The haematological features of HIV infection British Journal of Haematology, 1997, 99, 1-8 Review...

The haematological The haematological features of HIV infectionfeatures of HIV infection

British Journal of British Journal of Haematology, 1997, 99, 1-8Haematology, 1997, 99, 1-8

Review articleReview article

B. J. Bain B. J. Bain

Why?Why?

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

The haematological The haematological features of HIV infectionfeatures of HIV infection

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

Causes of the Causes of the haematological changeshaematological changes

• The haematological abnormalities The haematological abnormalities may be attributable to the:may be attributable to the:

• Direct and indirect effect of HIV infectionDirect and indirect effect of HIV infection• opportunistic infectionsopportunistic infections• Toxicity of the drugsToxicity of the drugs

Diagnostic confusionDiagnostic confusion

• It is important for the haematologist to It is important for the haematologist to be aware of the features of HIV infection be aware of the features of HIV infection and AIDS since and AIDS since diagnostic confusiondiagnostic confusion can can otherwise occur.otherwise occur.

• HIV infection can simulate the:HIV infection can simulate the:– MDSMDS– MPD, andMPD, and– T-cell lymphoma T-cell lymphoma

Primary infectionPrimary infection

• Brief Brief febrilefebrile illness illness• PharyngitisPharyngitis and and cervical lymphadenopathycervical lymphadenopathy are are

common, simulate infectious mononucleosis.common, simulate infectious mononucleosis.• Initial Initial lymphopenialymphopenia• Followed by Followed by lymphocytosislymphocytosis with atypical with atypical

lymphocytes.lymphocytes.• False positive Paul Bunnell testFalse positive Paul Bunnell test..• Neutropenia, thrombocytopenia and transient Neutropenia, thrombocytopenia and transient

pancytopenia can also occur.pancytopenia can also occur.

Established infection Established infection

• Primary infection is followed by a period Primary infection is followed by a period of of clinical latencyclinical latency or or asymptomaticasymptomatic infection.infection.

• IsolatedIsolated thrombocytopenia thrombocytopenia as a result of as a result of immuneimmune destruction of platelets can destruction of platelets can occur.occur.

• There is increased platelet associated There is increased platelet associated IgIg..

General haematological features of General haematological features of AIDSAIDS

• Peripheral bloodPeripheral blood– During the During the asymptomaticasymptomatic period, there is period, there is

• GradualGradual fall fall in the number of in the number of CD4 +CD4 + lymphocytes lymphocytes• Initial Initial increaseincrease in in CD8CD8 lymphocytes lymphocytes

– By the time of By the time of diagnosisdiagnosis there is there is • LymphopeniaLymphopenia• Often Often pancytopeniapancytopenia• AnaemiaAnaemia which is usually normochromic, which is usually normochromic,

normocytic but sometimes macrocytic.normocytic but sometimes macrocytic.

Peripheral blood changesPeripheral blood changes

• Red cell changesRed cell changes– Anisocytosis, Anisocytosis, – poikilocytosis, poikilocytosis, – rouleaux formationrouleaux formation– increased background staining.increased background staining.– Occasionally the blood film shows features Occasionally the blood film shows features

of microangiopathic haemolytic anaemia.of microangiopathic haemolytic anaemia.


• Neutrophils Neutrophils may show may show dysplasticdysplastic features: features: – toxic granulationtoxic granulation– Dohle bodiesDohle bodies– cytoplasmic vacuolation cytoplasmic vacuolation – left shiftleft shift– presence of detached nuclear fragmentspresence of detached nuclear fragments– hypogranularity and occasional Pelger formshypogranularity and occasional Pelger forms

Neutrophil with a detachedNeutrophil with a detached nuclear fragment in AIDS nuclear fragment in AIDS

• a detached a detached nuclear fragment can nuclear fragment can be seen in AIDS be seen in AIDS patients patients

• It can also be caused It can also be caused by multi-agent by multi-agent cytotoxiccytotoxic

chemotherapychemotherapy


• ThrombocytopeniaThrombocytopenia , usually normal , usually normal size platelets.size platelets.

• Except when there is Except when there is immuneimmune destruction, destruction, large sizelarge size platelets platelets may be seen.may be seen.

Bone marrow aspirateBone marrow aspirate

• It is initially It is initially hypercellularhypercellular, but is , but is hypocellularhypocellular in the later stages. in the later stages.

• Trilineage Trilineage dysplasiadysplasia is common. is common.


• Changes in the erythrocytes includeChanges in the erythrocytes include::– Nuclear lobulation and fragmentationNuclear lobulation and fragmentation– Howell-Jolly bodiesHowell-Jolly bodies– Bi- and multi-nuclearityBi- and multi-nuclearity– Cytoplasmic bridgingCytoplasmic bridging– Cytoplasmic vacuolationCytoplasmic vacuolation– Basophilic stipplingBasophilic stippling– Megaloblastosis.Megaloblastosis.– Occasional ring sideroblasts.Occasional ring sideroblasts.


