Abstract
About 5% to 10% of HIV-infected patients develop thrombocytopenia during the course of the disease, and immune thrombocytopenic purpura (ITP) may be the sole clinical manifestation of HIV infection. The clinical picture is indistinguishable from the classic auto-ITP. Treatment is the same as that given for classic ITP as the pathogenesis is in many ways similar. Steroids, intravenous immunoglobulins (IVIGs), and antiretroviral therapy (ART) have all been tried with varied results but have been associated with fall in platelet count on withdrawal of therapy. We report a case of a 13-year-old girl who presented with thrombocytopenic purpura and had no response to ART but had normalization of platelet count while on steroids, which immediately fell below the normal range on withdrawing the steroids.
Keywords
Introduction
About 5% to 10% of HIV-infected patients develop thrombocytopenia during the course of the disease, 1,2 and immune thrombocytopenic purpura may be the sole clinical manifestation of HIV infection. 3 However, the exact immune mechanism leading to platelet destruction is unclear. Elevated levels of antiplatelet immunoglobulin G (IgG) antibodies and nonspecific deposition of circulating immune complexes and complements have been suggested as the cause of increased clearance of platelet. 4 However, studies have depicted that increased levels of antiplatelet IgG antibodies are not causally related to the development of thrombocytopenia in children. 2,5 With evidence of viral RNA present in megakaryocytes, a direct role of HIV in the pathophysiology of thrombocytopenia may be present. 1 Treatment consists of antiretroviral therapy (ART), intravenous immunoglobulins (IVIGs), steroids, anti-rhesus immunoglobulin, danazol, or vincristine in a symptomatic patient. 1 We present a 13-year-old HIV-infected girl with thrombocytopenic purpura whose thrombocytopenia had a short-lived response to steroids and no response to antiretroviral (ARV) drugs.
Case Report
A 13-year-old girl born of nonconsanguineous marriage was referred to our pediatric HIV clinic for further management of her HIV infection. At the age of 11 years, she had petechial rash all over her body, associated with thrombocytopenia (platelet count = 90 000/mm3). A bone marrow aspiration and biopsy was done by the hematologist at that time, which showed giant megakaryocytes. Thus, she was diagnosed with idiopathic thrombocytopenic purpura (ITP). She was screened for viral infections and showed a positive HIV enzyme-linked immunosorbent assay (ELISA) test suggestive of probably HIV-related ITP. Her HBsAg and Anti–hepatitis C virus (HCV) were negative. She was treated for her ITP with platelet transfusion every 4 months. She had a past history of herpes zoster at 11½ years of age. On presentation to us, she had pallor with insignificant cervical lymphadenopathy. Her height was 134cm (<5th centile) and weight was 25 kg (<5th centile). She was in Sexual Maturation Rating stage II as per Tanner’s staging for puberty. There was no skin rash, and other systemic examination was normal. Her HIV status was confirmed by a positive Western blot test. To determine the mode of transmission of HIV, both the parents were screened for HIV by the ELISA test after verbal informed consent. The mother had a positive HIV ELISA test, whereas the father was HIV negative. Mother had received 2 blood transfusions during her pregnancy 13 years ago. Thus, the child was determined to have vertical mode of transmission of HIV. In view of her failure to thrive and recurrent thrombocytopenia, she was counseled regarding ART. Her baseline HIV load was 145 086 copies/mL with absolute CD4 count of 137 cells/mm3, CD4 percentage of 11%, and CD4:CD8 ratio of 0.14. Her chest X-ray was normal and the Mantoux test was negative. In view of symptomatic severe immune suppression, she was started on 3-drug ART consisting of zidovudine (ZDV; 180 mg/m2/dose 2 times daily), lamivudine (3TC; 8 mg/kg/d), and efavirenz (EFV; 300mg once daily). Her baseline hemogram showed anemia (hemoglobin = 9.9 gm/dL) with thrombocytopenia (platelet count = 92 000/mm3) and reticulocyte count of 0.3%. Her liver transaminases and serum amylase were normal. After 2 months of therapy, her platelet count improved to 484 000/mm3, and she had gained 3kg of weight. However, at the end of 3 months of therapy, her platelet count again fell to 58 000/mm3. A repeat bone marrow examination was done, which showed cellular marrow with giant megakaryocytes. Her antiplatelet antibodies could not be done as a result of facilty nonavailability. She was continued on ART with serial monitoring of her hemogram. At the end of 6 months of ART, her CD4 count had increased to 436 cells/mm3 and CD4 percentage was 15.9% with normal serum biochemistry. Her weight had increased by 5 kg from baseline and she was clinically asymptomatic. Her platelet count had now decreased to 22 000/mm3, and she had an episode of epistaxis. She was now started on a short course of steroids for the ITP following which her platelet count normalized (platelet = 220 000/mm3), within 15 days of steroids. Steroids were tapered off over a period of 1½ months and her platelet count again reduced after 1 month of stopping steroids. Her serial platelet counts are listed in Table 1. Currently, she is on her ART, her platelets have improved after 2 years of therapy, and she is asymptomatic.
Serial Platelet Counts.
Abbreviation: ART, antiretroviral therapy.
Discussion
Thrombocytopenia in HIV-infected patients has an overall prevalence varying between 5% and 10%. Peripheral destruction of platelets due to immune mechanisms is the most common cause of HIV-associated thrombocytopenia with typical response to IVIG, steroids, and splenectomy, other causes being adverse effect of medications and direct affection of megakaryocytes by HIV. 6 In our patient, at the onset of thrombocytopenia, her bone marrow examination had showed presence of megakaryocytes, ruling out direct affection of megakaryocytes by HIV, and she was also not on any medication suggestive of HIV-induced immune mechanism as her cause of thrombocytopenia.
Though HIV-associated ITP clinically resembles classic ITP, it rarely leads to bleeding and splenomegaly, and lymphadenopathy is also quite rare. 7 Thus, aggressive treatment is seldom required. However, if platelet count is very low or if bleeding is present, treatment is mandatory. Treatment of thrombocytopenia varies depending on the cause. Zidovudine has led to increased platelet count in a large number of patients. 8 However, our patient showed an initial transient response on starting ART, but subsequently showed a drop in platelet count in spite of being on ZDV. High doses of IVIG often result in an improved platelet count but tend to be short-lived, and long-term periodical infusions usually lose the therapeutical effect. 7 Our patient could not be given IVIG because of the cost. Although steroids give a good response, on lowering its dose, there is often a fall in platelet count, 3,4 as was seen in our patient. Also corticosteroids may further compromise the deteriorated immune function in these children and hence should be given only when the cellular immunity is unaffected. In our patient too, steroids were given only after the CD4 count had improved and the child had bleeding in the form of epistaxis.
Other drugs that have been tried are alpha interferon, danazol, specific anti-D immunoglobulins, and thrombopoietin but results are conflicting. 9 These agents are required only if the patients have active bleeding or severe life-threatening thrombocytopenia not responding to steroids or ART.
Thus, one may conclude that though thrombocytopenia is often seen in HIV-infected individuals and can occur due to a variety of causes, treatment in the form of ART, steroids, and IVIG may be warranted if the child has bleeding episodes.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.