A blood film looks at our three cell types (erythrocytes, leukocytes & platelets) under a microscope to identify any abnormalities to give visual clues regarding the functional state of the bone marrow & any systemic diseases.
You should treat this article as a reference for where you can read up on differentials based on the blood film reports you read.
Whilst reviewing a blood film seems like a job specifically for a haematologist, being able to interpret the report of a peripheral blood film can help support your clinical assessment. As a doctor, you can correlate what you see in front of you with the blood film report much like how you’d interpret a chest x-ray or the trend in inflammatory markers.
Contents
Everything in context!
- Unfortunately, there are hundreds of different appearances and many are non-specific or multifactorial
- Therefore, upon reviewing the report consider the long list of differentials listed below & apply this to your clinical assessment of the patient in front of you
- Important factors include the age & whether the patient is clinically well
- Viral illness can cause very odd appearances in children’s blood films
- In an otherwise well patient, an abnormal appearance could be artefactual & simply may need repeating
- Older patients or those with lymphadenopathy/hepatosplenomegaly with an abnormal film are far more concerning of myelodysplastic syndromes or malignancy
Whenever in doubt, a call to a haematologist can help makes things a lot clearer.
Interpretation
First, look at the Full Blood Count (FBC) – this also may be known as a complete blood count or CBC. Here is a list of common abbreviations and their meaning:
| Abbreviation | Result Name | Explanation |
|---|---|---|
| RBC | Red Blood Count | Total RBC count |
| WBC | White Blood Count | Total WBC Count |
| Hgb | Haemoglobin | Grams of Haemoglobin per decilitre (g/dL) |
| Hct | Haematocrit | The proportional volume of blood occupied by RBCs |
| MCV | Mean Corpuscular Volume | Mean RBC volume (i.e. their average size) |
| MCH | Mean Cell Haemoglobin | Amount of haemoglobin per RBC “Hyperchromic/hypochromic” (Does not factor in the size of the RBC) |
| MCHC | Mean Cell Haemoglobin Concentration | The concentration of haemoglobin per unit of RBC volume. (Chromia linked to cell size – more accurate result if MCV is abnormal) |
| RDW | Red Cell Distribution Width | The variation in RBC size |
| Plt | Platelets | Total Platelet Count |
| MPV | Mean Platelet Volume | Mean platelet volume (i.e. size) |
| PDW | Platelet Distribution Width | The variation in platelet size |
The report usually then comments on the appearance of each cell type and then finally any other abnormalities.
Erythrocytes
Normal, healthy erythrocytes (RBCs) are pink, biconcave discs, roughly all the same size, shape and colour (all have a “central pallor” which indicates the biconcave shape). Morphological abnormalities are rarely specific to a single condition but do give clues about the functional problem causing the abnormality.
Abnormalities of Erythrocytes
Written below are the most common abnormalities and their significance.
There is a lot of information here. The functional significance is useful to learn but given the non-specific nature of the abnormalities, the listed pathologies are better used as a reference.
1. Macrocytosis/High MCV (Large RBC)
Type 1:
Functional Significance:
RBCs decrease in size as they mature, so the presence of abnormally large RBCs indicates either disordered erythropoiesis or immature release from the bone marrow.
Associated Pathologies:
Macrocytic anaemias:
• Consequence of Haemolysis
• Pregnancy
• Hypothyroidism
• Chronic Respiratory/Liver Failure
• Aplastic/Pernicious anaemia
Type 2:
Functional Significance:
Oval macrocytosis
Associated Pathologies:
• Megaloblastic Anaemia (Folate/B12 Deficiency)
• Myelodysplasia
Type 3:
Functional Significance:
Round macrocytosis
Associated Pathologies:
Liver disease/alcoholism
The presence of abnormally small RBCs, often seen in association with hypochromia.
Associated Pathologies:
• Macrocytic anaemias:
• Fe-deficiency anaemia
• Thalassaemia
• Anaemia of Chronic-Disease
• Congenital Sideroblastic Anaemia
• Rheumatoid Arthritis
• Sickle Cell Anaemia
Variation in RBC size. The more anisocytosis there is the bigger the RDW will be.
Associated Pathologies:
• Thalassaemia
• Fe-deficiency
• Megaloblastic Anaemia
• Haemolytic Anaemia
• Sepsis
Describes heterogeneity in the size of RBCs, usually two distinctive size populations.
