Haematology list (red and orange)

Question 1

Myelodysplasia (red).

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 1

1. This is a group of acquired bone marrow disorders where there is degeneration of stem cells in the one marrow, affecting one or more cell lineages (RBC/WBC/platelets). Bone marrow failure occurs naturally as we age but this accelerates, as such this is common in over 70s
2. Chromosomal abnormalities (primary) or secondary to chemotherapy or radiotherapy. RF = ionising radiation, alkylating agents.
3. Bone marrow fails causing reducition of certain cell lineages, leading to anaemia, infection etc.

Question 2

Myelodysplasia (red).

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 2

4. Usually asymptomatic, but can present with symptoms of anaemia, leukopenia and thrombocytopenia
5. Blood film, bone marrow aspirate, FBC, reticulocyte count, serum B12
6. Aplastic anaemia, HIV, AML

Question 3

Myelodysplasia (red).

7. Management
8. Complications
9. Prognosis

Answer 3

7. Supportive treatment (red cell and platelet transfusions) is given to elderly patients with symptomatic disease. For younger patients, intensive chemotherapy (as used for acute myeloblastic leukaemia) or allogenic BMT are used.
8. Infection, bleeding AML
9. Many patients die from infection in the myelodysplastic syndrome stage of their disease. May progress to AML

Question 4

Acute Leukaemia (red)

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 4

1. Malignant neoplasm of haematopoietic stem cells, replacing bone marrow. In acute, there is malignancy of poorly differentiated myeloid (AML) or Lymphoid (ALL) progenitors. Leukaemias are relatively rare.
   ALL - childhood, AML - adults.
2. Exposure to carcinogens (chemicals, drugs, radiation, viruses, genetics), end point of other bone marrow pathologies
3. Features are owed to infiltration of bone marrow and other tissues

Question 5

Acute Leukaemia (red)

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 5

4. Bone marrow failure - anaemia, bleeding, infection. (AML and ALL present same, immunophenotyping differentiates). Can be lymphadenopathy.
5. Peripheral blood film (Auer rods indicates AML), bone marrow aspirate, FBC
6. Other types of leukaemia

Question 6

Acute Leukaemia (red)

7. Management
8. Complications
9. Prognosis

Answer 6

7. Chemotherapy differs between the two, generally give at intervals for bone marrow to recover and consolidation. AML - Cytarabine/Daunorubicin, ALL - VDAD.
8. Cause of death usually infection or bleeding (cytopenia).
9. Both have good prognosis with 80% remission. ALL has worse prognosis in adults.

Question 7

Chronic leukaemia (red).

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 7

1. Similar to acute leukaemia, but blood cells are almost fully developed. Can be CML (rare) or CLL (the most common form of leukaemia and affects older people)
2. CML is caused by philadelphia gene, CLL has unknown (carcinogens - viruses, chemicals, drugs etc.)
3. Similar to acute, symptoms are due to bone marrow infiltration and peripheral infiltration of extra cells. CLL is characterised by uncontrolled proliferation of mature B lymphocytes.

Question 8

Chronic leukaemia (red).

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 8

4. CLL has indolent course, generally asymptomatic. Any symptoms are a consequence of BM failure (anaemia, infections and bleeding), lymphadenopathy/ hepatosplenomegaly.
5. Blood count, bone marrow aspirate, blood film
6. ALL/AML

Question 9

Chronic leukaemia (red).

7. Management
8. Complications
9. Prognosis

Answer 9

7. For CLL give fludarabine (chemo), rituximab (CD20 monoclonal antibody) for remssion if advanced (watchful waiting). CML give imatinib (tyrosine kinase blocker).
8. infection, anaemia, bleeding
9. CLL very variable prognosis, depends on disease stage, and cytogenetic monitors. CML has effective treatment.

Question 10

Hodgkin Lymphoma (red).

