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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 145-148

Atypical hemolytic-uremic syndrome - A case series from a tertiary care hospital from Eastern India

1 Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Nephrology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission13-Nov-2020
Date of Decision20-Jan-2021
Date of Acceptance29-Jan-2021
Date of Web Publication30-Apr-2021

Correspondence Address:
Dr. Sibabratta Patnaik
Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_184_20

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Atypical hemolytic–uremic syndrome (aHUS) is a form of thrombotic microangiopathy that occurs due to dysregulation of alternate pathway of complement system, which progressively causes systemic complications, end-stage renal disease, and death. As prognosis is poor compared to typical hemolytic–uremic syndrome, early diagnosis and treatment is crucial for favorable outcome. We came across seven patients of aHUS in our pediatric intensive care unit in the last 5 years. Plasma exchange (PE) along with immunosupressives was used for treatment. First child who did not receive PE died. Rest six patients underwent PE and attained hematological remission; however, one later on progressed to chronic kidney disease and expired. All others are on regular follow-up and doing well. A high index of suspicion is required to diagnose aHUS. Early PE can give a better prognosis.

Keywords: Atypical hemolytic–uremic syndrome, eculizumab, mycophenolate, plasma exchange

How to cite this article:
Jain MK, Rout NK, Rup AR, Patnaik S, Behera CK, Mishra R, Sahoo B. Atypical hemolytic-uremic syndrome - A case series from a tertiary care hospital from Eastern India. J Pediatr Crit Care 2021;8:145-8

How to cite this URL:
Jain MK, Rout NK, Rup AR, Patnaik S, Behera CK, Mishra R, Sahoo B. Atypical hemolytic-uremic syndrome - A case series from a tertiary care hospital from Eastern India. J Pediatr Crit Care [serial online] 2021 [cited 2023 Jun 2];8:145-8. Available from: http://www.jpcc.org.in/text.asp?2021/8/3/145/315259

  Introduction Top

Hemolytic uremic syndrome (HUS), which was first described in 1955, is a triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute renal failure.[1] Majority of HUS occurs after infection with Shiga toxin producing Shigella dysenteriae or Escherichia coli O157:H7. Atypical HUS (aHUS) is associated with abnormalities in complement and coagulation pathways, constituting for 5%–10% of all cases of HUS found in children.[2] In occasional cases, aHUS is seen in disorder of Vitamin B12 metabolism. In aHUS of Indian children, antibodies to complement factor H (CFH) is common.[3] As there is high chance of mortality, recurrence, and permanent renal damage, it is highly imperative to diagnose and treat early. Although there are various ways to classify HUS, we have followed the one which was discussed by Dixon and Gruppo.[4] Here, we describe a series of seven cases of aHUS in children, diagnosed and treated in our hospital.

  Case Series Top

It was a hospital record-based retrospective study conducted after taking clearance from the institutional ethics committee. The seven patients reported in this study were admitted to the pediatric intensive care unit (PICU) of Kalinga Institute of Medical Sciences, Bhubaneswar, during the last 5 years (April 2015–March 2020). All seven cases are summarized in [Table 1] [Table 2] [Table 3].
Table 1: Clinical features

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Table 2: Diagnostic assessment

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Table 3: Therapeutic interventions

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All seven patients in this study had MAHA, thrombocytopenia, and acute renal failure. Out of seven patients, four were males (57.1%) and three females (42.9%) with age group range between 3 and 18 years. All patients (100%) had hematuria, proteinuria, and hypertension. Three of our patients (42.9%) had oliguria. One (14.3%) out of seven patients (case-4) had seizures, presenting as posterior reversible encephalopathy syndrome (PRES), who was managed with controlled reduction of hypertension and antiepileptics. All cases required antihypertensive medication; one required single agent while three required two medications and other three required three antihypertensives to control blood pressure. Anti-CFH antibody was positive in four patients (57.1%). Five patients were treated with corticosteroid (prednisolone) after discussing with nephrologist. In one patient steroid was started before the anti-CFH report and was stopped as it came out to be negative. Our first case had received only plasma infusion and immunosuppressive agent could not be administered due to nonavailability of anti-CFH antibody level assay and any institutional protocol for aHUS at that point of time. In subsequent cases, we followed AIIMS, New Delhi, guideline for plasma exchange (PE) and immunosuppression. Daily PE was done with 1.5 times the plasma volume (40 ml/kg) for at least 5 days and until platelets >100,000/mm3 for 2 days. Further exchange was performed with one plasma volume on alternate days, with subsequent tapering depending upon the hematological and biochemical parameters on case-to-case basis. Hemodialysis and PE were done on the next six patients (85.7%) and all of them recovered except one (case-6), who progressed to chronic kidney disease (CKD: Stage-4) subsequently. Among six patients who received PE, all had attained hematological remission. Three patients (42.85%) required continuation of mycophenolate mofetil (MMF) at a dose of 500 mg/m2 along with enalapril due to initial high level of anti-CFH antibodies level (>1500 AU/ml) and persistent proteinuria. Two patients (28.6%) required mechanical ventilation and three (42.3%) required inotropes. One child required inotrope support transiently during PE (case-4), the second one has features of myocardial dysfunction (case-6), while the third child (case-1) required inotrope support during terminal phase of illness.