• Changes in the Changes in the myeloidmyeloid series series include:include:– DysplasticDysplastic changes changes– Giant metamyelocytesGiant metamyelocytes are common are common

even in the absence of megaloblastic even in the absence of megaloblastic erythropoiesis.erythropoiesis.

Giant metamyelocyteGiant metamyelocyte

A hypogranular A hypogranular giant giant metamyelocyte in metamyelocyte in the peripheralthe peripheral

blood of a patient blood of a patient with AIDS.with AIDS.


• Changes in megakaryopoiesis Changes in megakaryopoiesis – MegakaryocytesMegakaryocytes are are increasedincreased earlyearly in in

the disease and the disease and decreased decreased in thein the later later stagesstages..

– They show They show dysplasticdysplastic features features• Bizzare nuclear shapesBizzare nuclear shapes• Hyperchromatic nucleiHyperchromatic nuclei• Nuclear hypolobulationNuclear hypolobulation


• Reactive changesReactive changes include: include:– Increased lymphocytesIncreased lymphocytes– Increased plasma cellsIncreased plasma cells– Increased macrophagesIncreased macrophages– Haemophagocytic syndromeHaemophagocytic syndrome

Differences between HIV and Differences between HIV and MDS in the BMAMDS in the BMA

In HIVIn HIV• Ring sideroblasts are Ring sideroblasts are

not a prominent not a prominent featurefeature

• Myeloblasts are not Myeloblasts are not increasedincreased

• Micromegas are not Micromegas are not commoncommon

• Auer rods are not Auer rods are not seenseen

In MDSIn MDS• Giant Giant

metamyelocytes metamyelocytes (common in AIDS) (common in AIDS) are quite are quite uncommon in uncommon in MDS.MDS.

Bone marrow trephine biopsyBone marrow trephine biopsy

• Initially shows Initially shows hypercellularityhypercellularity with neutrophil with neutrophil and megakaryocytic hyperplasia.and megakaryocytic hyperplasia.

• Megakaryocytes are Megakaryocytes are clusteredclustered and and dysplasticdysplastic• There is increased number of There is increased number of barebare

megakaryocyte nuclei.megakaryocyte nuclei.

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

• The The megakaryocytes are megakaryocytes are hypolobulated and hypolobulated and clustered.clustered.

Bone marrow trephine biopsyBone marrow trephine biopsy

• ReticulinReticulin is often increased. is often increased.• Late Late in the course of the disease the trephine in the course of the disease the trephine

biopsy will show biopsy will show hypocellularhypocellular BM with BM with gelatinous degenerationgelatinous degeneration

• Patches of Patches of necrosisnecrosis• Patients with specific infections may show BM Patients with specific infections may show BM

granulomas.granulomas.• LymphomatousLymphomatous infiltration infiltration

A random focal lymphoidA random focal lymphoid infiltrate (H & E) infiltrate (H & E)

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

Specific infections in AIDSSpecific infections in AIDS

• Opportunistic infections are very Opportunistic infections are very common in AIDS, among these are:common in AIDS, among these are:

• MycobacterialMycobacterial and other bacterial and other bacterial infectionsinfections– Mycobacterium tuberculosisMycobacterium tuberculosis– Atypical mycobacterial infectionAtypical mycobacterial infection– Mycobacterium avium intracellulareMycobacterium avium intracellulare

• The bone marrow in patients with The bone marrow in patients with mycobacterial infection may show well-formed, mycobacterial infection may show well-formed, or less formed or less formed granulomas.granulomas.

• CaseationCaseation may occur in tuberculous may occur in tuberculous granulomas.granulomas.

• Sometimes there is marked proliferation of Sometimes there is marked proliferation of foamy macrophagesfoamy macrophages

• CultureCulture for mycobacteria is for mycobacteria is obligatory obligatory whenever a BM examination is performed to whenever a BM examination is performed to investigate investigate fever of unknown originfever of unknown origin in an HIV + in an HIV + patient.patient.

Trephine biopsy in atypicalTrephine biopsy in atypical

mycobacterial infection mycobacterial infection

Trephine biopsy Trephine biopsy stained with a stained with a Giemsa stain, Giemsa stain, showing faintlyshowing faintly

staining organisms staining organisms within the foamy within the foamy macrophagesmacrophages..

Trephine biopsy in atypicalTrephine biopsy in atypical mycobacterial infection (H & E) mycobacterial infection (H & E)

• Poorly formed granuloma Poorly formed granuloma composed of epithelioidcomposed of epithelioid

macrophages, many of macrophages, many of which havewhich have

vacuolated cytoplasm.vacuolated cytoplasm.

This infection is only This infection is only likely to be detected on likely to be detected on

bone marrow bone marrow examination of severely examination of severely immunosuppressed immunosuppressed individuals.individuals.

