Annals of African Medicine

ORIGINAL ARTICLE
Year
: 2008  |  Volume : 7  |  Issue : 2  |  Page : 72--76

Autoimmune hemolytic anemia in HIV-infected patients: A hospital based study


E Olayemi1, OA Awodu2, GN Bazuaye2,  
1 Department of Haematology, University of Ghana Medical School, Korle Bu, Ghana
2 Department of Haematology and Blood Transfusion, University of Benin, Benin City, Edo State, Nigeria

Correspondence Address:
E Olayemi
Department of Haematology, University of Ghana Medical School, P.O. Box 4236, Korle Bu
Ghana

Abstract

Background : The prevalence of anemia in HIV/ AIDS patients is high, with a multitude of possible etiologies; autoimmune hemolytic anemia (AIHA) in HIV/AIDS patients has been associated with a poor prognosis when treated with red cell transfusion. Our aim was to demonstrate the frequency of AIHA in a cohort of adult Nigerian HIV/AIDS patients and to see if the presence or not of AIHA is related to the severity of the disease with regards to the CD4 counts and the presence or absence of opportunistic infections. Method : Ninety- eight adult patients with HIV infection were screened for the presence of AIHA using the packed cell volume (PCV), direct antiglobulin test (DAT) and reticulocyte count (RC). Results : The frequency of AIHA was 3.06%, 36.74% of our study population were anemic; 11.22% had a positive DAT. Mean RC was 2.22 +/- 0.90 for all the patients. There was no statistically significant difference in the PCV of patients that had positive and negative DAT. There was no correlation between the presence of AIHA, use of ART, presence of opportunistic infections or CD4 counts. Conclusion : We conclude that in spite of the low frequency of AIHA in HIV/AIDS patients, the fact that most patients will respond to standard treatment makes it imperative to screen HIV/AIDS patients with anemia for the presence of AIHA. Again since HIV/AIDS patients with AIHA may have a fatal reaction to red cell transfusion, we suggest that anemic patients with HIV/AIDS in non-emergency situations be screened for the presence of AIHA before receiving red cell transfusions when indicated.



How to cite this article:
Olayemi E, Awodu O A, Bazuaye G N. Autoimmune hemolytic anemia in HIV-infected patients: A hospital based study.Ann Afr Med 2008;7:72-76


How to cite this URL:
Olayemi E, Awodu O A, Bazuaye G N. Autoimmune hemolytic anemia in HIV-infected patients: A hospital based study. Ann Afr Med [serial online] 2008 [cited 2019 Sep 20 ];7:72-76
Available from: http://www.annalsafrmed.org/text.asp?2008/7/2/72/55677


Full Text

 Introduction



Infection with the human immunodeficiency virus (HIV) which causes the acquired immunodeficiency syndrome (AIDS) has remained a scourge in the developing countries of the world; recent research has shown that while only about 10% of the worlds population lives in sub-Saharan Africa, the region is home to about 64% of people living with HIV/AIDS globally.[1] Nigeria has the largest population in Africa and an HIV/AIDS prevalence of about 5%.[2] In spite of the recent availability of antiretroviral therapy (ART) at subsidized rates in Nigeria, only a small fraction of patients are currently being treated. In fact, in 2005 only about 17% of persons in need of ART in sub-Saharan Africa received It.[1]

Anemia is prevalent among HIV/AIDS patients, it is said to be present in 10%-20% of patients at initial presentation and in over 70% over the course of the disease.3 Anemia in HIV/AIDS has multiple etiologies, these include: decreased production following suppression of hemopoiesis by lymphoma cells, infections such as tuberculosis (TB) and inflammatory cytokines; disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and immune and non-immune hemolysis; or ineffective production due to vitamin B12 or/ and folic acid deficiency; made worse by therapy with Zidovudine which is known to suppress erythropoiesis.[3] It is certain that the presence of anemia in people living with HIV worsens the prognosis since it is associated with progression to AIDS[4] and shorter survival times for HIV infected patients,[5] it has been shown that anemia is a predictor of poorer prognosis for HIV infected patients independent of the CD4 count.[6]

Despite the high frequency of anemia and a positive direct antiglobulin test (DAT) in these patients, autoimmune hemolytic anemia (AIHA) is less frequently diagnosed; this may be related to the frequent lack of reticulocytosis[7] which makes the diagnosis of AIHA more difficult, further complicated in our environment by the fact that autoimmune disorders are more common in Caucasians than the indigenous African population. This finding may be as a result of the endemicity of infectious and parasitic diseases in Africa which impair hosts T-cell immunity.[8],[9] An earlier clinical and serological study from Ethiopia confirmed that autoimmune diseases are rare in many parts of Africa and concluded that indigenous Africans that develop autoimmune diseases may have hereditary predisposition.[10] Though more recent reports show that some forms of autoimmune diseases may actually be more common in Africans than earlier thought.[11] The annual incidence of AIHA is estimated to be one per 75 000-80 000 population.[12] Autoimmune hemolytic anemia is characterised by binding of anti- erythrocyte autoantibodies to red cells and the subsequent destruction of the coated cells in the reticuloendothelial system.[8]

