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thrombocytopenic purpura (ITP) with increased megakaryocytes in the bone marrow along with
peripheral platelet destruction. Unlike classic ITP, however, men are more often affected, and
the antibodies are primarily directed against platelet glycoprotein IIIa (GPIIIa). There are also
increased numbers of CD5+ B lymphocytes producing IgM rheumatoid factor and anti-
GPIIIa.[209,839] Drugs induced myelosuppression with thrombocytopenia most often occurs
with antiretroviral drugs zidovudine and stavudine, but can complicate antibiotics including
acyclovir, amphotericin B, and trimethoprim-sulfamethoxazole. A myelophthisic process with
suppression of hematopoiesis can accompany widespread infections such as fungal and
mycobacterial diseases, as well as malignancies including lymphomas.[843]
Thrombotic microangiopathies (TMA), including hemolytic-uremic syndrome (HUS) and
thrombotic thrombocytopenic purpura (TTP), have been reported in persons with HIV infection.
The incidence appears to have decreased in the era of antiretroviral therapy. Thrombotic
microangiopathy is more likely to occur in persons who have lower CD4 lymphocyte counts and
who have other AIDS-related illnesses. At least four of the five classic findings
(thrombocytopenia, microangiopathic hemolytic anemia, neurologic changes, renal
manifestations, and fever) are present in most cases. Neurologic problems, including seizures,
and hemorrhagic complications are likely to be seen. The blood lactate dehydrogenase (LDH) is
elevated, as is serum creatinine. Proteinuria is common. A Shiga-like toxin producing
Escherichia coli may be found. Therapy with plasmapheresis is less likely to be successful with
TTP in HIV infection than with sporadic cases in non-HIV-infected persons.[844]
The pathologic findings in acute TMA lesions include occlusive thrombi in glomeruli and
small arteries and arterioles, detachment of glomerular endothelium from the basement
membrane, mesangiolysis, and widening of the glomerular subendothelial space widening. In
chronic TMA there is reduplication of glomerular capillary basement membranes from new
basement membrane synthesis and/or “splitting” of capillary walls. There can be segmental
sclerosis, tubular atrophy, and interstitial fibrosis. Arterioles and arteries may show onionskin
intimal reduplication. Microvascular thrombi can be highlighted with trichrome stain. In severe
vascular lesions cortical necrosis may occur.[844]
Etiologies for TMA in HIV infection appear heterogeneous, with some cases having
markedly reduced levels of ADAMTS13, with or without detectable inhibitor, while normal
levels were present in others. Direct viral or cytokine-mediated endothelial cell injury may play a
role in the pathogenesis of HIV-related TMA.[845]
Lymphopenia is present in about a third of AIDS cases due to the decrease in T4
lymphocytes. Neutropenia can be common in patients with AIDS and is a risk factor for both
bacterial and fungal infections. The most common cause for neutropenia is drug therapy, and the
drugs most often implicated are the antiretroviral agent zidovudine, the antibiotic combination of
trimethoprim-sulfamethoxazole, and the antiviral agent ganciclovir. Additional causes may
include chemotherapy for AIDS-related neoplasia and non-Hodgkin lymphomas. Neutrophilia
may indicate bacterial sepsis. Bone marrow failure leading to death in patients with AIDS is
very uncommon.[497,839,840,846]
Neutropenia that accompanies HIV infection can increase the risk for infection or worsen
the course of infection. Neutropenia can result from involvement of bone marrow by
opportunistic infections, from pharmacologic therapies such as trimethoprim-sulfamethoxazole,
and from direct effects of HIV through accelerated apoptosis. Both chemotaxis and phagocytic
functions of neutrophils also appear to be impaired. The use of granulocyte colony stimulating
factor (G-CSF) may aid in increasing neutrophil counts and preventing bacterial infections.[847]