Anaemia Archives - almostadoctor

Summary of Anaemias

Dr Tom Leach — Wed, 14 Jun 2017 13:44:35 +0000

Microcytic

Type

Aeitology

Clinical features

Investigations

Management

Iron Deficiency Anaemia

Blood loss: GI bleeding (peptic ulcer, diverticulitis), Menorrhagia, hookworm (developing countries)

Poor Diet

Malabsorption

– Brittle hair + nails

– Atrophic glossitis

– Angular stomatitis

– Koilonychia

– (Rare: post- cricoid webs)

– Hb ↓, ↓MCV

– RBC microcytic, hypocgromic, anisocytosis, poikilocytosis.

-Serum ferritin ↓

-Serum Iron ↓

– TIBC ↑

– Treat underlying cause.

– Oral iron – ferrous sulphate (SE = constipation)

Anaemia of chronic disease

Diseases: infection, colloagen vascular disease, rheumatoid arthritis, malignancy, renal failure, chronic inflammatory disease (crohns), TB, endocarditis.

↓ release of iron from bone marrow to developing erythroblasts, inadequate erythropoietin response to the anaemia, ↓RBC survival.

Normochromic, normocytic or microcytic anaemia

– ↓serum iron levels

– ↓ serum iron binding capacity

– ↑or normal serum ferritin.

– Treat underlying cause

– If due to renal failure then anaemia partly due to erythropoeitin deficiency – thus recombinant erythropoietin is useful.

Sideroblastic

– Inherited

– Acquired

· 2* to myelodysplasia,

· alcohol,

· lead or isoniazid poisoning,

· idiopathic,

· malignancy,

· anti- TB drugs,

· – malabsorption

There is iron available but the body is unable to synthesize it into the RBCs’

· Dyserythropoiesis (defective developement of eyrocytes)

· iron loading bone marrow

· haemosiderosis (storage of iron compound – haemosiderin in various places e.g. endocrine, liver, cardiac damage)

Disorder of haem synthesis:

· refractory anaemia

· hypochromic cells in the peripheral blood

· ring sideroblasts in bone marrow. (erythrocytes with granules of iron in their cytoplasm)

– Withdraw causative agents

– some response to pyridoxine (Vit B6)

– Maybe transfusion dependent and iron overload is a problem.

Thalassemia

See haemolytic anaemias

Macrocytic – Macrocytosis – presence of abnormally large red blood cells in the blood

Type

Aetiology

Clinical Features

Investigations

Management

Megaloblastic

The presence in the bone marrow of developing RBCs with delayed nuclear maturation relative to that of the cytoplasm.

– defective DNA synthesis,

– ↓WC (leukopenia)- may be hyper-segmented,

– ↓ platelets (thrombocytopenia)

Causes:

– B12/ Folate deficiency

– Drugs (hydroxycarbamide/ hydroxyurea)

– Usually asymptomatic as the fall in the levels of Hb in response to the falling levels of B12/ folate occur over a long period of time therefore allowing the body to adjust.

Blood film:

– hypersegmented polymorphs (B12 ↓), target cells (liver disease).

– ESR

– Malignancy

– LFTs

– T4

– Serum B12 and serum folate/ red cell folate.

Bone marrow biopsy if above unsignificant:-

Megaloblastic

– B12/folate deficiency, cytoxic drugs

Normoblastic marrow

– liver damage, myoxedema (coarsening of skin due to hypothyroidism)

Increased erythropoiesis

– e.g. haemolysis

Abnormal erythropoiesis

– sideroblastic anaemia,

leukaemia, aplasia.

Vit B12 Deficiency

Diet: If no animal products are consumed (vegan)

Impared absorption:

– Pernicious anaemia,

– Gastrectomy (no IF from terminal ileum),

– illeal disease/resection, coeliac disease.

Peripheral neuropathy – dorsal column degen.

(Rarely – dementia)

– Treat cause
– IM B12 injections

NB confirm whether B12 or folate deficient as folate will correct Hb in B12 deficiency but will not treat neuropathy

Pernicious anaemia

Autoimmune condition where there is atrophy of the gastric mucosa, with failure of Intrinsic Factor (and acid production)→ B12↓ absorption.

– usually older people,

– ↑common in women, fair hair blue eyes.

– Associated with other autoimmune conditions:

e.g. Thyroid,

Vitiligo

Addisons.

