The haematological features of HIV infection

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The haematological features of HIV infection

• British Journal of Haematology, 1997, 99, 1-8
• Review article
• B. J. Bain

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Why?

• With the continuing rise in the prevalence of HIV
  world-wide, knowledge of the haematological
  features of HIV infection and AIDS is becoming
  increasingly important.

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The haematological features of HIV infection

• Infection by the HIV and the consequent fully
  developed AIDS can have profound haematological
  effects in
• the primary infection period
• the phase of clinical latency, and
• patients with advanced disease

4
Causes of the haematological changes

• The haematological abnormalities may be
  attributable to the
• Direct and indirect effect of HIV infection
• opportunistic infections
• Toxicity of the drugs

5
Diagnostic confusion

• It is important for the haematologist to be aware
  of the features of HIV infection and AIDS since
  diagnostic confusion can otherwise occur.
• HIV infection can simulate the
• MDS
• MPD, and
• T-cell lymphoma

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Primary infection

• Brief febrile illness
• Pharyngitis and cervical lymphadenopathy are
  common, simulate infectious mononucleosis.
• Initial lymphopenia
• Followed by lymphocytosis with atypical
  lymphocytes.
• False positive Paul Bunnell test.
• Neutropenia, thrombocytopenia and transient
  pancytopenia can also occur.

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Established infection

• Primary infection is followed by a period of
  clinical latency or asymptomatic infection.
• Isolated thrombocytopenia as a result of immune
  destruction of platelets can occur.
• There is increased platelet associated Ig.

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General haematological features of AIDS

• Peripheral blood
• During the asymptomatic period, there is
• Gradual fall in the number of CD4 lymphocytes
• Initial increase in CD8 lymphocytes
• By the time of diagnosis there is
• Lymphopenia
• Often pancytopenia
• Anaemia which is usually normochromic, normocytic
  but sometimes macrocytic.

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Peripheral blood changes

• Red cell changes
• Anisocytosis,
• poikilocytosis,
• rouleaux formation
• increased background staining.
• Occasionally the blood film shows features of
  microangiopathic haemolytic anaemia.

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Peripheral blood changes

• Neutrophils may show dysplastic features
• toxic granulation
• Dohle bodies
• cytoplasmic vacuolation
• left shift
• presence of detached nuclear fragments
• hypogranularity and occasional Pelger forms

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Neutrophil with a detached nuclear fragment
in AIDS

• a detached nuclear fragment can be seen in
  AIDS patients
• It can also be caused by multi-agent cytotoxic
• chemotherapy

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Peripheral blood changes

• Thrombocytopenia , usually normal size platelets.
• Except when there is immune destruction, large
  size platelets may be seen.

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Bone marrow aspirate

• It is initially hypercellular, but is
  hypocellular in the later stages.
• Trilineage dysplasia is common.

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Bone marrow aspirate

• Changes in the erythrocytes include
• Nuclear lobulation and fragmentation
• Howell-Jolly bodies
• Bi- and multi-nuclearity
• Cytoplasmic bridging
• Cytoplasmic vacuolation
• Basophilic stippling
• Megaloblastosis.
• Occasional ring sideroblasts.

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Bone marrow aspirate

• Changes in the myeloid series include
• Dysplastic changes
• Giant metamyelocytes are common even in the
  absence of megaloblastic erythropoiesis.

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Giant metamyelocyte

• A hypogranular giant metamyelocyte in the
  peripheral
• blood of a patient with AIDS.

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Bone marrow aspirate

• Changes in megakaryopoiesis
• Megakaryocytes are increased early in the disease
  and decreased in the later stages.
• They show dysplastic features
• Bizzare nuclear shapes
• Hyperchromatic nuclei
• Nuclear hypolobulation

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Bone marrow aspirate

• Reactive changes include
• Increased lymphocytes
• Increased plasma cells
• Increased macrophages
• Haemophagocytic syndrome

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Differences between HIV and MDS in the BMA

• In HIV
• Ring sideroblasts are not a prominent feature
• Myeloblasts are not increased
• Micromegas are not common
• Auer rods are not seen

• In MDS
• Giant metamyelocytes (common in AIDS) are quite
  uncommon in MDS.

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Bone marrow trephine biopsy

• Initially shows hypercellularity with neutrophil
  and megakaryocytic hyperplasia.
• Megakaryocytes are clustered and dysplastic
• There is increased number of bare megakaryocyte
  nuclei.

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Bone marrow trephine biopsy in AIDS showing
dysplastic megakaryocytes (H E)

• The megakaryocytes are hypolobulated and
  clustered.

