|Year : 2015 | Volume
| Issue : 4 | Page : 547-549
Childhood hepatitis A virus infection associated with immune thrombocytopenic purpura: Report of two cases
Biswajit Biswas1, Monojit Mondal1, Rajoo Thapa2, Debkrishna Mallick3
1 Department of Pediatrics, Burdwan Medical College and Hospital, Burdwan, West Bengal, India
2 Department of Pediatrics, Golisano Children's Hospital, Upstate Medical University, Syracuse, New York, India
3 Department of Pediatrics, St. Mary's Hospital, PO30 5TG Newport, Wales, India
|Date of Web Publication||14-Jul-2015|
Department of Pediatrics, Burdwan Medical College and Hospital, Burdwan - 713 104, West Bengal
Source of Support: None, Conflict of Interest: None
Hepatitis A virus (HAV) infection is a benign, self-limited gastrointestinal infection of the children belonging to the developing countries. Extra-intestinal, especially autoimmune hematological manifestations rarely develop during the course of infection in children. We describe two children, aged 8 months and 5 years who developed immune thrombocytopenic purpura (ITP) during the course of otherwise uncomplicated HAV infection. In both children, bleeding secondary to thrombocytopenia was the initial presentation. An 8-month-old infant was anicteric at presentation and HAV infection was discovered during the course of investigations. Both were treated with platelet concentrates and intravenous immunoglobulin therapy successfully. HAV should be included in the differentials in any child (including infants) who presents with ITP, even in the absence of well-recognized features of the disease.
Keywords: Anicteric, hepatitis A virus infection, immune thrombocytopenia, infant
|How to cite this article:|
Biswas B, Mondal M, Thapa R, Mallick D. Childhood hepatitis A virus infection associated with immune thrombocytopenic purpura: Report of two cases. Med J DY Patil Univ 2015;8:547-9
|How to cite this URL:|
Biswas B, Mondal M, Thapa R, Mallick D. Childhood hepatitis A virus infection associated with immune thrombocytopenic purpura: Report of two cases. Med J DY Patil Univ [serial online] 2015 [cited 2023 Feb 1];8:547-9. Available from: https://www.mjdrdypu.org/text.asp?2015/8/4/547/160827
| Introduction|| |
Most hepatitis A virus (HAV) infections in young children are asymptomatic or are characterized by a mild flu-like illness such as fever, nausea, or abdominal discomfort. More serious symptoms (e.g., anorexia or high fever) are observed in only 16% of cases in those 1-2 years of age, and jaundice is reported in only 7% of children younger than 4 years.  In contrast, >70% of older children and adults are symptomatic, with 40-70% becoming clinically jaundiced,  Infection with hepatitis B virus, parvovirus, and Epstein-Barr virus are occasionally associated with extra-hepatic autoimmune phenomena which are extremely rare in acute HAV infection. Although transient hematologic abnormalities are commonly observed during the course of otherwise uncomplicated acute HAV infection in children, autoimmune manifestations such as immune thrombocytopenic purpura (ITP), aplastic anemia, vasculitis, and hemophagocytic syndrome are rare.
| Case Report|| |
Two children (case 1: 8-month-old male and case 2: 5-year-old male) with immune thrombocytopenia, developing during the course of HAV infection are reported. Both were otherwise healthy with no significant past medical history. There was no history of recent upper respiratory tract infections, diarrhea, hematological, and hepatic diseases, immunization or intake of drugs. They were hemodynamically stable at presentation.
The important clinical features and laboratory findings are summarized in [Table 1]. The serum gamma-glutamyl transferase, albumin, prothrombin time, activated partial thromboplastin time, fibrinogen, and D-dimer were normal. Viral serologic studies were negative for hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, rubella virus, and parvovirus B19. Toxoplasma gondii serology was negative also. Direct and indirect Coombs tests, antinuclear antibody, anti-double stranded DNA, anti-cardiolipin, and anti-phospholipid IgM and IgG antibodies were negative in both children. Quantitative serum immunoglobulins and complement (C3 and C4) levels were normal. The bone marrow findings were consistent with the diagnosis of immune thrombocytopenia without evidence of hemophagocytosis or emperipolesis. Both children were treated with platelet concentrates and intravenous immunoglobulin (IVIG), with prompt normalization of the platelet count. Both had no further complications during the hospital stay. The clinical examination and the blood biochemistry were normal in case 1 at the end of 6 weeks. Case 2, however was lost to follow-up.
| Discussion|| |
Hepatitis A virus is a common, mostly self-resolving gastrointestinal infection occurring in children of the developing world. At times, this relatively benign infection may be associated with fulminant hepatic failure, resulting in increased morbidity and mortality.  Extra-hepatic manifestations and/or complications, especially hematological ones, secondary to HAV infection is rare in children. Most reports on hematological manifestations as a result of HAV infection in the literature concern adults. The reported hematological manifestations in association with HAV include hemolysis, aplastic anemia, vasculitis, thrombocytopenia, pancytopenia without aplastic anemia, red cell aplasia, and the hemophagocytic syndrome. ,,,,,
To the best of our knowledge, ITP associated with HAV infection has been reported in five children previously. ,,,, Majority of the children had clinically recognizable icterus at the time of presentation. Tanir et al.  reported a 5-year-old boy who presented with purpura and echymoses secondary to HAV infection that was recognized only on serological studies. Thrombocytopenia may either be the initial manifestation , or may develop late during the course of the HAV infection. 