Anemia in patients with HIV infection may respond to treatment with ART, however, patients who continue to have symptomatic anemia while on ART may need additional intervention[13] such as erythropoietin.[3] Corticosteroids and immunoglobulin are considered the first line treatments for AIHA in immune competent patients, while splenectomy is reserved for those cases that do not respond.[14] In patients with HIV/AIDS and AIHA care must be taken in placing them on steroids as it may further worsen their immune suppression. Research has shown that HIV/ AIDS patients with AIHA who receive red cell transfusions have an increased risk of thromboembolism which may be fatal.[15] People living with HIV/AIDS with resolved anemia have been shown to have a better prognosis than those with anemia or those with anemia that did not respond to therapy.[16]

The aim of our study was to demonstrate the frequency of AIHA among a cohort of adult HIV/AIDS patients attending the HIV clinic in UBTH; and to see if the presence or not of AIHA is related to the severity of the disease with regard to the CD4 counts of these patients and the presence or absence of opportunistic infections.

 Subjects and Methods



Ninety- eight unselected, consecutive, adult HIV positive patients attending the outpatient clinic for people living with HIV/AIDS at the University of Benin Teaching Hospital were screened for the presence of AIHA using the packed cell volume (PCV), direct antiglobulin test (DAT) and the reticulocyte count (RC). They included: 48 males and fifty female patients. Only patients who gave informed consent were included in the study. For the purposes of this study, presence of AIHA was defined as a PCV less than 30%, positive DAT and a RC greater than 2.5%

Four milliliters of blood was withdrawn from each patient by clean venepunture and placed in an EDTA bottle for use in estimation of PCV, RC and DAT . PCV, RC and DAT were carried out as previously described.[17],[18] While the mircrohemaocrit method and new methylene blue reagent were used for PCV and RC respectively; DAT was carried out as follows: the test cells were washed four times with a minimum of 3 ml of saline per wash, as much of the supernatant as possible was removed after each wash to achieve maximum dilution of residual serum and then made up to 3% suspension in saline. Two volumes of the antiglobulin reagent was added to two volumes of the 3% cell suspension, the test tube was immediately centrifuged after thorough mixing and then read for agglutination. The same procedure was repeated with Coomb's positive and negative cells as control for each batch.

Patients were interviewed and information entered onto a standardized data form, additional data such as the CD4 counts were extracted from the case notes, patients who had not done a CD4 count within the previous 4 weeks were excluded from the study. The study was approved by the hospital's ethics committee.

Data collected in this study were analyzed on a computer with SPSS (Statistical Package for Social Sciences) software version 12.0. Means were compared using the Students' t test; level of significance was taken as PP>.05. Patients with AIHA had a mean CD4 count of 161.0+/- 37.57 cells/mL compared with 230.19 +/- 119.97 cells/ mL in those without AIHA; P>.05

Twenty-four (24.49%) patients had pulmonary tuberculosis (PTB) which was the only opportunistic infection found in the patients we studied. There was no statistically significant difference in CD4 counts between patients with PTB and those without: 203. 21 +/- 137.26 cells/ mL cells / compared with 232.39 +/- 110.17 cells/ mL.

Eighty-one (82.65%) patients were already on ART, which consisted of: Stavudine, nevirapine and lamivudine. Eighty- eight (89.8%) patients were infected with HIV-1 virus, 10(10.20%) with both HIV 1 and 2 viruses. No patient was found with only the HIV-2 virus.

 Discussion



Anemia was present in 36.74% of patients in this study, this agrees with earlier studies which concluded that anemia was a frequent complication of HIV infection. [16] The frequency of AIHA in this study is 3.06%. This value agrees with previous studies which reported that AIHA is not frequently seen in the HIV/ AIDS patient and may be as a result of the difficulty in making a diagnosis as reticulocytosis is often absent in HIV/AIDS patients with AIHA,[7] the rather low frequency in our patients may also be related to the low frequency of autoimmune disorders in the black African.[8]

Eleven (11.22%) patients in the study had positive DAT, mean PCV among these patients was lower than the mean PCV among the DAT negative group, though this difference was not statistically significant, it is in agreement with previous studies which have shown that HIV/AIDS patients with positive DAT have lower PCV.[19],[20]

Mean CD4 count was significantly lower in DAT positive patients compared to DAT negative patients. This may be as a result of the higher incidence of immune dysregulation in patients with progressive HIV/ AIDS, especially as it has been previously suggested that there may be serological anti- erythrocyte autoimmunity without hemolytic effects in a large majority of HIV/ AIDS patients.[7]

There was a statistically significant difference in mean PCV, CD4 and RC counts in patients that had AIHA and those that did not. Also patients without AIHA had higher PCV and CD4 counts than those with AIHA, this may suggest that patients with a lower CD4 count are more likely to develop AIHA. However, the fact that there was no correlation between AIHA and the CD4 count and also between AIHA and the presence of PTB infection, further confirms the earlier finding that red cell autoantibodies may be present in HIV patients in the absence of features overt hemolysis.[20]

There was no correlation between PCV and RC in our study, this may be due to suppression of erythropoiesis by the HIV virus or ART drugs.