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Bone marrow trephine biopsy

• Reticulin is often increased.
• Late in the course of the disease the trephine
  biopsy will show hypocellular BM with gelatinous
  degeneration
• Patches of necrosis
• Patients with specific infections may show BM
  granulomas.
• Lymphomatous infiltration

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A random focal lymphoid infiltrate (H E)

• A random focal lymphoid infiltrate arrow in
  a patient with AIDS.

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Specific infections in AIDS

• Opportunistic infections are very common in AIDS,
  among these are
• Mycobacterial and other bacterial infections
• Mycobacterium tuberculosis
• Atypical mycobacterial infection
• Mycobacterium avium intracellulare

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• The bone marrow in patients with mycobacterial
  infection may show well-formed, or less formed
  granulomas.
• Caseation may occur in tuberculous granulomas.
• Sometimes there is marked proliferation of foamy
  macrophages
• Culture for mycobacteria is obligatory whenever a
  BM examination is performed to investigate fever
  of unknown origin in an HIV patient.

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Trephine biopsy in atypical mycobacterial
infection

• Trephine biopsy stained with a Giemsa stain,
  showing faintly
• staining organisms within the foamy
  macrophages.

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Trephine biopsy in atypical mycobacterial
infection (H E)

• Poorly formed granuloma composed of epithelioid
• macrophages, many of which have
• vacuolated cytoplasm.
• This infection is only
• likely to be detected on bone marrow examination
  of severely immunosuppressed individuals.

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Other opportunistic infections

• Viral infections
• CMV infection is common in AIDS
• BM features are non specific, with atypical
  lymphocytes and haemophagocytosis
• Parvovirus B19
• This might lead to chronic red cell aplasia
• There is disproportionate anaemia with
  reticulocyte count close to zero
• BMA TB show red cell aplasia and giant
  proerythroblast.
• Confirmed by detection of viral DNA in the serum.

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Other opportunistic infections

• Fungal infections
• Sometimes detected in BMA either within the
  macrophages or free
• But more readily detected in the trephine biopsy
  specimen.
• A cryptococcal antigen test on the PB is a very
  good screening test for cryptococcosis, and PB
  cultures are often positive in HIV pt with
  fungal infections these tests may make marrow
  exam unnecessary.

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Bone marrow aspirate in AIDS showing
Cryptococcus neoformans

• Bone marrow aspirate in AIDS showing a
  budding form of Cryptococcus neoformans.

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Bone marrow aspirate in AIDS showing
Histoplasma capsulatum

• - Bone marrow aspirate in a patient with AIDS
  with histoplasmosis
• showing histoplasma within a macrophage.
• - Histoplasma are small yeast forms.

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Other opportunistic infections

• Parasitic infections
• Leishmaniasis is usually readily detected in BMA
  TB
• Toxoplasmosis
• American trypanosomiasis
• Rarely Pneumocystis carinii has been detected in
  the BM of pt with AIDS.

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Leishmania donovani in a monocyte

• Blood film in a patient with AIDS
• showing Leishmania donovani in a monocyte.
• Leishmania in circulating monocytes or
  neutrophils is rarely seen except in patients
  with AIDS.

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Lymphoproliferative disorders in AIDS

• The incidence of NHL is increased 60-200 fold in
  pt with AIDS.
• The incidence of HD may be increased to 8-fold

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NHL in AIDS patients

• The great majority are of B-lineage.
• The strongest association is with
• Burkitt lymphoma
• Burkitt like lymphoma
• Large cell lymphoma of B-lineage
• Persistant generalized lymphadenopathy often
  precedes the development of lymphoma and is
  indicative of increased risk of development of
  lymphoma.

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HD in AIDS patients

• It usually presents in patients in advanced
  stage.
• Often with B symptoms.
• Bone marrow infiltration
• The TB may be the initial or the only diagnostic
  material.
• Histopathology often shows poor prognostic types
  ( MC, or LD).

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conclusions

• HIV infection is associated with a great variety
  of haematological abnormalities.
• HIV pt may have abnormalities due to drug therapy
  or opportunistic infections.
• Diagnostic confusions specially with MDS can
  occur.
• BMA TB have a role in the diagnosis of
  opportunistic infections and of lymphoma.

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conclusions

• Certain features are common although not
  pathognomonic of HIV infection, but sufficient to
  suggest this diagnosis
• numerous bare megakaryocyte nuclei
• polymorphic lymphoid aggregates
• gelatinous degeneration
• detached nuclear fragments in granulocytes
• giant metamyelocytes in the absence of
  megaloblastosis.

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