Decreased platelet count has been attributed to various etiologies like bone marrow depression, secondary to disseminated intravascular coagulation (DIC), in association with hemophagocytosis and immunologic destruction of platelets in the peripheral circulation secondary to circulating immune-complex deposits or anti-cardiolipin and anti-phospholipid antibodies. ,,, Virus-associated hemophagocytic syndromes with emperipolesis may also be responsible for the decrease in platelet count seen during active infection.  There was no evidence of pancytopenia suggestive of bone marrow suppression in our children. Hemophagocytic syndrome was ruled out on the basis of a non-suggestive bone marrow examination. DIC was ruled out on the basis of a normal D-dimer assay. The bone marrow picture of megakaryocytosis with abundance of mature and immature platelets and prompt hematological response to IVIG therapy suggested immunological basis for the observed thrombocytopenia.
All the children reported thus far ,,,, were older ones, with no infants being reported until date. Case 1, in the present report was 8 months old at the time of diagnosis, which to our knowledge, is the youngest patient to develop immune-mediated thrombocytopenia during the course of HAV infection.
| Conclusion|| |
Our report serves to emphasize that ITP may be seen occasionally during the course of otherwise uncomplicated HAV infection in children. It may be the sole manifestation of the underlying infection. HAV infection should be among the differentials in any child presenting with ITP, even in the absence of icterus and other well-recognized symptoms of the disease and worth remembering that no age-group is immune to the development of the complication.
| References|| |
Armstrong GL, Bell BP. Hepatitis A virus infections in the United States: Model-based estimates and implications for childhood immunization. Pediatrics 2002;109:839-45.
Lednar WM, Lemon SM, Kirkpatrick JW, Redfield RR, Fields ML, Kelley PW. Frequency of illness associated with epidemic hepatitis A virus infections in adults. Am J Epidemiol 1985;122:226-33.
Yazige N, Balistreri WF. Viral hepatitis. In: Behrman RE, Kliegman RM, Jenson HD, Stanton BF, editors. Nelson Textbook of Pediatrics. 18 th
ed. Philadelphia: Saunders, Elsevier; 2007:1680-87.
Doménech P, Palomeque A, Martínez-Gutiérrez A, Viñolas N, Vela E, Jiménez R. Severe aplastic anaemia following hepatitis A. Acta Haematol 1986;76:227-9.
Inman RD, Hodge M, Johnston ME, Wright J, Heathcote J. Arthritis, vasculitis, and cryoglobulinemia associated with relapsing hepatitis A virus infection. Ann Intern Med 1986;105:700-3.
Schiff ER. Atypical clinical manifestations of hepatitis A. Vaccine 1992;10 Suppl 1:S18-20.
Shenoy R, Nair S, Kamath N. Thrombocytopenia in hepatitis A - An atypical presentation. J Trop Pediatr 2004;50:241-2.
Tomida S, Matsuzaki Y, Nishi M, Ikegami T, Chiba T, Abei M, et al
. Severe acute hepatitis A associated with acute pure red cell aplasia. J Gastroenterol 1996;31:612-7.
Walia A, Thapa BR, Das R. Pancytopenia in a child associated with hepatitis A infection. Trop Gastroenterol 2006;27:89-90.
Avci Z, Turul T, Catal F, Olgar S, Baykan A, Tekfam O, et al
. Thrombocytopenia and emperipolesis in a patient with hepatitis A infection. Pediatr Hematol Oncol 2002;19:67-70.
Ertem D, Acar Y, Pehlivanoglu E. Autoimmune complications associated with hepatitis A virus infection in children. Pediatr Infect Dis J 2001;20:809-11.
Scott JX, Gnananayagam EJ, Gupta S, Simon A, Mukhopadhya A. Thrombocytopenic purpura as initial presentation of acute hepatitis A. Indian J Gastroenterol 2003;22:192-3.
Tanir G, Aydemir C, Tuygun N, Kaya O, Yarali N. Immune thrombocytopenic purpura as sole manifestation in a case of acute hepatitis A. Turk J Gastroenterol 2005;16:217-9.