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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 1  |  Page : 47-49
Lupus anticoagulant in human immunodeficiency virus -infected patients on highly active antiretroviral therapy


1 Department of Hematology and Blood Transfusion, School of Medicine, College of Medical sciences, University of Benin, Benin City, Nigeria
2 Department of Hematology, University of Ghana Medical School, P.O. Box 4236, Korle Bu, Accra, Ghana
3 Department of Medicine, School of Medicine, College of Medical Sciences University of Benin, Benin City, Nigeria

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Date of Web Publication19-Jan-2010
 

   Abstract 

Background: Lupus anticoagulant (LA) is a heterogeneous group of antibodies that causes a variety of clinical and laboratory effects; has been described in infections such as human immunodeficiency virus. LA has not been previously described in Nigerians with human immunodeficiency virus infection on highly active antiretroviral therapy (HAART). Aim: To determine the frequency of LA in patients infected with the human immunodeficiency virus on HAART. Methods: Cross sectional study of patients with human immunodeficiency virus infection undergoing HAART at a tertiary hospital in Nigeria. Screening for LA was done using the activated partial thromboplastin time (aPTT) and kaolin clotting time (KCT). Mixing experiments were conducted on samples with prolonged clotting time. KCT ratio was calculated. A positive result was taken as KCT ratio greater than or equal to 1.2. Fisher's exact test was used to test the association between LA and sex. Association between aPTT and KCT was tested according to Pearson. P-value < 0.05 was considered significant. Results: Fifty-eight patients aged 18- 60 years were studied, comprising of 28 males (mean age 40.50 plus/minus 8.8 years) and 30 females (mean age 35.4 plus/minus 9.02). Frequency of LA among human immunodeficiency infected patients was 5.2%, (frequency in males and females were 3.6 and 6.7 % respectively). This was lower than 46% reported in patients not on HAART. There was no statistically significant difference in LA prevalence between males and females P greater than0.05. A positive correlation was observed between the clotting tests aPTT and KCT (r is equal to 0.9406, p less than 0.0001). Conclusion: HAART may prevent development of LA in HIV-infected patients.

Keywords: Antiretroviral therapy, HIV/AIDS, lupus anticoagulant

How to cite this article:
Awodu OA, Olayemi EE, Bazuaye GN, Onunu AN. Lupus anticoagulant in human immunodeficiency virus -infected patients on highly active antiretroviral therapy. Indian J Pathol Microbiol 2010;53:47-9

How to cite this URL:
Awodu OA, Olayemi EE, Bazuaye GN, Onunu AN. Lupus anticoagulant in human immunodeficiency virus -infected patients on highly active antiretroviral therapy. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Oct 23];53:47-9. Available from: http://www.ijpmonline.org/text.asp?2010/53/1/47/59182



   Introduction Top


Lupus anticoagulant (LA) is a heterogeneous group of antibodies that cause a variety of clinical and laboratory effects. They are usually IgG, IgM or both. LA has been associated with venous thrombosis, recurrent spontaneous abortions, pre-eclampsia and lymphoma. [1],[2],[3],[4],[5],[6],[7],[8]

Syphilis was the first infection associated with antiphospholipid antibodies and a number of other infections have been linked to these antibodies, although the pathogenic role of the antibodies is not obvious in most cases. [3]

The association of LA with a number of viral infections including Hepatitis C virus, cytomegalovirus and human immunodeficiency virus has been reported. [9],[10],[11] LA has been associated with the catastrophic antiphospholipid syndrome in human immunodeficiency virus (HIV)-infected patients. [11] Bloom et al[12] reported an LA prevalence of 46% in patients who were not on highly active antiretroviral therapy (HAART).

HIV infection is a pandemic with devastating effects in countries like Nigeria. This study aims at detecting the frequency of LA in Nigerians living with the virus who are on HAART.


   Materials and Methods Top


Subjects : Patients diagnosed with the HIV, on treatment with HAART for at least six months, were recruited into the study following informed consent. The study was approved by the Hospital's Ethics Committee.

