Effect of antiretroviral therapy on hemoglobin A2 values can have implications in antenatal beta-thalassemia screening programs.

BACKGROUND: Raised hemoglobin-A2 (HbA2) is the diagnostic hallmark of beta-thalassemia trait (ßTT). Diagnostic difficulties may arise in HIV-positive patients on antiretroviral therapy (ART). We compared the effect of various antiretroviral drugs on HbA2 levels. We attempted to determine which drugs elevate HbA2 levels causing a false-positive diagnosis of ßTT and correlate the findings with red cell indices. METHODS: A retrospective analysis of the records of an antenatal thalassemia screening program was carried out for 78 HIV-positive adults (70 antenatal women and 8 husbands) to study the effect of antiretroviral drugs on HbA2 levels. Three had ßTT; 20 treatment-naïve subjects constituted controls. The effects of zidovudine (36 cases), stavudine (7 cases), and tenofovir (12 cases) were evaluated. High-performance liquid chromatography was done for HbA2 levels. Values of 3.5-3.9% were borderline and ≥ 4% with hypochromic microcytosis was considered to be ßTT. RESULTS: Twenty individuals not on ART had normal HbA2%. Three patients had ßTT and showed hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on treatment (25.5%) had borderline HbA2 values (mean 3.7%): 11 were on a zidovudine-based regimen and 3 on a stavudine-based regimen. One patient on zidovudine had 4.1% HbA2 with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a false suspicion of ßTT. All patients on tenofovir had normal HbA2. Hematological parameters, including mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and HbA2 levels were increased due to antiretroviral drugs zidovudine and stavudine. CONCLUSION: Treatment-naïve subjects and those on tenofovir showed no effect on HbA2 levels compared with zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had borderline elevated HbA2 levels, which could lead to a false impression of ßTT.

Bone marrow infiltration in Langerhan's cell histiocytosis - An unusual but important determinant for staging and treatment.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a reactive proliferative disease of unknown pathogenesis characterized by proliferation of Langerhans cells. Involvement of bone marrow (BM), liver and lung are related to high risk factors and poor survival. The aim of this report is to highlight the clinical and haematological findings of 5 cases of LCH with BM infiltration which may help to predict involvement of BM. CASE SERIES: Five cases of Langerhan's cell histiocytosis with bone marrow infiltration were retrieved from archives of Department of Hematology, PGIMER and Chandigarh for review and further analysis. Male to female ratio was 3:2 with mean age of 9.4 months. Two out of 5 patients had obvious skull swelling; however, radiography of the skull revealed lytic lesion of skull in 4 cases and 2 had skin rashes. Hepatomegaly was present in 4 cases and 2 of whom also had lymphadenopathy and splenomegaly. All patients had anaemia at the time of presentation. Bone marrow aspiration and trephine biopsy in all 5 cases revealed infiltration by large histiocytes with abundant cytoplasm and coffee bean shaped nucleus. Nodules of these Langerhans cells with admixture of eosinophils were seen on trephine biopsy. Immunohistochemistry showed positivity for CD1a stain. CONCLUSION: BM evaluation is important in LCH patients to categorize disease which further determines the type of therapy to be given. Clinical details may help to predict the BM involvement; however, demonstration of CD1a positive cells in marrow is most important tool to diagnose marrow infiltration by LCH.