Associated Pathologies:
• Partially treated anaemia
• Mixed deficiency anaemia (e.g. Folate/B12 AND Fe-deficiency together)
• Following transfusion
• Sideroblastic Anaemia
1. Hyperchromia
Functional Significance:
Increased haemoglobinisation and the lack of a central pallor.
Associated Pathologies:
• Spherocytes
• Irreversible sickle cells
• Irregularly contracted cells (ICC or pyknocytes)
Functional Significance:
Impaired staining of RBCs due to reduced Hb in RBC.
Associated Pathologies:
• Fe-Deficiency Anaemia
• Thalassaemias
• Sideroblastic Anaemia
• Chronic inflammation
• Lead poisoning
Heterogeneous staining of RBCs due to RNA retention in larger immature cells, indicates bone marrow stress or haemolysis.
Associated Pathologies:
• Post haemorrhage
• Haemolysis
• Dyserythropoiesis
• Treated deficiency anaemias
1. Reticulocytes/Reticulocytosis
Functional Significance:
Reticulocytes are immature, oversized RBCs released from the bone marrow to circulate for around 1 day before maturing into erythrocytes. They should only comprise of about 1-2% of total RBCs and are a good indicator of bone marrow activity.
Type 1: Increased reticulocyte count
This indicates a high bone marrow activity
Associated Pathologies:
• Haemolytic anaemia
• Post-haemorrhage
• Severe hypoxia
• Polycythaemia, marrow infiltration
• Following marrow recovery post-chemotherapy
• Treatment of deficiency anaemias
This indicates a reduced bone marrow activity or infiltration
Associated Pathologies:
• Aplastic/pernicious anaemia
• Anaemia of deficiency /chronic disease
• Chemotherapy
• Leukaemia/ myeloma/ lymphoma/ other malignancies
• Malnutrition
• Uraemia
• Drugs
Functional Significance:
Nucleated RBCs are a precursor of reticulocytes and still have a nucleus. They should not normally be seen in an adult blood film and are pathological (leucoerythroblastosis). The circulating erythroblasts can be normoblasts (normal maturation), or megaloblasts (megaloblastic changes)
They are released into the bloodstream when:
a) There is a high demand for the bone marrow to produce RBCs so normal precursor cells are released prematurely
Associated Pathologies:
• Severe Anaemia (Haemolytic/Myelophthisic/Haemorrhagic)
• Thalassemia
• Hypoxia
• Sepsis
Associated Pathologies:
• Myelofibrosis
Associated Pathologies:
• Leukaemia
• Lymphoma
• Myeloma
• Secondary metastasis
Functional Significance:
• Rounded RBCs that have lost their biconcave shape due to membrane loss (usually in the spleen) and become spheres.
• This usually indicates active haemolysis.
• As a result of the shape, they cannot bend through capillaries as easily.
Associated Pathologies:
• DIC
• Autoimmune Haemolytic Anaemia
• Post-transfusion reaction
• Hereditary Spherocytosis
• G6PD deficiency
• Severe burns
Functional Significance:
• Similar to spherocytes but elliptical.
• Can cause fewer haemolysis symptoms than spherocytes due to less abnormal shape
Associated Pathologies:
• Hereditary Elliptosis/Spherocytosis
• Myeloproliferative disorder
• Myelodysplastic syndrome
Functional Significance:
• Type of elliptocyte
Associated Pathologies:
• Occurs in Fe-deficiency anaemia
• Thalassaemia trait and syndromes
•Pyruvate kinase disease
Functional Significance:
• Oval/rectangular area of central pallor due to a loss of concavity on one side
Associated Pathologies:
• Liver disease
• Alcoholism
• Electrolyte imbalance
• Hereditary Stomatocytosis
• Rh-null disease
• Obstructive lung disease
• Haemolytic Anaemia
• Volume overload
• Central area of increased staining surrounded by a ring of hypodense straining and a further ring of dense staining at the edge of the cell.
• Occurs due to an increase in the surface membrane to volume ratio, either by increased membrane surface area or decreased intracellular haemoglobin.
• Not specific
Associated Pathologies:
• Thalassaemia
• Severe Fe-Deficiency Anaemia
• Liver disease (cholestasis)
• Sickle cell disease
• Haemoglobinopathies (abnormal inherited forms of haemoglobin – eg. Haemoglobin C trait / CC disease)
• Asplenia
Functional Significance:
• Like codocytes but with thin borders that are also severely hypochromic
Associated Pathologies:
• Liver disease
Functional Significance:
• Fragmented RBCs – caused by intravascular strands of fibrin or spleen dysfunction as the spleen removes RBCs from circulation.