General:

– Glossitis

– Angular stomatitis

– Mild jaundice

– weakness + tiredness

– Dysponea

– Diarrhoea

– Premature grey hair

– Mild Splenomegaly

– Fever

Neurological – fits with very low levels of B12 and in

Polyneuropathy – weakness, ataxia, paraplegia

Optic atrophy – dementia, visual disturbances.

Macrocytic anaemia

– MCV > 110 with hypersegmented neutrophil nuclei

– in severe cases leucopoenia and thrombocytopenia.

– Hb ↓

– WCC + Platelets ↓

– Serum B12 ↓ < 50ng

– Red cell folate ↓

– Serum autoantibodies. Parietal cell antibodies 90% , IF antibodies 50%.

– Serum Bilirubin ↑ (↑ breakdown of haemoglobin, due to ineffective erythropoiesis in the Bone marrow)

– Schilling test

(to differenciate PA from small bowel malabsorption)

– Bone marrow exam

-Hypercellular BM with megaloblastic changes.

– IM Hydroxocobalamin

– x2 weekly for 3 weeks to replenish body stores, 3 monthly for life.

– watch for hypokalaemia when tx begins – oral K+ may be required

Folate Deficiency

Poor Intake

– old age

– poverty

– alcohol excess

– anorexia
Sources = green veg, beans, whole grains, some breakfast cereals

Malabsorption

– coeliac disease

– tropical sprue

Excess utilization

– pregnancy, lacatation, prematurity

– chronic haemolytic anaemia, malignant and inflammatory diseases,

– dialysis

Anaemia symptoms

– Red cell folate ↓

– Serum folate ↓

– jejunal biopsy to look for small bowel disease.

– Tx of underlying conditon.

– Oral folic acid 5mg daily for 4 months, higher doses if due to malabsorption.

– Prophylactic folic acid is given to pts with chronic haemolysis and pregnant women.

Normocytic

Type

Aeitology

Clinical features

Investigations

Management

Aplastic anaemia

Pancytopenia

– deficiency of all cell elements of the blood,

Aplasia

– hypocellularity of the bone marrow

– Congenital

– Idiopathic acquired (50%)

Chemicals e.g benzenes

Drugs e.g. cytotoxics, chemotherapy, chloramphenicol, gold, insecticides, ionising radiation

– Infections e.g. viral hepatitis, HIV

Resulting from deficiency of RBCs, WBCs, Platelets.

– Anaemia

– ↑ likelyhood of infection

– Bleeding

– Bruising

– Bleeding gums

– Epistaxis

– Mouth infections are common

FBC – pancytopenia with low/ abscent reticulocytes.

Bone marrow exam –hypocellular marrow with ↑fat spaces.

Tx Cause:

– Supportive care

– Transfusions of RBC, platelets

– Antibiotic tx.

Poor prognosis:

– peripheral blood neurtophil count < 0.5 x10⁹/L

– peripheral blood platelet count < 20×10⁹/L

– reticulocyte count of <40×10⁹/L

If no recovery:

– Bone marrow transplantation

– Immunosuppressive tx with antilymphocyte gobulin and ciclosporin (where BMT is not possible due to ↑GVHD risk)

Haemolytic anaemias overview

There is increased destruction of red cells and a reduction of circulating lifespan to which the bone marrow is unable to compensate for the increased loss.

This may be:

extravascular (within reticuloendothelial system) they are removed from the circulation as they are defective

intravascular (within blood vessels)e.g. due to trauma, complement fixation or other extrinisic factors.

Causes:

RBC membrane defect:

– Hereditary spherocytosis

– Hereditary elliptocytosis

Haemoglobin abnormlaities:

– Thalassaemia

– Sickle cell disease

RBC metabolic defects:

– Glucose-6-phosphate dehydrogenase defieciency

-Pyruvate kinase defeicency

Immune:

– Autoimmune haemolytic anaemia

– Haemolytic transfusion reactions

-Drug induced

Non-Immune:

– Paroxysmal noctural haemoglobinuria

– Microangiopathic haemolytic anaemia

– March haemoglobinuria

Other:

– Infections (e.g. malaria)

– Drugs/chemicals

– Hypersplenism

– Trauma

Jaundice

Hepatospenomegaly

Hx:

– family history

– race

–haematuria

-drugs

-previous anaemia

Is there significant haemolysis:-

Is there increased cell breakdown:-

– bilirubin↑ (unconjugated),

– urinary urobilinogen ↑,

– haptoglobin↓.

