Page 2546 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 157 Hematologic Manifestations of HIV/AIDS 2269

disease are often treated with one or more medications that can affect
BOX 157.3 Etiologies of Cytopenias
RBC production and survival.
The etiologies of cytopenias are multifactorial. The common etiologies Before the HAART era, treatment of HIV disease with high doses
for anemia, thrombocytopenia, and neutropenia include HIV infection of zidovudine was a major cause of myelosuppression and anemia in
and its effect on the bone marrow, medications, and bone marrow patients with AIDS. More recent studies, even in the era of HAART,
infiltration with infectious agents or malignancies. Hence the first step continue to report a high prevalence of anemia among HIV-infected
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in the treatment of any cytopenia is to optimize antiretroviral therapy. patients. Acute and chronic inflammation is the most frequent cause
Any offending agent/agents causing the cytopenia should be discon- of anemia in HIV infection. This is characterized by the classic
tinued if possible and infections or malignancies involving the bone findings of decreased serum iron concentration, reduced total iron
marrow should be appropriately treated. In addition, appropriate binding capacity, a normal or high ferritin, an inappropriately low
workup should be done to diagnose conditions that can affect specific reticulocyte count for the degree of anemia, and reduced blood levels
cell lines. For instance, the cause of anemia includes anemia of chronic
disease with a blunted production as well as response to erythropoietin, of erythropoietin. HIV infection itself may account for anemia.
which can be effectively treated with erythropoietin. Parvovirus B19 Therefore initiation of HAART may result in improvement or nor-
can cause isolated red cell aplasia and can be treated with red cell malization of hemoglobin levels in patients who are anemic at baseline.
+
transfusion and IVIg. Other causes of anemia encountered in the Frequently this occurs in parallel with improvement in CD4 lym-
+
immune competent population should be considered and appropriately phocyte count, but can occur with only marginal increase in CD4
treated. HIV-related autoimmune thrombocytopenia responds to lymphocyte numbers. The use of HIV protease inhibitors in HAART
HAART, steroids, anti D, IVIg, and splenectomy. G-CSF/GM-CSF also appears to improve hematopoiesis. A report by the Women’s
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should be used when needed to treat neutropenia. The treatment of Interagency HIV Study has shown that the use of HAART is associ-
thrombosis in patients with HIV/AIDS is similar to treatment of this ated with decreased prevalence of anemia among women. HAART
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condition in the general population.
may also decrease the risk of anemia developing in patients who are
AIDS, Acquired immunodeficiency syndrome; G-CSF, granulocyte-colony not anemic at the initiation of therapy. Although the use of HAART
stimulating factor; GM-CSF, granulocyte-macrophage–colony stimulating factor; is associated with decreased prevalence among people with AIDS
HAART, highly active antiretroviral therapy; HIV, human immunodeficiency generally, the prevalence of anemia remains high among persons with
virus; IVIg, intravenous immunoglobulin. 15
low CD4 counts.
Parvovirus B19 is a member of the Parvoviridae family and is
responsible for several diseases in humans, including erythema
infectiosum (fifth disease) in children, hydrops fetalis, acute arthropa-
Red Blood Cell Abnormalities and Anemia thy in adults, aplastic crisis in patients with chronic hemolytic disor-
ders, and pure red cell aplasia in immunocompromised individuals.
Anemia can occur at any stage of HIV disease, but is more frequent Parvovirus-induced pure red cell aplasia in association with HIV
8
16
and severe in advanced disease. There is increasing evidence suggest- infection was described over a decade ago. Parvovirus B19 infection
ing that anemia in HIV disease is independently associated with an is generally limited to human erythroid progenitor cells and leads to
increased risk of disease progression and mortality. 8,11 Anemia is erythroid cell death. In hosts with normal immune responses and
associated with an increased risk of death in HIV-infected patients normal erythrocyte production, acute infection causes a self-limited
regardless of CD4 count, and survival is not significantly different (4–8 days) interruption in the production of erythrocytes that does
between patients with drug-related anemia and anemia attributed to not result in significant anemia. However, if host immune responses
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other causes. Correction of anemia in HIV-infected patients has are impaired, this can result in persistent infection of erythroid pre-
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been associated with measurable improvements in quality of life and cursors leading to a prolonged and severe anemia.
increased survival. 8 The seroprevalence of parvovirus B19 infection is similar among
Detection and treatment of the underlying cause of the anemia HIV-infected and noninfected individuals. Furthermore, HIV-
should be an immediate goal, which may involve the treatment of infected individuals who have serologic evidence of parvovirus B19
opportunistic infections or gastrointestinal blood loss. In general, the infection usually do not have evidence of active infection (i.e., par-
etiology of anemia seen in HIV infection is often multifactorial, with vovirus B19 viremia). Parvovirus B19–induced red cell aplasia seen
several mechanisms playing a role in an individual patient. Diagnos- in HIV patients often occurs in individuals with low or absent levels
ing the cause or causes of anemia is essential to proper therapy. of B19-specific antibodies. 16
Clinically the disease presents in patients with findings consistent
Anemia Resulting From Decreased Red Blood with profound anemia characterized by weakness, pallor, dyspnea,
and tachycardia. Hemoglobin values as low as 4 to 5 g/dL and
Cell Production absolute reticulocyte counts of less than 5 × 10 /L (<0.1%) are
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commonly reported. Detection of parvovirus IgG and IgM is not
The most common cause of anemia in HIV disease is decreased RBC reliable because levels of antibodies may be low or undetectable
production. Frequently encountered mechanisms responsible for among patients and are not diagnostic of acute parvovirus B19 red
decreased RBC production in patients with HIV disease are listed in cell aplasia. The most reliable diagnostic study of parvovirus B19
Table 157.5. Examples include anemia of acute and chronic inflam- infection is the detection of parvovirus DNA by either PCR or
mation (chronic disease anemia) with a blunted production of and dot-blot hybridization. Because the high sensitivity of PCR may lead
response to erythropoietin and cytokine suppression of bone marrow to positive test results for months after the original infection, dot-blot
colony-forming unit–granulocyte, erythrocyte, macrophage, mega- hybridization may be a better test for making a diagnosis of acute
karyocyte (CFU-GEMM). Infection or infiltration of bone marrow infection resulting in red cell aplasia. Histologic examination of bone
by infectious agents such as atypical mycobacterium, tuberculosis, marrow aspirates reveals hypocellularity, markedly decreased matur-
CMV, and/or fungal organisms can result in profound anemia, ing erythrocytes, and occasional giant pronormoblasts. The presence
although most often associated with pancytopenia. Parvovirus B19 of giant pronormoblasts in a bone marrow aspirate or biopsy is
can cause isolated red cell aplasia in the more severely immuno- diagnostic of parvovirus B19 infection. 6
compromised individuals. Bone marrow infiltration by HIV-associated Initial therapy for parvovirus-induced red cell aplasia should be
lymphomas, in addition to anemia, can cause neutropenia and aimed at correcting the anemia through RBC transfusions. Treatment
thrombocytopenia. Nutritional deficiencies, including vitamin B 12 with intravenous immunoglobulin (IVIg 0.4 g/kg daily for 5 days)
and folic acid deficiency, are not uncommon. Other causes of anemia can lead to a rapid decrease in the level of parvovirus viremia, improve-
including anemia secondary to blood loss or hemolysis as seen in the ment in the reticulocyte count, and resolution of the anemia. Recur-
non-HIV patient population can also occur in patients infected with rence is commonly seen if there is no improvement in the patients’
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HIV. Most significant is that most patients with advanced HIV immunologic function. If the anemia recurs within 6 months of the