Diagnosis Of Atypical Hemolytic Uremic Syndrome Research Articles

Atypical hemolytic-uremic syndrome in pregnancy: a case report

Introduction: The diagnosis of Atypical hemolytic-uremic syndrome (aHUS) is largely imprecise. Improving outcomes requires accurate diagnosis and timely management. Acute kidney damage, thrombocytopenia, and microangiopathic hemolytic anemia are all signs of aHUS. The condition is brought on by pregnancy, and in genetically susceptible women, it progresses to a terrible hemolytic illness marked by widespread endothelium damage and platelet consumption. The sickness is a potentially fatal ailment that demands quick identification and treatment.Case Presentation: Our facility provided treatment for severe anemia, thrombocytopenia, and acute renal damage in a 24-year-old G1P1A0 postpartum lady with Caesarean sectio and a HELLP syndrome suspicion. An aHUS diagnosis was later verified. The condition of the patient failed to improve in the first 24 hours after birth. Inside this presence of TMA, the patient began on daily TPE and ran in parallel prednisone medication (1 mg/kg/day). After six TPE cycles, the laboratory values began to rise.Conclusion: AHUS can be challenging to diagnose early since it frequently mimics other illnesses. To enhance results, proper diagnosis and prompt management are essential. The management strategy includes a multidisciplinary team, early plasmapheresis, and complement inhibition. To lessen the effects of aHUS, TPE should be carried out as soon as feasible on a daily basis.

Multifaktorska etiologija atipičnog hemolitičko uremijskog sindroma - prikaz slučaja

Introduction: Hemolytic uremic syndromes are characterized by the simultaneous occurrence of hemolytic anemia, microangiopathy, thrombocytopenia, and acute renal insufficiency. In terms of the clinical prodrome, they can be classified as typical, which is more common and occurs in 90% of cases, often preceded by diarrheal syndrome induced by enterohemorrhagic Escherichia coli. Alternatively, there is an atypical and rarer form associated with pneumococcal infection, dysregulation of the alternative complement pathway, and cases involving the use of cyclosporine. Hemolytic anemia is confirmed in laboratory analyses (presence of fragmented red blood cells, decreased hemoglobin, undetectable haptoglobin values, and elevated LDH values), along with thrombocytopenia and an increase in nitrogenous substances (urea and creatinine). Case report: The report details the case of an 18-month-old girl who experienced acute renal insufficiency subsequent to a respiratory infection. Ten days preceding admission, the patient exhibited nasal discharge, and during the seven days leading up to hospitalization, she presented with fever. Furthermore, two days prior to admission, the onset of persistent vomiting and abdominal pain occurred. Suspected of bowel intussusception, the patient underwent a surgical assessment where acute surgical pathology was ruled out. The absence of urination, coupled with heightened urea and creatinine levels, prompted consideration of hemolytic-uremic syndrome, later confirmed as atypical during hospitalization. This was grounded in the clinical presentation, devoid of diarrhea syndrome but marked by nasal discharge over the preceding ten days. The administration of fresh frozen plasma yielded no improvement, and there were decreased values of the C3 complement component, H factor, and reduced ADAMTS13 activity. The lack of verotoxins from enterohemorrhagic Escherichia coli further supported the diagnosis of atypical hemolytic-uremic syndrome. After the first dose of eculizumab, a terminal complement C5 component inhibitor, the girl recovered renal function and established diuresis. Conclusion: The prompt diagnosis of atypical hemolytic-uremic syndrome is challenging due to nonspecific symptoms like nasal discharge, vomiting, fatigue, and abdominal pain. Laboratory analyses, lacking specific criteria, make it difficult to conclusively identify aHUS at the disease's onset. In Serbia, pneumococcal immunization is recommended as a preventive measure, administered through a conjugated vaccine in three doses starting from the second month of life. Rapid and accurate differentiation between typical and atypical HUS is crucial for effective treatment and prognosis. Typical HUS requires hemodialysis and plasmapheresis, whereas atypical HUS is managed with plasmapheresis, immunosuppressive therapy, and eculizumab. Administering eculizumab heightens the risk of meningococcal infection by inhibiting the C5 complement component. Therefore, it is crucial not to disregard the importance of meningococcal immunization.

Clinical case of fulminant course of atypical hemolytic-uremic syndrome

This clinical observation describes a case of a fulminant course of an atypical hemolytic-uremic syndrome. The initial stage of the course of the disease is of particular interest, which was not accompanied by typical manifestations of atypical hemolytic-uremic syndrome according to the type of acquired autoimmune hemolytic anemia. Thus, revealing this clinical observation may help in the diagnosis of atypical hemolytic-uremic syndrome with atypical initial manifestations and avoid errors, delays and adverse outcomes of this disease.