• Small amounts can be seen in a normal individual.
Associated Pathologies:
• Intravenous haemolysis
• Renal failure
• Thrombotic micro-angiopathic Haemolytic Anaemias (TTP, DIC, HUS)
• Malignant hypertension
• Mechanical heart valve
• Atherosclerosis
• Severe burns
• Splenectomy
• Due to compression of RBCs during release either from a fibrosed bone marrow or extramedullary haemopoiesis (RBCs produced outside the bone marrow e.g. Spleen)
Associated Pathologies:
• Myelofibrosis and Myeloproliferative disorders (Leukaemia, Lymphoma, Myeloma)
• Metastatic marrow infiltration (Myelopthtisia)
• Myelodysplastic syndrome
• Severe Fe deficiency
• Hereditary Elliptocytosis/Pyropikilocytosis
• Megaloblastic Anaemia
• Thalassemia
• Organ failure
Functional Significance:
• Crescent shaped RBCs due to misshapen haemoglobin causing rigid sickled RBCs
Associated Pathologies:
• Sickle cell anaemia/disease
• Cytoplasmic projections that fuse together creating a vacuole on the edge of the membrane, giving the appearance of a blister, created by inclusion bodies being removed by splenic macrophages, or by impalement of the RBC by fibrin strands, and the membrane reforming to produce the vacuole.
Associated Pathologies:
• Microangiopathic Haemolytic Anaemias
• Mechanical haemolysis
• Heinz body haemolytic anaemias (G6PD Deficiency, Thalassaemia)
Functional Significance:
• Describes where the splenic macrophages have removed part of erythrocyte (e.g. to remove Heinz bodies – see below).
• If a blister cell ruptures it becomes a bite cell.
Associated Pathologies:
• G6PD deficiency
• Thalassaemia
• Oxidative stress
• Congenital Heinz body anaemia
• Spiculated (spikey / irregularly edged cells) RBCs with 3-20 irregular spicules.
• They are microcytes and lack central pallor unlike echinocytes.
• The cell membrane damage is due to a decrease in membrane cholesterol
Associated Pathologies:
• Asplenia
• Alpha/beta-lipoproteinaemia
• Chronic liver disease
• Renal disease
• Hypothyroidism
• Alpha-Thalassaemia
• Hereditary Acanthocytosis
• Pyruvate Kinase deficiency
• Thrombotic micro-angiopathic haemolytic anaemias (TTP, DIC, HUS)
• Can also be artefact
• Describes cells with many (10-30) regular spicules.
a) Burr Cells: type of Echinocyte, found in patients with uraemia
Associated Pathologies:
• Any cause of Uraemia
• Malnutrition
• Renal failure
• Hypokalaemia
• Liver disease
• Pyruvate Kinase deficiency
Associated Pathologies:
• Artefact (prolonged storage/slow drying)
1. Rouleaux
Functional Significance:
• Stacks/clumps of RBCs which develops when plasma acute-phase protein concentration is high.
• Often an indicator of a high ESR.
Associated Pathologies:
• Infections/Autoimmune conditions
• Chronic inflammation
• Paraproteinaemia
• Multiple Myeloma
• Waldenstroms macroglobulinaemia
• Diabetes Mellitus
• Indicative of bound RBC antibodies.
• Distinguished from Rouleaux by diluting the blood with saline, rouleaux is dispersed but agglutination is not.
• Can falsely increase the MCV
Associated Pathologies:
• Cold haemagglutinin disease
• Waldenstroms macroglobulinaemia
1. Basophilic stippling (punctuate basophilia)
Functional Significance:
• Describes the presence of small granular bodies (denatured RNA fragments) within the RBC cytoplasm due to disordered/accelerated erythropoiesis meaning RBCs with immature cytoplasm are released from the bone marrow.
Associated Pathologies:
• Haemaglobinopathies (Thalassaemias)
• Lead/Arsenic poisoning
• Megaloblastic/Haemolytic/Sideroblastic Anaemia
• Severe infections
• Pyrimidine 5’ Nucleotidase deficiency
• Nutritional deficiencies
• Myelofibrosis
Functional Significance:
• Denatured Haemoglobin due to oxidative damage/unstable Hb.
• Normally removed by the spleen (becoming a bite/blister cell).
• Appears as “nose” or pale circle with specific staining.
