|Year : 2021 | Volume
| Issue : 1 | Page : 96-99
Diagnosis and management of hemolytic uremic syndrome in children: A transfusionist's perspective
Suvro Sankha Datta1, Dibyendu De2, Archana Naik3
1 Department of Transfusion Medicine, The Mission Hospital, Durgapur, West Bengal, India
2 Department of Clinical Hematology, BALCO Medical Centre, Chhattisgarh, India
3 Department of Transfusion Medicine, AIIMS, Bhubaneswar, Odisha, India
|Date of Submission||04-Mar-2021|
|Date of Decision||30-Apr-2021|
|Date of Acceptance||10-May-2021|
|Date of Web Publication||29-May-2021|
Suvro Sankha Datta
Department of Transfusion Medicine, The Mission Hospital, Durgapur, West Bengal
Source of Support: None, Conflict of Interest: None
Hemolytic uremic syndrome (HUS) is one of the important causes of severe acute kidney injury in children. Among many etiologies which are responsible for this syndrome, herein we are reporting two interesting cases of HUS caused by anticomplement factor H autoantibodies and Streptococcus pneumoniae infection where the transfusion medicine department played a crucial role in early diagnosis and prompt management.
Keywords: Atypical hemolytic uremic syndrome, pneumococcal hemolytic uremic syndrome, therapeutic plasma exchange, Thomsen-Friedenreich antigen
|How to cite this article:|
Datta SS, De D, Naik A. Diagnosis and management of hemolytic uremic syndrome in children: A transfusionist's perspective. Glob J Transfus Med 2021;6:96-9
|How to cite this URL:|
Datta SS, De D, Naik A. Diagnosis and management of hemolytic uremic syndrome in children: A transfusionist's perspective. Glob J Transfus Med [serial online] 2021 [cited 2021 Dec 7];6:96-9. Available from: https://www.gjtmonline.com/text.asp?2021/6/1/96/317125
| Introduction|| |
Hemolytic uremic syndrome (HUS) is one of the important causes of severe acute kidney injury (AKI) in children. A significant proportion of patients require renal replacement therapy and subsequently about one-third shows features of chronic kidney disease. HUS might be associated with infections due to Shiga toxin-producing organisms, neuraminidase-producing Streptococcus pneumoniae (pneumococcal HUS [pHUS]) or with disorders of complement dysregulation (atypical HUS [aHUS]). Unlike Western cohort, aHUS associated with anticomplement factor H (CFH) antibodies is more common in India, and therapeutic plasma exchange (TPE) is considered the best treatment option for managing aHUS in our country. The precise pathophysiology of the pHUS is still not clear, but Thomsen-Friedenreich antigen (T-antigen) plays an important role in disease progression. T-antigens are normally hidden by sialic acid on the surface of erythrocytes, platelets, and glomerular endothelial cells till they get unmasked by an infection with a sialidase-producing pathogen such as S. pneumonia. Preformed anti-T IgM antibodies present in host plasma bind to the exposed T antigens directly and initiate cascade of events along with uninhibited complement activation, leading to AKI, thrombocytopenia, and hemolysis.. Herein, we are reporting two interesting cases of aHUS and pHUS where the transfusion medicine department took a crucial role in early diagnosis and prompt management.
| Case Reports|| |
A 9-year-old boy was admitted with a 1-week history of recurrent vomiting, pain in abdomen, reduced urine output with dark discoloration of urine, and red spots over body. He had a history of febrile illness 10-day back. On examination, his body weight was 34 kg, body surface area was 1.15 m2, and heart rate was 102/min with blood pressure of 110/60 mm of Hg. He had severe pallor, mild icterus, and abdominal tenderness. Multiple petechial spots were observed over the lower extremities. Laboratory evaluation revealed Hb of 38 g/L, platelet count of 30 × 109/L with ~ 5% schistocytes, and occasional target cells in peripheral blood smear [Figure 1]a. Blood group was O positive and direct antiglobulin test (DAT) was negative. Blood urea nitrogen (72.85 mmol/L), creatinine (344.84 μmol/L), lactate dehydrogenase (LDH) (3464 U/L), and liver enzymes were raised. A blood test for anti-CFH antibodies was sent to the national referral laboratory and found positive over a significant titer (>150 AU/ml). The diagnosis was confirmed as aHUS due to anti-CFH autoantibodies. The patient was managed by serial TPEs [Figure 1]b and two doses of rituximab (375 mg/m2) for 4 weeks. Total 12 TPEs were performed starting daily with 1.5 times plasma volume (60–75 ml/kg) per session for 5 days followed by alternate days at 40 ml/kg for 2 weeks and then twice a week for 1 week according to the Indian HUS consensus protocol. The plasma was exchanged by an intermittent-flow apheresis machine (MCS+, Haemonetics, US) and circuit was primed with 110–120 ml of O positive compatible allogenic red blood cells to manage the extracorporeal volume. Ionized calcium was maintained >1 mMol/l by slow infusion of 10% calcium gluconate during the procedure under cardiac monitoring. Acid-citrate-dextrose was used as anticoagulant and group O fresh frozen plasma (FFP) and 5% human serum albumin (50:50) were used as replacement fluid. No adverse reaction was observed during the plasma exchanges. The plasma color was suggestive of intravascular hemolysis [Figure 1]c and urine color was started improving after the first TPE [Figure 1]d. The hematological remission was achieved at day 28 after admission [Figure 2]. He was discharged at day 32 under maintenance dose of mycophenolate mofetil along with low-dose prednisolone and followed up for 1 year without any evidence of relapse.
