 (25;71)×109/L and 53 (29;78) ×109/L, respectively, need for dialysis, 79% and 57%, respectively, duration of anuria, 13 (7;16) and 12 (8;15) days, respectively, mortality, 3.4% (aHUS) and 2.9% (on the background of COVID-19), respectively, incidence of Shigatoxin-producing E. coli in faecal samples, 33% and 37%, respectively. The cause of HUS outbreak remained undetermined. Conclusions. Thus, the incidence of HUS in children in Belarus remains one of the highest in Europe. A national algorithm should be developed to detect the source of infection and to indicate and identify the pathogen in STEC infections. © 2022, Professionalnye Izdaniya. All rights reserved.

Case report: Diarrhea-associated hemolytic uremic syndrome in the Era of COVID-19.

Over the past two years, a growing number of SARS-CoV-2 infection-associated clinical pediatric phenotypes have been identified, including a hemolytic uremic syndrome (HUS) form of thrombotic microangiopathy. Oregon's high prevalence of Shiga toxin-producing Escherichia coli (STEC) infections gives it a unique perspective to discuss the impact of COVID-19 and HUS. We seek to highlight SARS-CoV-2 as a potential new infectious etiology of severe diarrhea-associated HUS, based on two cases from Portland, Oregon, occurring in non-COVID-19 immunized children. The first case is a previously healthy ten-year-old who presented with SARS-CoV-2 infection and bloody diarrhea after an appendectomy, followed by full-blown oligo-anuric HUS. Second is a previously healthy six-year-old who presented with short-lived bloody diarrhea, rapidly evolving to HUS, and who tested positive for COVID-19 via polymerase chain reaction and STEC toxins one and two. These two cases highlight two main points. First, SARS-CoV-2 must be included in the differential diagnosis of diarrhea-associated HUS, either as the sole agent or concurrent with a STEC infection. Second, when managing STEC gastroenteritis the recommendation has been to maintain excellent hydration as a strategy to prevent the progression to oligo-anuric acute kidney injury and HUS. This strategy may need to be re-evaluated in a patient with SARS-CoV-2 infection or co-infection.

Anti-factor H antibody and its role in atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives.

Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: Literature Review.

Coronavirus disease 2019 (COVID-19) can lead to clinically significant multisystem disorders that also affect the kidney. According to recent data, renal injury in the form of thrombotic microangiopathy (TMA) in native kidneys ranks third in frequency. Our review of global literature revealed 46 cases of TMA in association with COVID-19. Among identified cases, 18 patients presented as thrombotic thrombocytopenic purpura (TTP) and 28 cases presented as atypical hemolytic uremic syndrome (aHUS). Altogether, seven patients with aHUS had previously proven pathogenic or likely pathogenic genetic complement abnormalities. TMA occurred at the time of viremia or even after viral clearance. Infection with COVID-19 resulted in almost no or only mild respiratory symptoms in the majority of patients, while digestive symptoms occurred in almost one-third of patients. Regarding the clinical presentation of COVID-19-associated TMA, the cases showed no major deviations from the known presentation. Patients with TTP were treated with plasma exchange (88.9%) or fresh frozen plasma (11.1%), corticosteroids (88.9%), rituximab (38.9%), and caplacizumab (11.1%). Furthermore, 53.6% of patients with aHUS underwent plasma exchange with or without steroid as initial therapy, and 57.1% of patients received a C5 complement inhibitor. Mortality in the studied cohort was 16.7% for patients with TTP and 10.7% for patients with aHUS. The exact role of COVID-19 in the setting of COVID-19-associated TMA remains unclear. COVID-19 likely represents a second hit of aHUS or TTP that manifests in genetically predisposed individuals. Early identification of the TMA subtype and appropriate prompt and specific treatment could lead to good outcomes comparable to survival and recovery statistics for TMA of all causes.