Overview

Blood is composed of plasma (a straw-coloured liquid) that carries red blood cells, white blood cells, platelets, clotting factors, glucose, electrolytes, and proteins (such as hormones and immunoglobulins).

Once the red cells and clotting factors are removed from the blood, the remaining solution is called serum.

Blood Cell Lineage

Blood cells develop in the bone marrow, principally found in the pelvis, vertebrae, sternum, and ribs. Cell lines are important in haematology as they are used to identify disease processes.

Haematopoietic stem cells specialise to become one of the following:

  • Myeloid stem cells
  • Myeloblasts
  • Lymphoid stem cells

From here on, these stem cells specialise into more specific cell types as summarised below:

Haematopoietic stem cell lineages

For example, the excessive proliferation of neutrophils and clinical signs and symptoms of leukaemia suggest that there may be myeloid leukaemia, as neutrophils are derived from the myeloid stem cells.

Full Blood Count and Anaemia

Overview

In general, the full blood count shows red cell parameters, a total white cell count (WCC), and white cell differentials – these are the subtypes of white blood cells, usually neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

Anaemia is a symptom and not a disease itself and is the result of pathology somewhere in the body. It describes a reduction in the amount of haemoglobin or red blood cells.

Red cell parameters

The following parameters relate to red cells and are used to help identify the type of anaemia a patient may have:

  • Haemoglobin (Hb) concentration:
    • The concentration of haemoglobin in the blood
    • Used to initially identify problems with the blood, such as anaemia/polycythaemia
  • Mean corpuscular volume (MCV):
    • Measures the average size of red blood cells
    • Classifies anaemia into microcytic, normocytic, or macrocytic categories.
  • Mean cell haemoglobin (MCH):
    • Measures the mass of haemoglobin in a single red blood cell
    • Calculated by dividing haemoglobin by the number of cells present
    • May be low in conditions where red blood cells are smaller (as they can carry less haemoglobin), such as iron-deficiency anaemia
    • May be high in conditions where red blood cells are larger (as they can carry more haemoglobin), such as a B12 deficiency
  • Mean corpuscular Hb concentration (MCHC):
    • Measures the mass of haemoglobin per unit volume of red blood cell
    • Calculated by dividing haemoglobin by the volume of cells present
    • Useful in microcytic anaemias
    • Low in iron-deficiency anaemia and thalassaemia
    • High in dehydration and hereditary spherocytosis 

Microcytic anaemia

Anaemia with a low MCV is microcytic and can be:

Normocytic anaemia

Anaemia with a normal MCV is normocytic and can be:

Macrocytic anaemia

Anaemia with a raised MCV can be further subdivided into:

  • Megaloblastic macrocytic anaemia: – megalocytes (enlarged red cells) and segmented neutrophils are present. Causes may be:
    • Vitamin B12 deficiency
    • Folate deficiency
  • Normoblastic macrocytic anaemia which can be due to:
    • Alcohol
    • Liver disease
    • Hypothyroidism
    • Pregnancy
    • Reticulocytosis
    • Myelodysplastic syndromes

Raised haemoglobin

Polycythaemia is the term used to describe a raised haemoglobin. Its causes can be:

Patients with raised haemoglobin have an increased risk of thrombosis. They usually have other investigations:

  • Haematocrit (packed cell volume):
    • Measures the volume percentage of red blood cells in the sample
  • Red cell count (RCC):
    • Often high in polycythaemia and low in aplasias
  • Red cell distribution width (RDW):
    • Measures the range of red cell sizes in a sample
    • This can help with anaemia

Causes of Anaemia

The following flowchart can help to identify what possible condition someone may have based on blood findings.

Classification of anaemia based on blood findings

White Cell Counts

Overview

White cell count (and differential) provides information about the types and numbers of white blood cells in a person’s blood. They generally measure neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

Neutrophils

Neutrophilia is the term used to describe a raised neutrophil count which can be due to:

  • Bacterial infection
  • Corticosteroids
  • Inflammation
  • Stress/exercise – mild increases are seen here
  • Haematological malignancy

Neutropenia is the term to describe a low neutrophil count which can be due to:

  • Drugs that cause bone marrow suppression e.g. clozapine/carbimazole etc.
  • HIV
  • Epstein-Barr virus (EBV)
  • Haematological malignancy
  • Severe sepsis
  • Ethnic variation – common in people of African descent
  • Chemotherapy
  • Radiotherapy
  • Felty’s syndrome

Lymphocytes

Lymphocytosis is the term used to describe a raised lymphocyte count which can be due to:

Lymphopenia is the term used to describe a lower lymphocyte count which can be due to:

  • Corticosteroid use
  • AIDS
  • Legionella pneumonia
  • Chemotherapy
  • Radiotherapy

Eosinophils

Eosinophilia is the term used to describe a raised eosinophil count which can be due to:

Monocytes

Monocytosis is the term used to describe a raised monocyte count which can be due to:

  • Acute and chronic infection, particularly tuberculosis
  • Haematological malignancy
  • Myelodysplastic syndromes

Basophils

Basophilia is the term used to describe a raised basophil count which can be due to:

  • Viral infections
  • Splenectomy
  • Haematological malignancy

Platelets

Thrombocytosis

Thrombocytosis is the term used to describe a raised platelet count which can be due to:

  • Infection and acute inflammation – platelets are an acute phase reactant
  • Haematological malignancy
  • Essential thrombocytosis
  • Haematological malignancy
  • Hyposplenism/splenectomy
  • Haemolysis
  • Iron-deficiency

Thrombocytopenia

Thrombocytopenia is the term used to describe a lower platelet count which can be due to:

Blood Film

Overview

Also known as a peripheral blood smear, a blood film is where a thin layer of blood is smeared on a slide and examined using a microscope. They provide information about cells including their size, shape, colour, and inclusions.