Is there increased red cell production:-

e.g. reticulocytosis,

-polychromasia,

-macrocytosis,

-marrow hyperplasia.

Is the haemolysis mainly intra/extra vascular:-

E: → splenic hypertrophy

I: methaemalbuminaemia,

– free plasma haemoglobin,

– haemoglobinuria,

– ↓haptoglobin,

– haemosiderinuria.

-FBC,

-Reticulocytes,

-Bilirubin,

-LDH,

-Haptoglobin,

-Urinary urobilinogen.

Blood films:polychromasia, macrocytosis, spherocytes, elliptocytes, fragmented cells or sickle cells.

Direct Coombs’ test: identifies RBCs coated with antibody/complement and a positive result ususally indicates an immune cause.

Chromium labelling: for RBC lifespan and the major site of breakdown

Thalassaemia

Multiple gene defects → ↓ rate of production of one or more globin chains.

The imbalance of globin chain production leads precipitation of globin chains within red cells or precursors. This → cell damage, death of RBC precursors in the bone marrow and haemolysis.

– α thalassaemia: reduced α chain synthesis

– β thalassaemia: reduced β chain synthesis

– Symptoms may be mild–severe, depending on how many α/β chain genes have been deleted

– FBC

– MCV

– Film

– Iron

– HbA2

– HbF

– Hb

– Electrophoresis

– Transfusion keep Hb >9g/dL

– Iron chelators e.g. desferrioxamine. To protect against cardiac disease & DM.

– ↑ doses of ascorbic acid (vitamin C) also ↑iron output

– Splenectomy , if hypersplenism px.

– Folate supplements

– BMT

Sickle cell anaemia

Inheritance of the β-globin gene.

May have:

sickle cell anaemia HbSS

sickle cell trait HbAS

HbSC – one S haemoglobin and one C haemoglobin group, (the C group causes the red blood cells to develop).

HbAS – there are usually no symptoms unless the patient is exposed to extreme hypoxia

HbAC – a milder course of HbSS but there is a ↑likelyhood of thromboses occuring.

HbSS – symptoms due to haemolysis and vaso-occlusion. As the sickled cells are fragile and haemolyse and block small vessels.

…continued in large box below….

– ↓ Hb

– ↑ Reticulocyte count

– Bilirubin may be raised

– Blood film shows sickled erythrocytes

Dx:

Viz electrophoresis showing 80-90% HbSS and absent Hb A.

– Folic acid in patients with severe haemolysis

– pneumococal vaccine to ↓ infection risk, daily oral penecillin

– Exchange transfusions to ↓ frequency of crises

– Hydroxycarbamide (hydroxyurea) raises the conc of fetal Hb

– possible BMT

Haemolysis:

– mild anaemia (usually no symptoms due to hyperdynamic circulation and a lower O₂ affinity of HbS than normal Hb).

– jaundice

– painful swelling of hands and feet

– recurrent sickle cell crises

– recurrent haemolysis → formation of pigment gallstones

Vaso-occlusion:

A vascular necrosis of BM results in the bone marrow pain crisis, may be precipiated by hypoxia, dehydration or infection

– usually affects ribs, spine, pelvis in adults

– hands and feet (dactylitis) in children

– may require addmission to hospital for analgesia

Other complications:-

– Splenic atrophy

resulting in ↑infection risk with Pneumococcus, Salmonella species and Haemophilus

– Cerebral infection

causing fits and hamiplegia

– Retinal ischaemia,

may precipitate proliferative sickle retinopathy and visual loss.

Other:-

– renal papaillary necrosis

– chronic renal failure

– leg ulcers

– acute chest syndrome (commonest cause of death in adults with sickle cell )

– fever

– cough

– dysponea

– pulmonary infarcts on the CXR

Caused by infection, fat emboli from necrotic bone marrow or pulmonary infarction due to sequestration of sickle cells

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Anaemia of Chronic Disease

Dr Tom Leach — Sat, 10 Jun 2017 23:29:06 +0000

Introduction

Anaemia of Chronic Disease (ACD) is common, particularly in the hospital setting. It occurs as a result of:

Chronic infection
Chronic inflammation
Neoplasia
Chronic kidney disease

The anaemia is typically:

Normochromic – the concentration of Hb within each individual RBC is normal
Normocytic – the size of the red bloods cells themselves is within the normal range

As such, the anaemia is defined in terms of the total Hb and haematocrit.

