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

thrombocytopenia, attributed to increased coinfection with hepatitis C TABLE 81–10. Pancytopenia in Human
and hepatic cirrhosis. A British study evaluated selective testing for HIV
in patients who presented with specific medical conditions, including Immunodeficiency Virus
thrombocytopenia. They found an increased rate of HIV infection in • Advanced HIV with high viral load
patients presenting with thrombocytopenia, providing a rationale for • Medication side effect
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including HIV testing in the evaluation of patients presenting with iso- • Malignancy in the marrow
lated thrombocytopenia. In the ART era, 26 percent of 5290 patients • Non-Hodgkin lymphoma, Hodgkin lymphoma
followed at the British Columbia Center for Excellence in HIV/AIDS
had at least one platelet count less than 100,000/μL, and 3 percent had • Infection in the marrow
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at least one platelet count less than 20,000/μL. A study of the fre- • Mycobacterium avium complex, histoplasmosis, cytomegalovi-
quency and severity of thrombocytopenia in a large cohort of patients rus, Mycobacterium tuberculosis
in the Collaboration in HIV Outcomes Research/U.S. study (CHORUS) • Castleman disease
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included 6300 HIV+ people from 1997 to 2006 and found a preva- • Hemophagocytic syndrome
lence of thrombocytopenia (platelet count <150,000/μL) of 14 percent. • Alcohol abuse
However, this cohort excluded patients who had hepatitis C or hepati- • Vitamin B or folate deficiency
tis B infection, so the prevalence of thrombocytopenia would likely be 12
higher if these patients had been included. In this study, 3.1 percent
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of patients had a platelet count of 50,000/μL or less, and 1.7 percent
of patients had a platelet count of 30,000/μL or less. The majority of may also have a component of low-grade disseminated intravascular
patients with severe thrombocytopenia who had not started ART had coagulation.
a CD4 count greater than 200 cells/μL, demonstrating that thrombocy- Evaluation of thrombocytopenia in HIV+ patients is similar to
topenia can occur prior to severe immunodepletion. These data are con- HIV– patients and should include a thorough history and physical
sistent with the findings of the British Columbia Center for Excellence exam looking for symptoms and signs of platelet-type bleeding, to
in AIDS/HIV study, in which the CD4 count at diagnosis of ITP was 200 assess the clinical severity of the thrombocytopenia. The blood film
or greater in 72 percent of patients. 271 should be reviewed to confirm that the patient does have low platelets,
Mild thrombocytopenia also occurs during primary HIV infec- rather than platelet clumping, and to evaluate for abnormalities in red
tion, a time of unfettered HIV replication and intense immune acti- blood cell and white blood cell numbers and morphology. If not already
vation. In one study of 957 patients evaluated during primary HIV done, the patient should be tested for hepatitis C. The HIV viral load
infection, 9.7 percent had a platelet count of less than 150,000/μL, 2.3 and CD4 count should be determined, as noncompliance or develop-
percent had a platelet count of less than 100,000/μL, and none had a ment of resistance to the current ART regimen can exacerbate HIV-
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platelet count of less than 50,000/μL. Of those who started ART, the associated thrombocytopenia. The patient should be asked what percent
time to platelet recovery was approximately 1 month. Of those who did of the patient’s HIV medications are taken, or alternatively how many
not start ART, the time to platelet recovery was just under 2 months. missed doses the patient has had in the past month. The medication list,
Those who developed thrombocytopenia during acute HIV infection including nonprescription medications, naturopathic medications, and
had a threefold higher incidence of developing a low platelet count in dietary supplements, should be thoroughly reviewed. The differential
the next 3 years (13.3 percent) in comparison to those who maintained diagnosis for isolated thrombocytopenia includes HIV-associated ITP,
a normal platelet count throughout. Thus, most patients who develop hepatitis C-associated ITP, Helicobacter pylori–associated ITP, medica-
thrombocytopenia during primary HIV infection recover quickly, even tion side effect, or antiphospholipid antibody syndrome. If the patient
if ART is not started immediately. A study to evaluate the risk factors also has anemia, immunohemolytic anemia with ITP (Evans syndrome)
for HIV-associated thrombocytopenia included 73 HIV+ people with or TTP should be considered. In a febrile and ill patient who has addi-
a platelet count of less than 100,000/μL for 3 months matched to 73 tional cytopenias, Castleman disease and hemophagocytic syndrome
nonthrombocytopenic controls. Identified risk factors were an HIV should be included in the differential diagnosis (Table 81–10).
viral load of greater than 400 copies/mL, hepatitis C coinfection, and
cirrhosis. The platelet count correlated inversely with the viral load in
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a study of 207 patients naïve to ART. 275 Treatment of Human Immunodeficiency Virus–Associated
Platelet kinetic studies demonstrate shortened platelet survival Idiopathic Thrombocytopenic Purpura
in HIV+ patients not on ART (92 hours) compared to HIV– healthy ART improves the platelet count in patients with HIV-associated ITP
volunteers (198 hours). Even HIV+ patients with normal platelet over a period of approximately 3 months in the majority of patients. 278–280
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counts had modestly diminished platelet survival in these studies as The primary treatment of HIV-associated ITP is initiation of ART if the
well as decreased platelet production in comparison to HIV– normal patient is not on ART, and assessment of the effectiveness of ART if the
volunteers. As discussed above, some human hematopoietic progeni- patient is taking ART. Reasons for failure of ART include suboptimal
tor cells can be infected with HIV in vivo, and these cells demonstrate compliance with the medications, as the ability of ART to control the
impaired megakaryopoiesis in vitro. Additionally megakaryocytes HIV viral load is related to adherence. Alternatively, the patient’s HIV
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can be infected with HIV and these observations may contribute to may have developed ART resistance which can be detected by resis-
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the decreased production of platelets in the marrow of HIV+ individ- tance testing. Close communication between the hematologist and the
uals. The more frequent and severe thrombocytopenia seen in patients infectious disease/HIV physician is essential for optimal management
with HIV and hepatitis C coinfection can be explained by the increased of these issues.
risk of cirrhosis in people coinfected with HIV and hepatitis C. The Because ART typically takes 3 months to improve the platelet
combined effects of diminished production of thrombopoietin, the count, additional interventions are needed if the patient is experienc-
major thrombopoietic growth factor, together with portal hyperten- ing severe thrombocytopenia (platelets <20,000/μL) or has platelet-type
sion, splenomegaly, and sequestration of platelets in the enlarged spleen bleeding. If the patient is Rh+ and has an intact spleen, intravenous
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can result in severe thrombocytopenia. Patients with severe liver failure anti-D can be very effective. In a study that included both HIV+ and

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