Revise Notes Heamatology Flashcards

Question

Warfarin

Answer 1

Warfarin Vitamin K antagonist → interferes with factors II, VII, IX, X → delayed thrombin generation Takes 2 – 3 days to exert its full effects -> Initially procoagulant Half life: 36-48 hours Prolonged INR/PT with increasing doses Reversal Prothrombin complex concentrate (PCC) / Beriplex

Answer 2

Uses (INR target): PE, DVT (2–3) Recurrence of DVT whilst on warfarin (3–4) AF (2–3) Artificial aortic valve (2.5 – 3.5) Artificial mitral valve (3–4) Dosing: Where a patient requires rapid anticoagulation: Loading dose of 5 – 10mg→ titrate to achieve target INR Where there is no need to anticoagulate rapidly (e.g. AF): Initial dose of 2 – 3mg → this will take several weeks to achieve target INR When giving patients a loading dose of warfarin it is important to cover with: LMWH/heparin infusion -> initial doses of warfarin transiently make the patient more hypercoagulable

Answer 3

Monitoring: Must check INR regularly By the patient themselves using a finger-prick blood test Or at anticoagulant clinics Frequency: Twice a week for 1 – 2 weeks Then weekly until stable Then every 6 – 12 weeks when stable

Answer 4

Take the prescribed dose at the same time every day Report any bruising or bleeding immediately Avoid pregnancy as warfarin is teratogenic Avoid NSAIDs and aspirin → use paracetamol as an analgesic Avoid activities with a high risk of injury → do not prescribe warfarin to patients with a high falls risk Avoid heavy alcohol use and cranberry/grapefruit juice

Answer 5

Stop warfarin IV vitamin K (phytomenadione) 5mg Prothrombin complex concentrate (PCC-factors II, VII, IX, and X) Fresh frozen plasma if unavailable

Answer 6

Greater than 8 with minor bleeding Stop warfarin and give IV vitamin K 1-3mg Repeat vitamin K dose after 24 hours if the INR is still too high Restart warfarin when the INR is less than 5

Answer 7

Stop warfarin PO (use IV preparation orally) vitamin K 1-5mg Repeat dose after 24 hours if the INR is still too high Restart warfarin when the INR is less than 5

Answer 8

Stop warfarin IV vitamin K 1-3mg Restart warfarin when the INR is less than 5

Answer 9

Withhold 1 or 2 doses of warfarin Reduce subsequent maintenance dose

Answer 10

Warfarin should be stopped 5 days prior to elective surgery if risk of bleeding is greater than the risk of thrombosis Aiim INR < 1.5 on day of operation LMWH bridging can be used to anticoagulate in the interim period before surgery In emergency surgery give PCC, or if surgery can be delayed >6 hours, IV vitamin K

Answer 11

Antiplatelet Therapy Key learning Aspirin: COX inhibitor used for secondary prevention of cardiovascular disease. Avoid in <16 years, peptic ulcers, bleeding disorders. Clopidogrel/Prasugrel: P2Y12 ADP receptor antagonists. Clopidogrel commonly used for lifelong secondary prevention of TIA/stroke and peripheral vascular disease. Prasugrel used post PCI/ACS for 12 months alongside aspirin. Ticagrelor: P2Y12 receptor antagonist. Used alongside aspirin post-PCI/ACS for 12 months (DAPT). Pre-op: Stop all antiplatelets 7 days before elective surgery.

