Page 205 - AIDSBK23C

Page 205

BONE MARROW AND PERIPHERAL BLOOD IN AIDS

PERIPHERAL BLOOD.-- Cytopenias are commonly seen in association with HIV
infection. Anemia, thrombocytopenia, neutropenia, lymphocytopenia, monocytopenia, or
combinations of any or all of these can occur in over 90% of patients with AIDS. The
microenvironment of the marrow may also be altered by HIV infection of stromal cells including
fibroblasts, endothelial cells, reticular cells, macrophages, osteoclasts, and adipocytes, resulting
in dysregulation of hematopoietic cell growth with reduced hematopoiesis.[839]
Anemia is present in over half of patients early in the course of AIDS and in nearly all
AIDS patients late in the course. The anemia is often normochromic and normocytic, typical of
anemia of chronic disease, and iron stores are increased by measurement of serum ferritin.
Though CD34+ stem cells poorly express CD4 receptors and, hence, they are relatively resistant
to HIV infection, mononuclear cells are infected and produce cytokines such as TGF-β, TNF-α,
and IL-1 that suppress hematopoiesis. Cytopenias can be potentiated by drug therapy including
zidovudine (ZDV), ganciclovir, amphotericin B, or trimethoprim-sulfamethoxazole and may
require dose reduction or cessation of therapy. A positive direct antiglobulin test may be present
in a third of HIV-infected persons and is associated with anemia, particularly with more
advanced HIV infection, but marked hemolysis anemia is uncommon.[840,841]
Chronic B19 parvovirus infection may produce red cell aplasia or chronic anemia in up to
25% of HIV-infected persons, though it may not be severe in others. Diagnosis of parvovirus
infection can be made serologically. In bone marrow biopsies, there may be overall
hypercellularity and the presence of giant multinucleated erythroblasts and giant pronormoblasts
with finely granulated cytoplasm and glassy, variably eosinophilic, intranuclear inclusions with a
clear central halo (so-called lantern cells). Giant early erythroid cells are seen on Wright-Giemsa
stain. Pronormoblasts show prominent intranuclear viral inclusions, which are eosinophilic and
compress the chromatin against the nuclear membrane. Severe anemia from parvovirus B19
infection is treatable with intravenous immunoglobulin therapy. [842]
An iron deficiency type of anemia may prompt testing for occult blood in stool, the
presence of which may suggest Kaposi's sarcoma or malignant lymphoma as a likely cause.
Cytomegalovirus and fungal lesions produce gastrointestinal bleeding less often. Macrocytic
anemias in AIDS are usually the result of chronic liver disease associated with chronic
alcoholism or hepatitis, particularly when injection drug use is a risk factor, but they may also
result occasionally from use of drugs that act as folate antagonists (trimethoprim-
sulfamethoxazole).
Thrombocytopenia was seen in up to 23% of HIV-infected persons prior to widewspread
us of antiretroviral drugs, but the prevalence decreases with antiretroviral therapy. However,
thrombocytopenia increases with decreasing CD4 lymphocytes counts. The reduction in
platelets is rarely severe enough to cause spontaneous hemorrhage. It may be primarily as a
result of HIV effects upon the marrow or secondary to peripheral consumption (splenomegaly,
immune complexes, drug effects). Though marrow hematopoietic stem cells express receptor
CD4 and coreceptors CXCR4 or CCR5, they do not appear to become productively infected with
HIV. Hence, thrombocytopenia with HIV infection is likely due to secondary, peripheral
causes.[843]
Thrombocytopenia may appear in some HIV-infected persons prior to development of
clinical AIDS. In some cases, the presentation is indistinguishable from classic idiopathic