Hematology & Oncology
1. What this chapter covers, and how NEET PG actually tests it
Stems give a blood count with indices, a smear description, a coagulation profile, or an acute complication in a patient with cancer.
The organising principle differs between the two halves.
In haematology the sequence is fixed: the count tells you which lines are affected, the indices narrow the cause, the smear characterises it, and one confirmatory test settles it.
In oncology the first question is never the diagnosis but the intent: is this treatable with cure in mind, and is there an emergency that must be handled before the cancer itself.
2. Anaemia
2.1 Sorting by cell size
Mean corpuscular volume divides anaemia into three groups before any other information is considered.
| Microcytic | Macrocytic | Normocytic |
|---|---|---|
| Iron deficiency | Vitamin B12 or folate deficiency | Acute blood loss |
| Thalassaemia | Alcohol, liver disease | Anaemia of chronic disease |
| Anaemia of chronic disease | Hypothyroidism | Haemolysis |
| Sideroblastic anaemia | Myelodysplasia | Renal failure |
Anaemia of chronic disease appears twice because it begins normocytic and becomes microcytic as it progresses.
2.2 Separating the microcytic causes
| Test | Iron deficiency | Thalassaemia trait | Chronic disease |
|---|---|---|---|
| Ferritin | Low | Normal | Normal or high |
| Total iron binding capacity | High | Normal | Low |
| Red cell count | Low | Normal or high | Low |
| Red cell distribution width | High | Normal | Normal |
Ferritin is an acute phase reactant, so a normal value does not exclude iron deficiency in an inflamed patient, and transferrin saturation must then be used instead.
The Mentzer index, the mean corpuscular volume divided by the red cell count, is below thirteen in thalassaemia trait and above thirteen in iron deficiency, because the thalassaemic marrow produces many small cells while the iron-deficient marrow produces few.
Beta thalassaemia trait is confirmed by a raised haemoglobin A2 on electrophoresis, which matters greatly in India for genetic counselling of couples.
2.3 Megaloblastic anaemia
Vitamin B12 and folate deficiency produce identical blood pictures with hypersegmented neutrophils and oval macrocytes.
Methylmalonic acid is raised only in B12 deficiency, because folate is not involved in that pathway, and neurological features occur only with B12.
Folate given alone to a B12-deficient patient corrects the anaemia but precipitates or worsens subacute combined degeneration, which is why B12 is replaced first whenever both are deficient or the status is uncertain.
3. Haemolysis
Haemolysis is established before its cause is sought, and four findings do that: a raised lactate dehydrogenase, raised unconjugated bilirubin, low haptoglobin and reticulocytosis.
| Feature | Intravascular | Extravascular |
|---|---|---|
| Site | Circulation | Spleen and liver |
| Haptoglobin | Very low | Moderately reduced |
| Urine | Haemoglobinuria, haemosiderinuria | Normal |
| Spleen | Not enlarged | Enlarged |
The direct antiglobulin test separates immune from non-immune causes and is the single most useful next test once haemolysis is confirmed.
| Condition | Diagnostic feature |
|---|---|
| Glucose-6-phosphate dehydrogenase deficiency | Bite cells and Heinz bodies after an oxidant trigger |
| Hereditary spherocytosis | Spherocytes, abnormal membrane binding assay, splenomegaly |
| Paroxysmal nocturnal haemoglobinuria | Loss of CD55 and CD59 on flow cytometry, thrombosis |
| Autoimmune haemolysis | Positive direct antiglobulin test |
Enzyme assay in glucose-6-phosphate dehydrogenase deficiency is falsely normal during an acute crisis, because the deficient old cells have already been destroyed and the surviving young cells have near-normal enzyme levels, so testing is deferred for some weeks.
4. Bleeding disorders
4.1 Which system has failed
| Feature | Platelet or vessel defect | Coagulation factor defect |
|---|---|---|
| Site | Skin and mucous membranes | Joints, muscles, deep tissue |
| Lesion | Petechiae, purpura | Haematoma, haemarthrosis |
| Timing after injury | Immediate | Delayed |
4.2 Interpreting the screen
| Prothrombin time | Activated partial thromboplastin time | Interpretation |
|---|---|---|
| Prolonged | Normal | Factor VII, early warfarin, early liver disease |
| Normal | Prolonged | Haemophilia A or B, von Willebrand disease, heparin |
| Both prolonged | Both prolonged | Common pathway, disseminated coagulation, advanced liver disease |
A mixing study distinguishes deficiency from inhibitor: correction on adding normal plasma indicates a missing factor, while failure to correct indicates an inhibitor such as a lupus anticoagulant or an acquired antibody.
