Pattern Recognition in Haematology Laith Tafesh F1

Aims of this session Focus on MCQs NOT preparation for MOSLERs Haematology by pattern recognition NOT ins and outs of disease process – though this helps with memory

MCQ1 A 67 year old gentlemen presents with a five week history of lethargy and lower back pain. In the last three days, his wife has noticed that he has become increasingly confused. Initial bloods on arrival to MAU are as follows: Hb – 75 Ca – 3.5 WCC – 3.5 Creatinine – 220 Platelets - 120 Urea – 14.5 Na – 140 PTH – low K – 4 LFTs – normal Which of the following would be the most appropriate initial investigation considering the most likely diagnosis? Renal biopsy Skeletal survey Serum electrophoresis and free light chains CT chest, abdomen, pelvis Bone marrow biopsy

MCQ1 A 67 year old gentlemen presents with a five week history of lethargy and lower back pain. In the last three days, his wife has noticed that he has become increasingly confused. Initial bloods on arrival to MAU are as follows: Hb – 75 Ca – 3.5 WCC – 3.5 Creatinine – 220 Platelets - 120 Urea – 14.5 Na – 140 PTH – low K – 4 LFTs – normal Which of the following would be the most appropriate initial investigation considering the most likely diagnosis? Renal biopsy Skeletal survey Serum electrophoresis and free light chains CT chest, abdomen, pelvis Bone marrow biopsy

Multiple Myeloma - Overview Plasma cell malignancy Characterised by presence of paraprotein (monoclonal immunoglobulin or light chain) End organ damage

Multiple Myeloma - CRAB C – Hypercalcaemia R – Renal impairment A – Anaemia (and pancytopenia) B – Bone pathology (e.g. lytic lesions, bone pain)

Multiple Myeloma – Key Investigations Laboratory (Bloods): Serum electrophoresis – monoclonal band (paraprotein) Serum free light chains U/Es – renal impairment Calcium FBC – anaemia/pancytopenia Imaging: Skeletal survey – looking for lytic lesions (e.g. ‘pepper pot’ skull) Diagnostic: bone marrow aspirate + trephine NB: various other Ix, but above are probably most important to know

MCQ2 A 75 year old lady presents to her GP with a five month history of generalised fatigue and weight loss. On examination, she has cervical and inguinal lymphadenopathy, and she also has significant hepatosplenomegaly. The GP performs a FBC, which reveals the following: Hb – 95 Platelets – 190 WCC – 25 Lymphocyte count – 18 Neutrophil count – 1.5 Which of the following is the most likely diagnosis? Hodgkin’s lymphoma Diffuse large B-cell lymphoma Myelofibrosis Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia

MCQ2 A 75 year old lady presents to her GP with a five month history of generalised fatigue and weight loss. On examination, she has cervical and inguinal lymphadenopathy, and she also has significant hepatosplenomegaly. The GP performs a FBC, which reveals the following: Hb – 95 Platelets – 190 WCC – 25 Lymphocyte count – 18 Neutrophil count – 1.5 Which of the following is the most likely diagnosis? Hodgkin’s lymphoma Diffuse large B-cell lymphoma Myelofibrosis Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia Failure of apoptosis => accumulation of mature B cells Complications Autoimmune haemolytic anaemia Bone marrow failure (infiltration) Immunodefiency (hypogammaglobulinaemia) => infection

Significant Lymphocytosis Chronic Lymphocytic Leukaemia Elderly Lymphadenopathy/ Hepatosplenomegaly Significant Lymphocytosis Chronic Lymphocytic Leukaemia

MCQ3 A 45 year old gentleman with acute myeloid leukaemia has gone through successful induction chemotherapy and is currently in remission. His haematologist has referred him for stem cell transplantation. His two siblings are being tested to see if they’re a suitable match to serve as stem cell donors. Which of the following is the most important factor in determining donor-recipient compatability? Sex Age HLA typing ABO blood group RhD blood group

MCQ3 A 45 year old gentleman with acute myeloid leukaemia has gone through successful induction chemotherapy and is currently in remission. His haematologist has referred him for stem cell transplantation. His two siblings are being tested to see if they’re a suitable match to serve as stem cell donors. Which of the following is the most important factor in determining donor-recipient compatability? Sex Age HLA typing ABO blood group RhD blood group

Haemopoeitic stem cell transplantation Autologous vs allogeneic MRD vs MUD Benign and malignant disorders Allows intensive chemotherapy HLA typing – 12 alleles Major morbidity and mortality Complications GvHD (acute and chronic) Infection