A case of development of membranous nephropathy against the background of atypical hemolytic-uremic syndrome activated as a result of acute respiratory viral infection

The article considers a clinical case of atypical hemolytic-uremic syndrome, which was the starting mechanism for the development of membranous nephropathy. Patient X. 23 years after acute respiratory viral infection, signs of nephrotic syndrome, arterial hypertension, and impaired kidney function appeared. Puncture nephrobiopsy was performed and the morphological picture corresponds to immunocomplex glomerulonephritis, most likely membranous nephropathy with the presence of segmental glomerulosclerosis, cellular half-moons. In parallel, the patient had verified signs of thrombotic microangiopathy in the form of microangiopathic anemia, thrombocytopenia, increased lactate dehydrogenase levels as a sign of cytolysis (primarily intravascular hemolysis). During the differential diagnosis, we stopped at the diagnosis of atypical hemolytic-uremic syndrome. The uniqueness of the described clinical case is that cases of glomerulonephritis against the background of atypical hemolytic-uremic syndrome are extremely rare, and membranous nephropathy is described for the first time.

Atypical hemolytic uremic syndrome and pregnancy outcomes: a cohort study

Atypical Hemolytic Uremic syndrome (AHUS) is a rare microangiopathy. As a dearth of information was available on the effect of this condition on pregnancy, our study aimed to examine the association between maternal AHUS and obstetrical and neonatal outcomes. Using the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the US, a retrospective cohort study was conducted consisting of women who delivered between 1999-2015. ICD-9 code 283.11 was used to identify women with a diagnosis of AHUS. Multivariate logistic regression estimated the effect of AHUS on maternal and neonatal outcomes, while adjusting for maternal baseline variables. There were 13,792,429 women who delivered between 1999-2015, of which 115 had a diagnosis of AHUS (8/1,000,000). Women with AHUS, compared with those without this diagnosis, had greater prevalence of pre-existing diabetes, hypertension, and obesity. AHUS was associated with several adverse outcomes: maternal death, odds ratio 355.49, 95% CI 161.36-783.18, preeclampsia, 30.21, 20.61-44.27, eclampsia, 10.68, 1.49-76.68, placental abruptio, 16.77, 10.22-27.52, disseminated intravascular coagulation, 260.53, 134.30-505.40, venous thromboembolism, 18.82, 7.60-46.59, sepsis, 134.81, 48.73-372.96, myocardial infarction, 429.13, 102.99-1788.15, post-partum hemorrhage, 19.16, 13.09-28.04, requiring a blood transfusion, 121.43, 83.25-177.12, and cesarean delivery, 3.93, 2.63-5.86. Neonates born to women with AHUS were at increased risk for preterm birth, 3.89, 2.53-5.97, intrauterine growth restriction, 3.64, 1.83-7.25, and stillbirth, 13.66, 7.29-25.59. There was a greater risk of adverse maternal and neonatal outcomes, including maternal and fetal death, among AHUS-impacted pregnancies; hence, such pregnancies should be attentively monitored.

A97 TACROLIMUS-ASSOCIATED HEMOLYTIC UREMIC SYNDROME IN A PEDIATRIC LIVER TRANSPLANT RECIPIENT

Abstract Background Tacrolimus associated hemolytic uremic syndrome (HUS) has been reported in renal and pediatric cardiac transplantation. Furthermore, in adults receiving liver transplant, there are reports of multiorgan failure, death, and end stage renal failure secondary to tacrolimus induced HUS [J NEPHROL 2003; 16: 580–585]. Although tacrolimus is commonly used in pediatric liver transplantation, there are no reports of the same entity. Aims To describe a case of tacrolimus induced HUS in a pediatric liver transplant patient and subsequent re-initiation of tacrolimus. Methods The patient was followed during his hospital admission and after discharge. Results An 8-year-old male with Progressive Familial Intrahepatic Cholestasis (PFIC) Type III, diagnosed at age 2, presents for living unrelated donor liver transplantation. He was previously well compensated but began to deteriorate in the months leading up to transplant with rising liver enzymes, ascites, and mild encephalopathy after presumed viral gastroenteritis. He receives a left lateral segment liver transplantation and is started on tacrolimus immunosuppression post liver transplant as per protocol. On initiation of tacrolimus, the patient’s hemoglobin trends downward to a trough of 59 g/L four days post transplantation. Concurrently, his haptoglobin is <0.10g/L, total bilirubin peaks at 708 umol/L, creatinine rises to a peak of 71 umol/L, urea peaks at 23.0 mmol/L. Platelets reach a nadir at 27x10^9/L, seven days post transplantation. Direct antibody test was negative, and blood cultures remained negative. Given the constellation of hemolytic anemia, thrombocytopenia, and acute kidney injury following initiation of tacrolimus, a diagnosis of atypical HUS is made. Tacrolimus is discontinued, intravenous methylprednisolone is started and the patient is switched to cyclosporine immunosuppression. Both the hemolysis and kidney injury resolve gradually. The patient develops side effects from cyclosporine including hypertension and excessive hair growth. One month post discontinuation of tacrolimus, he is started on sirolimus, while weaning steroids and cyclosporine. Seven weeks post discontinuation of tacrolimus, he is restarted on tacrolimus and is currently tolerating dual immunosuppression with no signs of HUS recurrence. Conclusions Atypical HUS secondary to tacrolimus post liver transplant in children is a rare entity. In the acute period, discontinuation of tacrolimus is essential to preserve renal function given potentially devastating outcomes seen in adults. Cyclosporine is an alternative immunosuppressive agent used in pediatric solid organ transplantation, although it has also been implicated in causing HUS. Funding Agencies None