Other opportunistic Other opportunistic infectionsinfections

• Viral infectionsViral infections– CMVCMV infection is common in AIDS infection is common in AIDS

• BM features are non specific, with BM features are non specific, with atypical atypical lymphocyteslymphocytes and and haemophagocytosishaemophagocytosis

– Parvovirus B19Parvovirus B19• This might lead to This might lead to chronic red cell aplasiachronic red cell aplasia• There is disproportionate anaemia with There is disproportionate anaemia with

reticulocyte count close to zeroreticulocyte count close to zero• BMA & TB show red cell aplasia and BMA & TB show red cell aplasia and giant giant

proerythroblast.proerythroblast.• Confirmed by detection of Confirmed by detection of viral DNAviral DNA in the serum. in the serum.


• Fungal infectionsFungal infections• Sometimes detected in Sometimes detected in BMABMA either within either within

the macrophages or freethe macrophages or free• But more readily detected in the But more readily detected in the trephine trephine

biopsybiopsy specimen. specimen.• A A cryptococcal antigen testcryptococcal antigen test on the PB is a on the PB is a

very good screening test for cryptococcosis, very good screening test for cryptococcosis, and and PB culturesPB cultures are often positive in HIV + are often positive in HIV + pt with fungal infections; these tests may pt with fungal infections; these tests may make marrow exam make marrow exam unnecessaryunnecessary..

Bone marrow aspirate in AIDSBone marrow aspirate in AIDS showing Cryptococcus showing Cryptococcus neoformans neoformans

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

Bone marrow aspirate in AIDSBone marrow aspirate in AIDS showing Histoplasma showing Histoplasma capsulatum capsulatum

- Bone marrow - Bone marrow aspirate in a patient aspirate in a patient with AIDS with with AIDS with histoplasmosishistoplasmosis

showing histoplasma showing histoplasma within a within a macrophage.macrophage.

- Histoplasma are - Histoplasma are small yeast forms.small yeast forms.


• Parasitic infectionsParasitic infections– LeishmaniasisLeishmaniasis is usually readily is usually readily

detected in BMA & TBdetected in BMA & TB– ToxoplasmosisToxoplasmosis– American trypanosomiasisAmerican trypanosomiasis– Rarely Rarely Pneumocystis cariniiPneumocystis carinii has been has been

detected in the BM of pt with AIDS.detected in the BM of pt with AIDS.

Leishmania donovani in aLeishmania donovani in a monocyte monocyte

• Blood film in a Blood film in a patient with AIDSpatient with AIDS

showing Leishmania showing Leishmania donovani in a donovani in a monocyte. monocyte.

• Leishmania in Leishmania in circulating circulating monocytes or monocytes or neutrophils is rarely neutrophils is rarely seen except in seen except in patients with AIDS. patients with AIDS.

Lymphoproliferative Lymphoproliferative disorders in AIDSdisorders in AIDS

• The incidence of NHL is increased The incidence of NHL is increased 60-200 fold in pt with AIDS.60-200 fold in pt with AIDS.

• The incidence of HD may be The incidence of HD may be increased to 8-foldincreased to 8-fold

NHL in AIDS patientsNHL in AIDS patients

• The great majority are of The great majority are of B-lineageB-lineage..• The strongest association is with The strongest association is with

– Burkitt lymphomaBurkitt lymphoma– Burkitt like lymphomaBurkitt like lymphoma– Large cell lymphoma of B-lineageLarge cell lymphoma of B-lineage

• Persistant generalizedPersistant generalized lymphadenopathylymphadenopathy often precedes the development of often precedes the development of lymphoma and is indicative of increased lymphoma and is indicative of increased risk of development of lymphoma.risk of development of lymphoma.

HD in AIDS patientsHD in AIDS patients

• It usually presents in patients in It usually presents in patients in advanced stageadvanced stage..

• Often with Often with BB symptoms. symptoms.• Bone marrow infiltrationBone marrow infiltration• The TB may be the initial or the only The TB may be the initial or the only

diagnostic material.diagnostic material.• Histopathology often shows poor Histopathology often shows poor

prognostic types ( prognostic types ( MC, or LDMC, or LD).).

conclusionsconclusions

• HIV infection is associated with a great variety HIV infection is associated with a great variety of haematological abnormalities.of haematological abnormalities.

• HIV pt may have abnormalities due to drug HIV pt may have abnormalities due to drug therapy or opportunistic infections.therapy or opportunistic infections.

• Diagnostic confusions specially with MDS can Diagnostic confusions specially with MDS can occur.occur.

• BMA & TB have a role in the diagnosis of BMA & TB have a role in the diagnosis of opportunistic infections and of lymphoma.opportunistic infections and of lymphoma.

conclusionsconclusions

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

megaloblastosis.megaloblastosis.

The haematological features of HIV infection British Journal of Haematology, 1997, 99, 1-8 Review...

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