Haematology Revision Guide ✅

🩸 Haematology becomes much easier when you divide it into four questions: is the problem with red cells, white cells, platelets/coagulation, or bone marrow/lymphoid tissue? For clinical reasoning, always connect the full blood count to physiology: anaemia = oxygen-carrying problem, neutropenia = infection risk, thrombocytopenia = primary haemostasis problem, and coagulation factor deficiency = deep bleeding/prolonged clotting problem.

✅ 1. Core Haematology Principles

🧪 1.1 Reading the Full Blood Count

• Hb: measures anaemia/polycythaemia; interpret with symptoms, MCV and reticulocytes.
• MCV: helps classify anaemia into microcytic, normocytic or macrocytic.
• WCC: total white cell count; look at the differential, not just the total.
• Neutrophils: key for bacterial/fungal infection defence; severe neutropenia is dangerous.
• Lymphocytes: high in viral illness, CLL and some lymphoproliferative disorders.
• Platelets: low increases bleeding risk; high may be reactive or myeloproliferative.
• Reticulocytes: show marrow response; high in bleeding/haemolysis, low in marrow failure or deficiency states.

🧠 Exam pearl: Anaemia is not a diagnosis. The key next step is to use MCV + reticulocyte count + blood film to decide whether the marrow is under-producing cells or responding to blood loss/haemolysis.

🔬 1.2 Blood Film Clues

🩸 2. Anaemia

📉 2.1 Anaemia Symptoms and Signs

• Symptoms: fatigue, breathlessness, reduced exercise tolerance, dizziness, palpitations, chest pain if severe or cardiac disease.
• Signs: pallor, tachycardia, flow murmur, koilonychia in iron deficiency, jaundice in haemolysis, glossitis in B12/iron deficiency.
• Severity depends on Hb level, speed of onset and comorbidity.
• Chronic anaemia may be surprisingly well tolerated; acute bleeding can cause shock before Hb fully falls.

🧱 2.2 Microcytic Anaemia

• Iron deficiency anaemia is the commonest cause worldwide.
• Causes: menstrual blood loss, GI bleeding, pregnancy, poor intake, malabsorption, coeliac disease, bariatric surgery.
• Blood pattern: low Hb, low MCV, low ferritin, high TIBC/transferrin; ferritin may be falsely normal/high in inflammation.
• In adult men and postmenopausal women, iron deficiency anaemia needs GI blood loss/malignancy consideration.
• Thalassaemia trait: microcytosis often disproportionate to anaemia, normal/high RBC count, target cells; confirm with haemoglobin electrophoresis.
• Anaemia of chronic disease can be normocytic or microcytic with low iron but normal/high ferritin.

🌿 2.3 Macrocytic Anaemia

• Megaloblastic causes: vitamin B12 deficiency, folate deficiency, antifolate drugs.
• Non-megaloblastic causes: alcohol, liver disease, hypothyroidism, reticulocytosis, myelodysplastic syndrome, drugs.
• B12 deficiency: neuropathy, posterior column signs, cognitive change, glossitis, macrocytosis.
• Folate deficiency: macrocytosis without neurological signs; risk in poor intake, alcohol, pregnancy, malabsorption and some drugs.
• Do not give folate alone if B12 deficiency is possible because neurological injury may progress.

🧬 2.4 Normocytic Anaemia

• Causes: acute blood loss, anaemia of chronic disease, CKD, haemolysis, marrow failure, mixed deficiencies.
• CKD causes reduced erythropoietin production and functional iron restriction.
• Reticulocyte count helps: high suggests bleeding/haemolysis; low suggests underproduction.
• Consider myeloma, inflammatory disease, malignancy and endocrine causes if persistent unexplained normocytic anaemia.

🧨 3. Haemolysis

Haemolysis means premature destruction of red cells. It may be intravascular or extravascular, inherited or acquired. The marrow usually responds with reticulocytosis unless it is unable to compensate.

• Features: anaemia, jaundice, dark urine, splenomegaly, gallstones, raised reticulocytes.
• Bloods: raised unconjugated bilirubin, raised LDH, low haptoglobin, raised reticulocytes.
• DAT/Coombs test: positive in autoimmune haemolytic anaemia.
• Blood film helps identify spherocytes, schistocytes, sickle cells, bite cells or parasites.
• Intravascular haemolysis can cause haemoglobinuria and AKI.

🧠 Exam pearl: Anaemia plus jaundice plus high reticulocytes is haemolysis until proven otherwise. Add platelets and film: schistocytes with thrombocytopenia should trigger concern for TTP/DIC.