However, it can also be:

Microcytic – small red blood cells
Hypochromic – reduced amounts of haemoglobin in each individual red blood cell

In this case may be difficult to distinguish from an iron deficiency anaemia (IDA), and in many cases, an iron deficiency anaemia may co-exist with anaemia of chronic disease.

Sometimes, anaemia of CKD is considered separately to the other causes of anaemia of chronic disease. In this artifice we will try to explain where the differences arise between the causes of anaemia of chronic disease.

Other definitions

MCV – mean corpuscular volume – this tells you if it is micro / normo / macrocytic

MCH – mean corpuscular haemoglobin – this tells you if it is normo/hyper/hypo chromic

MCHC – mean corpuscular haemoglobin concentration – this is a calculation using MCV and MCH – it is not that useful!

Epidemiology

In chronic kidney disease

About 12% of patients will have an anaemia of chronic disease
This increases as the eGFR falls
Patients with CKD and diabetes are a greater risk of anaemia

Pathology

The anaemia is not related to bone marrow, bleeding or haemolysis, and is generally mild (Hb of 8.5-11.5g/dl).

There are varying pathologies depending on the cause.

In CKD it is thought to arise from reduced renal synthesis of EPO.

In chronic inflammatory conditions, neoplasm and infection it is thought to arise from defects in iron utilisation, in particular, iron is not released from transferrin as well as normal. This seems to have an effect on erythropoiesis, and the level of EPO is reduced, although it often appears very low for such a mild anaemia. Basically – there is inhibition of erythrocyte production by cytokines.

The administration of EPO to patients with rheumatoid arthritis has shown to be of benefit to these patients.
Note that transferrin is the protein used to transport iron in the blood. It binds iron very strongly, but reversibly.
Ferritin is a compound that binds free iron within cells. In anaemia of chronic disease, levels of ferritin are often raised.

There are normal levels of iron stores in the bone marrow, but this, for some reason, is not released properly, and so developing erythroblasts do not receive enough of it. Therefore, the actual RBCs will mimic those of iron deficiency anaemia.

Anaemia of chronic disease is generally a normocytic normochromic anaemia, but sometimes it can be a microcytic hypochromic anaemia.

Iron deficiency anaemia (IDA) is a microcytic hypochromic anaemia

It is thought that somewhere along this process of iron release, interferons, TNF and cytokines, such as IL-1, interfere with the release of iron.

It can be difficult to differentiate ACD from iron deficiency anaemia – they both have a low MCV. You may need to try a trial of oral iron. In ACD this will not improve the situation, but in IDA it should.

In ACD measures that treat the underlying condition will generally result in resolution of the anaemia.

You could also do an immunoassay to look at the number of serum transferrin receptors, as levels of these differ between diseases.

Anaemia	Ferritin	Iron	TIBC	Transferrin saturation	Soluble transferrin receptor
Iron deficiency	Low	Low	High	Low	High
ACD	High/Normal	Low	Low	Low	Low/normal

Normochromic – this means the concentration of haemoglobin within an RBC is normal.

Management

Treatment is generally just that of the underlying disorder. – However, in those with terminal malignancy and chronic kidney disease, you may be able to improve quality of life by giving EPO to reduce the level of anaemia. In cases of renal failure this is particularly effective as the levels of EPO are directly affected. A typical dosing regimen might include:

Darbepoetin alpha – given once every 2 weeks
- Contraindicated in uncontrolled hypertension
- Side effects include:
  - Hypertension
  - Flu-like symptoms
  - Headaches
  - Increased platelets
  - Increase risk of thromboembolic events
  - Hyperkalaemia
  - Skin reactions
Epoetin alpha
- An alternative drug, but less widely used due to shorter half-life, and as such requires stricter dose control and more dosage alterations
Iron supplementation is required for all patients on EPO agents
- Aim for ferritin 200 – 500 μg/L
- Transferrin saturation >20%

Treatment with EPO can reduce the need for blood transfusions – which is important in patients who may be considered for a future renal transplant

Complications

Anaemia puts strain on the heart, increasing the risk of left ventricular hypertrophy
Strongly associated with increased mortality

References

Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
Anaemia in chronic kidney disease – Patient.info