Methods: A cross-sectional study of HIV-infected patients on HAART at a tertiary hospital was conducted in Nigeria. Screening for LA was done using the kaolin clotting time (KCT). Activated partial thromboplastin time (aPTT) was also done. Mixing experiments were conducted on samples with prolonged initial clotting time according to the method of Exner. [13] Normal plasma and patient's plasma were mixed in a plastic tube in ratios of normal to patients: 10:0, 9:1, 8:2, 5:5, 2.8, 0:10; 0.2 ml of each mixture was pipetted into a glass tube at 37 0 C. A volume of 0.1ml kaolin suspension 20g/l in Tris buffer (PH 7.4) was added and incubated for three minutes, thereafter 0.2 ml of Cacl 2 was added and the clotting time was recorded. The clotting time was then plotted against mixtures of test plasma and normal plasma. The slope of the graph was calculated using the ratio of KCT at 20% test plasma and KCT at 100% normal control plasma. A positive result was taken as KCT ratio greater than or equal to 1.2. Statistical analysis was conducted using the GraphPad Instat® . Fisher's exact test was used to test the association between LA and sex. Association between aPTT and KCT was tested according to Pearson. Results are presented as mean plus/minus standard deviation and frequencies where necessary, P- value of less than 0.05 was considered significant.


   Results Top


A total of 58 subjects aged 18- 60 years on antiretroviral therapy were screened for the presence of the lupus anticoagulant. Subjects comprised of 28 males [mean age 40.50 plus/minus 8.8 years] and 30 females [mean age years 35.4 plus/minus 9.02]. Mean KCT was found to be 79.54[SD 23.99] seconds in males and 82.27[SD 28.34] in females, mean aPTT was 32.2[8.72] and 33.0[10.21] in males and females respectively. [Table 1] shows the hematological and hemostatic parameters.

LA was present in 5.2% of patients infected with the virus; it was present in 3.6% of males compared to 6.7% of females. There was no statistically significant difference in LA prevalence between males and females P greater than 0.05. [Table 2] shows the frequency of LA in our subjects. A positive correlation was observed between the clotting tests aPTT and KCT [r is equal to 0.9406, P less than 0.0001]. The curves positive for LA, obtained from the two females, are shown in [Figure 1]; they both showed a type 1 curve signifying the presence of LA. [13] The KCT graph of the male patient positive for LA is shown in [Figure 2]; it indicates a type 1 pattern. Anemia was observed in 43.1% of patients with 6.9% of patients having severe anemia, ranges of packed cell volume seen in our study subjects is shown in [Table 3].


   Discussion Top


LA has generated a lot of interest in the last three decades in view of its association with thrombosis and recurrent fetal loss among other conditions.

In this study we screened for the presence of LA in patients infected with HIV who were on HAART. LA was present in 5.7% of our patients, this contrasted with the prevalence of 46% reported earlier by Bloom et al. [12] The marked difference between the two studies is - all our patients were on HAART; the immune reconstitution that occurs in HIV infected patients on HAART could explain the lower frequency of LA seen in our patients.

No thrombotic episode was observed in any of the 58 patients studied. This agrees with the work of Coll et al. [14] who found no thrombotic phenomenon in the 84 patients studied. Anemia is a common clinical condition in HIV infection and has been reported in 10-20% of cases at initial presentation and 70-80% of patients during the course of the disease, [15] In this study, a prevalence of 43.1% was obtained which is in agreement with an earlier study from Nigeria where a prevalence of 36.74% was found. [16] Severe anemia was observed in 6.9% of patients studied.

A number of reasons have been cited for anemia in HIV including decrease in red cell production resulting from suppression of CD34+ colony-forming-units-granulocyte-erythroid-monocyte-macrophage(CFU_GEMM) by cytokines or the virus. [17] Thrombocytopenia has also been associated with HIV infection and has been reported in about 40% of patients during the course of the infection. [18] In the present study 22.4% of patients have thrombocytopenia (platelet count less than 95,000 x 10 9 /I). Among the reasons adduced for thrombocytopenia in patients infected with the virus are, increased platelet destruction, decreased platelets production and the direct infection of megakaryocytes by HIV. [19] Thrombocytopenia is also associated with the presence of LA. [20]

In conclusion, we screened for the presence of LA in Nigerians living with HIV and undergoing HAART for at least six months. A prevalence of 5.7% was obtained which differs from higher prevalence reported from patients who were not on HAART. Our study suggests that HAART prevents the development of LA in HIV/AIDS patients.