🧬 4. Haemoglobinopathies

🧱 4.1 Sickle Cell Disease

• Autosomal recessive haemoglobinopathy caused by HbS polymerisation under low oxygen states.
• Pathophysiology: sickling causes haemolysis, vaso-occlusion, inflammation and organ damage.
• Triggers for crisis: infection, dehydration, hypoxia, cold, stress, acidosis and pregnancy.
• Painful vaso-occlusive crisis: severe pain often in bones, back, chest or abdomen.
• Acute chest syndrome: chest pain, fever, hypoxia and new pulmonary infiltrate; life-threatening.
• Functional asplenia increases risk of encapsulated organisms; vaccination and prophylactic antibiotics are important in childhood.
• Management includes hydration, analgesia, oxygen if hypoxic, antibiotics if infection suspected, transfusion/exchange transfusion in selected emergencies, hydroxycarbamide for prevention.

🧬 4.2 Thalassaemia

• Inherited reduced globin chain production causing microcytic anaemia.
• Alpha thalassaemia severity depends on number of alpha gene deletions.
• Beta thalassaemia trait causes mild microcytic anaemia; beta thalassaemia major causes severe transfusion-dependent anaemia.
• Blood film may show target cells and basophilic stippling.
• Major complications: iron overload, splenomegaly, bone deformity and endocrine damage.
• Treatment may include regular transfusions, iron chelation, folate and specialist curative options such as stem cell transplant in selected patients.

🧫 5. White Cells, Neutropenia and Infection Risk

🛡️ 5.1 Neutropenia

• Neutropenia increases risk of bacterial and fungal infection.
• Causes: chemotherapy, sepsis, drugs, viral infection, autoimmune disease, marrow failure, B12/folate deficiency, hypersplenism.
• Severe neutropenia is often defined as neutrophils below 0.5 × 10⁹/L.
• Fever in neutropenia is a medical emergency even if the patient looks well.
• Management: sepsis assessment, blood cultures, broad-spectrum IV antibiotics rapidly, search for source, oncology/haematology input.

🚨 5.2 Neutropenic Sepsis

• Suspect in any patient receiving chemotherapy or with known marrow failure who develops fever or sepsis features.
• Symptoms may be subtle because neutrophils are needed to produce pus and local inflammatory signs.
• Do not wait for blood results if clinical suspicion is high.
• Give empirical IV antibiotics urgently according to local neutropenic sepsis policy.
• Assess for line infection, chest infection, urinary infection, abdominal sepsis, mucositis and skin sources.

🚨 Safety pearl: In neutropenic sepsis, delay kills. The patient may have a normal-looking chest, urine and skin because they cannot mount a normal inflammatory response.

🩹 6. Platelets and Bleeding Disorders

🟣 6.1 Thrombocytopenia

• Platelet bleeding is usually mucocutaneous: petechiae, purpura, epistaxis, gum bleeding, menorrhagia.
• Causes: ITP, drugs, alcohol/liver disease, sepsis, DIC, TTP, marrow failure, hypersplenism, pregnancy-related disease.
• Always exclude pseudothrombocytopenia due to EDTA clumping if unexpected.
• Assess severity by bleeding symptoms, platelet count, trend and cause.
• Dangerous combinations: low platelets plus neurological symptoms, renal failure, fever, haemolysis or abnormal coagulation.

🧬 6.2 Immune Thrombocytopenia

• Autoimmune platelet destruction causing isolated thrombocytopenia.
• Often triggered by viral infection or associated with autoimmune disease/lymphoproliferative disease.
• Blood film should not show blasts or schistocytes.
• Treatment depends on bleeding and platelet count: observation, steroids, IVIG, thrombopoietin receptor agonists or rituximab/splenectomy in selected cases.

🧪 6.3 Coagulation Disorders

• Coagulation factor problems cause deep bleeding: haemarthroses, muscle haematomas, delayed bleeding after surgery.
• Haemophilia A: factor VIII deficiency; Haemophilia B: factor IX deficiency.
• von Willebrand disease causes impaired platelet adhesion and reduced factor VIII survival, giving mucocutaneous bleeding and sometimes prolonged APTT.
• Liver disease reduces clotting factor synthesis and can cause thrombocytopenia from portal hypertension.
• Vitamin K deficiency or warfarin prolongs PT/INR first because factor VII has a short half-life.

🧨 7. Thrombotic Microangiopathy and DIC

⚡ 7.1 TTP

• Thrombotic thrombocytopenic purpura is caused by severe ADAMTS13 deficiency, leading to widespread platelet-rich microthrombi.
• Classic pentad: thrombocytopenia, microangiopathic haemolytic anaemia, neurological symptoms, renal dysfunction and fever.
• The full pentad is often absent; suspect with thrombocytopenia plus haemolysis/schistocytes.
• Coagulation tests are usually relatively normal, helping distinguish from DIC.
• Medical emergency: urgent plasma exchange, steroids and specialist haematology care.