We conclude that in spite of the fact that AIHA may have a low prevalence in HIV/AIDS patients, the fact that most patients will respond to standard treatment and that those that do respond have a good prognosis makes it imperative to screen HIV/AIDS patients with anemia for the presence of AIHA. Again it has been reported previously that HIV/AIDS patients with AIHA may have a fatal reaction to red cell transfusion, it becomes imperative that anemic patients with HIV/AIDS in non-emergency situations be screened for the presence of AIHA before receiving red cell transfusions when indicated.

References

1Centers for Disease Control and Prevention (CDC). The Global HIV/AIDS Pandemic.MMWR Morb Mortal Wkly Rep 2006;55:841-844.
2Iregbu KC, Elegba OY. Prevalence of Kaposi's sarcoma among adult HIV- sero-positive patients seen in a designated HIV treatment and care centre in Abuja, Nigeria.J Int Assoc Physicians AIDS Care 2006;5:115-118.
3Lim ST, Levine AM. Hematologic aspects of human immunodeficiency syndrome. In: Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT (eds). Williams Hematology. McGraw- Hill Medical 2006:1109-1134.
4Morfeldt-Månson L, Böttiger B, Nilsson B, von Stedingk LV. Clinical signs and laboratory markers in predicting progression to AIDS in HIV-1 infected patients.Scand J Infect Dis 1991;23:443-449.
5Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: Severe anemia as a prognostic factor.Am J Pediatr Hematol Oncol 1990;12:449-453.
6Mocroft A, Kirk O, Barton SE, et al. Anemia is an independent predictive marker for clinical prognosis in HIV infected patients from across Europe.AIDS 1999;13:943-950.
7Telen MJ, Roberts KB, Bartlett JA. HIV associatedautoimmune haemolytic anemia: report of a case and review of the literature.J Acquir Immune Defic Syndr 1991;4:1163-1164.
8Salawu L, Durosinmi MA. Autoimmune haemolytic anemia: pattern of presentation and management outcome in a Nigerian population: a ten year experience. Afr J Med Med Sci 2002;31:97-100.
9Bakari AG, Onyemelukwe GC. Rarity of myasthenia gravis in northern Nigerians.Ann Afr Med 2002;1:25-27.
10Tsega E, Choremi H, Bottazzo GF, Doniaah D. Prevalence of autoimmune diseases and autoantibodies in Ethiopia.Trop Geogr Med 1980;32:231-236.
11Akinyanju OO, Okany CC. Pernicious anemia in Africans.Clin Lab Haematol 1992;14:33-40.
12Packman CH. Hemolytic anemia resulting from immune injury. In: Lichtman MA, Beutler E, Kipps TJ, Kaushansky K, Prchal JT. (eds). Williams Hematology. Mcgraw-Hill Medical 2006;729-750.
13Moore RD, Forney D. Anemia in HIV- infected patients receiving highly active antiretroviral therapy.J Acquir Immune Defic Syndr 2002;29:54-57.
14Oliveira LA, Oliveira BM, Murao M, Vieira ZM, Gresta LT, Viana MB. Clinical course of autoimmune haemolytic anemia: an observantional study.J Pediatr 2006;82:58-62.
15Saif MW, Morse EE, Greenberg BR. HIV– associated autoimmune haemolytic anemia complicated by pulmonary embolism following a red blood cell transfusion: a case report and review of the literature.Conn Med 1998;62:67-70.
16Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JW. Epidemiology of anemia in human immunodeficiency virus (HIV) infected persons: Results from the multistate adult and adolescent spectrum of HIV disease surveillance project.Blood 1998;1:301-308.
17Bain BJ, Bates I. Basic haematological techniques. In: Lewis SM, Bain BJ, Bates I. (eds). Practical Haematology. Churchill Livingstone, Edinburgh 2001; 19-46.
18U.S Department of Health and Human Services. Fundamental diagnostic haematology: Anemia 1992; 92-95.
19Volberding PA, Baker KR, Levine AM. HIV haematology. Haematology 2003; 2003:294-313.
20Lai M, ViscontiE. D' onofrio G, Tamburrini E, Cauda R, Leone G. Lower haemoglobin levels in human immunodeficiency virus infected patients with a positive direct antiglobulin test (DAT): relationship with DAT strength and clinical stages.Transfusion 2006;46:1237-1243.