**5.1. Cellular abnormalities**

Platelet destruction normally occurs early in the course of the disease. The destruction is often antibody mediated [59]. There are HIV-specific antibodies that have been shown to share a common epitope with antibodies against glycoprotein on the platelet surface (platelet GPIIb/ IIIa) [59]. Nonspecific absorption of immune complexes onto platelets also occurs which predisposes the cell to immune thrombocytopaenia. Interestingly, there was a study that correlated the presence of lupus anticoagulant and anticardiolipin antibodies in HIV patients with the presence of thrombocytopaenia [60]. The other common cause of reduced platelet production in HIV patients is direct infection of megakaryocytes by the virus itself [61]. This gives rise to abnormal megakaryocytes morphology in the marrow. Other causes of throm‐ bocytopenia include marrow infiltration by opportunistic infection or lymphoma, presence of complications such as thrombothic thrombocytopaenic purpura, and myelosuppressive effects

Leucopaenia is the reduction in total white blood cell (WBC) count. In adults, normal WBC

predominantly due to lymphopenia, decrease in the number of lymphocyte count, mainly

immunologic abnormalities of HIV infection and is one of the important prognostic indicators

Production of granulocytes and monocytes is also reduced, but less well recognized feature as compared to lymphopaenia. Occurance of neutropaenia is hinged on several other factors which are commonly seen in patients with advanced HIV disease. It can also occur due to concurrent infections, immune mediated or therapy related factors. Another cause of neutro‐ paenia might be decreased bone marrow production of granulocytes due to inhibition of granulocyte progenitors. It has been postulated that a glycoprotein present in the marrow of infected patients might have an inhibitory effect [62]. Despite cellularity changes, morpholog‐ ical changes may occur in HIV patients. The changes are mainly due to dysplasia [38]. Peripheral blood smear will show some neutrophil changes such as detached nuclear frag‐ ments, abnormal nuclear fragmentation either hypofragmentation or hyperfragmentation, and

In 2012, Parinithia and Kulkarni had done a study among 250 HIV patients to determine the haematological changes that occur in HIV patients as well as to evaluate its correlation with the CD4 cell count. They reported that among the HIV patients studied, anaemia, lymphopenia and thrombocytopenia was found in 210 (84%), 163 (65.2%) and 45 (18%) cases respectively

leucopenia, lymphopenia and thrombocytopenia was observed in 91.4% 26.8%, 80% and 21.7%

. In patients with CD4 cell counts less than 200 cells/mm3

*4.2.1.4. Haematological changes in HIV infection with correlation to CD4 cell count*

[61]. Majority of the cases (70%) had CD4 cell counts below 200 cells/mm3

lymphocytes. Leucopaenia generally correlates with the disease progression in HIV

/L. Leucopaenia is frequently seen in HIV patients and

T-cells occurs as one of the earliest

, 54 cases (21.6%) had

, anaemia,

and in 21 cases (8.4%), the CD4 count is more

of drug therapy.

*4.2.1.3. Leucopaenia*

CD4+

count is between 4.5 to 11.0 x 109

abnormal nuclear granulation.

than 500 cells/mm3

patients [62]. Reduction in absolute number of CD4+

120 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

of risk of developing opportunistic infections.

CD4 cell counts between 200 to 499 cells/mm3

The cellularity of the bone marrow can be assessed based on trephine biopsy. It can be normal, reduced or increased, depending on the patients' condition. Normally the bone marrow will show normal or increased cellularity. However, the marrow cellularity does not always correlate with the peripheral blood findings. The commonly observed pancytopenia (reduction in the 3 major cell lineages, which are red cells, white cells and platelets) in the peripheral blood is often associated with an active marrow [45], suggesting dysmyelopoiesis or increased peripheral destruction. Other than cellularity, the morphology and function of the cells can be altered. These include presence of severe nutritional deficiencies in advanced stages of HIV infection, bone marrow suppression by opportunistic infections or neoplasm, underlying chronic and toxic side effects of antiretroviral compounds (or other medications used to treat the complications of HIV disease). Megaloblastic changes where the red cell series are macrocytic, are occasionally seen in the bone marrow aspiration of HIV patients and this may reflect myelodysplastic changes or concurrent effect of treatment [45]. There is possibility of HIV directly infecting the haematopoietic precursor cells and inhibiting their differentiation and maturation [45].

The increased number of plasma cells has been observed in some HIV patients. This may be related to repeated infections that always occur in immunocompromised patients. Haemo‐ phagocytosis is frequently seen in a bone marrow examination, especially in patients with CMV and herpes simplex infection. Features of increased macrophage activity may also be seen in tuberculosis [63] and histoplasmosis infection associated with HIV disease [64].
