|Year : 2021 | Volume
| Issue : 4 | Page : 232-235
Autoimmune hemolytic anemia in children: Clinical profile and outcomes
Vinod Paul1, Amanta Lucy Ittoop2, Anand Prakash3
1 Department of Paediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
2 Department of Anaesthesia, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
3 Division of Paediatric Hematology Oncology, St John's Medical College, Bengaluru, Karnataka, India
|Date of Submission||15-Dec-2020|
|Date of Decision||15-Jan-2021|
|Date of Acceptance||16-May-2021|
|Date of Web Publication||18-Jan-2022|
Dr. Anand Prakash
Division of Pediatric Hematology Oncology, St Johns Medical College Hospital,Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Autoimmune hemolytic anemia is a rare disorder with varied presentations. A primary physician could misdiagnose this condition for other simpler causes of anemia, if not aware of the spectrum of the signs and symptoms of this disease. This may lead to further worsening of the patient, due to delay in starting of the therapy with immunosuppresants. Hasty blood transfusion could cause exacerbation of hemolysis. Both IgG and IgM antibodies could cause this disease, and they are termed as warm and cold antibody hemolytic anemia, respectively. Monitoring and follow-up of patients are also very necessary along with careful tapering of the medications. Evolution of other autoimmune disorders such as systemic lupus erythematosus is also noticed in such children. There is a paucity of literature about this disease, especially from the developing world. In this study, we have shown the clinical profile of 21 children with autoimmune hemolytic anemia, with the treatment given and the response. An attempt to compare our data with the available data from various studies has also been made so that a primary care physician could easily identify the most common symptoms and signs of this disease and treat such children.
Keywords: Autoimmune hemolytic anemia, cold antibodies, Evan's syndrome, warm antibodies
|How to cite this article:|
Paul V, Ittoop AL, Prakash A. Autoimmune hemolytic anemia in children: Clinical profile and outcomes. J Appl Hematol 2021;12:232-5
| Introduction|| |
Autoimmune hemolytic anemia (AIHA) is a condition, in which autoantibodies bind to the surface of the erythrocytes and cause their premature destruction with or without complement activation. It is rare in children with the incidence of 0.3 in 100,000.
Need for study
The rarity of AIHA, young age of a child, rapidity of onset, and complications pose significant challenges to primary care physicians. Blood transfusion could lead to severe hemolytic adversities. This study describes a series of children with AIHA and compares our data with other studies, to guide early diagnosis and appropriate management.
| Subjects and Methods|| |
This is a retrospective study conducted in the Division of Pediatric Hematology-Oncology, St John's Medical College Hospital. A chart review of all children diagnosed with AIHA from 2010 to 2016 was done. Diagnosis of AIHA was made in children with anemia (hemoglobin level <11 g%), indirect hyperbilirubinemia, and reticulocytosis in the presence of a positive direct comb test (DCT). Secondary causes of AIHA were excluded from this series. Clinical parameters and examination findings, with laboratory investigations, and treatment received and duration were recorded. Children were followed up for an average period of 5 years. The outcomes were analyzed using descriptive statistics.
| Results|| |
The age of presentation ranged from 3 months to 17 years, with a median age of 9.5 years. Twelve of them were females (57.14%) and 9 (42.86%) were males. Fever was noted in 15 of the children. Thrombocytopenia was seen in ten of the children, and none of them had any other cell line deficits (range – 2000–1.27 lakhs). Icterus was noticed in 7 (33.33%), dark-colored urine (suggestive of hemoglobinuria) was seen in 7- (33.33%). Sixteen of these children had hepatomegaly (76.19%) and 11 had splenomegaly (52.38%).
The mean Hb was 5.02 (range of 2.7–7) at presentation. The mean reticulocyte count was seen to be 20.5 (range of 0.29–44.9). Seventeen of the children had reticulocytosis.
Two children were found to be DCT negative, of which one had an indirect Coomb's test positive. Twelve children were subject to monospecific DCT test, of which 7 had IgM, and 5 had IgG positivity. Blood transfusion was done in 12 children, in view of severe anemia leading to heart failure. The mean hemoglobin of those who were transfused was 5.25 (range of 2.7–7). Difficulty in cross matching was observed in 4 of the cases. Steroids were started as the first-line treatment in all the children, of which 16 of them had remission – 80.95%. Second-line therapy (cyclosporine/azathioprine) was added in four cases (19.04%) and 2 among these were also given rituximab (9.5%). However, one child was lost to follow-up. Time to response is shown in [Table 1].
