• RBC has average lifespan 100-120d

• EPO released in response to reduced oxygen levels in blood

• reticulocytes initially larger then decrease over several days as they mature

• increased reticulocyte = MCV eevated

Microcytic anaemia

• MCV \<80 with anaemia

• cell size decrease due to decrease Hb

• test serum ferritin

  • iron storage protein

  • relfects true iron stores

  • fluctuates less than serum iron and total iron binding capacity

  • ≤15-20 = iron defiency

  • acute phase protin

    • raised by inflammation, infection, chronic disease, malignancy

  • stored in liver

    • liver disease/inflammation also increase

Iron deficiency anaemia

• blood loss

• dietary deficiency

• occasionally malabsorption

• cause always needs to be investigatied

• primary causes:

  • Obstetric/gynaecological

    • menorrhagia

    • normal menstruation combined iwth deficient diet

    • pregnancy

      • ferritin \<30 suggestive of early iron depletion

      • likely to progress unless treated

    • subjuctive assessments highly unreliable

  • Gastrointestinal bleeding

    • oesophagitis

    • oesophageal varices

    • ulcerated hernia

    • peptic ulcer

    • inflammatory bowel disease

    • malignancy

    • angiodysplasia

  • Malabsoption

    • coeliac disease

    • atrophic gastritis

    • H.Pylori infection

  • Pharmacological

    • medicines that cause gastric erosions/ulceration

      • NSAIDs

      • steroid

    • medicines that interfere with coagulation/platelet

      • OAC

      • SSRI

  • increase demands

    • pregnancy

    • growth spurts

  • dietary deficiency

    • vegans

    • older people

    • toddlers fed exclusively milk

  • other

    • blood donation

    • blood loss from non-gi sources

      • nosebleeds

      • trauma

      • surgery

• hook worm infection most common cause in developing nations

• Coeliac serology should be considered for all people with unexplained iron deficiency anaemia

  • 10-15%

Red flags:

• Upper and lower GI studies considered in all males and post menopausal

• FOB not beneficial for investigating people iwth iron def. anaemia

• insensitive

• non specific

• GI symptoms and unexplained anaemia -> urgent referral

• especially aged >50yo

• family history of colorectal cancer

• males \<110 and non-menstruating F \<100 == urgent referral

• those who don’t respond: referred

tests

• serum iron:

  • decreased where iron deficiency anaemia

  • acute and chornic inflammation

  • increase in thalassaemia and siderolastic

  • also affected by recent diet and time of day

  • give an idea about dynamic iron trasnport rather than stores

• Total iron binding capacity

  • measure of maximum amount of iron blood can carry

  • = serum transferrin

  • noraml/increase in people with iron deficiency

  • decreased in chronic inflammation

  • unchanged thalassaemia/sideroblastic

• Transferrin saturation

  • calculated from serum iron and iron binding capacity

  • measure of iron trafficking and avialbaity for erythropeoiesis

  • not a measure of iron stores

  • elevated fasting transferrin saturation indication of iron loading

• Serum soluble transferin receptor

  • mesaure of erythropoietic activity

  • related to number of erythroblasts in marrow

  • less affected by inflammation than serum ferritin

  • elevated chronic haemolysis, iron def. ineffecteive myelodysplasia

Iron deficinency without anaemia

• iron deficiency doesn’t always develop into anaemia

• 3 times more common than iron deficeiency anaemia

• latent iron deficiency

• lack of clear guidelines

• supplement symptomatic patients

• malignnacy is rarely detected in patients with iron deficiency without aneamia

  • considered >50yo

• if recurs within 12mo consider coeliac disease and GI malignancy

Management

• review and correct any dietary factors

• coeliac - begin gluten free diet

  • correct iron, b12, calcium, vitD

• oral iron supplementation

  • 100-200mg elemntal iron/day

    • ferrous fumarate 200mg (65mg) 2-3/day (FS)

    • ferrous sulphate 325mg (105mg) 1-2/day (PS)

  • vit C no longer thought to meaningfully increase uptake

  • take on empth stomach

  • GI irritation can occur

    • nausea

    • epigastic pain

    • altered bowel function

      • inc. fibre and fluid intake

  • Hb should rise 1g/L / day

  • 20g/L higher after 3-4 weeks

• iron tranfusion

  • consider if unable to tolerate oral iron supplementation

  • not for women who are pregnant

  • caution if immune/inflammatory condition

    • asthma/eczema/RA

      • higher risk of allergic reaction

  • iron polymaltose 318mg/2mL (100mg/2mL elemental iron)

    • IV

  • total dose of elemental iron should be 1500mg for most patients

  • lower dose recommended in elderly or frail people with mild anaemia (Hb ≥ 100)

