Hematologic Sequelae Viral illness:Parvovirus,Epstein-Barr Virus,HIV

4th Pediatric Infectious Diseases Conference

ISSN 0973 - 0958

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HEMATOLOGICAL MANIFESTATIONS OF SYSTEMIC ILLNESS

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Systemic and Chronic Illnesses and Infections

Bone Marrow Infiltration

Dr. Bharat R. Agarwal
Pediatric Hematologist-Oncologist, Division of Pediatric Hem-Onco,
B.J. Wadia Hospital for Children

Viral Illnesses with Marked
Hematologic Sequelae :

Parvovirus :
Parvovirus B19 is associated with transient erythroblastopenic crisis, particularly in individuals with an underlying hemolytic disorder. In addition, it can produce thrombocytopenia, neutropenia, and a hemophagocytic syndrome. In immunocompromised individuals, parvovirus B19 infection can produce prolonged aplasia.
Epstein-Barr Virus :

Epstein-Barr Virus (EBV) infection is associated with the following hematologic manifestations :-
- Atypical lymphocytosis
- Acquired hemolytic anemia
- Agranulocytosis
- Aplastic anemia
- Lymphadenopathy and splenomegaly
- Immune thrombocytopenia
Epstein-Barr virus infection also has immunologic and oncologic associations :
- X-linked lymphoproliferative syndrome is associated with fatal EBV infection, acquired hypogammaglobulinemia, and lymphoma.
- EBV has also been associated with clonal T-cell proliferations.
- EBV can produce an acquired hemophagocytic syndrome.
- EBV is associated with the endemic form of Burkitt's lymphoma in Africa.
Human Immunodeficiency Virus :
The main pathophysiology of human immunodeficiency virus (HIV) infection is a constant decline in CD4+ lymphocytes, leading to immune collapse and death. The other bone marrow cell lines also decline in concert with CD4+ cell numbers as HIV disease (acquired immunodeficiency syndrome [AIDS]) progresses.

HIV infection has the following hematologic manifestations :

Thrombocytopenia : Thrombocytopenia occurs in about 40% of patients with AIDS. Initially, the clinical findings resemble those of immune thrombocytopenic purpura (ITP). Some degree of splenomegaly is common and the platelet-associated antibodies are often in the form of immune complexes that may contain antibodies with anti-HIV specificity. Megakaryocytes are normal or increased and production of platelets is reduced in the bone marrow.

Thrombotic thrombocytopenic purpura (TTP) is also associated with HIV disease. This occurs in advanced AIDS.
Anemia and neutropenia : HIV-infected individuals develop progressive cytopenia as immunosuppression advances. Anemia occurs in approximately 70-80% of patients and neutropenia in 50%. Cytopenias in advanced HIV disease are often of complex etiology and include the following:
- A production defect appears to be most common.
- Antibody and immune complexes associated with red and white cell surfaces may contribute. Up to 40% have erythrocyte-associated antibodies. Specific antibodies against i and U antigens have occasionally been noted. About 70% of patients with AIDS have neutrophil-associated antibodies.
The pathogenesis of the hematologic disorders include :-

Infections : Myelosuppression is frequently caused by involvement of the bone marrow by infecting organisms (e.g. mycobacteria, cytomegalovirus [CMV], parvovirus, fungi, and rarely, Pneumocystis carinii).

Neoplasm : Non-Hodgkin's lymphoma (NHL) in AIDS patients is associated with infiltration of the bone marrow in up to 30% of cases. It is particularly prominent in the small, non-cleaved, histologic subtype of NHL.

Medication : Widely used antiviral agents in AIDS patients are myelotoxic, for example, zidovudine (AZT) causes anemia in approximately 29% of patients. Ganciclovir and trimethoprim / sulfamethoxazole or pyrimethamine / sulfadiazine cause neutropenia. In general, bone marrow suppression is related to the dosage and to the stage of HIV disease. Importantly, the other nucleoside analogues of anti-HIV compounds (dideoxycytidine [ddC], dideoxyinosine [ddI], stavudine [d4T], or lamivudine [3TC], are usually not associated with significant myelotoxicity.