Associated Pathologies:
• G6PD Deficiency
• Alpha-Thalassemia
• Autoimmune Haemolytic Anaemia
• Splenectomy/Asplenia
• Use of antioxidant drugs/sulphonamides
• Oxidative stress
• Congenital Heinz body anaemia
• Nuclear remnant found in RBCs, normally excluded before becoming reticulocytes and removed by the spleen
Associated Pathologies:
• Post-splenectomy
• Anatomical/Functional Asplenia
• Hereditary Spherocytosis
• Sickle Cell Anaemia
• Megaloblastic/Fe-deficiency anaemia
• (Rarely in Leukaemia)
• Red staining, circular/figure-of-eight structures thought to represent nuclear membrane remnants.
Associated Pathologies:
• Found in conditions similar to Howell-Jolly bodies
• Phagosomes containing ferruginous granules found in RBCs.
• May contribute to spurious platelet counts by electro-optical counters
Associated Pathologies:
• Iron-overloading disorders (Hereditary Haemochromatosis)
• Sideroblastic anaemia
• Haemolytic anaemia
• Sickle Cell Disease
• Carcinomatosis
• Post-splenectomy
• Characteristic ‘golf ball’ appearance of RBC with Brilliant Cresyl Blue staining which show the haemoglobin H bodies (beta globin chains from impaired formation of alpha-chains)
Associated Pathologies:
• Alpha-thalassaemia
• Haemoglobin H disease
• Parasites seen within the cytoplasm
Associated Pathologies:
• Plasmodium
• Babesia
• Malarial parasites
The haematologist will sometimes give an opinion about differential diagnoses based on the film appearance and the clinical information provided, but it is useful for you to be able to recognise the abnormalities and patterns yourself. For example:
“Hyposplenic film” is a description of the collection of abnormalities found in these patients. They include Howell-Jolly bodies, target cells, occasional nucleated RBCs, lymphocytosis, macrocytosis and acanthocytes. There may also be evidence of infectious mononucleosis, any viral infection, toxoplasmosis and drug reactions.
Leucocytes
- As with Erythrocytes, the number and morphology of each type of leucocyte is assessed in the peripheral smear.
- Leucocytosis is an increase in the number of WBCs and leukopenia is a decrease in the number of WBCs.
- Neutrophils are the most abundant type of leukocytes (40-70%), followed by lymphocytes (20-45%), eosinophils (1-6%), monocytes (2-10%) and basophils (<1%).
- Increases or reductions in any WBC type may be either relative (normal white cell count) or absolute (abnormal white cell count)
Abnormalities of Leukocytes
Thrombocytes (Platelets)
Thrombocytopaenia (decrease in number) can result from:
- Reduced production (bone marrow failure syndromes)
- Increased peripheral destruction (thrombotic micro-angiopathies)
- Increased splenic sequestration (hypersplenism)
Thrombocytosis (increase in number) can result from:
- Infections
- Major surgeries
- Post-splenectomy
- Haemorrhage
- Acute haemolysis
- Fe-deficiency
- Connective tissue disorders
- Use of cytokines, and certain drugs
- Malignant conditions especially myeloproliferative neoplasms (polycythaemia vera, myelofibrosis, essential thrombocythaemia)
Megathrombocytes (increased size) are caused by hyperactivity of megakaryocytes due to increased demand commonly due to B12/folate deficiency or myeloproliferative disorders, or more rarely due to congenital thrombocytopaenic conditions (Bernard-Soulier syndrome, May-Haggelin anomaly (along with Dohle-doy inclusions) or Wiskott-Aldrich syndrome).
Platelet hypogranularity is seen in myelodysplastic syndrome and myelofibrosis, along with megakaryocytes.
Other abnormalities
- Parasite, fungal, or circulating carcinoma cells might be seen
Useful Resources & References
- Buku app – free haematology app
- Labpedia - Red Blood Cells
- Haematology Learning
- Peripheral Blood Film - a review, PubMed Article
- Lab tests online - Blood film
- Patient - peripheral blood film
- Medschool - hypochromia
- Memorang - Anaemia
- Mind the Bleep - Reviewing and Requesting Bloods
- Pathology Student
- Labpedia - Anaemia
- Mind the Bleep - Jaundice and deranged LFTs
- Laboratoryinfo - Anisocytosis
- Haematology Atlas
Written by Dr Kristen Sellick (FY3)
Reviewed by Dr Ailsa Gemmell (IMT1)
Edited by Mr Mudassar Khan (Y3 Medical Student)
6 thoughts on “Interpreting Blood Films”
excellent review
Nice one. This was really helpful. Please review and add more images of other conditions.
Which conditions would you like us to include?
everything is perfect.
Thank you so much!
So educative