JBM  Vol.4 No.10 , October 2016
Estimation and Assessment of Plasma D-Dimer Levels in HIV Patients
ABSTRACT
Background: The elevation of plasma D-dimer levels is fully described and associated with the increase of the mortality of patients with HIV. The present study was aimed to estimate and assess the plasma D-dimer levels in HIV patient. Material and Methods: A case control study done in May 2015. A total of 100 subjects were enrolled in this study; 50 were patients professionally diagnosed by HIV; 25 (50%) were males and 25 (50%) were females; their mean age is 35 years. Further 50 normal healthy individuals as normal control group: their gender and age were matched with patient groups. The platelets poor plasma (PPP) was immediately prepared from citrated blood, then the plasma D-dimer level was measured using (MISPA-i2 Reagent) Switzerland. Data were analyzed using statistical packing for social sciences program (SPSS) 20. Results: The D-dimer levels was significantly higher in patient with HIV compared with the normal healthy control group (Mean and STD 502.2 ± 287.8 vs 251.8 ± 152.7 P. value 0.01). Conclusion: The D-dimer level was significantly higher in patient with HIV compared with those in normal healthy control group.
KEYWORDS
HIV, AIDS, D-Dimer, Sudan

1. Introduction

HIV is lentivirus (sub group of retrovirus) that causes HIV infection and acquires immunodeficiency syndrome (AIDS) [1] [2] . AIDS is a condition in humans in which progressive failure of the immune system allows life-threating opportunistic infections and cancers to thrive without treatment average survival time after infection with HIV is estimated to be 9 to 11 years depending on the HIV subtype [3] . HIV infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells [4] . The infection of HIV leads to low levels of CD4+ Tcells through a number of mechanisms, including pyroptosis of abortively infected T cells [5] , direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells [6] . Infection with HIV occurs by the transfer of, blood, semen, vaginal fluid, pre-ejacute, or breast milk. It is a global pandemic [7] . As of 2012 approximately 35.5 million people are living with HIV globally, of these approximately 17.2 million are men, 16.8 million are women and 3.4 million are less than 15 years old [8] [9] . Sub-Saharan Africa has the most serious HIV and AIDS epidemic in the world. In 2013, an estimated 24.7 million people were living with HIV, accounting for 71% of the global total. In the same year, there were an estimated 1.5 million new HIV infections and 1.1 million AIDS-related deaths [10] .

As reported in SMART study, the hypercoagulable state was associated with the disease mortality and may be considered as one of causes that lead to death in HIV disease [11] . Several studies confirm the SMART study in fact that the D-dimers has a strong correlated with cardiovascular disease [12] . D-dimer levels forecast the present of throm- bosis whatever venous or arterial in all individuals and with those affected by HIV infection [3] [12] - [18] . The mechanism of present hypercoagulability which detected by D-dimer and pathophysiology of HIV were still unclear; even though many researchers reported the endothelial damage and vascular dysfunction [19] - [21] .

2. Material and Methods

This is a case control study done in May 2015. A total of 100 subjects were enrolled in this study. 50 were patients professionally diagnosed with HIV, 25 (50%) were males and 25 (50%) were females; their mean age is 35 years. Further 50 normal healthy used as control groups their gender and age was matched with patient groups. This study was approved from Alneelain university ethical committee, the consent was also taken from all participant enrolled in this study before the samples were collected. Then 3 ml of venous blood were collected in a container contains 3.2% trisodium citrate at a ratio of 9:1 as anticoagulant, then platelets poor plasma (PPP) was immediately prepared by centrifuged for 15 minutes at 3000 rpm. The plasma D-dimer levels were measured by using (MISPA-i2 Reagent) Switzerland. Every patient with a history of thrombosis and liver disease excluded from this study. Data analyzed by statistical packing for social sciences program (SPSS) 20. A value of less than 0.05 was considered significant.

3. Results

The present study showed that the D-dimer level was significant increased in patient with HIV when compared with the normal healthy control group (Mean and STD were 502.2 ± 287.8 vs 251.8 ± 152.7 P. value 0.01) respectively (Table 1).

Table 1. Correlation of D-dimer levels HIV patient versus normal control group.

