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Complete Guide to Anaemia

Anaemia is not a single diagnosis. It is a symptom with many causes. Identifying the type of anaemia through blood tests is essential before starting any treatment.

Written by Suman Konda, PharmD, Clinical Pharmacist · Editorial policy · Not medical advice

Last updated: · How we check our content

What is anaemia?

Anaemia is defined as haemoglobin below the normal range for sex and age: below 13.5 g/dL in adult men, below 12.0 g/dL in adult women, and below 11.0 g/dL in pregnant women. It affects approximately 1.6 billion people globally, making it one of the most common medical conditions. The cause determines the treatment, which is why a systematic approach using blood tests is essential.

Anaemia pathway by red cell sizeHow mean cell volume narrows the likely cause of anaemia.Red cell size narrows the cause of anaemiaLow haemoglobinNext: look at MCVMCV < 80 fLMicrocyticIron deficiency,thalassaemia, chronicdiseaseMCV 80–100 fLNormocyticBlood loss, chronicdisease, kidney disease,haemolysisMCV > 100 fLMacrocyticB12 or folate deficiency,alcohol, thyroid, drugsThe reticulocyte count then separates reduced production from increased loss or destruction:low reticulocytes point to a production problem, high to bleeding or haemolysis.
Scroll sideways to see the whole diagram
How mean cell volume and reticulocytes narrow the cause of anaemia.
What the diagram shows. Once anaemia is confirmed, the mean cell volume splits the causes into three groups. Small cells suggest iron deficiency or thalassaemia; normal-sized cells suggest blood loss, chronic disease or kidney disease; large cells suggest B12 or folate deficiency, alcohol or thyroid disease. The reticulocyte count then separates a marrow that is not producing enough cells from one responding normally to bleeding or destruction.

Step 1: CBC + blood film, classifying anaemia by red cell size

MCV (mean cell volume)Red cell appearanceLikely cause
Low MCV (<80 fL)Microcytic (small cells)Iron deficiency (most common), thalassaemia, sideroblastic anaemia
Normal MCV (80–100 fL)Normocytic (normal size)Anaemia of chronic disease, haemolysis, blood loss (acute), kidney disease
High MCV (>100 fL)Macrocytic (large cells)Vitamin B12 deficiency, folate deficiency, alcohol, hypothyroidism, liver disease

Step 2: Iron deficiency anaemia workup

TestIron deficiency finding
Ferritin<30 ng/mL (often much lower): most sensitive marker
Serum ironLow
TIBCHigh (body compensates by making more transport protein)
Transferrin saturation<16%
MCVLow (<80 fL)
Blood filmMicrocytic, hypochromic cells; target cells

Why a Normal Ferritin Does Not Rule Out Iron Deficiency

Ferritin is the standard first test for iron stores, and for most people a low result settles the question. The difficulty is what it does when something else is going on, because ferritin is also an acute-phase protein: the body raises it during inflammation, infection, and tissue injury, quite independently of how much iron you actually have.

So inflammation pushes ferritin up while iron deficiency pushes it down, and the two can cancel out. Someone with an inflammatory condition, a chronic infection, kidney disease or obesity can be genuinely iron deficient and still return a ferritin in the normal range. Reviews of iron deficiency in chronic kidney disease make this explicit: inflammation raises ferritin regardless of iron status, and in doing so weakens ferritin’s ability to predict either iron stores or the response to iron treatment.1

The effect is measurable in ordinary populations too. In a study across normal-weight, overweight and obese participants, ferritin rose with body mass index and tracked C-reactive protein closely, while moving in the opposite direction to haemoglobin, serum iron and transferrin saturation — the markers that actually reflect iron availability. Its authors concluded that in these groups ferritin behaves as an inflammation marker rather than an iron marker, and that a full iron profile rather than ferritin alone is needed to identify deficiency.2

What to ask for when ferritin looks normal but you have symptomsA CRP alongside the ferritin, so a raised ferritin can be interpreted rather than taken at face value, and transferrin saturation with total iron binding capacity, which are far less disturbed by inflammation. A low transferrin saturation with a normal ferritin, in someone with a raised CRP, is a recognisable pattern rather than a contradiction.

This matters most in exactly the people most likely to be told their iron is fine: those with inflammatory bowel disease, rheumatoid arthritis, chronic kidney disease, heart failure, or obesity. If you are tired, your ferritin is unremarkable and nobody has looked at your CRP or your transferrin saturation, the question has not been fully answered.

Step 3: Megaloblastic anaemia workup

TestB12 or folate deficiency finding
Serum B12<200 pg/mL (deficiency); <100 (severe)
Serum folate<3.0 ng/mL
MCV>100 fL (macrocytic)
Blood filmOval macrocytes; hypersegmented neutrophils (5+ lobes)
Peripheral blood smearHypersegmented neutrophils are pathognomonic of megaloblastic anaemia

Step 4: Haemolytic anaemia workup

TestFinding in haemolysis
LDHElevated (released from lysed red cells)
Indirect bilirubinElevated (breakdown product of haemoglobin)
HaptoglobinLow or absent (mops up free haemoglobin; depleted in haemolysis)
Reticulocyte countHigh (bone marrow compensating)
Blood filmSpherocytes (hereditary spherocytosis), sickle cells, fragmented cells (microangiopathy)
Direct Coombs testPositive in autoimmune haemolytic anaemia

Common treatments by anaemia type

TypeTreatment
Iron deficiencyFerrous sulfate oral iron (200 mg 2-3x daily) or IV iron; identify and treat source of blood loss
Vitamin B12 deficiencyIM cyanocobalamin/methylcobalamin injections; or high-dose oral B12 (1,000 mcg daily)
Folate deficiencyFolic acid 5 mg daily for 4 months; address underlying cause
Anaemia of chronic diseaseTreat underlying condition; EPO injections for kidney disease-associated anaemia
Thalassaemia (minor)Usually no treatment needed; genetic counselling

Questions to ask your doctor

  • What type of anaemia do I have based on MCV?
  • Why am I iron deficient: is there internal bleeding?
  • Do I need B12 injections or will tablets work?
  • Should I have a haemoglobin electrophoresis for thalassaemia?
  • Is my anaemia related to a chronic illness?

References

The clinical information on this page is drawn from peer-reviewed sources indexed by the US National Library of Medicine. Links go to the source so you can read it yourself.

  1. Ueda N, Takasawa K. Impact of inflammation on ferritin, hepcidin and the management of iron deficiency anemia in chronic kidney disease. Nutrients. 2018;10(9):1173. PMID 30150549 · doi:10.3390/nu10091173
  2. Khan A, Khan WM, Ayub M, Humayun M, Haroon M. Ferritin is a marker of inflammation rather than iron deficiency in overweight and obese people. J Obes. 2016;2016:1937320. PMID 28116148 · doi:10.1155/2016/1937320

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Medical Disclaimer: This page is for general educational purposes only and does not constitute medical advice. Always consult a qualified doctor for diagnosis and treatment.