An approach to CBC for practitioners

Dr. RM. Subbaiah,

Clinical haematologist, Kauvery Hospitals, Trichy, India

Background

The complete blood count is the most common blood investigation done in the world, be it a primary healthcare centre in a rural area or the most advanced referral care centre in the country. It’s essential for every practitioner to understand the basics of CBC interpretation. A simple CBC could be analysed by automated coulters within a few minutes and could give enormous information about a patient’s status. It’s a simple investment which gives high dividends and continues to be the most common blood test done in the evaluation of a patient. Newer versions of existing automated coulters have incorporated cytomorphometry where complex analyses of cells flown are done aiding in diagnosis. CBC with a careful and meticulous peripheral smear examination is a powerful initial tool in the diagnosis of many haematological and non-haematologic disorders. It’s essential for every practitioner to understand reading a basic CBC for a successful outcome in patient management.

Interpretation parameters

When a CBC report or a printout from a Coulter is obtained, one will see numerous parameters. Red cells, white cells, and platelet are three lineages represented as quantity along with their respective indices. Red cell average size in volume (MCV), the average amount of haemoglobin within each cell (MCH), the average concentration of haemoglobin per unit volume of the red cell (MCHC), distribution width (numerical counterpart of cell size variation), red cell proportion of blood or solid component (PCV) are red cell parameters in a CBC report. Similarly, for platelets, the average size in volume (MPV), and distribution width can be seen. Total White cell count and differential count (neutrophils, lymphocytes, monocytes, eosinophils and basophils) can also be seen. Some coulters have 3 parts only as a differential (neutrophils, lymphocyte and mid-series) where eosinophils, basophils and monocytes are grouped as mid-series cells. Abnormal cells and nucleated red cells should also be looked for if any. Normal values if known is better though labs do print reference values aside.

Anaemia approach

Haemoglobin less than 13 g% in males, less than 12 g% in females and less than 11 g% in pregnancy needs evaluation. Paediatric age group anaemia would be based on nomograms with specific values for age and sex. MCV and reticulocyte count (some Coulters have it automated) are 2 important parameters which help in classifying or categorising anaemia. MCV less than 80 fL would be microcytic anaemia. Iron deficiency, Thalassemias, anaemia of chronic disease and sideroblastic anaemia must be considered. Mostly the bet is between the first two causes. Low RBC count and increased red cells distribution width would favour iron deficiency anaemia. Serum ferritin done in the absence of inflammatory conditions would help in confirming it or ruling it out. Mentzer index (MCV/RBC) if less than 13 would favour Thalassemia. Peripheral smear helps a lot in differentiating both. Anaemia of chronic disease usually has an underlying chronic illness or a systemic illness causing it, MCV is mildly microcytic (usually >75 fL) or near normal. Sideroblastic anaemia is very rare where frequent transfusion, organomegaly and inappropriately low retic count would give clues and always require a bone marrow examination.

MCV of more than 100 fL would be defined as macrocytic anaemia. Vitamin B12 or folate deficiency, liver disease, hypothyroidism, antiretroviral therapy or hydroxyurea-induced, acute haemolytic anaemia needs to be considered. Peripheral smear examination and other biochemical evaluation (indirect bilirubin, raised LDH) for haemolytic anaemia along with reticulocyte count would help. Autoimmune haemolytic anaemia might have marked macrocytosis (MCV more than 130 fL) due to clumping or red cells. High normal MCV or mildly macrocytic red cells (MCV 100-110 fL) with moderate thrombocytopenia (50-100 K/cu.mm) and giant platelets may be due to chronic liver disease. An inappropriately low retic count would guide towards the need for a bone marrow examination. Macrocytic anaemia with inappropriately low retic count and normal LDH should raise the suspicion of a myelodysplastic syndrome. Acute blood loss may present with normocytic or mild macrocytic anaemia, due to reticulocytosis whereas chronic blood loss presents as microcytic anaemia usually due to underlying iron deficiency state.

MCV between 80-100 fL would be defined as normocytic anaemia. Inflammatory, infiltrative marrow pathology or renal failure should be considered. Unexplained normocytic anaemia with Rouleaux formation may give a clue towards paraproteinemia. Most scenarios of normocytic anaemia with an inappropriately low retic count would need a bone marrow examination.

A peripheral smear examination may sometimes clinch a diagnosis in certain infections such as malaria, filariasis, Babesiosis, and infectious mononucleosis.

