HEMATOLOGICAL MANIFESTATION IN HAART NAÏVE HIV-1 INFECTED CHILDREN IN INDIA IN A RESOURCE LIMITED SETTING
Ira Shah, Bhushan Katira
Pediatric HIV Clinic, B. J. Wadia Hospital for Children, Parel, Mumbai, India
Address for Correspondence
Dr. Ira Shah, 1/B Saguna, 271/B, St Francis Road, Vile Parle (W), Mumbai 400056. India.
Email
info@pediatriconcall.com
Abstract
Aim:
Hematological problems in HIV infected children have never been studied in India. This study was thus undertaken to assess the hematological manifestations in HAART naive HIV-1 infected children.

Setting:
Pediatric HIV Clinic at B.J.Wadia Hospital for Children, Mumbai

Study Design:
Prospective cross-sectional study.

Methods & Materials:
50 HIV infected children referred to our HIV Clinic over a period of 6 months in 2005 underwent a baseline hematological analysis. All patients underwent a through clinical examination and factors such as age, sex, growth, CD4 count, opportunistic infections and their association with various hematological manifestations were studied.

Results:
45 patients (90%) had elevated ESR, 35 patients (70%) had anemia, 14 patients (28%) had leucocytosis, 12 patients (24%) had lymphopenia, 5 patients (10%) had thrombocytopenia and 1 patient (2%) had leukopenia with neutropenia. Patients with lymphopenia had a mean age of 6.8+3.5 years Vs 4.7 + 2.1 years which was statistically significant (p = 0.01) whereas patients with thrombocytopenia had a mean age of 7.5 + 4.1 years Vs 5.0 + 2.3 years (p = 0.03) and patients with elevated ESR had a mean age of 4.9+ 2.3 years Vs 7.6 + 4.0 years (p = 0.03). All patients with anemia had microcytic hypochromic anemia. Thrombocytopenia was more common in patients with Tuberculosis in the past (p = 0.049). There was no correlation with lymphopenia and decrease in CD4 count (p=0.81) or CD4 percent (p=0.34). Growth parameters, sex, mode of transmission, immunological profile and opportunistic infections had no statistical association with hematological manifestations.

Conclusion:
Hematological problems in HIV infected children in India are common. Elevated ESR and anemia are the commonest features. Elevated ESR may be used as a marker to screen a child for HIV infection. Microcytic hypochromic anemia is the commonest type of anemia seen.
Introduction
Hematological abnormalities are common in HIV infected children (1). Of these abnormalities, peripheral cytopenias and bone marrow abnormalities are common. Anemia is the most common hematologic manifestation (1, 2, 3). Other hematological findings include neutropenia, thrombocytopenia and coagulation abnormalities. Several mechanisms have been postulated in the pathophysiology of these abnormalities. Both impaired production of blood cells (defective hematopoiesis) due to direct infection of the progenitor cell or through cytokine mediated and autoantibody-mediated increased peripheral destruction may occur (4, 5, 6). Though hematological abnormalities have been reported from Brazil (2)(1,3), USA (8) in HIV infected children, data from Indian HIV-1 infected children is lacking. This study was thus undertaken to determine the common hematological manifestations of HIV in ART naive Indian children.
Methods & Materials
This prospective cross-sectional study was done over a period of 6 months from May 2005 to November 2005. 50 patients with HIV infection were referred to our Pediatric HIV Clinic for further management. All children underwent a thorough history and clinical examination. Their HIV status was reconfirmed by a repeat HIV ELISA test and/or Western Blot test. Mode of transmission was determined by checking the parents HIV by ELISA and also by history of blood transfusion. All children were screened for opportunistic infections, organ dysfunctions and growth failure.

The proportions were analyzed by Chi square test and by Anova-1 test using ANALYSE-IT software (version 1.7).
Results
The mean hemoglobin was 9.4 + 2.0 gm/dl with median of 9.5gm/dl (96.7%Cl = 8.5 to 9.8 gm/dl). The mean ESR was 71.7 + 38.1 mm at end of 1 hour with median of 65 mm at end of 1 hour. The mean WBC count was 9584 + 3693/cu mm with median of 9250/cu mm (96.7%Cl = 7800 to 9900/cu mm). Mean neutrophil count was 5234 + 2844/cu mm with median of 4258/cu mm (96.7% Cl = 3480 to 5248/cu mm) and mean lymphocyte count was 3964 + 1898/cu mm and median of 3715/cu mm (96.7%Cl = 2750 to 4560/cu mm). The average platelet count was 294300 + 160020/cu mm with median of 260000/cu mm (96.7%Cl = 225000 to 310000/cu mm). The age of patients included in the study ranged from 3 years to 13 years with mean of 5.2 + 2.6 years and median of 5 years. Male:Female ratio was 33:17.