Out of seven patients, two patients (28.57%) died, one due to bleeding and seizure within 1 month of discharge (case-1) and another (case-6) after 18 months of illness due to CKD along with dilated cardiomyopathy, while five patients recovered (71.42%). On follow-up; all recovered patients were clinically normal without any persistent renal dysfunction or urine abnormality except one (case-2) who had intermittent proteinuria with normal serum creatinine and still on antihypertensive drugs. None of our patients had any form of relapse until the last follow-up.

  Discussion Top

aHUS occurs due to genetic and acquired disorder of complement regulatory pathways, which leads to pathological activation of complement system. It is strongly associated with uncontrolled activation of alternative pathway of complement system.[5] Mutations of some complement proteins and autoantibodies to factor H result in impaired regulations of alternate complement pathway, leading to endothelial damage and microvascular thrombosis. Although aHUS as initially thought to be a disease of exclusively complement abnormality, the role of various genes and proteins regulating coagulation system has recently been recognized. In a single patient, even more than one mutation has been reported.[6] Clinically, aHUS manifest as. MAHA, thrombocytopenia, and acute kidney injury with exclusion of Shiga-like toxin-producing E. coli HUS and thrombotic thrombocytponenic purpura. aHUS consists of 5%–10% of all HUS.[7] There are different modalities for the treatment of HUS depending on the types and primary etiology. Shiga toxin-induced HUS usually requires supportive treatment whereas parenteral hydroxycobalamin along with oral folic acid and betaine will suffice for cobalamin C defect-HUS. In patients with S. pneumoniae-HUS, proper antibiotics which include vancomycin and cephalosporin are helpful, while plasma infusion and unwashed RBC transfusion should be avoided.[8] For patients of aHUS with anti-CFH antibodies, in developed countries, eculizumab (C5 monoclonal antibody) is used as standard treatment as it blocks terminal complement pathway by preventing formation of membrane attack complex. In developing countries like India, PE along with immunosuppression with steroids and antimetabolites is the treatment of choice due to unavailability of anticomplement therapies and eculizumab being highly expensive.[9] Eculizumab is suggested for refractory cases, cases with life-threatening features, and inherited defect in complement regulation. A genetic cause may be suspected in patients with negative anti-CFH. Plasma exchange has no role in these group of patients as they do not have any antibody. However, there is a definite role of plasma infusion and eculizumab in them.[8] For attaining hematological remission (platelet >1 lakh/cmm, schistocytes <2%, and LDH less than upper limit of normal for 2 consecutive days) and preserving renal function, PE is to be started early and followed by maintenance plasma infusion or PE.[9] We found hematuria in all seven patients, similar to previous study.[10] Older age group of children are more affected in aHUS compared to typical HUS. Our study shows that the mean age of presentation was 8.5 years with males affected more than females, similar to previous study.[11] The present study revealed 100% of patients had hypertension, which differs from another study where author had observed, 75% of their patients had hypertension.[12] Among all patients, 42.9% had oliguria which differs from previous study in which all patients had oliguria on presentation.[10] Only one patient (14.3%) had seizure, while a previous study found seizures in 5.6% of their patients.[10] Around one third of patients with aHUS usually showed evidence of low C3 at presentation without any correlation between degree of low C3 level and disease severity.[13] However, in our series, we found low C3 in 57.14% of patients. Anti-CFH antibody was positive in 57.1%, similar to study by Sinha et al., where they found that 56.1% of their patients had anti-CFH antibody positive.[3] In India, anti-CFH antibody is associated with about 50% of pediatric aHUS.[3] In our study, all seven patients required admission in the PICU in view of hemodynamic instability, out of which 42.3% of patients required inotropes and 28.3% required mechanical ventilation. PE was done in 85.7% of our patients; it differs from previous study where 50% of patients required PE.[12] The present study revealed that recovery rate (characterized by hematological remission and resolution of renal dysfunction) was 85.7%, more than the previous study done in 2002 by D'souza et al., in which recovery rate was found to be 25% where one patient died due to inadequate dialysis and another two patients (renal biopsy showing significant changes) with history of seizure and delayed plasmapheresis developed CKD on follow-up out of four patients.[12] This signifies the importance of early diagnosis and management with PE. In all of our patients who recovered initially from disease, PE was performed. One patient died after few weeks of illness, where PE could not be done due to financial constraint, and only plasma infusion was given. In anti-CFH antibody–positive aHUS, the aim of therapy is to reduce antibody titer rapidly, which can be achieved by PE. It has been observed that after 5–7 cycles of PE, there is 80% reduction of antibody titer.[8] Immunosuppression is to be used after confirming anti-CFH antibody. Therapy includes prednisolone (1 mg/kg/day) daily for 4 weeks followed by alternate day with tapering doses over 10–12 months.[8] Other immunosuppressive agents used include cyclophosphamide with dose of 500 mg/m2 intravenously once in 4 weeks for five doses and IV rituximab of 500 mg/m2 once weekly for 2 weeks. MMF and azathioprine are being used for maintenance therapy for 18–24 months with tapering doses of steroid to reduce risk of relapse.[9] In our study, 71.4% of patients required corticosteroid treatment. Three patients (42.85%) required continuation of MMF along with enalapril due to initial high level of anti-CFH antibodies level and persistent proteinuria. Relapse rate of aHUS is 15%–30%, with early relapse predicted by high anti-CFH titer (>1500 AU/ml).[14],[15],[16] In aHUS, the long-term prognosis is not satisfactory with almost 50% progress to end stage renal disease and in acute phase 25% death occurs.[3] One of our patients developed CKD stage 4 after 12 months of illness and died later on due to dilated cardiomyopathy. It is crucial to diagnose and start treatment early with PE, which improves outcome.