Von Willebrand disease is the commonest inherited bleeding disorder and produces a mixed picture, because von Willebrand factor also carries factor VIII.
4.3 The thrombocytopenias
| Condition | Distinguishing feature |
|---|---|
| Immune thrombocytopenia | Isolated low platelets with an otherwise normal count and smear |
| Thrombotic thrombocytopenic purpura | Deficient ADAMTS13, fragmented cells, fever, renal and neurological features |
| Haemolytic uraemic syndrome | Children, preceding bloody diarrhoea, prominent renal failure |
| Disseminated intravascular coagulation | Low platelets with prolonged times, low fibrinogen, high D-dimer |
Platelet transfusion is contraindicated in thrombotic thrombocytopenic purpura, because the problem is excessive platelet consumption in microthrombi and adding platelets fuels the process. Plasma exchange is the treatment and is urgent.
Fibrinogen falls in disseminated intravascular coagulation and not in the other thrombocytopenias, which is the most useful discriminating measurement.
4.4 Thrombosis and anticoagulation
Inherited thrombophilia is suspected in unprovoked thrombosis, thrombosis in an unusual site, recurrent events, or a strong family history.
Factor V Leiden is the commonest inherited cause, and it works by making activated factor V resistant to cleavage by protein C.
Antiphospholipid syndrome is the acquired cause that must not be missed, because it causes both arterial and venous thrombosis and recurrent fetal loss, and it paradoxically prolongs the activated partial thromboplastin time while causing clotting rather than bleeding.
That paradox is the point: the antibody interferes with the phospholipid-dependent laboratory reaction but promotes thrombosis in vivo, which is why the prolonged time does not correct on mixing.
Testing for thrombophilia is deferred until the patient is off anticoagulation and away from the acute event, because both the clot and the treatment alter the levels being measured.
5. Transfusion
Group O red cells lack A and B antigens and can be given to anyone, while group AB plasma lacks anti-A and anti-B and is the universal plasma donor.
| Reaction | Timing and cause |
|---|---|
| Acute haemolytic | Minutes; ABO incompatibility, usually a clerical error |
| Febrile non-haemolytic | Within hours; cytokines and leucocyte antibodies |
| Allergic or anaphylactic | Minutes; plasma proteins, severe in immunoglobulin A deficiency |
| Transfusion-related acute lung injury | Within six hours; donor antibodies against recipient leucocytes |
| Circulatory overload | Within six hours; volume rather than immunology |
| Delayed haemolytic | Days to weeks; anamnestic antibody response |
Acute haemolytic reaction is almost always a bedside identification error rather than a laboratory failure, which is why patient identity is checked at the bedside against the unit immediately before transfusion.
Transfusion-related lung injury and circulatory overload both cause breathlessness within six hours, and the distinction is that overload has raised venous pressure and responds to diuresis while lung injury does not.
Massive transfusion depletes platelets and clotting factors and causes hypocalcaemia through citrate binding, hypothermia and hyperkalaemia from stored cells.
6. Leukaemia and lymphoma
| Disease | Genetic or morphological hallmark |
|---|---|
| Chronic myeloid leukaemia | t(9;22), the BCR-ABL fusion, treated with tyrosine kinase inhibitors |
| Acute promyelocytic leukaemia | t(15;17), treated with all-trans retinoic acid |
| Burkitt lymphoma | t(8;14) placing MYC under immunoglobulin control |
| Follicular lymphoma | t(14;18) overexpressing BCL2 |
| Mantle cell lymphoma | t(11;14) overexpressing cyclin D1 |
| Chronic lymphocytic leukaemia | Smudge cells, elderly, often found incidentally |
| Hodgkin lymphoma | Reed-Sternberg cells, contiguous nodal spread |
Acute promyelocytic leukaemia is the one leukaemia that is a medical emergency at diagnosis, because it presents with disseminated intravascular coagulation, and retinoic acid is started on clinical suspicion before genetic confirmation.
Chronic myeloid leukaemia was transformed by tyrosine kinase inhibition from a fatal disease into one with near-normal life expectancy, and it is the standard example of targeted therapy.
Hodgkin lymphoma spreads contiguously from one nodal group to the next, which is why staging is predictable, while non-Hodgkin lymphoma spreads unpredictably.
B symptoms, meaning fever, drenching night sweats and unexplained weight loss, upstage the disease and indicate a worse prognosis in both groups.