Of the 50 HIV infected children included in the study, 45 patients (90%) had elevated ESR, 35 patients (70%) had anemia, 14 patients (28%) had leucocytosis, 12 patients (24%) had lymphopenia, 5 patents (10%) had thrombocytopenia and 1 patent (2%) had leucopenia with neutropenia. All patients with anemia had hypochromic microcytic anemia on peripheral smear examination. Patients with leucocytosis had a mean age of 4.1 + 1.5 years Vs 5.7 + 2.8 years which was statistically significant (p = 0.048). Patients with lymphopenia had a mean age of 6.8 + 3.5 years Vs 4.7 + 2.1 years which was also statistically significant (p = 0.01) whereas patients with thrombocytopenia had a mean age of 7.5 + 4.1 years Vs 5.0 + 2.3 years (p = 0.03) and patients with elevated ESR had a mean age of 4.9 + 2.3 years Vs 7.6+ 4.0 years (p = 0.03). 3 patients (60%) with thrombocytopenia had past history of tuberculosis which was statistically significant (p = 0.049). There was no correlation with lymphopenia and decrease in CD4 count (p=0.81) or CD4 percent (p=0.34).

Other factors analyzed with hematological manifestations are depicted in Table 1. It was found that age, sex, CD4 count and percent, other opportunistic infections, organ dysfunctions, mode of transmission and immune category had no statistical effect on the various hematological manifestations.

Table 1: Factors associated with Hematological manifestations of HIV
Featu
res
Anemia Leucocytosis Lymphopenia Thrombocytopenia Elevated ESR
n (%) Mean p value n (%) Mean p value n (%) Mean p value n (%) Mean p value n (%) Mean p value
Age
(years)
35 5.1+
3
0.56 14 4.1+
1.5
0.048 12 6.8 +
3.5
0.01 5 7.5 +
4.1
0.03 45 4.9 +
2.3
0.03
Height
centile
35 10.1
+15.
4
0.35 14 10.5
+16.
8
0.78 12 15 + 21 0.4 5 3.4 + 0.9 0.25 45 12.3
+17.
3
0.34
Weight
centile
35 4 +
2.0
0.48 14 4.2+
1.9
0.88 12 3.5 +
0.9
0.23 5 3.8 +
1.0
0.7 45 4.2 +
2.2
0.4
CD4
count
(/cu mm)
15 577.9
+468.
8
0.59 5 776
+ 488
0.17 5 582
+ 661
0.81 2 224
+ 168
- 23 551.3
+ 440
0.54
CD4
percent
14 16.3
+ 6.2
0.57 6 16.7
+ 7.2
0.75 4 19
+ 3.7
0.34 1 19 - 20 15.9
+ 7.3
0.90
Gender
Male
Female
23 12 - 0.79 7
7
- 0.25 8
4
- 0.77 4
1
- 0.84 30
15
- 0.84
CDC
A 2 (5.7%) -   1 (7.1%) -   1 (8.3%) -   0 -   3 (6.
7%)
-  
B 22 (62.
9%)
11 (78.
6%)
7 (58.
3%)
2 (40%) 27 (60%)

C

11 (31.
4%)

2 (14.
3%)

4 (33.
3%)
3 (60%) 15 (33.
3%)
TB 30
(85.7%)
- 0.52 12 (85.
7%)
- 0.99 9 (75%) - 0.77 5
(100%)
- 0.62 38 (84.
4%)
- 0.46
Past TB 5 (14.
2%)
- 0.52 1 (7.1%) - - 4 (33.
3%)
- 0.25 3 (60%) - 0.0
49
8 (17.8%) - 0.62
Diarrhea 10 (25.
6%)
- 0.36 5 (35.
7%)
- 0.86 6 (50%) - 0.32 3 (60%) - 0.43 16 (35.
6%)
- 0.84
LRTI 21 (60%) - 0.90 8 (57.
1%)
- 0.81 7 (58.
3%)
- 0.76 2 (40%) - 0.70 27 (60%) - 0.70
Fever 10 (25.
6%)
- 0.36 5 (35.
7%)
- 0.86 5 (41.
7%)
- 0.77 4 (80%) - 0.07 17 (37.
8%)
- 0.23
Herpes 2
(5.7%)
- 0.60 - - - 0 - - 0 - - 3 (0.0
7%)
- 0.69


