Full blood count and blood film
FBE screens, the film diagnoses
- The FBE is a screening test; the film is the diagnostic test. An automated analyser counts and sizes cells - it does not look at them
- *Ask for a film explicitly whenever the diagnosis depends on morphology* - suspected haemolysis, leukaemia, myelodysplasia, TMA, malaria, unexplained cytopenia
Core FBE parameters
| Normal (adult) | |
|---|---|
| Hb | M 130-180, F 115-165 g/L |
| MCV | 80-100 fL |
| MCH / MCHC | 27-33 pg / 320-360 g/L |
| RDW | 11-15% - red cell size variability (anisocytosis) |
| WCC | 4.0-11.0 x10^9/L |
| Platelets | 150-400 x10^9/L |
| Reticulocytes | 0.5-2.5% (25-100 x10^9/L) |
Reference intervals
- The most frequently requested test in medicine
- Reference intervals vary by age, sex, ancestry, pregnancy and altitude
- Duffy-null (benign ethnic) neutrophil count - a lower normal neutrophil range in people of African, Middle Eastern and West Indian ancestry
- Neonates: high Hb, high MCV, high WCC, physiological fall to a nadir at 6-9 weeks
Reading an anaemia - MCV first, then reticulocytes
| MCV | Causes |
|---|---|
| Microcytic (<80) | Iron deficiency, thalassaemia, anaemia of chronic disease (normocytic more often), sideroblastic anaemia, lead |
| Normocytic | Anaemia of chronic disease, acute blood loss, CKD, marrow failure/infiltration, haemolysis, mixed deficiency, hypothyroidism |
| Macrocytic - megaloblastic | B12 and folate deficiency, methotrexate, hydroxyurea, azathioprine, zidovudine |
| Macrocytic - non-megaloblastic | Alcohol, liver disease, hypothyroidism, MDS, reticulocytosis, myeloma |
- Iron deficiency vs thalassaemia trait (both microcytic, both common)
- Iron deficiency: high RDW, low ferritin, low reticulocytes, thrombocytosis
- Thalassaemia trait: normal/low RDW, disproportionately low MCV for the degree of anaemia, normal ferritin, raised red cell count
- Mentzer index (MCV / RBC): <13 -> thalassaemia; >13 -> iron deficiency
Spurious results - always consider before acting
- EDTA-dependent platelet clumping -> pseudothrombocytopenia. Repeat in citrate
- Cold agglutinins -> spuriously high MCV, low RBC and low Hct. Warm the sample
- Extreme leucocytosis -> spurious hyperkalaemia, hypoglycaemia, hypoxaemia on ABG
- Hyperlipidaemia, hyperbilirubinaemia, high paraprotein -> falsely high Hb
- Nucleated red cells counted as lymphocytes; giant platelets counted as red cells
- Delayed transport -> artefactual macrocytosis and cell degeneration
Initial investigation of anaemia
- Hb, haematocrit, MCV/MCH, WCC + differential, platelets, reticulocyte count and blood film - then targeted tests
- Add: ferritin and iron studies, B12, folate, UEC, LFT, TFT, CRP
Red cell morphology - what each finding means
| Finding | Points to |
|---|---|
| *Teardrop cells (dacrocytes)* | *Marrow fibrosis or marrow infiltration* - myelofibrosis, metastatic carcinoma, granulomatous disease |
| Schistocytes / fragments | TMA (TTP, HUS), DIC, mechanical valve, malignant hypertension, burns |
| Spherocytes | Warm AIHA, hereditary spherocytosis, burns, post-transfusion |
| Bite cells / blister cells + Heinz bodies | G6PD deficiency, oxidant drug injury |
| Target cells | Liver disease, thalassaemia, iron deficiency, hyposplenism, HbC |
| Sickle cells | Sickle cell disease |
| Howell-Jolly bodies | Hyposplenism / post-splenectomy, coeliac disease |
| Basophilic stippling | Lead poisoning, thalassaemia, sideroblastic anaemia |
| Rouleaux | Myeloma, Waldenstrom, high ESR/inflammation |
| Red cell agglutination | Cold agglutinin disease |
| Pencil cells, anisopoikilocytosis | Iron deficiency |