MCQ4 A 65 year old, previously fit and well, lady presents to her GP with progressive shortness of breath, lightheadedness and jaundice. Bloods are taken which reveal the following: Blood film reveals spherocytes. Which of the following investigations is most likely to be diagnostic? Direct antiglobulin test Chromium labeling Bone marrow aspirate Bone marrow trephine US liver Hb – 78 LDH – 800 WCC – 5 Bili – 58 Platelets - 230 ALP – 120 Reticulocytes - 1000 ALT– 25

MCQ4 A 65 year old, previously fit and well, lady presents to her GP with progressive shortness of breath, lightheadedness and jaundice. Bloods are taken which reveal the following: Blood film reveals spherocytes. Which of the following investigations is most likely to be diagnostic? Direct antiglobulin test Chromium labeling Bone marrow aspirate Bone marrow trephine US liver Hb – 78 LDH – 800 WCC – 5 Bili – 58 Platelets - 230 ALP – 120 Reticulocytes - 1000 ALT– 25

Haemolytic anaemia Premature red cell breakdown Acquired vs hereditary Immune vs non-immune Autoimmune haemolytic anaemia – idiopathic or secondary to lymphoproliferative disorders or autoimmune disease

Features in investigations Increased red cell breakdown: anaemia, hyperbilirubinaemia, raised LDH Compensatory increased red cell production: raised reticulocyte count Blood film Spherocytes – hereditary spherocytosis, autoimmune haemolytic anaemia Schistocytes – MAHA Sickle cells – sickle cell disease Direct antiglobulin test (direct Coombs test)

MCQ5 A 29 year old pregnant lady presents to the emergency department at 29 weeks gestation. She has developed sudden onset abdominal pain with severe vaginal bleeding. Placental abruption is suspected and bloods are taken in the resuscitation room. Hb – 85 APTT - 70 Platelets – 10 PT - 42 WCC – 6 Fibrinogen 0.5 Which of the following investigations would be most useful in confirming the most likely diagnosis? Bleeding time Thrombin time D-dimer Factor XIII assay Factor IX assay

MCQ5 A 29 year old pregnant lady presents to the emergency department at 29 weeks gestation. She has developed sudden onset abdominal pain with severe vaginal bleeding. Placental abruption is suspected and bloods are taken in the resuscitation room. Hb – 85 APTT - 70 Platelets – 10 PT - 42 WCC – 6 Fibrinogen 0.5 Which of the following investigations would be most useful in confirming the most likely diagnosis? Bleeding time Thrombin time D-dimer Factor XIII assay Factor IX assay

Coagulation Prolonged PT (extrinsic system) Warfarin, vitamin K deficiency, liver disease Prolonged APTT (intrinsic system) Haemophilia A and B, lupus anticoagulant, heparin DIC: ↑APTT, ↑PT, ↓Fibrinogen, ↑D-dimer, ↓Platelets

MCQ6 A 52 year old gentleman presents to his GP with a six month history of abdominal fullness, weight loss and fevers. Examination reveals massive splenomegaly. Blood counts reveal severe leukocytosis (WCC 110) with marked neutrophilia. Hb is 112 and platelet count is 320. Cytogenetics is likely to demonstrate a reciprocal translocation between which two chromosomes? 8 and 15 2 and 21 3 and 14 6 and 16 9 and 22

MCQ6 A 52 year old gentleman presents to his GP with a six month history of abdominal fullness, weight loss and fevers. Examination reveals massive splenomegaly. Blood counts reveal severe leukocytosis (WCC 110) with marked neutrophilia. Hb is 112 and platelet count is 320. Cytogenetics is likely to demonstrate a reciprocal translocation between which two chromosomes? 8 and 15 2 and 21 3 and 14 6 and 16 9 and 22

Chronic Myeloid Leukaemia Myeloproliferative neoplasm Hepatosplenomegaly Usually ↑↑↑WCC with raised neutrophil count Philadelphia chromosome – reciprocal translocation between 9 and 22 BCR/ABL fusion gene Chronic, accelerated, blast transformation TKI, e.g. imatinib

MCQ7 A 45 year old lady presents to A+E with intractable epistaxis. She has also been feeling gradually more lethargic over the last few weeks. Observations are stable and the patient is haemodynamically stable. The clerking doctor performs bloods, which reveal the following: Hb – 83 MCV – 95 WCC – 0.6 Neutrophils – 0.2 Platelets – 9 Reticulocyte count - 5 Coagulation screen – normal Other than severe neutropenia and thrombocytopenia, the blood film does not reveal anything significant. Which of the following is the most appropriate first line investigation? Bone marrow biopsy B12/folate CT chest, abdomen, pelvis Direct antiglobulin test Platelet function tests