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 10

1. Lymphomas are B and T cell malignancies of the lymphoid system and are quite common (»leukaemia). Classified into NHL or HL by histology as present the same. HL is a disease of young adults, indicated by Reed-Sternberg bodies
2. Idiopathic, may be associated with infection (EBV).
3. Lymphocytes multiply abnormally and collect in parts of the lymphatic system (lymph nodes). Lymphocytes lose their infection-fighting properties (vulnerable to infection). It can spread, most often to the liver, bone marrow (causing anaemia) or lungs

Question 11

Hodgkin Lymphoma (red).

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 11

4. Painless lymph node enlargement (lymphadenopathy), systemic B symptoms - fever, drenching night sweats, weight loss, fatigue, anorexia
5. Blood count, lymph node biopsy showing Reed-Sternberg cells (categorises)
6. Any other cause of lymphadenopathy (infection, leukaemia etc.)

Question 12

Hodgkin Lymphoma (red).

7. Management
8. Complications
9. Prognosis

Answer 12

7. Stage 1a, 2a, brief chemotherapy (ABVD) and irradiation at site of bulk disease. More advanced give same but 8 cycles of ABVD chemotherapy.
8. Weaknened immune system, secondary neoplasms as spreads (BM, lung, liver)
9. Worse than leukaemia (90% 5yr in stage 1, 60% in stage 4) symptoms = worse prognosis. Still good prognosis and remission rates.

Question 13

NHL (red)

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 13

1. Difference between HL and NHL, is in NHL there are no Reed-Sternberg cells. There is clonal expansion of lymphocytes and disease can be described as high or low grade. NHL>HL, presentation <40 is rare.
2. Same as HL (idiopathic, infection etc.)
3. Lymphocytes multiply abnormally and collect in parts of the lymphatic system (lymph nodes). Lymphocytes lose their infection-fighting properties (vulnerable to infection). It can spread, most often to the liver, bone marrow (causing anaemia) or lungs

Question 14

NHL (red)

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 14

4. Same as HL, Painless lymph node enlargement (lymphadenopathy), systemic B symptoms. More vaired in NHL and extra-nodal involvement is more common.
5. FBC, lymph node biopsy.
6. Infection, other neoplasms like leukaemia

Question 15

NHL (red)

7. Management
8. Complications
9. Prognosis

Answer 15

7. Watch and wait for low grade, chemotherapy (different course of CHOPR for NHL) and radiotherapy for high grade
8. Weaknened immune system, secondary neoplasms as spreads (BM, lung, liver)
9. Low grade NHL – median survival is 9-11 years .

Question 16

Myeloma (red)

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 16

1. Malignant disease of bone marrow, proliferation of bone marrow plasma cells usually capable of producing paraproteins (IgG or IgA). There are also light chains (FLC).
2. Aetiology unkown, family history/radiation exposure likely role.
3. MGUS is pre-myelomatous condition with some paraproteins. Smouldering means enough paraproteins producing to class as myeloma, but no symptoms. THen there is symptomatic myeloma and plasma cell leukaemia, where plasma cells circualte.

Question 17

Myeloma (red)

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 17

4. CRAB
   C - hypercalcaemia from activated osteoclasts
   R - AKI from deposition of light chains
   A - anaemia, BM infilration = infection, bleeding
   B - bone disease - back ache, spinal cord compression
5. Serum electrophoresis for monoclonal antibodies, Serum free light assay, blood count
6. MGUS, lymphoma, amyloidosis

Question 18

Myeloma (red)

7. Management
8. Complications
9. Prognosis

Answer 18

7. Incurable, but give chemotherapy (cyclophosphamide)/autologous stem cell transplantation. Correct anaemia (EPO), treat bone disease with bisphosphonates and AKI with hydration.
8. CRAB
9. Median survival is 7 years. 10% are dead in 6months due to spinal cord compression.

Question 19

Thrombocytopenia - TTP (thrombotic thrombocytopaenic purprua) (orange).

