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1252 Part IX: Lymphocytes and Plasma Cells Chapter 81: Hematologic Manifestations of Acquired Immunodeficiency Syndrome 1253

B19 is a small DNA virus that infects and lyses late human erythroid increased risk of thrombosis, a very rare risk of pure red cell aplasia,
precursor cells, causing transient reticulocytopenia in immunocom- and increased risk of tumor progression or recurrence in specific types
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petent patients. The clinical spectrum of parvovirus B19–related dis- of cancer, as well as high cost.
ease includes “slapped cheek rash” in children and arthralgias in adults,
but most immunocompetent patients are asymptomatic. Patients with
hemolytic anemia who depend on high production of reticulocytes may HUMAN IMMUNODEFICIENCY
develop transient aplastic crisis following infection with parvovirus B19.
Immunoincompetent individuals may not be able to mount an adequate VIRUS–ASSOCIATED THROMBOTIC
antibody response to clear parvovirus B19 from the blood and marrow, MICROANGIOPATHY
resulting in sustained infection with reticulocytopenia and anemia. In a Early in the HIV epidemic, it was reported that HIV+ people are at
series of HIV+ patients with parvovirus B19–related anemia, the median increased risk of thrombotic microangiopathy, either thrombotic throm-
CD4 count was 42 cells/μL, indicating that parvovirus B19–associated bocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). In a
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pure red cell aplasia is associated with advanced immunodeficiency. retrospective survey of 1223 patients with clinical AIDS in the pre-ART
Characteristically, these patients have a normocytic anemia with vir- era, 1.4 percent met criteria for thrombotic microangiopathy. However,
tual absence of reticulocytes, but normal white blood cells and plate- a prospective cohort of 347 patients followed from 1997 to 2000 identi-
lets. Parvovirus immunoglobulin (Ig) G and IgM levels are generally fied no patients with thrombotic microangiopathy, suggesting that the
not helpful in making the diagnosis, but PCR to detect parvovirus in incidence may have declined as a result of effective ART. In support
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the blood can be a reliable diagnostic test. Marrow evaluation may of this, a study done in the ART era followed 6022 HIV+ patients and
show characteristic giant proerythroblasts and markedly diminished found that 0.3 percent of patients developed thrombotic microangio-
late erythroid precursor cells, with full maturation of the myeloid and pathy. The group with thrombotic microangiopathy had a lower mean
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megakaryocytic lineages. Some patients respond to initiation of ART CD4 count, a higher plasma viral load, and a higher incidence of clinical
in addition to transfusion support, but the majority of patients require AIDS than did HIV+ patients without microangiopathy. Registries of
additional therapy. A high prevalence of antibodies to B19 parvovirus patients with TTP have been used to investigate what fraction of the
exists in the general population; therefore, pooled human IgG prepara- patients are HIV+; of 362 patients in the Oklahoma TTP/HUS registry
tions are a rich source of antiparvovirus antibody. Infusion of human from 1989 to 2007,1.84 percent were HIV+ while the prevalence of HIV
IgG results in clearance of parvovirus B19 from the blood and improved in the local community was 0.3 percent. In this study, several of the
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reticulocyte production and resolution of anemia in HIV+ patients with HIV+ patients were thought to have alternative causes of their microan-
parvovirus B19–induced pure red cell aplasia. 259,260 However, patients giopathic hemolytic anemia, reinforcing the importance of a thorough
with a CD4 count of less than 80 cells/μL are prone to relapse within 6 consideration of the full spectrum of illnesses causing thrombotic
months and may require retreatment. microangiopathy, which may, in turn, affect the decision to use plas-
mapheresis/plasma exchange. One series of 24 HIV+ patients with
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Medications and Anemia TTP reported that these patients presented with a mean hemoglobin of
An important cause of anemia in people living with HIV is medications; 6.8 g/dL, a mean platelet count of 20,000/μL, a mean LDH of 4.5-fold
both ART and medications used for prophylaxis against infections are normal, and a mean CD4 count of 236 cells/μL, and the majority had an
implicated. Zidovudine can cause macrocytic anemia and leukopenia, HIV viral load of greater than 10,000 copies/mL. Patients were treated
and is not commonly used at present because of its toxicity. Stavudine with prompt plasma exchange (mean of 13 treatments) and initiation
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is associated with anemia, although at lower rates than zidovudine. of ART and achieved excellent outcomes comparable to HIV– patients
Dapsone or trimethoprim-sulfamethoxazole, used for P. jiroveci prophy- with TTP, with death occurring in a single patient. However six of the
laxis, can cause hemolytic anemia in patients with glucose-6-phosphate 24 patients suffered relapse of TTP, often in the setting of increased
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dehydrogenase (G6PD) deficiency. Ganciclovir or valganciclovir, used to viral load, and required retreatment. A study of patients enrolled in
treat herpes simplex virus (HSV), Varicella-zoster, CMV, and sometimes the French thrombotic microangiopathy (TMA) network revealed that
HHV8, often cause pancytopenia. Trimethoprim-sulfamethoxazole can 29 of 236 patients were HIV+. Of the HIV+ patients who had a dis-
also cause myelosuppression and pancytopenia. integrin and metalloproteinase with a thrombospondin type 1 motif,
member 13 (ADAMTS 13) activity of less than 5 percent, outcome was
very similar to HIV– patients with a low ADAMTS 13 activity. How-
Treatment of Anemia ever the HIV+ patients with an ADAMTS 13 activity of greater than 5
Initiation of ART is the optimal treatment for HIV-associated anemia. percent tended to have far advanced HIV with a median CD4 count of
If a specific cause of anemia is identified, such as parvovirus B19, spe- 30 cells/μL, more infectious complications present at the diagnoses of
cific treatment can be provided. Early clinical trials demonstrated that thrombotic microangiopathy, multiple AIDS-associated complications,
erythropoietin treatment in anemic HIV+ patients taking zidovudine and a high mortality. Thus the outcome of TTP in HIV+ patients can
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can improve the hemoglobin and decrease red blood cell transfusion be excellent in patients without advanced HIV when treated promptly
requirements, although responses were confined to patients with with plasmapheresis/plasma exchange and ART.
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an endogenous erythropoietin level of 500 mU/mL or less. 262,263 Since
zidovudine is no longer commonly used as a component of ART, the
use of erythropoietin has declined. Nevertheless, treatment of anemia HUMAN IMMUNODEFICIENCY
caused by zidovudine in patients with HIV and an erythropoietin level
of 500 mU/mL or less is an FDA-approved indication for erythropoie- VIRUS–ASSOCIATED THROMBOCYTOPENIA
tin. However, a Cochrane analysis that included six studies and more In the pre-ART era, approximately 10 to 30 percent of people living
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than 500 anemic HIV+ patients treated with erythropoietin or placebo with HIV had thrombocytopenia, defined as a platelet count of less
concluded that erythropoietin did not reduce the risk of death and did than 150,000/μL, and thrombocytopenia was the initial manifesta-
not have a clear effect on quality of life. Additionally, erythropoietin tion of HIV in approximately 10 percent of patients. Those whose risk
has side effects including the potential to exacerbate hypertension, factor for HIV was intravenous drug abuse had a higher incidence of

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