Painless lymphadenopathy that becomes painful after alcohol is a curious but genuine association with Hodgkin lymphoma, and it appears in examinations more often than in clinics.
Multiple myeloma produces hypercalcaemia, renal impairment, anaemia and lytic bone lesions, with a monoclonal band on electrophoresis and rouleaux on the smear.
Myeloma lesions are purely lytic and therefore do not show on an isotope bone scan, which detects osteoblastic activity, so a skeletal survey or whole-body imaging is used instead.
6.1 The myeloproliferative neoplasms
These are clonal disorders of a marrow stem cell producing too many mature cells rather than blasts, and three of the four share a single mutation.
| Disorder | Feature |
|---|---|
| Polycythaemia vera | Raised haematocrit with a low erythropoietin; JAK2 mutation in almost all |
| Essential thrombocythaemia | Sustained high platelet count without another cause |
| Primary myelofibrosis | Marrow fibrosis, dry tap, tear-drop cells, massive splenomegaly |
| Chronic myeloid leukaemia | BCR-ABL fusion rather than JAK2 |
A low erythropoietin with a high haematocrit indicates a primary marrow disorder, while a raised erythropoietin indicates a secondary cause such as hypoxia, smoking or a tumour secreting the hormone.
Aspirin and venesection are the mainstay in polycythaemia vera, because the complications that kill are thrombotic rather than related to the cell count itself.
Tear-drop poikilocytes with a leucoerythroblastic film indicate marrow infiltration or fibrosis, and they point to myelofibrosis or metastatic marrow disease rather than to any deficiency.
7. Oncological emergencies
These are examined more often than the cancers themselves, because each requires action before diagnosis is complete.
| Emergency | Immediate action |
|---|---|
| Febrile neutropenia | Broad-spectrum antibiotics within one hour, before cultures return |
| Spinal cord compression | High-dose dexamethasone and urgent magnetic resonance imaging of the whole spine |
| Superior vena cava obstruction | Assess airway, imaging, then histology before treatment where possible |
| Tumour lysis syndrome | Aggressive hydration, allopurinol or rasburicase |
| Hypercalcaemia of malignancy | Intravenous saline, then a bisphosphonate |
Imaging of the whole spine is specified in cord compression because multiple levels are involved in a substantial minority, and treating only the symptomatic level leaves disease behind.
Tumour lysis produces high potassium, high phosphate, high urate and low calcium, and the calcium falls because it precipitates with the released phosphate.
Calcium is not replaced in tumour lysis unless the patient is symptomatic, since giving it worsens calcium phosphate deposition in the kidney.
Rasburicase converts urate to a soluble metabolite and is used where the urate load is high, but it causes haemolysis in glucose-6-phosphate dehydrogenase deficiency and must be avoided there.
Febrile neutropenia is defined by a single temperature above a threshold with a neutrophil count below half a thousand per cubic millimetre, and the one-hour antibiotic target exists because mortality rises measurably with each hour of delay.
Waiting for a source to be identified is the commonest and most dangerous error, since no focus is found in the majority of episodes and the absence of localising signs reflects the missing neutrophils rather than the absence of infection.
8. Paraneoplastic syndromes
| Syndrome | Usual tumour |
|---|---|
| Inappropriate antidiuresis | Small cell lung carcinoma |
| Ectopic corticotropin | Small cell lung carcinoma |
| Parathyroid hormone-related peptide | Squamous cell carcinoma |
| Lambert-Eaton myasthenic syndrome | Small cell lung carcinoma |
| Polycythaemia | Renal cell carcinoma, hepatocellular carcinoma |
Lambert-Eaton improves with repeated muscle use while myasthenia gravis worsens, because the presynaptic defect is partly overcome by accumulating calcium with repeated stimulation.
Paraneoplastic syndromes may precede the tumour by months, which is why an unexplained one prompts a search rather than symptomatic treatment alone.
8.1 Tumour markers and screening
Markers are used for monitoring treatment response and detecting recurrence, and almost never for making a diagnosis.
| Marker | Association |
|---|---|
| Alpha-fetoprotein | Hepatocellular carcinoma, non-seminomatous germ cell tumour |
| Carcinoembryonic antigen | Colorectal carcinoma, used in follow-up |
| Cancer antigen 125 | Ovarian carcinoma |
| Prostate specific antigen | Prostate carcinoma |
| Beta human chorionic gonadotropin | Choriocarcinoma, germ cell tumours |
| Calcitonin | Medullary thyroid carcinoma |
The reason markers do not screen well is arithmetic rather than biology. Most cancers are uncommon in the general population, so even a specific marker generates far more false positives than true ones, exactly as with any test applied at low prevalence.
