Hematologic Manifestations of HIV/AIDS

Published on 04/03/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 6927 times

Chapter 71 Hematologic Manifestations of HIV/AIDS

Howard A. Liebman, Anil Tulpule

Peripheral Blood Smear and Bone Marrow Morphology in HIV/AIDS

The peripheral blood smear of a patient with HIV/AIDS might show anisocytosis, poikilocytosis, and rouleaux formation. Anemia when present is usually normocytic and normochromic. Sometimes macrocytic anemia can be seen even in the absence of zidovudine therapy. Lymphopenia is seen in advanced disease. Hypogranular neutrophils and Pelger-Huët forms are rarely present. Platelets can be normal or hypogranular. In cases of thrombocytopenia the platelets can be normal-sized or large when thrombocytopenia is due to immune destruction with preserved marrow function.

The bone marrow is usually hypercellular but can be normocellular or hypocellular. Interstitial and perivascular polyclonal plasmacytosis is usually present. HIV-associated stromal changes include edema, gelatinous transformation, and increased reticulin fibers (dense collagen fibers are not a feature of HIV). Normal bone marrow architecture is often disturbed, and dysplastic changes can be seen, including dyserythropoiesis, dysgranulopoiesis, and abnormal megakaryocytes (including clusters and bare megakaryocytic nuclei). However, the following features distinguish the bone marrow morphology in HIV from that of myelodysplastic syndrome (MDS): Dysplasia is less severe in HIV. Dyserythropoiesis occurs mainly in patients on highly active antiretroviral therapy (HAART). Megaloblastic changes are associated with zidovudine therapy. Whereas erythropoiesis is usually hyperplastic in MDS, myeloid/erythroid ratio is usually normal in HIV. Increased blasts can be seen in MDS but never in HIV. Lastly, in contrast to MDS, the basement membrane in HIV often shows eosinophilia, lymphohistiocytic infiltrates, and plasmacytosis.

AIDS, Acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.

Figure 71-1 TYPICAL PERIPHERAL BLOOD AND BONE MARROW FINDINGS IN HIV.

The peripheral smear not uncommonly shows anemia, which is sometimes macrocytic (A), but can be normochromic and normocytic. There frequently is a neutrophilia with left shift, toxic granulation, and some mild dysplastic change in the granulocytes (B). In some patients, particularly those with severe disease, some of the segmented neutrophils show cytoplasmic inclusions similar to Howell-Jolly bodies seen in red cells (B, top, right cell). These are nuclear in origin and are not microorganisms. The bone marrow can show granulocytic hyperplasia with left shift and megaloblastoid change in the myeloid and erythroid cell lines (C). Typically, there is also a reactive plasmacytosis (D). The biopsy specimen can be hypocellular, normocellular, or hypercellular (E) and commonly shows cellular atypia/dysplasia (insert) and atypical reactive lymphoid infiltrates (F), poorly formed (G) or well-formed granuloma (H), and increased plasma cells (I).

Figure 71-2 ACID-FAST ORGANISMS IN GRANULOMA.

Large poorly formed granuloma in the bone marrow (A), is composed of loosely aggregated histiocytes, lymphocytes, and plasma cells (B), with occasional giant cells (C). The acid-fast stain shows rare elongated, slightly beaded organisms, typical of Mycobacterium tuberculosis (D, top). In Mycobacterium avium complex, the organisms frequently stuff histiocytes (D, bottom).

Figure 71-3 BURKITT LYMPHOMA INVOLVING THE BONE MARROW OF A PATIENT WITH ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS).

(Zhao X, Sun NC, Witt MD, et al: Changing pattern of AIDS: A bone marrow study. Am J Clin Pathol 121:393, 2004.)

Figure 71-4 CLASSIC HODGKIN LYMPHOMA INVOLVING THE BONE MARROW OF A PATIENT WITH ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS).

(Zhao X, Sun NC, Witt MD, et al: Changing pattern of AIDS: A bone marrow study. Am J Clin Pathol 121:393, 2004.)

Table 71-1 Surveillance Case Definition for HIV Infection in Adults and Adolescents (Age Over 13 Years)

Stage	Laboratory Evidence	Clinical Evidence
Stage1	Laboratory confirmation of HIV infection and CD4⁺ T-lymphocyte count of ≥500 cells/µL or CD4⁺ T-lymphocyte percentage of ≥29*	No AIDS-defining condition (see Table 71-2)
Stage 2	Laboratory confirmation of HIV infection and CD4⁺ T-lymphocyte count of 200-499 cells/µL or CD4⁺ T-lymphocyte percentage of 14-28*	No AIDS-defining condition (see Table 71-2)
Stage 3	Laboratory confirmation of HIV infection and CD4⁺ T-lymphocyte count of <200 cells/µL or CD4⁺ T-lymphocyte percentage of <14*	Documentation of an AIDS-defining condition with laboratory confirmation of HIV infection (see Table 71-2)
Stage unknown	Laboratory confirmation of HIV infection and no information on CD4⁺ T-lymphocyte count or percentage	No information on presence of an AIDS-defining condition

AIDS, Acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.

^*The CD4⁺ T-lymphocyte percentage is the percentage of the total lymphocyte count.

Table 71-2 Surveillance Definitions of AIDS-Defining Conditions

AIDS, Acquired immunodeficiency syndrome.