4. Discussion

Haemostatic abnormalities in coagulation factor levels and a hypercoagulable state in HIV-positive individuals have been reported years ago [22] - [24] . Exactly like any other chronic inflammation HIV infection associated with activated coagulation system [25] - [27] . D-dimer test is a common test used to diagnosis the present of thromboembolic disorders; it’s defined by a fibrin degradation product, which is the most predictive biomarker of overall mortality in HIV patients [28] [29] . D-dimer also has the probable to recognize subgroups warrant primary prophylaxis or prolonged anticoagulation [30] [31] . To our acquaintance, this is the first study to assess the plasma D-di- merin Sudanese HIV patients. This study revealed that the D-dimer levels were significantlyhigher in HIV patients when compared with normal healthy control group (p value 0.01). This Finding was in concordance with study done in 2009 cited by Jacqueline Neuhaus et al. who reported that the higher D-dimer levels was higher in HIV patient when compared with those normal control group [26] . The interesting findings of the current study are also in consistence with several recently studies done in different population in which the authors concluded that the D-dimer levels were significantly higher in patients with acquired immunodeficiency syndrome compared with normal control group [29] - [34] .

5. Conclusion

Based on our result, this study concluded that the Sudanese patients with HIV infection have hypercoagulable state.

Cite this paper
Himmat, W. and Gaufri, N. (2016) Estimation and Assessment of Plasma D-Dimer Levels in HIV Patients. Journal of Biosciences and Medicines, 4, 1-5. doi: 10.4236/jbm.2016.410001.
References
[1]   Weiss, R.A. (1993) How Does HIV Cause AIDS? Science, 260, 1273-1279.
http://dx.doi.org/10.1126/science.8493571

[2]   Douek, D.C., Roederer, M. and Koup, R.A. (2009) Emerging Concepts in the Immunopathogenesis of AIDS. Annual Review of Medicine, 60, 471-484.
http://dx.doi.org/10.1146/annurev.med.60.041807.123549

[3]   UNAIDS, WHO (2007) 2007 AIDS Epidemic Update (PDF). 10.

[4]   Cunningham, A.L., Donaghy, H., Harman, A.N., Kim, M. and Turville, S.G. (2010) Manipulation of Dentric Cell Function by Viruses. Currentopinion in Microbiology, 13, 524-529.
http://dx.doi.org/10.1016/j.mib.2010.06.002

[5]   Doitsh, G., Galloway, N.L.K., Geng, X., Yang, Z.Y., Monrole, K.M., Zepeda, O., Hunt, P.W., Hatano, H., Sowinski, S., Isa, M.-A. and Green, W.C. (2014) Cell Death by Pyroptosis Drives CD4 T-Cell Depletion in HIV-1 Infection. Nature, 505, 509-514.

[6]   Kumar, V. (2012) Robbins Basic Pathology. 9th Edition, 147.

[7]   Cohen, M.S., Hellmann, N., Levy, J.A., De Cock, K. and Lange, J. (2008) The Spread, Treatment, and Prevention of HIV-1: Evolution of a Global Pandemic. The Journal of Clinical Investigation, 118, 1244-1254.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276790/

[8]   “Fact Sheet” UNAIDS.org. 2013.

[9]   UNAIDS (2011) 1-10.

[10]   UNAIDS (2014) The Gap Report 2014.

[11]   Kuller, L.H., Tracy, R., Belloso, W., De Wit, S., Drummond, F., Lane, H.C., Ledergerber, B., Lundgren, J., Neuhaus, J., Nixon, D., et al., INSIGHT SMART Study Group (2008) Inflammatory and Coagulation Biomarkers and Mortalityin Patients with HIV Infection. PLoS Medicine, 5, e203.
http://dx.doi.org/10.1371/journal.pmed.0050203

[12]   Duprez, D.A., Neuhaus, J., Kuller, L.H., Tracy, R., Belloso, W., De Wit, S., Drummond, F., Lane, H.C., Ledergerber, B., Lundgren, J., et al., INSIGHTSMART Study Group (2012) Inflammation, Coagulation and Cardiovascular Disease in HIV-Infected Individuals. PLoS ONE, 7, e44454.
http://dx.doi.org/10.1371/journal.pone.0044454

