unexplained anaemia acute medicine update dr.srinivasan narayanan consultant in haematology...
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Unexplained AnaemiaAcute Medicine Update
Dr.Srinivasan NarayananConsultant in HaematologyUniversity Hospital Southampton NHSFT
Introduction
Common causes Rare causes Unexplained causes
?Pathophysiology Investigations Treatment options
Summary
Common causes of Anaemia
Diagnosis
Diagnosis
Diagnosis
Anaemia of chronic disease• Impaired erythropoietin production• Blunted response of marrow to endogenous
erythropoietin• Impaired iron metabolism mediated by
inflammatory cytokines and stimulates liver production of hepcidin
• Hepcidin reduces iron absorption and decrease iron release from macrophages
• Normocytic, hypochromic anaemia with low iron binding capacity, normal or high ferritin and increased marrow iron
Myelodysplasia Most often in older age groups Anaemia could be only presenting
feature Difficult to diagnose in early stages Blood film may help Bone marrow assessment is required to
confirm the diagnosis Epo<500 may respond to Epo
injections
MDS
MDS
Rare causes
Inherited Haemoglobinopathy disorders
eg.unstable Hb Enzyme and membrane disorders Congenital dyserythropoietic anaemias Sideroblastic anaemias
Acquired Aplastic anaemia Paroxysmal nocturnal haemoglobinuria
Diagnosis?
Sideroblastic anaemia
Inherited and acquired causes Mutation of genes in haem
biosynthesis Most common – ALA synthase gene
mutation Characterized by ring sideroblasts Accumulation in perinuclear
mitochondria within erythroblasts due to impaired iron utilisation
Acquired – MDS, alcohol, lead toxicity
Ring sideroblasts
Ring sideroblasts
Congenital dyserythropoietic anaemias
Rare congenital anaemias, 3 major subtypes
Mild to moderate anaemia due to ineffective erythropoiesis
Secondary iron overload due to increased iron absorption
Characteristic bone marrow changes and EM appearances of the erythroblasts
CDA-II
Diagnosis
Paroxysmal nocturnal Haemoglobinuria
Rare disease Acquired mutation of PIG-A gene Defect in the production of GPI protein
anchors which protects against complement destruction
Increased red cell destruction
Normal Hematopoietic Cells
Membrane lipid bilayer
Transmembraneprotein
CD55 CD59
GPI anchors
PNH Hemolytic screen Flow cytometry Bone marrow biopsy Treatment:
Anticoagulation Eculizumab – monoclonal antibody against
C5 Bone marrow transplantation
Unexplained anaemia Commonly mild anaemia (1-2 g/dl
low)
Normocytic
Usually multifactorial
Is it common?
Prevalance of anaemia increases over 50, >20% at 85 years or older
Is it clinically relevant?
Retrospective cohort study of over 300000 patients 1997-2004
Age over 65 years undergoing non-cardiac surgery
3 groups: Hct<39, 39-53.9, >54
30 day mortality increase by 1.6% for every 1% change in Hct<39–Wu et al
Features of unexplained anaemia
Possible causes
Age related renal insufficiency pronounced decline in DM/HT
Chronic inflammation Stem cell ageing
Reduced regenerative capacity Androgen insufficiency Shortened red cell survival
Investigations
Blood film Reticulocyte count Ferritin, STR, Haematinics Haemolytic screen Thyroid function Erythropoietin level Bone marrow biopsy
Erythropoietin
MW 30400Da
Discovered by Miyake et al in 1977
LC 4 alpha helical bundle class 1 cytokine
Erythropoietin
Renally secreted glycopeptide which stimulates erythropoiesis
Normally rises with anaemia Blunted response in chronic
inflammatory conditions, cancer, RA Helps in reducing/avoid blood
transfusions
Biology
Epo stimulates erythropoiesis Low oxygen supply increases the
production of Epo Produced by the interstitial cells in
kidney
32 week randomised, double blinded crossover trial with placebo and Epoetin alpha in elderly -Agnihotri P et al
62 patients with chronic anaemia
Increase in Hb>2 g/dl Improvement in QOL studies
Monitor blood pressure, risk of hypertension
Avoid in patients with recent MI/CVA Maintain Hb 100-120g/l, aim lower Hb
level in patients with thrombocytosis, ischaemic vascular disease.
Responds better after iron/folate replacement in deficient patients.
ICUS New terminology coined for unexplained
cytopenias, persists for at least 6 months Hb<110 g/l, with no clear reason Acknowledgement of diagnostic
uncertainty Does not meet the diagnostic criteria for
MDS or other conditions Recommend long term monitoring as it
may progress to MDS Suboptimal Epo production could be the
cause
Summary
Consider occult bleed, Anaemia of chronic disease or low grade haemolysis before UA.
Polypharmacy, inadequate nutrition, alcohol abuse also have a negative impact on erythropoiesis.
Associated neutropenia, low platelets are suggestive of bone marrow disorders.
Any Questions?