Page 2551 - Hematology_ Basic Principles and Practice ( PDFDrive )

2274 Part XIII Consultative Hematology

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thrombocytopenia (HIV-ITP), platelet count <150 × 10 /L) was thrombocytopenia developing early after infection more often
identified in approximately 5% to 30% of HIV-1 infected patients. resembles classic ITP in which thrombocytopenia is mediated pri-
Thrombocytopenia is more prevalent in patients with advanced HIV marily by peripheral destruction, whereas thrombocytopenia in
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infection defined as a CD4-lymphocyte count of <0.2 × 10 /L, clini- patients with immunologic AIDS (CD4 lymphocytes <2 × 10 /L) is
cal AIDS, and among intravenous drug abusers. The Multicenter attributable predominantly to decreased platelet production and
AIDS Cohort Study of 1611 HIV-positive homosexual and bisexual ineffective hematopoiesis. Although platelet counts may improve
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men reported a platelet count of <150 × 10 /L in 6.7%. The inci- with antiretroviral therapy in both patient populations, patients with
dence of thrombocytopenia was only 2.8% in men with CD4 lym- advanced disease are less likely to respond to classic primary ITP
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phocyte counts >0.7 × 10 /L, but rose to 10.8% in those with CD4 therapy such as splenectomy, corticosteroids, IVIg or anti-RhD.
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lymphocyte counts of <0.2 × 10 /L. A review of 1004 HIV-infected Initial studies of HIV- associated ITP suggested an immune complex
patients seen in two HIV/AIDS clinics, identified platelet counts of mechanism was responsible for the thrombocytopenia, wherein
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<150 × 10 /L on at least one determination in 110 (11%) patients, platelets were cleared from the circulation as “innocent bystanders.”
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42 (4.2%) patients had platelet counts of <100 × 10 /L and 15 More recent studies have shown that these immune complexes
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(1.5%) had a platelet count of <50 × 10 /L. Thrombocytopenia was contain antibodies that cross-react with both HIV and platelet GPs.
+
more prevalent in patients with a clinical AIDS (21.2%) and a CD4 These antibodies also cross-reacted with sequences on HIV nef, gag,
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lymphocyte count of <0.2 × 10 /L (20%). env, and pol proteins. Similar cross-reactivity between HIV viral
A review of the medical records of 36,515 HIV-infected partici- proteins and platelet GPs has been reported in the studies of Bettlaieb
pants in the Multistate Adult and Adolescent Spectrum of Disease and coworkers who eluted Ig from platelets from patients with HIV-
Project reported a 1-year incidence of thrombocytopenia of 3.7%, associated ITP and found these antibodies bound to antigenic epitopes
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defined as a platelet count of <50 × 10 /L. The incidence and severity common to both platelet GPIIIa and HIV GP160.
of thrombocytopenia was associated with the stage of disease with an Studies of platelet kinetics have demonstrated that HIV-ITP is
incidence of 1.7% among patients with HIV infection, but not clini- frequently associated with decreased platelet production. Megakaryo-
cal or immunologic AIDS, 3.1% among persons with immunologic cytes express the CD4 receptor and coreceptors necessary for HIV
+
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AIDS (CD4 lymphocytes<0.2 × 10 /L) and 8.7% in patients with infection. Cytopathic infection of HIV of the megakaryocyte has
clinical AIDS. By logistic regression analysis, clinical AIDS, CD4 been demonstrated and is the postulated primary mechanism for
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lymphocyte count of <0.2 × 10 /L, age >45 years, intravenous drug impaired megakaryopoiesis. However, the potential of cross-reactive
use, lymphoma and/or anemia was associated with a platelet count antibodies between HIV-related proteins and platelet GPs capable of
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<50 × 10 /L. inducing apoptosis of megakaryocytes as has been described with
An increased incidence and severity of thrombocytopenia in HIV- primary ITP has not been studied.
