Thrombocytopenic purpura.pdf

Jornal de Pediatria - Vol.76, Nº5, 2000 395 0021-7557/00/76-05/395 Jornal de Pediatria Copyright © 2000 by Sociedade Brasileira de Pediatria CASE REPORT Thrombocytopenic purpura after hepatitis B vaccine Renata Maezono1, Ana Maria de Ulhôa Escobar2 Abstract Objective: to demonstrate a case of idiopathic thrombocytopenic purpura after hepatitis B vaccine and drive attention to this possible relation when other causes have been excluded. Methods: description of a case of a patient who was 1 month and 16 days old and presented petechiae and ecchymoses one week before she entered the Emergency Room of the Hospital das Clínicas da Universidade de São Paulo. Other causes beyond Hepatitis B vaccine, received one month before the hemorrhagic state, were ruled out with the history and laboratory exams. A review of the literature about PTI revealed case reports of the disease connected with Hepatitis B vaccine administration. Results: the vaccine was considered the probable cause. The child was treated with intravenous immunoglobulin, improving from thrombocytopenia after three days, and remaining without symptoms during one month of follow up. Conclusion: the thrombocytopenic purpura after hepatitis B vaccine is a rare event whose causal relation is hard to prove. The diagnosis is based on the exclusion of other possible causes, but in this case, the hypothesis may be considered since new cases are being reported in the literature. J Pediatr (Rio J) 2000; 76(5): 395-8: thrombocytopenic purpura, thrombocytopenia, vaccines. Introduction Idiopathic thrombocytopenic purpura is a disease of probable autoimmune etiology, which affects children and adults in an estimated incidence of 10 to 125 per 1,000,000 people a year.1 It is defined as an isolated thrombocytopenia with no other clinical associated conditions or other causes of thrombocytopenia (infection by HIV, systemic lupus erythematosus, lymphoproliferative diseases, myelodysplasias, and thrombocytopenia induced by drugs).2 It usually affects children, and the incidence in this group peaks between the 2nd and the 4th years of age, affecting boys and girls in the same proportion.2 Idiopathic thrombocytopenic purpura is manifested through mucous and dermal bleeding, and serious hemorrhages, such as intracranial hemorrhages, occur in only 0.5 to 1% of the cases.3 About 85% of the cases present benign and self-limited evolution, with spontaneous and complete recovery in up to 6 months.3 The diagnosis is based on the patient’s history, on physical examination, and on the exclusion of the causes of thrombocytopenia. It generally occurs after a viral infection episode; however, there are reports of cases of idiopathic thrombocytopenic purpura that set after measles-mumpsrubella vaccine4,5 and hepatitis B vaccine.6-9 1. Resident, Department of Pediatrics, Children’s Institute, Universidade de São Paulo (USP) School of Medicine. 2. Chief, Pediatric Emergency Service, Children’s Institute, USP School of Medicine. 395 As platelets had fallen to 12. Fever or previous infections were not reported. presenting petechiae on her face. – normocellular megakaryocytic series.000 21. and feet.M. by a cesarean delivery.000 TP 10/INR: 0.5 cm away from the right costal margin.000 780. which revealed: – normocellular and normomaturative granulocytic. these blotches/ rashes were treated with topic hydrocortisone.0 Serologies negative July 28 .S. and it was maintained for 5 days.A. hepatitis B vaccine is applied to all children at birth. and cytomegalovirus. In July 1999. and the second dose for hepatitis B with 1 month and 15 days of life.400 Platelets (mm³) 24. 76.000/mm 3. and lympho-mono-plasmocytic series. there was an improvement in plateletopenia: 311.200 9.000 12. in São Paulo. Table 1 - The child was discharged from hospital after a 5-day treatment.000/mm3.8 Ht (%) 31. 1999. Two days after the beginning of the treatment.000/mm3. 