MCQ7 A 45 year old lady presents to A+E with intractable epistaxis. She has also been feeling gradually more lethargic over the last few weeks. Observations are stable and the patient is haemodynamically stable. The clerking doctor performs bloods, which reveal the following: Hb – 83 MCV – 95 WCC – 0.6 Neutrophils – 0.2 Platelets – 9 Reticulocyte count - 5 Coagulation screen – normal Other than severe neutropenia and thrombocytopenia, the blood film does not reveal anything significant. Which of the following is the most appropriate first line investigation? Bone marrow biopsy B12/folate CT chest, abdomen, pelvis Direct antiglobulin test Platelet function tests

Pancytopenia Increased peripheral destruction Hypersplenism, sepsis, autoimmune disease Decreased marrow production, i.e. bone marrow failure ALWAYS RULE OUT B12/FOLATE DEFICIENCY IN PANCYTOPENIA

Megaloblastic anaemia Bone marrow failure Hypocellular marrow Aplastic anaemia MDS Hypercellular marrow Infiltration Megaloblastic anaemia

MCQ8 A 69 year old patient who has renal anaemia and a haemoglobin of 73 is receiving a unit of red blood cells for relief of symptoms of anaemia. An hour into the blood transfusion, the nursing staff call you as he has become pyrexial. All other observations are normal and systemic examination is unremarkable. The patient feels shivery. What type of transfusion reaction does this likely represent? Acute haemolytic reaction Bacterial contamination Non-haemolytic febrile transfusion reaction Mild allergic reaction Anaphylaxis

MCQ8 A 69 year old patient who has renal anaemia and a haemoglobin of 73 is receiving a unit of red blood cells for relief of symptoms of anaemia. An hour into the blood transfusion, the nursing staff call you as he has become pyrexial. All other observations are normal and systemic examination is unremarkable. The patient feels shivery. What type of transfusion reaction does this likely represent? Acute haemolytic reaction Bacterial contamination Non-haemolytic febrile transfusion reaction Mild allergic reaction Anaphylaxis

Transfusion reactions Acute haemolytic transfusion reaction (ABO incompatibility) Bacterial contamination – septic signs Anaphylaxis – ABC problems Allergic reaction – urticaria, itch, low grade pyrexia Febrile reaction – pyrexia, shivery TACO – fluid overload secondary to transfusion TRALI – ARDS secondary to transfusion

MCQ9 A 24 year old lady with night sweats and lymphadenopathy is referred to the haematology clinic by her GP. The haematologists organise a lymph node biopsy, which reveals Reed-Sternberg cells. What is the most likely diagnosis? Non-Hodgkin’s lymphoma Hodgkin’s lymphoma Chronic lymphocytic leukaemia Acute lymphoblastic leukaemia Glandular fever

MCQ9 A 24 year old lady with night sweats and lymphadenopathy is referred to the haematology clinic by her GP. The haematologists organise a lymph node biopsy, which reveals Reed-Sternberg cells. What is the most likely diagnosis? Non-Hodgkin’s lymphoma Hodgkin’s lymphoma Chronic lymphocytic leukaemia Acute lymphoblastic leukaemia Glandular fever

Lymphoma Hodgkin’s lymphoma – Reed-Sternberg cell Non-Hodgkin’s – main subtypes Highly specialist subject – stick to basics for finals Malignant proliferation of lymphocytes – accumulate in lymphatic system B symptoms – fever >38, drenching night sweats, weight loss >10% in six months

MCQ10 A 70 year old gentleman is admitted to A+E with a GCS of 9 (M4, V3, E2) following a fall and head injury. The patient is on warfarin for atrial fibrillation. What is the most appropriate first step to take with regards to the management of this patient? Urgent CT head Administer prothrombin complex concentrate Administer IV vitamin K Urgent neurosurgical intervention Administer fresh frozen plasma

MCQ10 A 70 year old gentleman is admitted to A+E with a GCS of 9 (M4, V3, E2) following a fall and head injury. The patient is on warfarin for atrial fibrillation. What is the most appropriate first step to take with regards to the management of this patient? Urgent CT head Administer prothrombin complex concentrate Administer IV vitamin K Urgent neurosurgical intervention Administer fresh frozen plasma

Warfarin Vitamin K antagonist Indications: AF, VTE, mechanical heart valves INR target range – varies depending on indication (usually 2-3) Reversal: vitamin K (delayed onset), prothrombin complex concentrate (rapid onset but temporary effect)

Reversal - Bleeding Guidelines vary depending on Trust Life threatening bleed: Beriplex + IV vitamin K Significant bleed (haemodynamically stable): IV vitamin K Minor bleed: oral vitamin K

Reversal – No bleeding INR >8: oral vitamin K INR 5-7.9: omit or reduce dose, oral vitamin K if high risk

Summary Focus on haematology MCQs Unlikely to get in MOSLERs – except maybe splenomegaly Learn to recognise patterns laith.tafesh@nuth.nhs.uk