🧯 7.2 DIC

• Disseminated intravascular coagulation is systemic coagulation activation causing both thrombosis and bleeding.
• Triggers: sepsis, major trauma, malignancy, obstetric catastrophe, pancreatitis, transfusion reaction.
• Bloods: low platelets, prolonged PT/APTT, low fibrinogen, high D-dimer, schistocytes may be present.
• Management: treat underlying cause, supportive blood products guided by bleeding and labs, senior haematology input.

🚨 Exam pearl: TTP is a “do not miss” diagnosis. Thrombocytopenia plus neurological symptoms plus haemolysis should prompt urgent haematology discussion before waiting for confirmatory ADAMTS13.

🧊 8. Thrombosis, VTE and Anticoagulation

🦵 8.1 Venous Thromboembolism

• VTE includes DVT and pulmonary embolism.
• Risk factors: immobility, surgery, cancer, pregnancy/postpartum, oestrogen therapy, thrombophilia, previous VTE, obesity, acute illness.
• DVT features: unilateral leg swelling, pain, tenderness, pitting oedema, collateral veins.
• PE features: sudden dyspnoea, pleuritic chest pain, tachycardia, haemoptysis, syncope or shock.
• Assessment uses clinical probability, D-dimer and imaging such as compression ultrasound or CTPA/VQ scan.

💊 8.2 Anticoagulants

🧬 8.3 Thrombophilia

• Inherited thrombophilias include factor V Leiden, prothrombin gene mutation, protein C/S deficiency and antithrombin deficiency.
• Antiphospholipid syndrome is acquired and causes arterial/venous thrombosis and pregnancy morbidity.
• Testing is not needed for most provoked VTE and should not be done during acute thrombosis or while on interfering anticoagulants unless specialist advised.
• Testing is most useful when results would change management or inform family/pregnancy counselling.

🧬 9. Myeloproliferative Neoplasms

Myeloproliferative neoplasms are clonal stem cell disorders causing overproduction of mature myeloid cells. They can cause thrombosis, bleeding, splenomegaly and transformation to acute leukaemia.

🔴 9.1 Polycythaemia Vera

• Clonal red cell overproduction, usually associated with JAK2 mutation.
• Features: headaches, dizziness, visual disturbance, aquagenic pruritus, erythromelalgia, thrombosis, splenomegaly.
• Bloods: raised Hb/haematocrit, often raised WCC/platelets, low EPO.
• Management: venesection, low-dose aspirin if appropriate, cytoreduction in higher-risk patients.

🟡 9.2 Essential Thrombocythaemia

• Clonal platelet overproduction.
• Features: thrombosis, bleeding, headaches, erythromelalgia, miscarriage, splenomegaly.
• Mutations: JAK2, CALR or MPL.
• Management: aspirin and cytoreduction depending on risk; distinguish from reactive thrombocytosis.

⚫ 9.3 Myelofibrosis

• Marrow fibrosis causing extramedullary haematopoiesis.
• Features: anaemia, constitutional symptoms, massive splenomegaly, early satiety, weight loss.
• Film: tear-drop poikilocytes and leukoerythroblastic picture.
• Management: supportive care, JAK inhibitors, transfusion support, stem cell transplant in selected patients.

⚪ 9.4 Chronic Myeloid Leukaemia

• Myeloproliferative neoplasm caused by BCR-ABL1 fusion from Philadelphia chromosome t(9;22).
• Features: fatigue, weight loss, night sweats, splenomegaly, high WCC, basophilia.
• Can progress from chronic phase to accelerated phase and blast crisis.
• Treatment: tyrosine kinase inhibitors such as imatinib/dasatinib/nilotinib under specialist care.

🧫 10. Leukaemia

🚨 10.1 Acute Leukaemia

• Acute leukaemia is malignant proliferation of blasts causing marrow failure.
• Features: fatigue/anaemia, infections/neutropenia, bruising/bleeding/thrombocytopenia, bone pain, fever, weight loss.
• Blood film may show blasts; WCC can be high, normal or low.
• AML: more common in adults; Auer rods may be seen.
• ALL: commonest childhood cancer; may cause lymphadenopathy, hepatosplenomegaly and testicular/CNS involvement.
• Urgent same-day haematology discussion if blasts, suspected acute leukaemia or unexplained pancytopenia.

🧊 10.2 Chronic Lymphocytic Leukaemia

• Common adult leukaemia, often found incidentally as lymphocytosis.
• Features: lymphadenopathy, splenomegaly, infections, autoimmune haemolytic anaemia, B symptoms in advanced disease.
• Many patients are monitored with watchful waiting if asymptomatic.
• Treatment is indicated for symptomatic/progressive disease, marrow failure, bulky nodes/spleen or autoimmune complications not controlled.

⚠️ Safety pearl: A very high WCC with headache, confusion, visual symptoms or respiratory distress may be leukostasis - this is a haematology emergency.