 
   References Top

1.Mintz G, Acevedo-vazquez E, Gutierrez-Espinosa G, Guittierrez-Espinoza G, Avelar-Garnica F, et al. Renal vein thrombosis and inferior vena cava thrombosis in systemic lupus erythematosus. Rheum 1984;27:539-44.  Back to cited text no. 1      
2.Santoro A. Antiphospholipid antibodies and thrombotic disposition: Pathogenic mechanisms. Blood 1994;83:2389-91.  Back to cited text no. 2      
3.Ashenron RA, Cervera R. Antiphospholipid antibodies and infections. Ann Rheum Dis 2003;62:388-93.  Back to cited text no. 3      
4.Hughes GRV. Thrombosis, abortion, cerebral disease and the lupus anticoagulant. BMJ 1983;287:1088-9.  Back to cited text no. 4      
5.Howard MA, Firkin BG, Hearly DL, Choong SC. Lupus anticoagulant in women with multiple spontaneous miscarriages. AM J Hematol 1987;26:175-8.  Back to cited text no. 5      
6.Awodu OA, Enosolease ME. Activated partial thromboplastin time in Pregnancy. Ann Bio Sci 2003;2:42-6.  Back to cited text no. 6      
7.Awodu OA, Shokunbi WA, Ejele OA. Lupus anticoagulant in nigerian women with pre-eclampsia. West Afr J of Med 2003;22:240-2.  Back to cited text no. 7      
8.Pusterla S, Previtali S, Marziali S, Cortelazzo S, Rossi A, Barbui T, Galli M. Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 2004;5:341-6.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]  
9.Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, et al. Extrahepatic manifestations associated with hepatitis C infection. A prospective multicentre study of 321 patients. Medicine (Baltimore) 2000;79:45-6.  Back to cited text no. 9      
10.Uthman T, Tabbarah Z, Gharavi AE. Hughes syndrome associated with cytomegalovirus infection. Lupus 1999;8:775-7.  Back to cited text no. 10      
11.Petrovas C, Vlachoyiannopolos PG, Kordossis T, Moutsopolos MN. Antiphospholipid antibodies in HIV infection and SLE with or without antiphospholipid syndrome: comparisons phospholipids specificity, avidity and reactivity with beta 2-GPI. J Autoimmun 1999;123:347-55.  Back to cited text no. 11      
12.Bloom EJ, Abrams DI, Rodgers G. Lupus anticoagulant in the acquired immunodeficiency syndrome. JAMA 1986;258:491-3.  Back to cited text no. 12      
13.Exner T, Rickard K A, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioral patterns. Br. Haematol 1978;40:143-51.  Back to cited text no. 13      
14.Coll J, Gutierrez-Cebollada J, Yazbeck H, Berges A, Rubies-Prat J. Anticardiolipin antibodies and acquired immunodeficiency syndrome: Prognostic marker or association with HIV infection? Infection 1992;20:140-2.  Back to cited text no. 14      
15.Sullivan PS, Hanson DL, Chu SY, Jones JL, Ward JW. Epidemiology of anemia in human immunodeficiency virus infected persons: Results from the Multistate Adult and Adolescent spectrum of HIV Disease Surveillance Project. Blood 1998;91:301- 8.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Olayemi E, Awodu OA, Bazuaye GN. Autoimmune hemolytic anemia in HIV- infected patients: P hospital based study. Ann Afr Med 2008;7:72-6.  Back to cited text no. 16  [PUBMED]  Medknow Journal  
17.Zon LI, Arkin C, Groopman JE. Hematologic manifestations of human immunodeficiency virus (HIV). Semin Hematol 1998;25:208-15.  Back to cited text no. 17      
18.Sullivan PS, Hanson DL, Chu SY, Jones JL, Ciesielski CA. Surveillance for thrombocytopenia in persons infected with HIV: Results from Multistate Adult and Adolescence Spectrum of Disease Project. J Acquir Immune Defic Syndr 1997;4:374-9.  Back to cited text no. 18      
19.Zucker-Franklin D, Seremetis S, Heng ZY. Internalization of human immunodeficiency virus type 1 and other retroviruses by megakaryocytes and platelets. Blood 1990;75:1920-3.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]  
20.Cuadrado MJ, Mujic F, Munoz E, Khamastha MA, Hughes GR. Thrombocytopenia in the antiphospholipid antibody syndrome. Ann Rheum Dis 1997;56:194-6.  Back to cited text no. 20      

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Correspondence Address:
Edeghonghon E Olayemi
Department of Hematology, University of Ghana Medical School, P.O. Box 4236, Korle Bu, Accra
Ghana
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.59182

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