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 19

1. Thrombocytopenia is reduced platelets and so increased bleeding. TTP is a genetic defect in ADAMTS13 which is supposed to breakdown vWF so there is excessive platelet aggregation (they are used up). It is classified by MAHA and purpura. It is rare, effects black and 30-50.
2. USually genetic defect in ADAMTS13 but can be acquired due to an autoimmune process.
3. Excess vWF causes excess platelet carrier function forming microthrombi but platelets are used up causing thrombocytopenia. Microvascular thrombi cause pentad: MAHA, purpura, neurological symptoms, fever, renal disease

Question 20

Thrombocytopenia - TTP (thrombotic thrombocytopaenic purprua) (orange).

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 20

4. Neurological symptoms (coma, seizures), fever, bleeding symptoms (purpura)
5. Platelet count, Hb, ADAMTS-13 activity assay
6. HUS caused by E.coli

Question 21

Thrombocytopenia - TTP (thrombotic thrombocytopaenic purprua) (orange).

7. Management
8. Complications
9. Prognosis

Answer 21

7. Acute management - plasma exchange (with low vWF), corticosteroids, aspirin. For ongoing give long term aspirin
8. Ischaemic stroke, renal dysfunction, acute MI
9. Good with good treatment and many respond well to plasma exchange.

Question 22

Thrombocytopenia - ITP (immune thrombocytopaenic purprua) (orange).

1. Define/epidemiology
2. Aetiology/risk factors
3. Pathophysiology

Answer 22

1. Autoimmune destriction of platelets, idiopathic means no identifiable cause. It is common and common pregnancy.
2. ITP in children often follows viral infection. In adults it may occur with other autoimmune conditions.
3. There can be autoantibodies detectable in 60-70% ofcases.

Question 23

Thrombocytopenia - ITP (immune thrombocytopaenic purprua) (orange).

4. Clinical manifestations
5. Investigations
6. Differentials

Answer 23

4. Insidious onset with a fluctuating course - easy bruising, epistaxis, menorrhagia.
5. FBC, HIV serology
6. Sepsis MDS

Question 24

Thrombocytopenia - ITP (immune thrombocytopaenic purprua) (orange).

7. Management
8. Complications
9. Prognosis

Answer 24

7. If platelet is >30x10^9 then no treatment. Give corticosteroids (Pred/dexa) for immuno suppression. Can give IVIG. If no response then splenectomy or rituximab.
8. Life threatening bleeding
9. Most respond to treatment and have good prognosis.

Question 25

Thrombocytopenia - HIT (Heparin induced thrombocytopenia) (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology

Answer 25

1. Drug reaction to heparin causing a decrease in platelet count and hypercoagulability. 2. Taking heparin 3. Heparin is anticoagulant which works by binding to PF4 and inhibitng its procoagulant function. Immune system can make IgGs to the H-PF4 complex activating more platelets causing a hypercoagulable state.

Question 26

Thrombocytopenia - HIT (Heparin induced thrombocytopenia) (orange). 4. Clinical manifestations 5. Investigations 6. Differentials

Answer 26

4. Hx of heparin, signs/symptoms of thrombocytopenia - Petechaie, fatigue, purpura etc. 5. FBC, HIT antigen assay 6. TTP

Question 27

Thrombocytopenia - HIT (Heparin induced thrombocytopenia) (orange). 7. Management 8. Complications 9. Prognosis

Answer 27

7. stop heparin and alternative anticoagulant (Lepirudin/Danaparoid), consider DOAC. 8. Life threatening thromboembolism. 9. Recovery usually 1 week. No long term complications of HIT other than re-exposure to heparin.

Question 28

Polycythaemia (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology 4. Manifestation 5. Investigation 6. Management 7. Complication/prognosis

Answer 28

1. Myeloproliferative disorder where there is too many red blood cells (incr Hb, PCV/Haematocrit, RCC). Rare but common Myeloprol 2. Usually mutation in PV, secondary = incr EPO to hypoxa or secreting tumours. RF = FH. 3. JAK2 mutation causes increased EPO switched on. 4. Signs/symptoms result of hypovolaemia/ hyperviscosity - headache, vertigo, tinnitus, angina, claudication. Hepatosplenomegaly due to extramedullary haematopoiesis. 5. Hb, Haematocrit, WBC count, platelet count 6. No cure, venesection to PCV <0.45L/L. Maybe chemo, low dose aspirin, Allopurinol. 7. Risk of A or V thrombosis. Can become acute leukaemia. Median Px = 13 years.