[13]   Cushman, M., Lemaitre, R.N., Kuller, L.H., Psaty, B.M., Macy, E.M., Sharrett, A.R. and Tracy, R.P. (1999) Fibrinolytic Activation Markers Predict Myocardial Infarction in the Elderly. The Cardiovascular Health Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 493-498.
http://dx.doi.org/10.1161/01.ATV.19.3.493

[14]   Cushman, M., Folsom, A.R., Wang, L., Aleksic, N., Rosamond, W.D., Tracy, R.P. and Heckbert, S.R. (2003) Fibrin Fragment D-Dimer and the Risk of Future Venous Thrombosis. Blood, 101, 1243-1248.
http://dx.doi.org/10.1182/blood-2002-05-1416

[15]   Ford, E.S., Greenwald, J.H., Richterman, A.G., Rupert, A., Dutcher, L., Badralmaa, Y., Natarajan, V., Rehm, C., Hadigan, C. and Sereti, I. (2010) Traditionalrisk Factors and D-Dimer Predict Incident Cardiovascular Disease Events Inchronic HIV Infection. AIDS, 24, 1509-1517.
http://dx.doi.org/10.1097/QAD.0b013e32833ad914

[16]   Jong, E., Louw, S., Meijers, J.C., de Kruif, M.D., ten Cate, H., Buller, H.R., Mulder, J.W. and van Gorp, E.C. (2009) The Hemostatic Balance in HIV-Infected Patients with and without Antiretroviral Therapy: Partial Restoration with Antiretroviral Therapy. AIDS Patient Care and STDS, 23, 1001-1007.
http://dx.doi.org/10.1089/apc.2009.0173

[17]   Ledwaba, L., Tavel, J.A., Khabo, P., Maja, P., Qin, J., Sangweni, P., Liu, X., Follmann, D., Metcalf, J.A., Orsega, S., et al. and Project Phidisa Biomarkers Team (2012) Pre-ART Levels of Inflammation and Coagulation Markers Are Strong Predictors of Death in a South African Cohort with Advanced HIV Disease. PLoS ONE, 7, e24243.
http://dx.doi.org/10.1371/journal.pone.0024243

[18]   Musselwhite, L.W., Sheikh, V., Norton, T.D., Rupert, A., Porter, B.O., Penzak, S.R., Skinner, J., Mican, J.M., Hadigan, C. and Sereti, I. (2011) Markers of Endothelial Dysfunction, Coagulation and Tissue Fibrosis Independently Predictvenous Thromboembolism in HIV. AIDS, 25, 787-795.
http://dx.doi.org/10.1097/QAD.0b013e3283453fcb

[19]   Justice, A.C., Freiberg, M.S., Tracy, R., Kuller, L., Tate, J.P., Goetz, M.B., Fiellin, D.A., Vanasse, G.J., Butt, A.A., Rodriguez-Barradas, M.C., et al. and VACS Project Team (2012) Does an Index Composed of clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality among Those Aging with HIV? Clinical Infectious Diseases, 54, 984-994.
http://dx.doi.org/10.1093/cid/cir989

[20]   Baker, J., Quick, H., Hullsiek, K.H., Tracy, R., Duprez, D., Henry, K. and Neaton, J.D. (2010) Interleukin-6 and D-Dimer Levels Are Associated with Vascular Dysfunction in Patients with Untreated HIV Infection. HIV Medicine, 11, 608-609.
http://dx.doi.org/10.1111/j.1468-1293.2010.00835.x

[21]   Hileman, C.O., Longenecker, C.T., Carman, T.L., Milne, G.L., Labbato, D.E.,Storer, N.J., White, C.A. and McComsey, G.A. (2012) Elevated D-Dimer Isindependently Associated with Endothelial Dysfunction: A Cross-Sectional Study in HIV-Infected Adults on Antiretroviral Therapy. Antiviral Therapy, 17, 1345-1349.
http://dx.doi.org/10.3851/IMP2297

[22]   Bissuel, F., Berruyer, M., Causse, X., Dechavanne, M. and Trepo, C. (1992) Acquired Protein S Deficiency: Correlation with Advanced Disease in HIV-1-Infectedpatients. Journal of Acquired Immune Deficiency Syndromes, 5, 484-489.

