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      Profile of hematological abnormalities of Indian HIV infected individuals

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          Abstract

          Background

          Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection.

          Methods

          Two hundred HIV infected individual were screened for hematological abnormalities from March 2007–March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial), serology for Epstein Barr virus (EBV), Cytomegalovirus (CMV), Hepatitis B and C, and Parvo B19 infection.

          Results

          The most common hematological abnormality was anemia, seen in 65.5% (131/200) patients. Iron deficiency anemia was seen in 49.2% (/200) cases while anemia of chronic disease occurred in 50.7% (/200) cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL) and did not show any bone marrow infiltration. In remaining12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12) showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci), 25% (3/12) showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200) cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC) < 800 cells/μL. No case of coagulation abnormalities was found.

          Conclusion

          Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.

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          Most cited references11

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          Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of human immunodeficiency virus-infected and -uninfected women.

          We conducted a longitudinal study of 797 human immunodeficiency virus (HIV)-positive women (7732 visits) and 389 HIV-negative women (3651 visits) to characterize anemia. At enrollment, the prevalence of anemia was 28.1% among HIV-positive women and 15.1% among HIV-negative women (P<.0001), and during follow-up the cumulative incidence of anemia was 74% and 48%, respectively (P<.0001). Risk factors for anemia were African American race (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.73-2.69), age (per 5-year increase; OR, 1.12; 95% CI, 1.03-1.21), body mass index (OR, 0.96; 95% CI, 0.94-0.97), history of pneumonia (OR, 1.41; 95% CI, 1.20-1.65), oral candidiasis (OR, 1.42; 95% CI, 1.22-1.66), CD4+ lymphocyte count <200 cells/microL (OR, 1.68; 95% CI, 1.46-1.94), history of fever (OR, 1.42; 95% CI, 1.13-1.80), and zidovudine use (OR, 1.14; 95% CI, 1.01-1.30). Anemia was common and associated with an increased risk of death (hazards ratio, 1.64; 95% CI, 1.21-2.23) among HIV-positive women.
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            Is Nef the elusive cause of HIV-associated hematopoietic dysfunction?

            HIV-associated hematological abnormalities involve all lineages of blood cells, thus implying that the virus impairs the function of early HSCs. However, the underlying mechanisms of this defect are unknown, particularly since HSCs are largely resistant to HIV-1 infection. In this issue of the JCI, Prost and colleagues show that the viral accessory protein Negative factor (Nef) plays a potentially critical role in the pathogenesis of HIV/SIV-associated hematopoietic dysfunction by affecting the clonogenic potential of HSCs (see the related article beginning on page 1765). Soluble Nef induces PPARgamma in uninfected HSCs, thereby suppressing the expression of STAT5A and STAT5B, two factors necessary for proper HSC function. The identification of this novel activity of extracellular Nef defines a new mechanism of HIV/SIV pathogenesis and suggests that approaches aimed at increasing STAT5A and STAT5B expression may be considered in HIV-infected individuals with prominent hematological abnormalities. The results also raise the question of whether dysregulation of hematopoiesis by extracellular Nef plays a role in the development of T cell immunodeficiency and the high levels of chronic immune activation associated with AIDS.
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              Human megakaryocytes have a CD4 molecule capable of binding human immunodeficiency virus-1.

              Most human megakaryocytes (MGKs) express the CD4 antigen on their surface. Approximately 25% have a CD4 receptor density comparable to that of CD4+ T cells (Basch et al, Proc Natl Acad Sci USA 87:8085, 1990). In these studies, we show: (1) the presence of mRNA for CD4 in human MGKs; (2) the binding of human immunodeficiency virus-1 (HIV-1) to human MGKs; (3) the inhibition of binding by anti-CD4 (Leu3a) antibody or rCD4; (4) the infection of a human MGK line, CHRF-288 with HIV-1; and (5) inhibition of infection with anti-CD4. Human MGKs have mRNA for CD4 as shown by in situ hybridization with an RNA probe synthesized from a 3-kb cDNA sequence of plasmid pSP65.T4.8 containing the full-length CD4 sequence. MGKs (23% +/- 17%) bound HIV-1, as determined by anti-gp120 and anti-CD41 staining. Binding to human MGKs could be inhibited 55% to 75% with anti-CD4 or rCD4, respectively. Infection of a CD4+ MGK line (CHRF-288) could be accomplished with HIV-1, as determined by proviral DNA polymerase chain reaction and p24 production. Preincubation with anti-CD4 inhibited apparent proviral DNA infection by 100% and p24 production by 65% to 70%. Thus, human MGKs have a CD4 receptor capable of binding HIV-1. Using this receptor, HIV-1 can infect cells representative of the MGK lineage.
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                Author and article information

                Journal
                BMC Blood Disord
                BMC Blood Disorders
                BioMed Central
                1471-2326
                2009
                13 August 2009
                : 9
                : 5
                Affiliations
                [1 ]Department of Internal Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
                [2 ]Departments of Hematology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
                Article
                1471-2326-9-5
                10.1186/1471-2326-9-5
                2741436
                19678930
                6c7fd499-346b-482a-aee2-df925e1a0659
                Copyright © 2009 Dikshit et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 May 2009
                : 13 August 2009
                Categories
                Research Article

                Hematology
                Hematology

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