1999. rubella. with a booster dose 1 year and 6 months later. The liver was 1. she took the first dose of the hepatitis B vaccine. Laboratory examinations (see Table 1) initially indicated pancytopenia. She was reevaluated one month later. Post-vaccination thrombocytopenia continues to be an Laboratory examinations during hospitalization and alterations in the administration of intravenous immunoglobulin July 20 July 21 July 22 July 23 July 25 Hb (g/dl) 10.000 Intravenous immunoglobulin 311. No other alterations were found. Nowadays. with 1 month and 16 days of life. born on term on June 4. The mother reported the appearance of “blotches” on the patient’s face on the 15th day of life.Thrombocytopenic purpura after hepatitis B vaccine . but several cases of thrombocytopenia after recombinant vaccine have been described in literature.300 3. She was admitted at the Emergency Room of Hospital das Clínicas in July 20. weighing 2. Prenatal examinations showed no pathologies. rubella. presenting mainly acidophilic granular megakaryocytes without platelets (suggestive of idiopathic thrombocytopenic purpura).1 10.000/mm3. and ecchymosis on her thigh for 1 week.800 6. We required a myelogram. female.920 g. we observed another probable case of idiopathic thrombocytopenic purpura after hepatitis B vaccine in a 1 year-16 day old child. On the 12th day of life. with negative serologies (HIV.. Nº5. maintaining platelets at 620. Discussion A causal relation between the hepatitis B vaccine and idiopathic thrombocytopenic purpura is hard to be confirmed. besides normal coagulogram.Maezono R et alii 396 Jornal de Pediatria . and the spleen was impalpable. Case report L. with platelets at 780.5/IR: 1.6-9 On physical examination. with decreased plateletopenia. 2000 The hepatitis B vaccine is usually well tolerated.3 31 30 30 28 Leukocytes 4. with petechiae on her body and palate. She was vaccinated with BCG.Vol. toxoplasmosis.6 11.9 TTPA 27. and negative serologies for syphilis. and syphilis). a treatment with intravenous immunoglobulin was initiated in the dose of 400 mg/kg/dose. toxoplasmosis. hands.7 9. she presented a good general status.500 Myelo + 9. red. the first dose for Haemophilus influenzae.3 10. with few side effects. 000/mm3. 12:222-7. Thrombocytopenic purpura after recombinant hepatitis B vaccine. such as Davis and Raffles.Thrombocytopenic purpura after hepatitis B vaccine . Cecchi P. which suggests the diagnosis of idiopathic thrombocytopenic purpura.9 The hepatitis B vaccine has a good level of efficiency. Hessel L. Garvey B. Autret E. In 1994. Poullin P. Jonville-Béra AP. The side effects after hepatitis B vaccine are estimated in one case per 100. Ragnaud JM et al. Sadowitz D. Recently. Both the mother and the child presented negative serologies. Neau D. in which the latency period varied from 1 to 4 weeks. Scand J Infect Dis 1998. The latency period varied from some days up to 2 months. The antiplatelet antibody test was not performed.1. mumps and rubella vaccination. with a latency period of 4 and 3 weeks. several cases of post-vaccine thrombocytopenia were reported. Poullin & Gabriel6 described two cases of idiopathic thrombocytopenic purpura in two young women. Gary ER. such as the intracranial bleeding. On the admission examination. 78:273-4.14 One month later. Immune thrombocytopenic purpura after recombinant hepatitis B vaccine: Retrospestive study of seven cases. 3:335-40. and management of idiopathic thrombocytopenic purpura. A report on 23 patients.10-12 Some authors. In 1995.9 reported seven cases (four men and three women) that developed thrombocytopenia on average 7 weeks after having received recombinant hepatitis B vaccine. most of them are cases of children older than 7 years of age who rarely present postinfectious idiopathic thrombocytopenic purpura. in 1998. 11. Ronchi F. such as leukosis or medulla aplasia. 82:267-70. Kuhne T. pancytopenia could suggest other pathologies.000 administrated doses. varying from 1 to 34 days. 30:38-44. Idiopathic thrombocytopenic purpura: a guideline for diagnosis and management of children and adults. and its adverse effects. Bonnet F. References 1. the child was reevaluated. Thrombocytopenic purpura after measles. Thrombocytopenic purpura as adverse reaction to recombinant hepatitis B vaccine. Nieminen U. and the treatment with intravenous immunoglobulin was indicated. Acta Paediatr Suppl 1998. Pediatr Infect Dis J 1996. The myelogram performed demonstrated normal hematopoiesis and an increase in megakaryocytes. 