A high index of suspicion is required to diagnose aHUS in cases of acute renal failure associated with severe anemia and thrombocytopenia. Estimation of anti-CHF antibody is very useful in the management of aHUS. Early PE can give a better prognosis in these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hemolytic-uremic syndrome: Bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr 1955;85:905-9.  Back to cited text no. 1
George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014;371:654-66.  Back to cited text no. 2
Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, et al. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 2014;85:1151-60.  Back to cited text no. 3
Dixon BP, Gruppo RA. Atypical hemolytic uremic syndrome. Pediatr Clin North Am 2018;65:509-25.  Back to cited text no. 4
Basnayake BM, Wazil AW, Nanayakkara N, Samarakoon SM, Senavirathne EM, Thangarajah BU, et al. Atypical hemolytic uremic syndrome: A case report. J Med Case Rep 2020;14:11.  Back to cited text no. 5
Sartz L, Olin AI, Kristoffersson AC, Ståhl AL, Johansson ME, Westman K, et al. A novel C3 mutation causing increased formation of the C3 convertase in familial atypical hemolytic uremic syndrome. J Immunol 2012;188:2030-7.  Back to cited text no. 6
Nickavar A, Sotoudeh K. Assesment, treatment and prevention of atypical hemolytic uremic syndrome. Int J Prev Med 2013;4:6-14.  Back to cited text no. 7
Bagga A, Khandelwal P, Mishra K, Thergaonkar R, Vasudevan A, Sharma J, et al. Hemolytic uremic syndrome in a developing country: Consensus guidelines. Pediatr Nephrol 2019;34:1465-82.  Back to cited text no. 8
Khandelwal P, Bagga A. Guidelines on hemolytic uremic syndrome by Indian society of pediatric nephrology: Key messages. Indian Pediatr 2020;57:744-7.  Back to cited text no. 9
Patel RD, Vanikar AV, Gumber MR, Kanodia KV, Suthar KS, Patel HV, et al. Diagnosis and management of atypical hemolytic uremic syndrome in children: Single centre experience. Indian J Hematol Blood Transfus 2014;30:342-6.  Back to cited text no. 10
Yoshida Y, Kato H, Nangaku M. Atypical hemolytic uremic syndrome. Renal Replacement Ther 2017;3:1.  Back to cited text no. 11
D'Souza IE, Phadke KD, Subba Rao SD. Atypical hemolytic uremic syndrome. Indian Pediatr 2002;39:162-7.  Back to cited text no. 12
Cody EM, Dixon BP. Hemolytic uremic syndrome. Pediatr Clin North Am 2019;66:235-46.  Back to cited text no. 13
Puraswani M, Khandelwal P, Saini H, Saini S, Gurjar BS, Sinha A, et al. Clinical and Immunological profile of anti-factor H antibody associated atypical hemolytic uremic syndrome: A nationwide database. Front Immunol 2019;10:1282.  Back to cited text no. 14
Khandelwal P, Gupta A, Sinha A, Saini S, Hari P, Dragon Durey MA, et al. Effect of plasma exchange and immunosuppressive medications on antibody titers and outcome in anti-complement factor H antibody-associated hemolytic uremic syndrome. Pediatr Nephrol 2015;30:451-7.  Back to cited text no. 15
Durey MA, Sinha A, Togarismalemath SK, Bagga A. Anticomplement-factor H-associated glomerulonephritis. Nat Rev Nephrol 2016;12:563-578.  Back to cited text no. 16


  [Table 1], [Table 2], [Table 3]


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