Diagnosis of Atypical HUS Using Genetic Testing

<h3>ABSTRACT</h3> The patient was a 33-year-old woman at 31 weeks gestation with twins who presented to the emergency department complaining of shortness of breath, headache, and blurry vision. The patient’s preliminary complete blood count, red blood cell morphology, coagulation testing, and certain metabolic indicators were characteristic of a hemolytic process caused by microcirculatory lesions known as thrombotic microangiopathies. The major pathologies of this hemolytic process are thrombotic thrombocytopenic purpura, hemolytic uremic syndrome (HUS), disseminated intravascular coagulation, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Additional coagulation and biochemical testing indicated that the patient probably was experiencing HELLP syndrome, but atypical HUS (aHUS) could not be ruled out. Consequently, an aHUS genetic susceptibility panel was also ordered for this patient. The results of the genetic testing revealed that the patient did indeed have aHUS, a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes that encode complement regulator factors. With an accurate diagnosis established, the patient was able to receive treatment using an anti-C5 monoclonal antibody aimed specifically at controlling the dysregulated complement protein C5.

Eculizumab in the Treatment of Atypical Hemolytic Uremic Syndrome in Infants

A 28-day-old male newborn weighing 3.6 kg was given a diagnosis of atypical hemolytic-uremic syndrome, new-onset thrombotic microangiopathy (TMA; hemoglobin, 7.7 g/dL; schistocytes, 9%), thrombocytopenia (platelets, 49 × 10(3)/μL [49 × 10(9)/L]), and acute kidney failure (serum creatinine, 1.13 mg/dL [99.8 μmol/L], corresponding to estimated glomerular filtration rate [eGFR] of 15 mL/min/1.73 m(2) [0.25 mL/s/1.73 m(2)]). Repeated high-volume plasma infusions were ineffective. Plasma exchange was attempted, but not tolerated. The patient required mechanical ventilation and continuous renal replacement therapy. He developed multiple intestinal perforations and leg skin necrosis due to systemic TMA. A low C3 level (36 mg/dL) suggested complement activation. Eculizumab, 300 mg, was administered, and within 48 hours the patient recovered from acute kidney failure, with complete hematologic remission 2 weeks later. The infant, 14 months old at the time of writing, continues to receive eculizumab, 300 mg, every 3 weeks; he is free of disease activity and has a normal creatinine level of 0.2 mg/dL (17.68 μmol/L; corresponding to eGFR of 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]), but mild proteinuria (urinary protein-creatine ratio, 1 mg/g). Results of additional studies, including probing for cobalamin anomalies and measuring levels of ADAMTS13, complement factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP), were unremarkable. Antibodies to CFH were undetectable, and mutation testing of the genes for CFH, CFI, and MCP gave negative results. Treatment with eculizumab was life saving, and with continued treatment, the patient showed sustained freedom from clinical TMA complications.

WIESLAB ® Alternative Pathway assay as a specific test to support the diagnosis of atypical hemolytic-uremic syndrome: Results of a series of nine cases

WIESLAB ® Alternative Pathway assay as a specific test to support the diagnosis of atypical hemolytic-uremic syndrome: Results of a series of nine cases

A case of atypical hemolytic uremic syndrome as an early manifestation of acute lymphoblastic leukemia

= Abstract = Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children younger than 4 years and is characterized by microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. HUS associated with diarrheal prodrome is usually caused by Shiga toxin-producing Escherichia coli O157:H7 or by Shigella dysenteriae, which generally has a better outcome. However, atypical cases show a tendency to relapse with a poorer prognosis. HUS has been reported to be associated with acute lymphoblastic leukemia (ALL) in children. The characteristics and the mecha- nisms underlying this condition are largely unknown. In this study, we describe the case of an 11-year-old boy in whom the diagnosis of ALL was preceded by the diagnosis of atypical HUS. Thus, patients with atypical HUS should be diagnosed for the possibility of developing ALL. (Korean J Pediatr 2010;53:253-257)

HLA-DRB1*11: a Strong Risk Factor for Acquired Severe ADAMTS13 Deficiency-Related Idiopathic Thrombotic Thrombocytopenic Purpura in Caucasians.