Leucopenia approach

In clinical practice acquired leucopenia (T WBC < 4000/cu.mm) is more common than inherited conditions. Infection (viral infections, enteric fever, sepsis) or drugs (antineoplastic, NSAIDs, Azathioprine, antimicrobials, antiepileptics, deferiprone, methimazole) should be ruled out. If the above aetiologies have been ruled out and if cytopenia has been persisting for a few weeks then autoimmune disorder or Myelodysplastic syndrome should be ruled out. Peripheral smear examination and marrow studies would be required in most unexplained cases. Steroids, antithymocyte globulin, Covid-19 can cause lymphocytopenia. Monocytopenia is characteristic in hairy cell leukaemia where the patient presents with pancytopenia and splenomegaly. Often leukaemia or infiltrative marrow disorders may present as leucopenia. Congenital causes of neutropenia like Kostmann syndrome are extremely rare. Absolute neutrophil count <500/cu.mm is an emergency and patients with fever (febrile neutropenia) should be managed at the earliest with strict aseptic and supportive care.

Thrombocytopenia approach

Low platelet count could be transient as in infections (acute febrile illness), due to drugs (NSAIDs, antimicrobials) or chronic as in sequestration or marrow failure disorders. Pseudothrombocytopenia (artefactual clumping of platelets due to EDTA effect in vitro) should be ruled out by a careful smear examination. Thrombocytopenic emergencies (DIC, TTP, HUS) should also be ruled out by a careful smear examination for schistocytes or fragmented red cells. Clinical examination for palpable splenomegaly or adenopathy is important. Chronic liver disease or portal hypertension may result in thrombocytopenia due to sequestration. LFT, LDH, PT, aPTT any help in many cases. Chemotherapy or radiotherapy could cause cytopenia depending upon the intensity and duration of exposure. Pregnancy-associated thrombocytopenia is a special scenario and pregnancy-specific aetiologies (GTP, HELLP, PIH, AFLP) should be ruled out. Immune thrombocytopenia is a diagnosis of exclusion where all other possible causes are ruled out. ITP usually has no palpable organomegaly or adenopathy and also drugs should not be an offending agent. MDS can present as thrombocytopenia, especially in the elderly. Bone marrow examination would be needed in many instances. An associated splenomegaly can give a clue towards sequestration, lymphoma or storage disorders (in the paediatric age group) or haemophagocytic lymphohistiocytosis. Platelet count >30000/cu.mm is unusual to cause spontaneous bleeding in the absence of haemostatic challenge or platelet function abnormality.

Cytosis and approach

An expansion in red cell mass (Hb > 16.5 g% in males and Hb > 16 g% in females) should prompt an evaluation for polycythaemia especially if patients present with thrombosis. Haemoconcentration should be ruled out as in dehydration, and burns. Cardio-pulmonary disorders causing hypoxemia and subsequent erythrocytosis should be ruled out. A simple pulse oximetry or a blood gas analysis may give a clue. Microcytic blood picture, true erythrocytosis, splenomegaly and hyperuricemia may give clues towards a primary polycythaemia rubra vera. Erythropoietin, JAK2 mutation analysis, and bone marrow examination may be needed.

Raise in white cell count or platelet count with the presence of splenomegaly and absence of inflammation or other reactive conditions should raise the possibility of a myeloproliferative neoplasm (CML, PMF, ET, CEL, CNL, Mastocytosis). Left shift, basophilia, leucoerythroblastic blood picture, and tear drop cells may be pointers on a blood film for an underlying myeloproliferative neoplasm. Eventually, most patients would require a bone marrow examination, cytogenetic studies and molecular studies for MPN-related mutations. A dry tap would give a clue towards a myelophthisic process or myelofibrosis. Adequate trephine biopsy is mandatory in such cases. Leucocytosis with cytopenia involving other lineages could be acute leukaemia. Immunophenotyping may be needed in characterising the blasts only after morphological examination of bone marrow blasts.

Samples for cytogenetic studies and ancillary molecular tests where RNA extraction is needed (BCR-ABL, transcripts in acute leukaemia) should reach the lab inappropriate time after appropriate collection and transport conditions. History, and physical findings should be mentioned properly in the test request form.

Conclusion

CBC approach has been pivotal for diagnosing haematological and suspecting many non- haematological disorders. The age-old teaching of eliciting history carefully, meticulous physical examination, basic and ancillary investigations will clinch a diagnosis in most scenarios. Picking and addressing the abnormalities on CBC with a proper peripheral blood film examination is the crux of the whole exercise in the diagnosis and management of blood disorders. This exercise is more of a problem-solving approach, where proper algorithmic evaluation and constant practice by a physician would culminate in a rapid diagnosis with the least possible investigations thereby reducing costs and improving patient outcomes. Investing time in understanding and reading CBCs is a fruitful exercise for practitioners.

Dr. R. M. Subbaiah

Consultant Hemato Oncology

An approach to CBC for practitioners