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The haematological features of HIV infection

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presence of detached nuclear fragments. hypogranularity and occasional Pelger forms ... a detached nuclear fragment can be seen in AIDS patients ... – PowerPoint PPT presentation

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Title: The haematological features of HIV infection


1
The haematological features of HIV infection
  • British Journal of Haematology, 1997, 99, 1-8
  • Review article
  • B. J. Bain

2
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.

3
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

6
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.

7
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.

8
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.

9
Peripheral blood changes
  • Red cell changes
  • Anisocytosis,
  • poikilocytosis,
  • rouleaux formation
  • increased background staining.
  • Occasionally the blood film shows features of
    microangiopathic haemolytic anaemia.

10
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

11
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

12
Peripheral blood changes
  • Thrombocytopenia , usually normal size platelets.
  • Except when there is immune destruction, large
    size platelets may be seen.

13
Bone marrow aspirate
  • It is initially hypercellular, but is
    hypocellular in the later stages.
  • Trilineage dysplasia is common.

14
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.

15
Bone marrow aspirate
  • Changes in the myeloid series include
  • Dysplastic changes
  • Giant metamyelocytes are common even in the
    absence of megaloblastic erythropoiesis.

16
Giant metamyelocyte
  • A hypogranular giant metamyelocyte in the
    peripheral
  • blood of a patient with AIDS.

17
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

18
Bone marrow aspirate
  • Reactive changes include
  • Increased lymphocytes
  • Increased plasma cells
  • Increased macrophages
  • Haemophagocytic syndrome

19
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.

20
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.

21
Bone marrow trephine biopsy in AIDS showing
dysplastic megakaryocytes (H E)
  • The megakaryocytes are hypolobulated and
    clustered.

22
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

23
A random focal lymphoid infiltrate (H E)
  • A random focal lymphoid infiltrate arrow in
    a patient with AIDS.

24
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

25
  • 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.

26
Trephine biopsy in atypical mycobacterial
infection
  • Trephine biopsy stained with a Giemsa stain,
    showing faintly
  • staining organisms within the foamy
    macrophages.

27
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.

28
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.

29
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.

30
Bone marrow aspirate in AIDS showing
Cryptococcus neoformans
  • Bone marrow aspirate in AIDS showing a
    budding form of Cryptococcus neoformans.

31
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.

32
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.

33
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.

34
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

35
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.

36
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).

37
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.

38
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.

39
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