|Figure 1: Panel A is showing the peripheral blood smear in × 100 magnification after Leishman stains with schistocytes and target cells (small arrows). Panel B is showing the therapeutic plasma exchange procedure by apheresis. Panel C is showing color of plasma, suggestive of intravascular hemolysis. Panel D is showing improvement of urine color after the first episode of plasma exchange|
Click here to view
|Figure 2: Graph showing hematological remission (with respect to Serum LDH, S-Creatinine, Haemoglobin and platelet levels) achieved at day 28 after admission|
Click here to view
A 1.5-year-old boy was presented to the emergency with a 3-day history of high grade fever, cough, oliguria, and poor oral intake. On examination; he was found dehydrated, tachycardic, tachypneic, and in respiratory distress. Decreased breath sounds were appreciated over both the lungs. Chest X-ray revealed bilateral lung consolidations. Laboratory investigations revealed Hb 54 g/L; platelets were 20 × 109/L with occasional schistocytes, and target cells. Blood urea nitrogen (92.85 mmol/L), creatinine (394.84 μmol/L), and LDH (2582 U/L) were raised along with an elevated C-reactive protein (47.9 mg/L). The blood culture was performed at first referral center and found positive for S. pneumoniae. The child was put on ventilator at emergency and intravenous antibiotics were started. A polyspecific DAT was performed together with blood grouping (O positive; antibody screening negative) which showed a positive result. Furthermore, a monospecific DAT (DC-Screening I, Bio-Rad) showed a positive result in anticomplement 3d microcolumn. As pHUS was suspected an extensive immunohematology, workup was performed to identify poly-agglutination and T-antigens on patient's erythrocytes. Polyagglutination was confirmed according to the method described previously. Patient's erythrocytes were treated with six group AB adult donor sera at 22°C and 4°C, keeping AB group cord sera and adult O cells as negative controls. T-antigen presence was confirmed using an indigenously lectin panel which showed positive agglutination with peanut lectin (Arachis hypogea). The final diagnosis of pHUS was reached based on the combination of the clinical symptoms and the laboratory findings. The patient had received 15 ml/kg washed packed red cell concentrates and 20 ml/kg plasma reduced ABO-compatible random donor platelets. The decision of TPE was considered with 5% human serum albumin, but we lost the child within 24 h of admission due to sepsis and multiorgan failure before proceeding to the TPE.
| Discussion|| |
The diagnostic criteria of HUS consist of (i) microangiopathic hemolytic anemia, defined by anemia (hematocrit <30%), and fragmented red cells on peripheral smear (schistocytes ≥2%) with either elevated (LDH >450 IU/L) or undetectable haptoglobin; (ii) thrombocytopenia (platelet count <150 × 109/L); and (iii) AKI, defined as increase in serum creatinine by 50% over baseline level. Atypical HUS is characterized by dysregulation of the alternative complement pathway, resulting in endothelial damage and microvascular thrombosis. In Western countries, inherited genetic defects of the alternative pathway are the major cause of aHUS, and the standard of care for such patients is complement blockade with Eculizumab, a humanized anti-C5 antibody. However, the drug is expensive and not easily available in developing countries like India. Thus, a combination of prompt TPE and immunosuppressive therapy is recommended for HUS patients with anti-CFH antibodies. In case 1, our aim of therapy was to reduce the antibody titers by TPE and our line of treatment was in agreement with The American Society for Apheresis guidelines which assigns the indication of level I category to anti-CFH-associated HUS, implying that prompt starting of TPE is a primary therapeutic intervention for such cases.