  • 0.9% NaCl 250 given as infusion fluid @#@ 125mL/hr

  • test dose no longer recommended

  • infusion slowed if GI adverse effects ccur

  • Hb q3months for 1yr to monitor relapse

Anaemia of chronic disease

• also associated with normocytic

• cause by reduced iron availability due to body lowering plasma iron levels

• increase phagocytosis of RBC by macrophages

• Ferritin raised - acute phase protin

• typically mild anaemia

• Causes:

  • Situations of chronic inflammation

    • chronic infections

    • autoimmune conditions

      • RA

      • SLE

      • IBD

    • malignancy

    • cytokines inhibit iron trasnport by blockign iron from leaving macrophages

    • functional iron deficiency

      • also suppress EPO secretion

  • Chronic heart failure

    • multifactoral

      • iron def.

      • chronic inflammation

      • renal disease

      • ACEi/ARB

        • block AT2 -> reduce circulating EPO

  • Chronic kidney disease

    • inadequate EPO

    • chronic inflammation

    • RBC survival shortened

Haemoglobinopathies

• Thalassaemia

• more common in certain ethnicities

  • SE asian (alpha)

  • mediterranean (beta)

  • Pacific

• hypochromic microcytic red cells

• ineffective erythropoiesis

• imbalance in synthesis of alpha and beta globin chains

• severity depends on number and nature of mutations

• those with thalassaemia major require regular blood transfusion to reduce effects of aneamia nad iron chelation treatment

  • reduce iron toxicity

• folate and low iron diet

Sideroblastic anaemia

• mixed group of inherited and acquired disorders

• underlying cause = poor iron incorporation into haem

• dimorphic blood bilm

• rare

• commonly due to myelodysplasia

• excesive etoh

• heavy metal poisoning

• medicines

• copper deficiency

Normocytic anaemia

• primary causes:

  • Acute blood loss

  • haemolysis

  • early stage nutirent deficiencies

  • kidney disease

  • chronic disease

  • bone marrow disorder

• request reticulocyte count

  • determine: decrease RBC production or increase loss

• LFTs Cr and CRP

Heamolytic anaemia

• reticuloctye >2,5 time normal

• clinical features:

  • scleral jaundice

  • pallor

  • disoclouration of urine

  • splenomegaly

  • hepatomegaly

• bilirubin, LDH increase and haptoglobin low

• direct Coombs (antiglobulin) = autoimmune haemolytic anaemia

Macrocytic anaemia

• can be further classified:

  • megaloblastic

    • developing RBC larger than normal with nuclei less amture than their surrounding cytoplasm

    • DNA synthesis defective and slwoer compared to rest of cell

    • hypersegmented nuclei nutrophils

    • Vit b12/folate = usual casue

      • co-factors for DNA synthesis

      • causes;

        • coeliac disease

        • IBD

        • Crohn’s disease

        • long term etoh

      • may present with glossitis, angular stomatitis

      • severe deficiency: peripheral neuropahty, motor disturbances, visual disturbances, cognitive changes ranging from memory loss to demetia and psychiatric

    • medicines

      • methotrexate

      • trimethoprim

      • COCP

      • phenytoin

      • metformin

        • decrease absorption of vit b12

      • hydroxyurea

  • non-megaloblastic

    • DNA synthesis not affected

    • EtOH, liver disease, meylodysplasia

  • myelodysplasia commonly present with macrocytic anaemia with normal b12 and folate levels

  • myeloma (paraprotein) can cause increase in MCV without macrocytes being present

red flags = refer:

• MCV > 100 with accompanying cytopenia

• persistent and unexplained MCV >104

• VitB12 def. of unknown cause

investigating b12/folate deficiency

• investigate for coeliac disease

  • and other GI conditions

• pernicious anaemia

  • anti-parietal cell antibodies

    • High sensitive 90%

    • most pernicious anaemia will have positive

    • low speicific

      • high false positive

    • if + and IF - then not diagnostic but likely suggestive

  • intrinsic factor antibodies

    • very specific and virtually diagnostic

    • sensitivity low (60%)

  • associated with autoimmune destruction of gastric parietal cells

  • if neurological involvement d/w neurolgist

Treatment

• 1mg hydroxocobalamin IM 3 times/week for 2 weeks then 1mg every 3 months

  • foods rich in b12: meat, milk, eggs, fortified yeast extracts

• Folate;

  • 5mg folic acid daily for four months (or until term in pregnant women)

  • dietary folate levels increase by eating green vege, citrus, wholemeal bread, legumes, liver

  • pregnant and BF 50%-25% more folate/day than average adult