Question 29

Beta Thalassaemia (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology 4. Manifestation 5. Investigation 6. Management 7. Complication/prognosis

Answer 29

1. Mutation in one of the chains of haemoglobin. A is generally not compatible with life, B can be minor, intermedia or major. 2. Homozygous/ heterozygous inheritance. RF - being from Mediterranean/middle east 3. There is microcytic anaemia as A chains precipitate in RBCs causing damage in BM. There is increased HbF (one gamma) and HbA2 (one delta) 4. Asympatomatic, symptoms of anaemia (lethargy) 5. Blood film, PCR + genetic is diagnostic. Also Hb electrophoresis. 6. In severer forms blood transfusion to keep Hb>100g/L to suppress erythropoesis. Iron chelating agents for iron overload. 7. Can get thrombotic complications, anaemia, bone deformities. Major is fatal in first years of life. Heart failure is main cause of death.

Question 30

Deep vein thrombosis (red). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology

Answer 30

1. Development of a blood clot in major deep vein of the leg. Very common (500,000 per year). 2. Virchow's triad. RF: surgery, leg fracture or conditions with thromboembolic risk - cancer, trauma, oral contraceptive pill etc. 3. Most clots form across valves due to stasis and endothelium dysfunction. Fibrinolytic system begins breaking up clot incr FDPs.

Question 31

Deep vein thrombosis (red). 4. Clinical manifestations 5. Investigations 6. Differentials

Answer 31

4. Unilateral swelling, pain, redness, hot, tenderness (blocked venous return) 5. Quantitative D-dimer, Well's score, proximal duplex ultrasound (gold standard) 6. Cellulitis, Achille's tendon tear

Question 32

Deep vein thrombosis (red). 7. Management 8. Complications 9. Prognosis

Answer 32

7. LWMH for 5 days, then DOACs (rivaroxaban) + physical activity/stockings. Long term - maintain anticoagulants, physical activity, treat underlying cause. 8. Pulmonary embolism, HIT. 9. Survival is 95-97% for DVT, 77-94% for PE. Condition often reoccurs.

Question 33

Pulmonary embolism (red). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology

Answer 33

1. Life threatening condition caused from a dislodged thrombi formed in a deep vein, occluding the pulmonary vasculature. Around 50% of venous thrombi will embolise - very common (200,000 case per year UK). 2. Same as DVT - Virchow's triad. 3. The lungs act like a sieve for thrombi due to their capillary network.

Question 34

Pulmonary embolism (red). 4. Clinical manifestations 5. Investigations 6. Differentials

Answer 34

4. Dyspnoea, pleuritic chest pain, hypoxaemia, signs of DVT. If massive (rare), haemodynamic effects - hypotension, syncope, tachycardia, right sided heart failure. 5. Computed tomographic pulmonary angiography (CTPA), echo, D-dimer and FBC. Maybe ABG, ECG. 6. Unstable angina, MI, pneumonia, bronchitis.

Question 35

Pulmonary embolism (red). 7. Management 8. Complications 9. Prognosis

Answer 35

7. Give unfractionated (fast acting) heparin, oxygen, fluids and thrombolysis (Chemical: Anisterplase, tPA or Mechanical: catheter thrombolysis) or embolectomy but rarerly done. Prevent via mobilisation and hydration, LMWH. 8. Cardiac arrest/death, pulmonary infarction. 9. Between 1-11% risk of mortality, mortality owed to cardiogenic shock secondary to right ventricular collapse.