76. In literature. and the latency period between the vaccine and the appearance of the symptoms suggests this relation. Pediatr Emerg Care 1996. 9. respectively 21 and 15 years old. The child developed petechiae 1 month after having received the first dose of hepatitis B vaccine. Blanchette VS. when other possible causes for thrombocytopenia are discarded. 13 administrate intravenous immunoglobulin in platelet counts <20. mumps and rubella vaccination: a retrospective survey by the French Regional Pharmacovigilance Centres and Pasteur-Mérieux Sérums et Vaccins. Falcioni F.000/mm3. in order to prevent serious bleedings. there was no history of previous infections or use of drugs.3. 30:115-8. since it is considered unnecessary by some authors for the diagnosis of idiopathic thrombocytopenic purpura. 3. 10. there is a consensus about the treatment of children presenting platelet count below 20. Kühne E. Terndrup TE. 15:44-8. In literature. Muratori G et al. Minak G. platelets had fallen to 12. Both had no history of previous infection and use of drugs. KeKomäki R.10 Both the corticosteroid and the immunoglobulin decrease plateletopenia time. 5.Vol. 345:1638. The treatment with immunoglobulin improves plateletopenia in 2 days on average. Nº5. This good response to the treatment with intravenous immunoglobulin also suggests the diagnosis of idiopathic thrombocytopenic purpura.000/mm3. . Marsciani A. respectively. Current Opinion in Hematology 1996. Current management issues of childhood and adult immune thrombocytopenic purpura (IPT). Gabriel B. Galy-Eyraud C. Elinder G.10 After 2 days of treatment. Idiopathic thrombocytopenic purpura in children: Recognition and management. Syrjälä MT. other two articles about idiopathic thrombocytopenic purpura after hepatitis B vaccine were published. eight of them presented a possible reaction to the vaccine. James NG. Souid AK. Perel Y.Maezono R et alii exclusion diagnosis. because they believe that the side effects are mild in relation to the risks of serious hemorrhages due to plateletopenia. Mäkipernaa A.8 reported three cases of idiopathic thrombocytopenic purpura after the first dose of recombinant hepatitis B vaccine in children below 6 months of age.74 Suppl 2:309-14. 7. 2000 397 311. 2.000/ mm3.7 reported 28 cases of thrombocytopenia after hepatitis B vaccine (recombinant and non-recombinant). Edwards IR. Ann Med 1998. who developed the disease after the second and the third doses of the recombinant hepatitis B vaccine. Acute thrombocytopenic purpura following measles. Thrombocytopenia reported in association with hepatitis B and A vaccines. Vox Sang 1998. Steven HW. Peltola H. Meyboom et al. 424:75-81. Diagnosis. In this case. clinical course. Acta Paediatr 1993. Ronchi et al. 334: 1293.2 On the 3rd day of hospitalization. 6. and she remained asymptomatic. Lancet 1995. must not put its use in question. Immune thrombocytopenic purpura ITP. Imbach P. Only 3 to 5% of the cases become chronic. Fucik H. Meyboom RHB.3 The case reported here is probably another case of idiopathic thrombocytopenic purpura induced by hepatitis B vaccine. Michaud M. 8. Longy-Boursier M. Arch Dis Child 1998. 4. Neau et al. the platelets were already at the level of Jornal de Pediatria . The Lancet 1994. including idiopathic thrombocytopenic purpura. even in children with few symptoms. James NG. James NG.Maezono R et alii Correspondence: Dra. Raffles A. SP. 13. 58: 231-4. Workshop on Autoimmune (Idiopathic) thrombocytopenic purpura: pathogenesis and new approaches to therapy. 83 CEP 01415-000 – São Paulo. Am J Hematol 1998. Brazil Phone/fax: + 55 11 256. 76. Davis HP.2849 . Karpatkin S. Thrombocytopenic purpura after hepatitis B vaccine . Pankaj G. 350:1252-3. 349:1531-6. Nº5. Chilhood idiopathic thrombocytopenic purpura. Richard AH. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet 1997. 14.Vol. 2000 12. Robert M. Lancet 1997. Renata Maezono Rua Bela Cintra 884 – apt.398 Jornal de Pediatria .