Red cell abnormalities

Some common red cell abnormalities are as follows:

  • Anisocytosis – variation in red blood cell (RBC) size:
    • Seen in thalassaemia, microcytic/macrocytic anaemia
  • Basophilic stippling – granular bodies in red cell cytoplasm:
    • Seen in thalassaemia, lead poisoning, sideroblastic anaemia 
  • Bite cells:
  • Elliptocytes – oval-shaped cells:
  • Reticulocytes – large immature RBCs which still have RNA in them:
    • Increased when the bone marrow is actively trying to quickly produce red blood cells e.g. haemorrhage/haemolysis
    • Reduced in bone marrow infiltration (e.g. leukaemia, lymphoma, myeloma), or bone marrow suppression e.g. drug-induced, aplastic anaemia etc.
  • Schistocytes – fragmented RBCs:
    • Seen in causes of intravascular haemolysis, haemolysis secondary to mechanical heart valves, renal failure, DIC, and TTP
  • Heinz bodies – denatured haemoglobin due to oxidation:
    • Normally removed by the spleen and are never seen in healthy individuals
    • Seen in G6PD deficiency
  • Howell-Jolly bodies – nuclear remnants in RBCs:
    • Normally removed by the spleen and not seen in healthy individuals
    • Seen in all causes of hyposplenism/splenectomy
  • Poikilocytosis – describes variation in cell shape
  • Rouleaux – stacking of RBCs due to inflammation causing RBC “stickiness”:
    • Suggests inflammation and a high ESR – autoimmune disease, myeloma, paraproteinaemia, and chronic inflammation
  • Spherocytes – spherical RBC shape and suggest active haemolysis:
  • Target cells – RBCs look like an archery target:
  • Teardrop cells:
    • Seen in myelofibrosis, bone marrow metastases, and myelodysplastic

White cell abnormalities

Some common white cell abnormalities are as follows:

  • Auer rods:
  • Blast cells – immature white cell precursors:
    • Seen in myelofibrosis or leukaemia
  • Band cells – immature neutrophil precursors:
    • A mixture of blast and band cells suggests chronic lymphocytic leukaemia due to them being different stages of white cell maturation
  • Hypersegmented neutrophils:
  • Reed-Sternberg cells – multinucleated giant cells:
    •  They can also have a bilobed nucleus with eosinophilic inclusion-like nuclei
    • Associated with Hodgkin’s lymphoma
  • Reactive (atypical) lymphocytes:
    • Seen in infectious mononucleosis
  • Smear (smudge) cells – cells that have ruptured and smudged while preparing the blood film:
    • Seen in chronic lymphocytic leukaemia (CLL)

Iron Studies

Iron studies often involve looking at the following:

  • Serum iron:
    • Iron circulates in the blood as ferric (Fe3+) ions bound to the transferrin protein
    • It varies significantly, therefore it is not a very useful investigation alone
    • Factors affecting serum iron are dietary intake, inflammation, infection, and malignancy
  • Serum ferritin:
    • Ferritin is the form iron takes when stored and is the best value to measure in IDA
    • It is an acute-phase protein meaning it can be falsely normal/increased in inflammation/malignancy
  • Transferrin saturation:
    • This measures the number of binding sites on transferrin occupied by iron. A higher value means that more ‘spots’ for iron are taken up, suggesting more iron in the body.
  • Total iron-binding capacity (TIBC):
    • This measures the number of binding sites available for iron to bind to. A higher value means that there are more free ‘spots’ for iron to take up, suggesting there is less iron in the body.

Coagulation Studies

Coagulation studies often look at the following:

  • Activated partial thromboplastin time (APTT):
    • Measures the intrinsic pathway and common pathway
    • Factors assessed: I, II, V, VIII, IX, X, XI, and XII
    • Affected by:
      • Haemophilia A due to factor VIII deficiency
      • Haemophilia B due to factor IX deficiency
      • Von Willebrand Disease due to VIII deficiency (binds to vWF)
      • Liver disease – the liver synthesises factors I, II, V, VIII, XI
      • Problems with clotting factor synthesis or consumption e.g. disseminated intravascular coagulopathy (DIC)
      • Heparin – mainly inhibits activated factor X (Xa)
      • Antiphospholipid syndrome – lupus anticoagulant prolongs APTT
  • Prothrombin time (PT):
    • Measures the extrinsic pathway and final common pathway
    • Factors assessed: I, II, V, VII, and X
    • Affected by:
      • Deficiency of vitamin K – needed for factors II, VII, IX, X
      • Warfarin use – vitamin K antagonist
      • Liver disease – needed to synthesise factors
      • Problems with clotting factor synthesis or consumption e.g. disseminated intravascular coagulopathy (DIC)
  • International normalised ratio (INR):
    • This is a ratio of the patient’s PT to a control PT. The INR is calculated as there can be differences in PTs depending on the materials and methods used. Each manufacturer assigns and International Sensitivity Index (ISI) value for any testing materials they manufacture, which indicates how those materials compare to an international reference.
    • The INR is used to monitor coagulation in patients taking warfarin

Author