Hemolytic Anemia Exacerbated by Hepatitis A in a Child with Sickle Cell Trait A Case Report
Hepatitis A is a common infection in India and is known to cause fulminant hepatitis in children with sickle cell disease. This is a case report of an 18-month-old boy with sickle cell trait who presented with severe hemolysis. Investigations, diagnosis and treatment are discussed and patient recovered with supportive management. Hepatitis A can trigger severe hemolysis even in sickle cell trait patients.
Sickle cell disease (SCD) is a term used for a group of genetic disorders characterized by the production of hemoglobin “S”. By deﬁnition, the quantity of abnormal HbS in sickle cell trait should be less than 50% of the total hemoglobin. Sickle cell hemoglobinopathy occurs due to a mutation of the beta-globin gene situated on the short arm of chromosome 11, such that adenine is replaced by thymine in the codon that codes for the amino acid in the sixth position of the beta-globin chain. This leads to an amino acid change in beta chain of the hemoglobin (Hb) molecule from glutamic acid to valine. The result is a profound change in the molecular stability and solubility of this hemoglobin, called HbS, from the normal adult HbA.
The lifespan of people with sickle cell trait is normal and serious complications are rare as against those with sickle cell disease (Figure 1). Rare complications of sickle cell trait that can occur are sudden death during rigorous exercise, splenic infarction at high altitude, hematuria, hyposthenuria, deep vein thrombosis and susceptibility to eye injury with formation of hyphemia.
It is also seen that fulminant hepatitis A is more frequently seen in sickle cell disease.[1,2] Hepatitis A is the most common cause of viral hepatitis in India, and of fulminant hepatitis[4,5] and hence immunization of children with Hepatitis A Vaccine is essential.
An 18-month-old boy born out of non-consanguineous marriage presented for the ﬁrst time with fever for two days, pallor and fast breathing for one day, and yellow discoloration of eyes. On examination, patient had fever of 101.4˚F with respiratory rate of 48 per minute and heart rate of 160 beats per minute, blood pressure of 100/66 mm Hg. Also noted was hepatomegaly 2 cm from the costal margin with no palpable spleen.
Investigations revealed Hb 2.5 g%, total leukocyte count 33,900/µL, packed cell volume (PCV) of 7.8%, platelet count of 4,00,000/ml, peripheral smear showed marked hypochromia, moderate anisocytosis, microcytes, poikilocytosis with mild polychromasia. Serum iron was 289µg/dL, total iron binding capacity of 285µg/dL and normal transferrin saturation of 101.4%. Serum LDH was 1971 U/L and reticulocytes count was 5.3%. G6PD levels were normal with a negative direct Coombs test. The child had an elevated bilirubin of 14.3 mg/dL with raised liver enzymes serum glutamic-oxaloacetic transaminase (SGOT) of 498 IU and serum glutamic-pyruvic transaminase (SGPT) of 285IU and alkaline phosphatase of 255 U/L, serum albumin 4.4 g/dL. Hemoglobin electrophoresis revealed HbS of 24.4% and HbA of 67.8%. IgM hepatitis A was reactive.
As this child presented with severe anemia and jaundice, he was worked up for various conditions. The diﬀerential diagnosis of iron deﬁciency anemia, G6PD deﬁciency, and malaria being the most common were ﬁrst ruled out. Sickle cell trait was picked up on hemoglobin electrophoresis. The occurrence of congestive cardiac failure (CCF) in a child with hemolytic picture suggests acute hemolysis. Hepatitis A infection was the only risk factor detected in this child (Figure 2).
Severe hemolysis is less often seen in sickle cell trait, than in sickle cell disease; however, in the present case, hepatitis A infection probably lead to this severe hemolysis. The patient recovered after blood transfusion and supportive treatment and liver functions normalized after 3 days.
In children the predominant causative agent of hepatitis appears to be HAV alone or in combination with other infectious agents.[5-8] Though over 90% of hepatitis A infections in children remain subclinical, fulminant hepatitis A, either singly or in combination with other hepatotropic viruses, is being recognized in India.[1,3,4] The bilirubinemia appears to represent the increased load of red blood cell breakdown products on an acutely damaged liver and is not an eﬀect of anemia per se or a reﬂection of underlying liver disease.
- Presence of sickle cell trait needs to be evaluated as one of the risk factors for developing fulminant hepatitis.
- Non-immune sickle cell disease patients may be considered an important group for active immunization against hepatitis A.
- Hepatitis A can trigger hemolysis in patients with sickle cell trait, hence patients with fulminant hepatitis A need to be investigated for sickle cell trait.
- Lenge RL, Vani VS, et al. Fulminant hepatitis A in children with sickle cell disease. Indian Pediatrics. 2002; 39:186-189.
- Barrett-ConnorE. Sickle cell disease and viral hepatitis. Ann Intern Med. 1968;69(3):517-527.
- Tandon BN, Gandhi BM, Joshi YK. Etiological spectrum of viral hepatitis and prevalence of marker of hepatitis A and B infection in North India. Bull WHO 1984;62:67-73.
- Acharya SK, Dasarathy S. Fulminant hepatic failure in tropical population: Clinical course, cause and early predictors of outcome. Hepatology, 1996;23:1448-1455.
- Bendre SV, Bavdekar AR. Fulminant hepatic failure: Etiology, viral markers and outcome. Indian Pediatr. 1999;36:1107-1112.
- Arora NK, Nanda SK. Acute viral hepatitis types E, A and B singly and in combination in acute liver failure in children in North India. J Med Vir. 1996; 48: 215-221.
- Kapil D, Arvind B. e proﬁle and outcome of patients admitted in pediatric intensive care unit. Indian J Pediatr 1993; 60: 5-10.
8 . Shapiro CN, Margoles HS. World epidemiology of hepatitis A virus infection. J Hepatology.18 (Suppl 2): S11-S14