infected intravenous drug users compared with HIV infected
homosexuals has been reported. Mientjes et al reported a platelet
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count of <150 × 10 /L in 29/182 (16.4%) homosexual HIV-infected Clinical Manifestations
men compared with 38/181 (36.9%) HIV-infected intravenous drug
users. None of the homosexual men had a platelet count of <50 × HIV-seropositive patients can develop thrombocytopenia several
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10 /L, whereas 6 (5.8%) of intravenous drug users had a count of years before the development of overt AIDS, and the early disease is
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<50 × 10 /L. These differences may be explained, in part, by the clinically indistinguishable from classic ITP. However, the clinical
higher incidence of coinfection with hepatitis C and underlying liver picture of HIV-ITP is often mild, with only a minority of patients
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disease in HIV-infected intravenous drug users. having platelet counts of less than 50 × 10 /L. Major bleeding is rare
In a prospective multicenter cohort study of 738 HIV infected and only a few cases of fatal hemorrhage have been reported. There
hemophilia patients, the incidence over time of HIV-related condi- has been greater variability in patients with hemophilia A. For
tions was determined in 130 children and 193 adults. The 10-year example, Finazzi and coworkers documented thrombocytopenia
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cumulative incidence of thrombocytopenia (platelets <100 × 10 /L) (platelets <100 × 10 /L) in 14/124 (11%) hemophiliacs, only one of
after seroconversion was 43% ± 7% in adults and 27% ± 6% in whom had a major hemorrhage. In contrast, Ragni and colleagues
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children. The mean CD4 counts were significantly higher in children reported a platelet count of <100 × 10 /L in 30/87 (36%) hemo-
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(514 ± 61 cells/µl) than adults (260 ± 24 cells/µl) with thrombocy- philiac patients, with 11 (13%) having a platelet count <50 × 10 /L.
topenia (p = .0004). Nine of the 11 patients (82%) had major bleeding complications and
Most clinical data have been obtained before the widespread use 3 suffered fatal hemorrhage.
of HAART in patients with early HIV-infection. There are few data Severe thrombocytopenia in patients with advanced HIV infec-
on the current prevalence of thrombocytopenia in patients under tion is frequently associated with additional cytopenias. In a study of
active antiviral treatment. However, recent prospective data from the 52 HIV-infected intravenous drug users with thrombocytopenia, 4
Women’s Interagency HIV study have documented a reduction in the patients (8%) with advanced HIV infection had a hypocellular bone
incidence of anemia and neutropenia in HIV-infected women on marrow examination and pancytopenia. HIV-infected drug users
HAART. These findings are in accord with the impression that there were also more likely to have antibodies to both hepatitis B and C
has been a similar reduction in the incidence of thrombocytopenia, and to have abnormal liver function studies. The role of immune-
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especially platelet counts <50 × 10 /L in compliant patients. mediated platelet destruction versus bone marrow failure in patients
with advanced HIV disease is still uncertain.
Pathophysiology
Treatment of HIV-Associated Immune
Multiple mechanisms may contribute to the development of CITP Thrombocytopenia
in the HIV-infected patient and these have recently been reviewed.
Proposed mechanisms include accelerated platelet clearance because HIV-associated ITP is generally responsive to therapeutic interven-
of immune complex disease, and anti-platelet GP antibodies, and/or tions used in classic ITP. Therapy with prednisone produces a major
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anti-HIV antibodies that cross-react with platelet membrane GPs hematologic response (platelet count >100 × 10 /L) in over half of
(antigenic mimicry). The ability of the HIV-1 to rapidly mutate may all patients, although only a minority will maintain platelets >50 ×
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facilitate both its ability to escape immune surveillance and to mimic 10 /L after cessation of steroids. Despite the initial anxiety regarding
host antigens. Direct infection of megakaryocytes results in defective the use of corticosteroids in HIV-infected, immune-suppressed
platelet production and megakaryocytic apoptosis. patients, no deleterious effect of short-term treatment with predni-
Epidemiologic studies suggest that the pathogenesis of thrombo- sone have become evident. However, long-term treatment with
cytopenia is partially dependent on disease burden. HIV-associated corticosteroids should still be avoided and other coinfections such as