Abstract 2412Poster Board II-387Acquired idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy (TMA) resulting from excessive von Willebrand factor (VWF)-mediated platelet clumping and capillary occlusion in relation with an autoantibody-mediated defect in the VWF-cleaving protease ADAMTS13. So far, the mechanisms leading to the loss of tolerance of the immune system against ADAMTS13 remain unknown. The usually switched isotype of the secreted anti-ADAMTS13 antibodies implies a cooperation between T lymphocytes and B lymphocytes and thus a recognition by T cell receptors of ADAMTS13 epitopes bound to human leukocyte antigen (HLA) molecules. We therefore hypothesized that particular HLA alleles may be involved in the process leading to a loss of tolerance of the immune system against ADAMTS13. Particularly, alleles within class I A and B loci and class II DRB1 and DQB1 loci are those most frequently associated with susceptibility to autoimmune diseases.We have compared medium resolution typing of HLA class I (HLA-A, B) and II (HLA-DRB1, DQB1) loci in 61 Caucasian patients with idiopathic TTP and a documented severe (<5%) acquired, autoantibody-mediated, ADAMTS13 deficiency to 132 healthy Caucasian volunteer donors Caucasian individuals and to 42 Caucasian patients with atypical hemolytic uremic syndrome (HUS) who displayed a detectable ADAMTS13 activity.The frequency of HLA-A, -B and -DQB1 alleles was comparable between patients with acquired idiopathic TTP, healthy individuals and patients with other forms of TMA. By contrast, the HLA DRB1*11 allele was observed in 62% of patients with acquired idiopathic TTP, whereas the usually reported incidence of this allele ranges from 13.5% to 24.5%, with the lower incidence in Asian/Pacific Islanders and Caucasians and the greater incidence in Afro-Caribbeans (http://www.allelefrequencies.net). Comparison to our group of healthy individuals confirmed this striking difference, which was statistically significant (20%, P = 10-7, odd ratio [OR] = 6.43, CI95% =2.3-12.7). The increased incidence of DRB1*11 in acquired idiopathic TTP was also significant when compared to patients with a diagnosis of atypical HUS (17%, P= 6×10-5). By contrast, DRB1*11 frequency in this latter group was comparable to this observed in healthy individuals (P = n.s). All patients were heterozygous for this allele. We also observed a decreased incidence of the DRB1*04 allele in acquired idiopathic TTP when compared to healthy individuals (10% versus 30%, respectively, Pcorr = 0.025). DRB1*04, resulting in the DR53 antigen when associated with DRB4, could thus be involved as a protective allele in acquired idiopathic TTP, as suggested in a previous work. We found no association between DRB1*11 and clinical features of autoimmunity, central nervous system involvement, antinuclear antibodies, anti-ADAMTS13 inhibitors, flare-up and relapse episodes and survival. Of note, the association between DRB1*11 with acquired idiopathic TTP was not observed in Afro-Caribbeans (3/12, 25%, p=0.04). High resolution typing of DRB1*11 allele revealed that both DRB1*1101 and DRB1*1104 alleles were significantly over-represented, suggesting that the generic DRB1*11 (and not the DRB1*11 alleles) is the predisposing factor.The DRB1*11 was reported to be a risk factor for systemic sclerosis, early-onset juvenile chronic arthritis and sarcoidosis, and protective against multiple sclerosis and pemphigus vulgaris. Accordingly, we found no patient with one of those 2 latter diseases in our French National TTP registry, whereas a past history of systemic sclerosis, sarcoidosis and juvenile chronic arthritis was observed in 1 case each.Our findings propose DRB1*11 as a strong risk factor for acquired idiopathic TTP in Caucasians. Indeed, the autoimmune response in acquired idiopathic TTP may involve the recognition by T cells of a class II region of DRB1*11, bound to a peptide fragment of ADAMTS13. We also suggest that acquired idiopathic TTP represents a subset of TMA with specific genetic risk factors, distinguishing it from the other forms of idiopathic TMA. The incomplete rate of concordance may be explained by other yet unexplored mechanisms, including additional predisposing genes and environmental triggers. Forthcoming genomewide association studies should lead to the identification of additional alleles associated with the risk of acquired idiopathic TTP. Disclosures:No relevant conflicts of interest to declare.