Relapse was seen in 3 of the 21 children in our study. One of the girls who relapsed after 14 months, was 8 years old, and required transfusion and steroids. Another girl, who was 15 years old, had her first relapse after 2 years, was treated with steroids and azathioprine during her first relapse, and with steroids and rituximab during her second relapse. The child who relapsed the earliest within 3 months of stopping steroids was 15 years and had three relapses in a period of 5 years. IgM was positive, and she was managed with steroids during her 1st relapse, steroids and mycophenolate moefetil (MMF) during her 2nd, and danazol (other agents not used in view of financial constraints) with steroids in her 3rd relapse. Two children in our study later evolved into having systemic lupus erythematosus over the course of 5 years.
| Discussion|| |
AIHA could be idiopathic or primary (accounting for 23%–65% of cases in various studies). Secondary causes which are associated are infections (mostly in infants), immunodeficiency syndromes, and autoimmune conditions (in teenagers) and malignancies (mostly lymphoid in older children and adults). The clinical features of this disease, as described by the largest international case series by Aladjidi et al., a recent study by Sankaran et al., Naithani et al., and our study have been shown in [Table 2].,,
|Table 2: Comparative studies on auto immune hemolytic anemia in children|
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Monospecific DCT was done in 12 children. Forty-two percent showed IgG (Warm antibodies), which causes maximal hemolysis at 37° centigrade, through sequestration in the spleen (extravascular hemolysis) – usually without complement activation. Fifty-eight percent showed IgM antibody (Cold antibodies), which activate the complement system and cause intravascular hemolysis at 4° and extravascular hemolysis in the liver. DCT is considered to be the hallmark to identify AIHA. Very rarely, there could be instances where DCT could be negative such as in our study where 2 DCT − ve cases were seen. The explanation for this phenomenon could be that the quantity of autoantibody is low, the affinity of the antibodies to the RBC might be low or the circulating antibodies could be IgM and IgA., Treatment for all our patients were started with steroids as the first line. Sixteen of twenty one children (80.95%) had response with first line – steroids and among them 14 of them responded within 1 month – 66.66%. The ten children with anemia and thrombocytopenia (Evans syndrome) in our study were observed to have remission later than the other children – median of 18 days (range – 3–90 days), and a mean of 28.2 days as compared to median of 14 days, and mean of 21.4 days in the whole study group. This was similar to the experience noted in Miano where a higher dose of steroid for a longer duration is considered for such children. Two of these children also required second-line treatment with azathioprine or MMF and further rituximab. Similar results were also seen in the studies tabulated above. Steroids are started as the first-line drugs as shown above and reiterated in all the studies reviewed at a dose of 1–2 mg/kg/day. The response is seen within 2 weeks, and children who do not respond by 3 weeks are usually refractory to steroids. They are started on azathioprine, cyclosporine, MMF, or danazol which are considered the second line. Relapses were seen in three out of the 21 children (14.2%), of whom one of them had Evans syndrome and had two relapses. She was treated with MMF and rituximab. The other two children had one and three relapses, respectively. One of them recovered with only steroids, and the other child was treated with steroids and MMF during her 1st and steroids and danazol during her 2nd and 3rd relapses. MMF was not considered in her due to financial constraints.
| Conclusion|| |
Autoimmune hemolytic anemia is a rare entity which presents with features of sudden severe hemolysis. Blood transfusions should be reserved for severe cases with failure, in small aliquots, with strict monitoring for transfusion reactions. Associated features such as thrombocytopenia could be present which could be an indicator of prolonged and intensive course. The first-line therapy of steroids must be started after confirmation of the disease, and if found to be refractory must be started on the 2nd and 3rd line strategies with careful evaluation for evolving autoimmune diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Barcellini W, Fattizzo B. The changing landscape of autoimmune hemolytic anemia. Front Immunol 2020;11:946.
Fan J, He H, Zhao W, Wang Y, Lu J, Li J, et al
. Clinical features and treatment outcomes of childhood autoimmune hemolytic anemia: A retrospective analysis of 68 cases. J Pediatr Hematol Oncol 2016;38:e50-5.
Sankaran J, Rodriguez V, Jacob EK, Kreuter JD, Go RS. Autoimmune hemolytic anemia in children: Mayo clinic experience. J Pediatr Hematol Oncol 2016;38:e120-4.
Aladjidi N, Leverger G, Leblanc T, Picat MQ, Michel G, Bertrand Y, et al
. New insights into childhood autoimmune hemolytic anemia: A French national observational study of 265 children. Haematologica 2011;96:655-63.
Naithani R, Agrawal N, Mahapatra M, Kumar R, Pati HP, Choudhry VP. Autoimmune hemolytic anemia in children. Pediatr Hematol Oncol 2007;24:309-15.
Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, et al
. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev 2020;41:100648.
Goswami PR, Chaudhary SB. A clinico hematological correlation of autoimmune hemolytic anemia and its clinical implicat. Int J Med Res Rev 2016;4:1791-5.
Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol 2002;69:258-71.
Miano M. How I manage Evans syndrome and AIHA cases in children. Br J Haematol 2016;172:524-34.
Kalfa TA. Warm antibody autoimmune hemolytic anemia. Hematology 2016;2016:690-7.
Go RS, Winters JL, Kay NE. How I treat autoimmune hemolytic anemia. Blood 2017;129:2971-9.
[Table 1], [Table 2]