| Nucleated red cells + immature granulocytes = leucoerythroblastic film | *Marrow infiltration, myelofibrosis, severe sepsis, massive haemorrhage - always significant* |
White cell morphology
| Finding | Points to |
|---|---|
| Blasts | *Acute leukaemia - urgent* |
| Auer rods | AML (faggot cells -> APML) |
| Smudge/smear cells | CLL |
| Hypersegmented neutrophils (>5 lobes) | B12 or folate deficiency |
| Toxic granulation, Dohle bodies, left shift | Sepsis/inflammation |
| Pelger-Huet (bilobed) neutrophils | MDS (pseudo-Pelger with mycophenolate, tacrolimus) |
| Atypical/reactive lymphocytes | EBV, CMV, toxoplasma, HIV seroconversion, drug reaction |
| Myelocyte bulge + basophilia | CML |
| Hairy cells | Hairy cell leukaemia |
Platelet morphology
- Giant platelets - ITP, MYH9-related disorders, Bernard-Soulier, MPN
- Small platelets - Wiskott-Aldrich
- Clumps -> pseudothrombocytopenia
Infections visible on the film
- *Malaria (request thick and thin films specifically - the parasite is missed on a routine film), babesia, trypanosomes, microfilariae, Borrelia*, intracellular bacteria in overwhelming sepsis
When the FBE demands action today
When the FBE demands action today
- *Blasts on the film* -> urgent haematology referral; consider tumour lysis and DIC
- *Schistocytes with thrombocytopenia -> TMA. Send ADAMTS13, LDH, coagulation screen, DAT - plasma exchange if TTP is possible*
- Neutrophils <0.5 with fever -> febrile neutropenia protocol, antibiotics within 60 minutes
- Platelets <20 with bleeding, or <10 -> transfusion/haematology input
- Pancytopenia -> stop culprit drugs, exclude B12/folate deficiency, refer for marrow examination
- Hb <70 with symptoms -> transfuse; investigate the cause in parallel, never instead
- Leucocytosis >100 with symptoms -> hyperleucostasis; urgent cytoreduction
When to request a marrow examination
- Unexplained cytopenia in >1 lineage, leucoerythroblastic film, suspected leukaemia/myeloma/lymphoma, staging, suspected MDS, unexplained splenomegaly, pyrexia of unknown origin
Practical
- Always compare with previous results - a trend answers more questions than a single value
- *Ring the laboratory and speak to the haematologist* - the morphologist's description is worth more than the numeric report
Film findings by condition
- Hyposplenism - Howell-Jolly bodies, target cells, acanthocytes, thrombocytosis, lymphocytosis (coeliac disease, sickle cell, post-splenectomy)
- Myelofibrosis and marrow infiltration - teardrop cells, leucoerythroblastic film
- Lead poisoning - basophilic stippling, microcytic anaemia
- Alcohol - macrocytosis, thrombocytopenia, target cells
- Liver disease - target cells, acanthocytes, macrocytosis
- B12/folate deficiency - hypersegmented neutrophils, oval macrocytes, pancytopenia
- Malaria and other blood-borne parasites
- Paraproteinaemia - rouleaux, blue background staining
Trajectory and response times
- The FBE is a snapshot; the trajectory is the diagnosis
- Response times to remember:
- Reticulocyte response to haematinic replacement: peaks day 5-10
- Hb rise on iron: ~10 g/L per week
- Chemotherapy neutrophil nadir: day 7-14, recovery by day 21-28
- Platelet increment after transfusion: check at 1 hour and 24 hours (poor increment -> refractoriness)
Traps
- *A normal MCV does not exclude iron or B12 deficiency - mixed deficiency gives a normal MCV with a high RDW*
- *A normal FBE does not exclude marrow disease* - early MDS and myeloma may have a normal count
- An isolated abnormality in a well patient should always be repeated before it is investigated
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