🫘 11. Lymphoma

🧬 11.1 Hodgkin Lymphoma

• Usually presents with painless lymphadenopathy, often cervical or mediastinal.
• B symptoms: fever, drenching night sweats, weight loss.
• Alcohol-induced lymph node pain is a classic but uncommon clue.
• Histology: Reed-Sternberg cells.
• Highly curable in many cases with chemotherapy ± radiotherapy depending on stage.

🧫 11.2 Non-Hodgkin Lymphoma

• Diverse group ranging from indolent to aggressive lymphoid malignancies.
• Features: lymphadenopathy, B symptoms, extranodal disease, splenomegaly, marrow involvement.
• Diffuse large B-cell lymphoma is aggressive but potentially curable.
• Follicular lymphoma is often indolent but usually relapsing/remitting.
• Diagnosis requires tissue biopsy; avoid relying on FNA alone when lymphoma is suspected.

🚩 11.3 Lymphadenopathy Red Flags

• Persistent unexplained node enlargement.
• Hard, fixed or matted nodes.
• Supraclavicular lymphadenopathy.
• B symptoms: fever, night sweats, weight loss.
• Hepatosplenomegaly.
• Abnormal FBC, unexplained cytopenias or high LDH.

🦴 12. Myeloma and Plasma Cell Disorders

Multiple myeloma is a plasma cell malignancy producing monoclonal immunoglobulin or light chains. It causes bone marrow infiltration, bone disease, renal injury and immune suppression.

• CRAB features: hyperCalcaemia, Renal impairment, Anaemia, Bone lesions/pain.
• Other features: recurrent infections, weight loss, fatigue, spinal cord compression, hyperviscosity.
• Tests: FBC, U&E, calcium, ESR/CRP, serum protein electrophoresis, serum free light chains, urine Bence Jones protein, imaging and bone marrow biopsy.
• Blood film may show rouleaux formation.
• MGUS is a premalignant monoclonal gammopathy without myeloma-defining features.
• Treatment is specialist-led with combinations of proteasome inhibitors, immunomodulatory drugs, steroids, monoclonal antibodies, transplant in eligible patients and bone protection.

🧠 Exam pearl: Back pain plus anaemia, renal dysfunction or hypercalcaemia should make you think myeloma, not just “mechanical back pain”.

🩸 13. Transfusion Medicine

🅰️ 13.1 Blood Groups and Crossmatch

• ABO incompatibility can cause severe acute haemolytic transfusion reaction.
• Group and save identifies blood group and antibodies; crossmatch checks compatibility with donor units.
• O negative red cells may be used in life-threatening emergencies before group is known.
• Transfusion decisions should consider symptoms, bleeding, Hb, comorbidity and alternatives such as iron replacement.

⚠️ 13.2 Transfusion Reactions

🚨 Transfusion pearl: If a patient becomes unwell during transfusion, stop the transfusion first, keep IV access with saline, assess ABCDE and contact the blood bank.

🚨 14. Haematology Emergencies

📚 15. OSCE / Exam Pearls

• Iron deficiency anaemia in adult men or postmenopausal women needs GI blood loss/cancer consideration.
• Macrocytosis plus neuropathy suggests B12 deficiency; do not treat with folate alone.
• High reticulocytes suggest haemolysis or blood loss; low reticulocytes suggest marrow underproduction.
• Thrombocytopenia plus schistocytes is TTP/DIC until proven otherwise.
• Platelet bleeding is mucosal/petechial; clotting factor bleeding is deep tissue/haemarthrosis.
• Fever in neutropenia is an emergency even if the patient looks well.
• Blasts on blood film require urgent haematology discussion.
• CRAB features suggest myeloma.
• JAK2 mutation is associated with PV, ET and myelofibrosis.
• Philadelphia chromosome/BCR-ABL1 is classic for CML.

📌 16. Quick Differentials Table

📚 References

• NICE. Blood transfusion. NG24.
• NICE. Suspected cancer: recognition and referral. NG12.
• NICE. Myeloma: diagnosis and management. NG35.
• NICE. Sickle cell disease: managing acute painful episodes in hospital. CG143.
• NICE. Neutropenic sepsis: prevention and management in people with cancer. CG151.
• British Society for Haematology guidance should be checked for specialist pathways including anticoagulation, haemoglobinopathies, haemostasis, transfusion, TTP, DIC and haematological malignancy.

⚠️ Disclaimer

This article is for medical education and exam revision. Clinical decisions should follow current local guidelines, transfusion policies, anticoagulation protocols, chemotherapy pathways, antimicrobial guidance, senior advice and national guidance. Haematology emergencies such as neutropenic sepsis, TTP, DIC, acute leukaemia, sickle acute chest syndrome and major haemorrhage require urgent senior input.