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Unexplained Anaemia Acute Medicine Update

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Presentation on theme: "Unexplained Anaemia Acute Medicine Update"— Presentation transcript:

1 Unexplained Anaemia Acute Medicine Update
Dr.Srinivasan Narayanan Consultant in Haematology University Hospital Southampton NHSFT

2 Introduction Common causes Rare causes Unexplained causes Summary
?Pathophysiology Investigations Treatment options Summary

3 Common causes of Anaemia

4 Diagnosis

5 Diagnosis

6 Diagnosis

7 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

8 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


10 MDS

11 Rare causes Inherited Acquired
Haemoglobinopathy disorders eg.unstable Hb Enzyme and membrane disorders Congenital dyserythropoietic anaemias Sideroblastic anaemias Acquired Aplastic anaemia Paroxysmal nocturnal haemoglobinuria

12 Diagnosis?

13 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

14 Ring sideroblasts

15 Ring sideroblasts

16 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


18 Diagnosis

19 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

20 Normal Hematopoietic Cells
CD55 CD59 Normal Hematopoietic Cells Transmembrane protein GPI anchors Membrane lipid bilayer 20

21 PNH Hemolytic screen Flow cytometry Bone marrow biopsy Treatment:
Anticoagulation Eculizumab – monoclonal antibody against C5 Bone marrow transplantation

22 Unexplained anaemia Commonly mild anaemia (1-2 g/dl low) Normocytic
Usually multifactorial

23 Is it common?

24 Prevalance of anaemia increases over 50, >20% at 85 years or older


26 Is it clinically relevant?

27 Retrospective cohort study of over 300000 patients 1997-2004
Age over 65 years undergoing non-cardiac surgery 3 groups: Hct<39, , >54 30 day mortality increase by 1.6% for every 1% change in Hct<39–Wu et al

28 Features of unexplained anaemia

29 Possible causes Age related renal insufficiency Chronic inflammation
pronounced decline in DM/HT Chronic inflammation Stem cell ageing Reduced regenerative capacity Androgen insufficiency Shortened red cell survival


31 Investigations Blood film Reticulocyte count
Ferritin, STR, Haematinics Haemolytic screen Thyroid function Erythropoietin level Bone marrow biopsy

32 Erythropoietin MW 30400Da Discovered by Miyake et al in 1977
LC 4 alpha helical bundle class 1 cytokine

33 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

34 Biology Epo stimulates erythropoiesis
Low oxygen supply increases the production of Epo Produced by the interstitial cells in kidney

35 32 week randomised, double blinded crossover trial with placebo and Epoetin alpha in elderly -Agnihotri P et al 62 patients with chronic anaemia


37 Increase in Hb>2 g/dl
Improvement in QOL studies

38 Monitor blood pressure, risk of hypertension
Avoid in patients with recent MI/CVA Maintain Hb g/l, aim lower Hb level in patients with thrombocytosis, ischaemic vascular disease. Responds better after iron/folate replacement in deficient patients.

39 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

40 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.

41 Any Questions?

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