Laboratory reasoning
FBC and blood film — pattern recognition
Overview and approach
Interpret haemoglobin, cells and indices together; blood-film findings may identify urgent pathology.
- Look at the film when counts are abnormal; a film is vital to exclude clots and to look for blasts or dysplasia1.
- Start anaemia with the MCV: sort into microcytic, normocytic or macrocytic, then use the RDW, film and reticulocyte count to narrow the cause3,4.
First sort of anaemia by red cell size3,4.
| MCV | Main causes | Helpful extra clue |
|---|---|---|
| Low (below 80 fL) | Iron deficiency, thalassaemia; occasionally severe anaemia of chronic disease | RDW raised in iron deficiency, usually normal in thalassaemia trait |
| Normal | Anaemia of chronic disease, acute bleeding, haemolysis, CKD, marrow failure or infiltration | RDW normal in chronic disease, raised in haemolysis; check reticulocytes |
| High (above 100 fL) | B12 or folate deficiency, drug toxicity; alcohol and liver disease raise MCV even without anaemia | Oval macrocytes on the film point to B12 or folate |
- Reticulocytes tell you if the marrow is responding: a high count means loss or destruction (bleeding, haemolysis); a normal or low count in anaemia means underproduction (deficiency, marrow disease, low erythropoietin). The raw percentage overstates output in anaemia, so it is corrected for the haemoglobin; a production index above about 2.5 suggests haemolysis, below 2 an underproduction or maturation problem3,4.
- Reticulocytes start rising about 5-7 days after iron is started, which is the earliest sign that treatment is working; no rise suggests non-adherence or a wrong diagnosis3.
Assessment and clinical features
Symptoms, bleeding, infection, medicines, nutrition, ethnicity and prior counts.
- Thrombocytopenia: review drugs started in the previous 10 days (quinine, trimethoprim–sulfamethoxazole, vancomycin, heparin and chemotherapy are common culprits); consider liver disease, splenomegaly, B12 or folate deficiency, HIV, hepatitis C, recent infection or live vaccine, autoimmune disease, pregnancy1.
- Neutropenia: usually transient, related to infection or drugs; review drugs and alcohol; ask about sepsis symptoms2.
- Haemoglobin is a concentration: dehydration raises it; fluid overload and pregnancy (expanded plasma volume) lower it. Straight after an acute bleed it can still be normal, because cells and plasma are lost together; the fall shows once volume is restored3.
- Smoking and living at altitude push haemoglobin up4.
Differentials and investigations
Reticulocytes, film and targeted haemolysis/nutritional studies; several cytopenias suggest a broader process.
- First-line for thrombocytopenia: FBC and film, fibrinogen, D-dimer, clotting, haemolysis screen, B12 and folate, LFTs, HIV and hepatitis serology, renal function1. Isolated neutropenia referral information: serial FBC, E/LFTs, drug and alcohol history; flow cytometry and autoimmune screen if requested2.
- Film clues: polychromasia means young red cells released early (marrow responding, or marrow damaged); Howell-Jolly bodies mean no working spleen; target cells suggest thalassaemia or liver disease; teardrop cells with nucleated red cells suggest myelofibrosis or marrow infiltration; fragments suggest a mechanical valve, burns or microangiopathy; regular spiky burr cells suggest uraemia; basophilic stippling suggests lead poisoning; parasites mean malaria3,4.
- Neutrophilia: bacterial infection (highest in pus-forming infections), non-infective inflammation, tissue damage (surgery, burns, MI), solid tumours, hard exercise, pregnancy. More band forms ("left shift") means the marrow is pushing out young neutrophils in response to infection or inflammation3.
- A very high white count (often above 50 × 10^9/L) made of immature myeloid cells, with raised basophils, suggests chronic myeloid leukaemia3.
- Lymphocytosis: EBV (glandular fever) is the commonest cause of a marked isolated rise; also CMV, early HIV, hepatitis, pertussis, TB and toxoplasmosis. A very high lymphocyte count in an older adult is most likely CLL3.
- Eosinophilia: worm infections, allergic disease, sometimes Hodgkin lymphoma. Monocytosis: TB, endocarditis and other chronic bacterial infections3.
- Low counts: some viral infections cause mild neutropenia (often with a normal total white count because lymphocytes rise); overwhelming sepsis, aplastic anaemia, acute leukaemia and bone marrow metastases cause more serious neutropenia. Low lymphocytes occur in HIV, SLE, influenza, burns, surgery and acute inflammation3.
Management and follow-up
Treat cause and seek haematology advice for unexplained or severe abnormalities; transfusion decisions are clinical, not a number alone.
- Asymptomatic platelets 50 to 100 × 10^9/L with no other abnormality: repeat in 1 to 2 weeks; 100 to 150: repeat in a month or more1. Cease a suspected causative drug before referring1.
- Isolated neutropenia, no sepsis: below 0.5 × 10^9/L category 1 outpatient referral; 0.5 to 1.0 category 2; 1.0 to 1.5 category 32.
Red flags and clinical pearls
Blasts, severe neutropenia with fever, major thrombocytopenia/bleeding or microangiopathic haemolysis needs urgent review.
- Emergency referral: neutropenia below 1.0 × 10^9/L with sepsis signs, circulating blasts, abnormal lymphoid cells, low fibrinogen, pancytopenia2. Thrombocytopenia with bleeding, blasts, haemolysis with neurological or renal features (TTP/HUS), heparin exposure with skin necrosis (HIT: stop heparin), or DIC1.
- Blasts are not normally seen in peripheral blood; their presence almost always means an acute haematological malignancy3.
- Ferritin is an acute phase protein, so inflammation can lift it into the normal range despite iron deficiency. A ferritin of 10-15 μg/L means stores are depleted4.
References
- RACGP (AFP): Incidentally detected thrombocytopaenia in adults (2014)
- Queensland Health CPC: Neutropenia (isolated)
- Higgins C. Understanding Laboratory Investigations. 3rd ed. Chichester: Wiley-Blackwell; 2013. Chapter 15, Red blood cell count, haemoglobin and other red cell indices; Chapter 16, White cell count and differential.
- Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. Chapter 57, Anemia and polycythemia.
Last updated from Sen’s notes on 22 October 2026.