[23]   Lijfering, W.M., Sprenger, H.G., Georg, R.R., van der Meulen, P.A. and van derMeer, J. (2008) Relationship between Progression to AIDS and Thrombophilic Abnormalities in HIV Infection. Clinical Chemistry, 54, 1226-1233.
http://dx.doi.org/10.1373/clinchem.2008.103614

[24]   Shen, Y.M. and Frenkel, E.P. (2004) Thrombosis and a Hypercoagulable State in HIV-Infected Patients. Clinical and Applied Thrombosis/Hemostasis, 10, 277-280.
http://dx.doi.org/10.1177/107602960401000311

[25]   Calmy, A., Gayet-Ageron, A., Montecucco, F., Nguyen, A., Mach, F., et al. (2009) HIV Increases Markers of Cardiovascular Risk: Results from a Randomized, Treatment Interruption Trial. AIDS, 23, 929-939.
http://dx.doi.org/10.1097/QAD.0b013e32832995fa

[26]   Neuhaus, J., et al. (2010) Markers of Inflammation, Coagulation, and Renal Function Are Elevated in Adult with HIV Infection. The Journal of Infectious Diseases, 201, 1788-1795.
http://dx.doi.org/10.1086/652749

[27]   Fultz, S.L., McGinnis, K.A., Skanderson, M., Ragni, M.V. and Justice, A.C. (2004) Association of Venous Thromboembolism with Human Immunodeficiency Virus and Mortality in Veterans. American Journal of Medicine, 116, 420-423.
http://dx.doi.org/10.1016/j.amjmed.2003.10.011

[28]   Kuller, L.H., Tracy, R., Belloso, W., De Wit, S., Drummond, F., et al. (2008) Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection. PLoS Medicine, 5, e203.
http://dx.doi.org/10.1371/journal.pmed.0050203

[29]   DiNisio, M., Squizzato, A., Rutjes, A.W.S., Buller, H.R., Zwinderman, A.H. and Bossuyt, P.M.M. (2007) Diagnostic Accuracy of D-Dimer Test for Exclusion of Venous Thromboembolism: A Systematic Review. Journal of Thrombosis and Haemostasis, 5, 296-304.
http://dx.doi.org/10.1111/j.1538-7836.2007.02328.x

[30]   Cosmi, B., Legnani, C., Cini, M., Guazzaloca, G. and Palareti, G. (2011) D-Dimer and Residual Vein Obstruction as Risk Factors for Recurrence during and after Anticoagulation Withdrawal in Patients with a First Episode of Provoked Deep-Vein Thrombosis. Journal of Thrombosis and Haemostasis, 105, 837-845.
http://dx.doi.org/10.1160/TH10-08-0559

[31]   Ay, C., Dunkler, D., Quehenberger, P., Marosi, C., Zielinski, C., Chiriac, A.-L. and Pabinger, I. Prediction of Venous Thromboembolism in Cancer Patients. Blood, 116, 5377-5382.
http://dx.doi.org/10.1182/blood-2010-02-270116

[32]   Baker, J.V., Neuhaus, J., Duprez, D., Kuller, L.H., Tracy, R., et al. (2011) Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate versus Deferred Antiretroviral Therapy in Patients with HIV Infection. Journal of Acquired Immune Deficiency Syndromes, 56, 36-13.
http://dx.doi.org/10.1097/QAI.0b013e3181f7f61a

[33]   Harper, P.L., Theakston, E., Ahmed, J. and Ockelford, P. (2007) D-Dimer Concentration Increases with Age Reducing the Clinical Value of the D-Dimer Assay in the Elderly. Internal Medicine Journal, 37, 607-613.
http://dx.doi.org/10.1111/j.1445-5994.2007.01388.x

[34]   Strategies for Management of Antiretroviral Therapy (SMART) Study Group (2006) CD4+ Count-Guided Interruption of Antiretroviral Treatment. New England Journal of Medicine, 355, 2283-2296.
http://dx.doi.org/10.1056/NEJMoa062360

 
 
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