The incidence of HUS following invasive S. pneumoniae infections is estimated to be about 0.5%. A diagnosis of probable pHUS is made in patients, usually younger than 2 years, with sepsis, pneumonia, or meningitis, and positive DAT without features of DIC. The diagnosis criteria consist of the presence of either: (i) S. pneumoniae isolated by bacterial culture or detection of pneumococcal antigen by PCR or ELISA in appropriate body fluids or (ii) positive peanut lectin (Arachis hypogaea) agglutination assay. In our second case, DAT and the polyagglutination test on patient's erythrocytes were performed in the context of clinical and laboratory features, which might have been positive due to an infection with a sialidase-producing pathogen but also by incompatible drugs (e.g. antibiotics) or by autoimmune mechanisms. The final diagnosis was confirmed after the identification of uncovered T-antigen on the patient's red blood cells by a simple agglutination technique using an indigenously lectin panel. Parenteral cephalosporins and vancomycin were used to manage the infection. Albumin was considered as a replacement fluid for TPE in this case rather than FFP as per The American Society for Apheresis guidelines to avoid plasma products transfusion. The challenges in transfusion medicine services arise with plasma-rich blood components due to the presence of naturally occurring anti-T antibodies in the donor plasma portion of the blood product. In such cases of T-activation, washing is appropriate for cellular blood components for removal of the plasma portion. However, balancing the necessity of washing cellular blood components and the loss of quality and quantity of the blood components, particularly platelet products can be difficult.
| Conclusion|| |
We endorse from our first case that prompt starting of TPE along with immunosuppressive agents could be life saving for HUS patients with anti-CFH antibodies and the message we would like to convey through the discussion of our second case is that identification of T-antigens should be integrated in pHUS diagnostic algorithm. Finally, we conclude that a well-equipped transfusion medicine department could change the outcome of HUS in children by facilitating early diagnosis and prompt management.
Declaration of patient consent
The authors certify that they have obtained patient consent. Consent has been obtained from parents as patient is a minor in this case. They understand that every attempt to ensure anonymity of patient will be taken, however complete anonymity cannot be fully guaranteed
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Srivastava RN, Moudgil A, Bagga A, Vasudev AS. Hemolytic uremic syndrome in children in northern India. Pediatr Nephrol 1991;5:284-8.
Kumar A, Taneja N, Sharma M. An epidemiological and environmental study of Shiga toxin-producing Escherichia coli
in India. Foodborne Pathog Dis 2014;11:439-46.
Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, et al
. Indian HUS registry Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated haemolytic uremic syndrome in children. Kidney Int 2014;85:1151-60.
Von Vigier RO, Seibel K, Bianchetti MG. Positive Coombs test in pneumococcus associated haemolytic uremic syndrome. A review of the literature. Nephron 1999;82:183-4.
Shimizu M, Yokoyama T, Sakashita N, Sato A, Ueno K, Akita C, et al
. Thomsen-Friedenreich antigen exposure as a cause of Streptococcus
pyogenes-associated hemolytic-uremic syndrome. Clin Nephrol 2012;78:328-31.
Strobel E, Dreßel P, Strotmann P. Rapid diagnosis of Streptococcus
pneumonia induced haemolytic-uraemic syndrome. Blood Transfus 2014;12:425-7.
Chakrabarty R, Datta SS, Das SS, Ghosh S. Importance of indigenous lectin panel in immunohematology. Indian J Hematol Blood Transfus 2018;34:166-7.
Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, et al
. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2016;31:15-39.
Bagga A, Khandelwal P, Mishra K, Thergaonkar R, Vasudevan A, Sharma J, et al
. Indian Society of Pediatric Nephrology. Hemolytic uremic syndrome in a developing country: Consensus guidelines. Pediatr Nephrol 2019; 34:1465-82.
Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al
. Guidelines on the use of therapeutic apheresis in clinical practice-Evidence - based approach from the writing committee of the American Society for Apheresis: The Eighth special issue. J Clin Apher 2019;34:171-354.
Copelovitch L, Kaplan BS. Streptococcus pneumonia
associated hemolytic uremicsyndrome. Pediatr Nephrol 2008;23:1951-6.
Loupiac A, Elayan A, Cailliez M, Adra AL, Decramer S, Thouret MC, et al.
Diagnosis of Streptococcus pneumoniae
-associated hemolytic uremic syndrome. Pediatr Infect Dis J 2013;32:1045-9.
[Figure 1], [Figure 2]