anaemia and hiv - southern african hiv clinicians society anaemia.pdfhiv and the bone marrow “in...
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A R I F A P A R K E R
M I T C H E L L ’ S P L A I N H O S P I T A L / T Y G E R B E R G H O S P I T A L
ANAEMIA AND HIV
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ANAEMIA
• Most common cytopaenia in HIV
• 95% of patients in the disease course
• Anaemia is NOT a diagnosis
• Multitude of possible causes
• Often multifactorial
…..difficult in the setting of HIV!!
OPIE, Jessica. Haematological complications of HIV Infection. South African Medical
Journal, p. 465-468, mar. 2012.
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WHAT IS THE SIGNIFICANCE OF ANAEMIA IN HIV?
• Independent predictor of survival prior to HAART
Anaemia and survival in HIV. CID 2003:37
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WHAT IS THE SIGNIFICANCE OF ANAEMIA IN HIV?
• Predictor of disease progression
• Impact on quality of life…
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APPROACHES TO ANAEMIA
• A morphological approach
• A pathophysiological approach
• Red cell loss
• Decreased red cell production
• Increased red cell destruction
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IMPORTANT QUESTIONS:
• Acute or chronic?
• Isolated anaemia – or 2 or more cell lines affected?
• Is it just a blood problem – other systems involved?
Note:
Transfusion does not ‘cure’ anaemia – diagnosing
and treating the underlying cause is essential
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Ectopic pregnancy
PV bleeding
Haemoptysis
GIT bleeding,
think about KS
Red cell loss red cell
production red cell
destruction
Anaemia
APPROACH TO ANAEMIA
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Approach to Anaemia
Red cell loss
red cell production
Bone marrow problem
Bone marrow failure:
HIV
Drugs
Parvovirus B19
Haematological
Bone marrow infiltration:
Can’t make RBC (Ineffective production)
red cell destruction
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An approach to anaemia
Red cell loss
Bone marrow problem
Bone marrow failure:
HIV
Drugs
Parvovirus B19
Haematological
Bone marrow infiltration:
TB
Malignancy
MAC
Other OI
Can’t make RBC
red cell destruction
red cell production
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An approach to anaemia
Red cell loss
red cell production
Bone marrow problem
Can’t make RBC (ineffective production)
Anaemia of chronic disease
Can’t utilise FeCytokines inhibit EPO and haemopoeisis
• Malignancy
• Chronic infections
• Organ failure: renal,
liver, endocrine,
alcohol
Nutritional deficiency
• Fe
• Folate
• B12
Poor diet, absorption
red cell destruction
Lack of EPO:
Renal disease
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Approach to anaemia
Red cell loss red cell production
red cell destruction
Haemolytic anaemia
Intravascular haemolysis
• MAHA
• TTP/HUS
• DIC – sepsis, malignancy
• Infections
• Other
Extravascular haemolysis:
Immune:
Autoimmune
Drugs: rifampicin, EFZ
Inherited:
Abnormal membrane
Abnormal globin
Enzyme defects
Other acquired
Hypersplenism
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HIV AND THE BONE MARROW
“in most patients with advanced HIV pancytopenia is the rule”
• The main mechanism for anaemia is a disruption of bone marrow cytokine homeostasis. • HIV is cytotoxic to T-helper lymphocytes →leads to
dysregulation of B cells /altered release of cytokines.
• HIV-infected T cells directly suppress growth of bone marrow progenitors, thus suppressing haemopoiesis.
• CD4 is carried by T-helper lymphocytes, monocytes and microvascular endothelial cells (found in marrow)
• The infection of monocytes in the marrow →alters release of cytokines →haemopoietic progenitor cells fail to adequately respond to anaemia and other cytopenias.
OPIE, Jessica. Haematological complications of HIV Infection. South African Medical Journal, p.
465-468, mar. 2012.
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DRUGS AND ANAEMIA
AZT:• Anaemia and neutropaenia• Macrocytosis (not B12 / folate deficient)• D4T has same effects, but anaemia less
common and less severe
3TC:• Pure red cell aplasia• Rare• Diagnosis of exclusion • Stop 3TC, give alternative NRTIs
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DRUGS AND ANAEMIA
Cotrimoxazole: • Megaloblastic anaemia (via folate inactivation)• Neutropaenia• Thrombocytopaenia
Rifampicin:• Haemolytic anaemia• Immune thrombocytopenia
Amphotericin B:
• Hypochromic, normocytic anaemia
• Decreased erythropoetin production
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PARVOVIRUS B19 INFECTION
• Only one of the Parvovirus group that is a human pathogen
Clinical manifestations:
• Erythema infectiosum – slapped cheek syndrome
in children
• Febrile arthropathy in adults
• Nonimmune hydrops fetalis – in utero infection
• Aplastic crises in sickle cell pts
• Chronic PRCA in immunodeficient patients; mostly low CD4 counts
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PARVOVIRUS B19
• Infects actively replicating erythroid progenitor cells, which are destroyed
Immunocompromised:
• Failure to make neutralising Abs
• Results in persistent viraemia
• And chronic red cell aplasia
Normal host:
• erythroid aplasia transient, no detectable reduction in Hb
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PARVOVIRUS B19
Diagnosis:
• Parvovirus PCR
• Serology: parvovirus IgM, but may be poor Abresponse in HIV pts
• Giant abnormal pronormoblasts on bone marrow biopsy: pathognomonic
Treatment:
• Blood transfusion: may contain neutralising Abs, so cause temporary in erythropoiesis
• HAART
• IVIG: most pts respond
• If don’t respond – look again for other causes
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AUTO-IMMUNE HAEMOLYTICANAEMIA
• Rare in HIV
• However: 20-44% of asymptomatic HIV infected patients can be Coombs test +
Why?
• Non-specific binding of antiphospolipid antibodies
• Deposition of immune complexes on erythrocytes
• Coombs test is not a useful investigation in HIV pts
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EFFECT OF HAART
CID 2004:38
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HAART IMPROVES ANAEMIA
Johannessen et al. BMC Infectious Diseases 2011 11:190
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BLOOD TRANSFUSION
‘Blood transfusion is like marriage: it should not be entered upon lightly, unadvisedly or wantonly, or
more often than is absolutely necessary.’
Role of blood transfusion:
• Not a cure for anaemia
• ‘symptomatic anaemia’ – symptoms often due to underlying cause rather than anaemia itself: eg TB in patients with advanced HIV
• Severe respiratory symptoms: aim for Hb of 10
• Otherwise we usually transfuse if Hb < 5.5 g/dL
A review of the use of blood and blood products in HIV-infected patients.
SAJHIVMED June 2012
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SUMMARY
Anaemia is not a diagnosis
Look for the cause of the anaemia
• Is the anaemia acute or chronic?
• Is the patient bleeding?
• Look for KS
• Look for TB, including NTM
• Exclude and treat other causes; think of malaria
• Change any implicated drugs
• Treat Fe/ folate / B12 deficiencies if present
Treat the cause/Remove the offending drug/HAART
Responsible use of blood transfusion
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THANK YOU
Acknowledgements:Dr Rosie Burton
Dr Zahiera Ismail