Question 36

Bleeding disorders - vWD (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology 4. Manifestation 5. Investigation 6. Management 7. Complication /prognosis

Answer 36

1. Deficiency in vWF which causes defective platelet function and bleeding. See doc for types. VWD is the most common inherited bleeding disorder. 2. Mainly genetic, if acquired - autoantibodies. RF: FH. 3. vWF helps platelets aggregate and protects factor 8 from degradation, hence lack = bleeding. 4. Prolonged bleeding time Mucutaneous bleeding - Ecchymoses, GI bleeding. 5. PT (normal), APTT (prolonged), FBC 6. Factor replacement (8+vWF) in concentrates, platelet/ cyroprecipitate transfusion. DDAVP, desmopressin 7. Excess bleeding. Most patients require acute treatment throughout life but respond well to treatment.

Question 37

Bleeding disorders - Haemophilia A (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology 4. Manifestation 5. Investigation 6. Management 7. Complication /prognosis

Answer 37

1. Mutation of gene encoding factor 8 on X chromosome. Affects males, 1 in 5000. 2. X-linked recessive inheritance. Rarely acquired due to AID. RF: Fh, male. 3. Bleeding is impaired so clotting time is prolonged. 4. Bleed into muscles and joints (haemarthropathy) causing inflammation and bone deformities. depending on severity - spontaneous frequent bleeding. 5. APTT (prolonged), factor 8/9 assay, FBC 6. Recombinant factors in episodes/ prophylaxis (3x a week in severe). Give NovoSeven or FEIBA if patient has inhibitors (autoantibodies 30%). Can give immune tolerance therapy. 7. Cerebral haemorrahage, deformity from joint bleeding, infection from transfusion. Can give near normal lifestyle/length with new treatments.

Question 38

Bleeding disorders - DIC (orange). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology 4. Manifestation 5. Investigation 6. Management 7. Complication /prognosis

Answer 38

1. Widespread generation of fibrin in blood vessels due to initiation of coagulation pathway (microthrombi). Consumption of platelets and factors causes secondary bleeding. Difficult to estimate DIC. 2. Acquired, major initiator is release of tissue factor (TF) due to sepsis, trauma, tissue destruction, cancer, APML. 3. Thrombi lead to vascular occlusion. TF is a cofactor for factor 7 and initates coagulation. 4. None to complete haemostatic failure - excessive bleeding (epistaxis etc.), and clots (dyspnoea, delirium, coma) 5. Prolonged PT, APTT, TT, elevated D-dimer, blood film. 6. Acute - treat underlying conditon, give platelet concnetrates, FFP, cyroprecipitate and antithrombin 3. Chronic - give heparin + antifibrinolytic agents. 7. life threatening haemorrhage, AKI, gangrene. Mortality can be high (59%) in certain cases.

Question 39

Anaemia (red). 1. Define/epidemiology 2. Aetiology/risk factors 3. Pathophysiology

Answer 39

1. Lack of Haemoglobin causing less oxygen transport. Common(33% global population), Iron deficiency is the most common cause 2. Many - Microcytic RBCs: Iron deficinecy, thalassaemia. Normal RBCs: blood loss, Combined Iron (bleeding, pregnancy) and folate deficiency, marrow infiltration, haemolytic anaemias Macrocytic RBCs - vitamin B12/folate deficinecy, liver disease etc. 3. Depends on cause.

Question 40

4. Clinical manifestations 5. Investigations 6. Differentials

Answer 40

4. Depends on severity and onset as can adjust if slow. Non-specific symptoms: fatigue, faintness, breathlessness, exacerbation of comorbdities (angina, claudication, CHF etc.). Haemolytic anaemia - jaundice, splenomegaly 5. Hb, Haematocrit, platelet count, MCV and MCH, blood count and film, serrum ferritin, iron, serum folate/B12 (parietal cell autoantibodies) 6. Any cause of anaemia

Question 41

7. Management 8. Complications 9. Prognosis

Answer 41

7. Treat underlying cause. Depends on anaemia (Oral/parenteral iron/folic acid/B12). 8. Cognitive impairment, renal failure, impaired muscular performance 9. Depends on underlying cause (pregnancy = good prognosis, GI cancer = bad)