Anemia in HIV/AIDS

Anemia can occur at any stage of HIV disease but is more frequent and severe in advanced disease. Anemia in HIV disease is independently associated with an increased risk for disease progression and mortality. In general, the etiology of anemia seen in HIV infection is often multifactorial, with several mechanisms playing a role in an individual patient. Anemia could be due to decreased red blood cell (RBC) production, ineffective RBC production, or increased RBC destruction. A methodical workup of anemia in a patient with HIV should be similar to that for anemia in the HIV-negative individual.

The most common cause of anemia in HIV disease is decreased RBC production. Frequently encountered mechanisms responsible for decreased RBC production in patients with HIV include anemia of acute and chronic inflammation (chronic disease anemia), infection or infiltration of bone marrow by infectious agents such as atypical mycobacterium, tuberculosis, cytomegalovirus, and/or fungal organisms or malignancies such as lymphoma. Parvovirus B19 can cause isolated red cell aplasia in the more severely immunocompromised individuals. Medications used for treatment of HIV or other illnesses and for prophylaxis of opportunistic infections can cause anemia mostly due to decreased RBC production. The list of medications as in Tables 71-3 and 71-4 is extensive. Hence it is very important that a thorough review of all the medications is done. Nutritional deficiencies, including vitamin B₁₂ and folic acid deficiency, are causes of anemia due to ineffective production.

Other causes of anemia include anemia secondary to blood loss or hemolysis. Causes of hemolysis include medications such as sulfonamides and dapsone in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, thrombotic thrombocytopenic purpura or hemophagocytic syndrome. Patients with advanced HIV infection (AIDS) appear to acquire gastrointestinal defects resulting in B₁₂ malabsorption.

Diagnosing the cause or causes of anemia is essential to proper therapy. Treatment of anemia should be directed toward correcting the underlying cause whenever possible. The use of blood transfusion should be minimized and reserved for patients who have rapid decreases in hemoglobin levels, extremely low hemoglobin levels, or pronounced anemia-related symptoms. Antiretroviral medication combinations (highly active antiretroviral therapy [HAART]) have shown that suppression of HIV replication is associated with improvement in anemia. Erythropoietin supplementation has been shown to be beneficial in HIV-infected patients with well-established anemia and when the hemoglobin level is decreasing or has decreased slowly. The primary goal of treating anemia should be to maintain quality of life and functional status.

AIDS, Acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.

Figure 71-5 HUMAN PARVOVIRUS INFECTION IN HIV.

The peripheral blood smear shows anemia with no polychromasia (A). The marrow biopsy shows mostly granulocytic and megakaryocytic elements with a lack of erythroid forms (B), except for rare large pronormoblasts with nuclear inclusions (B, center). On the aspirate, the large degenerating pronormoblasts have nuclear inclusions that resemble large nucleoli (C). These are viral inclusions. Sometimes the pronormoblasts are totally degenerated and present as only bare nuclei with the viral inclusion still obvious (C, right). An immunostain for parvovirus in a degenerated pronormoblast is illustrated (D).

Table 71-3 Hematologic Toxicities of Antiretroviral Agents

Table 71-4 Agents for Treatment and Prevention of Opportunistic Infections With Hematologic Toxicities

Drug Class	Drug Toxicities	Hematologic
Antifungal agents	Amphotericin B deoxycholate and lipid formulations	Anemia
	Anidulafungin	Deep venous thrombosis (rare)
	Flucytosine	Bone marrow suppression
	Micafungin	Hemolysis, leukopenia
Anti-Pneumocystis pneumonia (PCP) agents	Dapsone	Methemoglobinemia, hemolytic anemia (especially in patients with G6PD deficiency), neutropenia
	Primaquine	Methemoglobinemia, hemolytic anemia (especially in patients with G6PD deficiency)
	Trimethoprim-sulfamethoxazole (TMP-SMX)	Bone marrow suppression
Antitoxoplasmosis agents	Pyrimethamine	Neutropenia, thrombocytopenia, megaloblastic anemia
	Sulfadiazine	Bone marrow suppression
Antimycobacterial agents	Rifampin	Thrombocytopenia, hemolytic anemia.
	Rifabutin	Neutropenia anemia, thrombocytopenia
Antiviral agents	Ganciclovir	Neutropenia, thrombocytopenia, anemia
	Interferon-α and peginterferon-α	Neutropenia, thrombocytopenia
	Ribavirin	Hemolytic anemia
	Valacyclovir	At a high dose of 8 g/day: thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported in advanced human immunodeficiency virus patients and in transplant recipients
	Valganciclovir	Neutropenia, thrombocytopenia, anemia
Antiparasitic agents	Albendazole	Neutropenia
	Benznidazole	Bone marrow suppression
	Fumagillin (investigational)	Oral therapy: neutropenia, thrombocytopenia Ocular therapy: minimal systemic effect or local effect
	Miltefosine	Leukocytosis, thrombocytosis
Treatment for syphilis	Pentavalent antimony (sodium stibogluconate)	Leukopenia, anemia, thrombocytopenia
	Penicillin G	Bone marrow suppression (rare), drug fever

PCP, Pneumocystis carinii pneumonia.

Table 71-5 Etiology of Anemia in HIV

BM, Basement membrane; CFU-GEMM, colony-forming unit–granulocyte, erythrocyte, macrophage, megakaryocyte; HIV, human immunodeficiency virus, MAI/MAC, Mycobacterium avium-intracellulare/Mycobacterium avium complex; RT, reverse transcriptase.