Discussion
Elevated ESR and anemia were the commonest hematological manifestations in HIV infected ART naïve patients in Indian children. Similarly, other studies from Brazil and Africa have also found that anemia was the commonest hematological abnormality in HIV-1 infected children (1, 2, 3) with anemia incidence ranging from 73% to 100%. In our study, 70% of patients had anemia. Though we were unable to do RBC indices in our patients, peripheral smear showed it to be hypochromic microcytic anemia and most studies have depicted it to be hypochromic and microcytic anemia (2). It has been suggested that iron depletion is the major cause of anemia (3) though 10% may be anemia of chronic infection (2). However, one must also keep in mind other causes of anemia such as drug induced anemia such as zidovudine, trimethoprim-sulfamethoxazole, opportunistic infections such as mycobacterium avium complex (MAC). Parvovirus B19, cytomegalovirus and HIV related malignancies (7). Studies have demonstrated an association between anemia and progression of disease with decrease in mean hemoglobin as disease progresses (1, 2). A large epidemiological study of 32,867 HIV infected adults and adolescents found that risk of death was 170% greater for persons with persistent anemia (hemoglobin < 10 gm/dl) compared with those whose anemia had resolved (9). However it remains unknown whether anemia remains as a marker of HIV disease. In our study, we did not get any difference in incidence of anemia and worsening stage of the HIV disease. Treatment of anemia should be towards correcting the underlying cause with iron supplementation for iron deficiency, control of opportunistic infections and stopping an offending drug and even erythropoietin with judicious use of blood transfusions (7).

ESR may be elevated in chronic infections especially with TB co-infection and similar findings have been reported by Erhabor et al in Nigerian HIV infected adults with mean ESR being higher than in healthy Africans (10). However, we did find that elevated ESR was more common in children less than 5 years of age. It may be postulated that younger children have an immature immune system are more prone to higher HIV viral load, more opportunistic infections and improper weaning and feeding practices which may lead to anemia and elevated ESR. We also found that these children were more lymphopenic as compared to older children thus further confirming a more immune deficiency state. Similar findings have not been reported in other studies.

Other hematological abnormalities that we noticed were leukocytosis, lymphopenia, thrombocytopenia and neutropenia which were not statistically related to age, gender, course of the disease or CD4 counts. Similar findings have been reported by Adetifa et al. However in our study, thrombocytopenia was seen in patients who had suffered from tuberculosis in the past. However, these were very few patients and more studies will be required to actually determine whether thrombocytopenia and tuberculosis are related to each other. In our study, 10% of the children had thrombocytopenia and similar incidence has been found in Brazil (2) and Africa (10). Thrombocytopenia is usually caused by immune-mediated destruction of the platelets or due to inadequate platelet production. Treatment options include antiretroviral therapy, corticosteroids, immunoglobulins, splenectomy and platelet transfusion.

Neutropenia in ART naïve HIV infected children is most commonly seen as drug-related toxicity and due to opportunistic infections. In our study, only one patient had neutropenia. Treatment of neutropenia includes granulocyte-colony stimulating factor (G-CSF).

Leucocytosis is commonly seen with any intercurrent infection as HIV infected untreated children are known to harbor several sub-clinical infections. The WBC count usually returns to normal, once the co-infection is treated.
Conclusion
Hematological problems such as elevated ESR and anemia are common in HIV infected children. Elevated ESR may be used as a marker to screen for HIV infection. Lymphopenia as a marker of immunosuppression needs further evaluation.
Funding
None
Conflict of Interest
None
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Last Updated : Sunday, May 01, 2011 Vol 8 Issue 5 Art #35
How to Cite URL :
Shah I, Katira B. HEMATOLOGICAL MANIFESTATION IN HAART NAÏVE HIV-1 INFECTED CHILDREN IN INDIA IN A RESOURCE LIMITED SETTING. Pediatric Oncall [serial online] 2011[cited 2011 May 1];8. Art #35. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=408&type=J&tid=&imgid=&reportid=104&tbltype=
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