Screening programmes are justified only where the cancer is common enough, has a detectable pre-invasive stage, and where treating it early demonstrably changes mortality, which is why cervical, breast and colorectal cancers are screened and most others are not.
Cervical cancer screening is the clearest success, because the pre-invasive stage lasts years and can be removed in an outpatient procedure.
9. Worked examples
Example 1. A patient has microcytic anaemia with a normal ferritin and a raised total iron binding capacity. What is the likely diagnosis?
Iron deficiency in an inflamed patient. Ferritin is an acute phase reactant and can be falsely normal, while a raised binding capacity still indicates iron deficiency, since chronic disease lowers it.
Example 2. A patient with fever, fragmented red cells, low platelets and confusion is offered a platelet transfusion. What is wrong?
Thrombotic thrombocytopenic purpura is the likely diagnosis, and platelets are contraindicated because they fuel the microthrombotic process. Urgent plasma exchange is the treatment.
Example 3. A patient with suspected glucose-6-phosphate dehydrogenase deficiency has a normal enzyme assay during a haemolytic crisis. How is this explained?
The deficient older cells have already been destroyed, leaving young cells with near-normal enzyme levels. Testing should be repeated several weeks after recovery.
Summary
In haematology the sequence is count, indices, smear, then one confirmatory test.
In oncology the first questions are the intent of treatment and whether an emergency exists.
Mean corpuscular volume divides anaemia before anything else is considered.
Anaemia of chronic disease starts normocytic and becomes microcytic.
Ferritin is low in iron deficiency and normal or high in chronic disease, but it is an acute phase reactant.
Total iron binding capacity is high in iron deficiency and low in chronic disease.
The Mentzer index is below thirteen in thalassaemia trait and above it in iron deficiency.
Beta thalassaemia trait shows a raised haemoglobin A2, which matters for Indian genetic counselling.
Methylmalonic acid is raised only in B12 deficiency, and only B12 causes neurological features.
Folate alone in B12 deficiency precipitates subacute combined degeneration.
Haemolysis is confirmed by high lactate dehydrogenase, high unconjugated bilirubin, low haptoglobin and reticulocytosis.
The direct antiglobulin test separates immune from non-immune haemolysis.
The enzyme assay is falsely normal during an acute crisis in glucose-6-phosphate dehydrogenase deficiency.
Platelet defects bleed into skin and mucosa immediately; factor defects bleed into joints and muscles late.
A mixing study that corrects indicates deficiency; failure to correct indicates an inhibitor.
Von Willebrand disease is the commonest inherited bleeding disorder and gives a mixed picture.
Platelets are contraindicated in thrombotic thrombocytopenic purpura, where plasma exchange is urgent.
Fibrinogen falls in disseminated intravascular coagulation and not in the other thrombocytopenias.
Acute promyelocytic leukaemia is an emergency, and retinoic acid is started on suspicion.
Chronic myeloid leukaemia is the standard example of successful targeted therapy.
Hodgkin lymphoma spreads contiguously; non-Hodgkin does not.
Myeloma lesions are purely lytic and do not appear on an isotope bone scan.
Febrile neutropenia requires antibiotics within one hour, before cultures return.
Cord compression requires dexamethasone and imaging of the whole spine, not only the symptomatic level.
Tumour lysis lowers calcium because it precipitates with phosphate, and calcium is not replaced unless symptomatic.
Lambert-Eaton improves with repeated use while myasthenia worsens.
Antiphospholipid syndrome prolongs the clotting time in the laboratory while causing thrombosis in the patient.
Thrombophilia testing is deferred until the patient is off anticoagulation and away from the acute event.
Acute haemolytic transfusion reaction is a bedside identification error, not a laboratory one.
Lung injury and circulatory overload both cause breathlessness within six hours, separated by venous pressure and response to diuresis.
A low erythropoietin with a high haematocrit indicates a primary marrow disorder rather than a secondary cause.
Tear-drop cells with a leucoerythroblastic film indicate marrow infiltration or fibrosis.
Tumour markers monitor treatment and detect recurrence; they almost never make a diagnosis.
Markers screen badly because low prevalence generates far more false positives than true ones.
Cervical cancer screening works because the pre-invasive stage lasts years and is removable in clinic.