Answer 12

Two typical doses 1. 75mg OD Secondary prevention: Stable angina Previous ACS/TIA/stroke/peripheral arterial diseases Following angiography/PCI/CABG 2. 300mg STAT ACS Ischaemic stroke/CVA Antiplatelet treatment is not routinely recommended for primary prevention of cardiovascular disease

Answer 13

Cautions/contraindications: < 16 years old- Risk Reye's syndrome Peptic ulcers (consider co-prescribing a PPI for prevention) Haemophilia/bleeding disorder Severe renal failure

Answer 14

Acutely: Clopidogrel 300mg STAT prior to PCI Prasugrel 60mg STAT prior to PCI Secondary prevention: Clopidogrel 75mg OD Prasugrel 10mg OD

Answer 15

Ticagrelor P2Y12 receptor antagonist Secondary prevention following PCI/ACS for 12 months alongside aspirin (dual-antiplatelet therapy- DAPT) 180mg STAT, 90mg BD for secondary prevention

Answer 16

Diagnosis 1st Line 2nd Line Acute Coronary Syndrome Aspirin (lifelong) & ticagrelor (12 months) Clopidogrel (lifelong) Percutaneous Coronary Intervention Aspirin (lifelong) & prasugrel or ticagrelor (12 months) Clopidogrel (lifelong) Transient Ischaemic Attack (TIA) Clopidogrel (lifelong) Aspirin (lifelong) & dipyridamole (lifelong) Ischaemic Stroke Clopidogrel (lifelong) Aspirin (lifelong) & dipyridamole (lifelong) Peripheral Arterial Disease Clopidogrel (lifelong) Aspirin (lifelong)

Answer 17

Clinical features Easy bruising Haematoma formation Haemarthroses (often spontaneous) - pain, swelling and decreased ROM Investigations Prolonged APTT (intrinsic pathway affected – F8/9/11) Mixing patients plasma 1:1 with donor plasma should normalise APTT Normal bleeding time Normal PT/ INR

Answer 18

Diagnosis - Decreased Factor 8 clotting activity: Severe haemophilia A: < 1% Factor 8 clotting activity Moderate haemophilia A: 1-5% Factor 8 clotting activity Mild haemophilia A: 6-40% Factor 8 clotting activity Accounts for 90% of cases of haemophilia and is less severe than haemophilia B Management: recombinant Factor 8

Answer 19

Severe haemophilia B: < 1% Factor 9 clotting activity Moderate haemophilia B: 1-5% Factor 9 clotting activity Mild haemophilia B: 6-40% Factor 9 clotting activity Less common, but more severe than Haemophilia A Management: Recombinant Factor 9

Answer 20

Acquired haemophilia Pathophysiology: IgG autoantibodies vs F8 Causes: Rheumatoid arthritis, IBD, phenytoin Management: If low autoantibody titre - F8 replacement If high autoantibody titre – Steroids/immunosuppression

Answer 21

Investigation Slightly increased APTT (due to impaired VWF carriage of F8) Reduced FVIII activity Prolonged bleeding time Diagnosis: PFA-100 test (>95% sensitive) - platelet function analysis Management Mild bleeding: Tranexamic acid (antifibrinolytic – inhibits plasminogen) Procedure prophylaxis: Desmopressin (Increases VWF release) F8 concentrate can also be used

Answer 22

Investigations Prolongation of all 3 of bleeding time, APTT and PT/INR Film: Schistocytes Thrombocytopenia and low fibrinogen (consumption) Management Supportive care + treatment of underlying condition

Answer 23

Vincristine Peripheral neuropathy Common uses: ALL, CML, lymphoma

Answer 24

Cisplatin Electrolyte derangement - Hypomagnesemia, hypokalaemia, hypocalcaemia, Peripheral neuropathy Ototoxicity and nephrotoxicity

Answer 25

Bleomycin Lung fibrosis, pulmonary toxicity Doxorubicin Acute cardiotoxicity (myopericarditis) - often presents within 2-3 days of administration with chest pain, palpitations, arrhythmias. Cardiomyopathy Other anthracyclines include: daunorubicin, epirubicin A baseline echocardiogram should be performed before commencing anthracyclines

Answer 26

Cyclophosphamide Haemorrhagic CYstitis Mesna (sodium-2-mercaptoethanesulfonate) should be co-prescribed with cyclophosphamide - it combines with acrolein and detoxifies it reducing bladder toxicity Decadron (Dexamethasone) Water retention, resulting in facial and ankle swelling. Hyperglycaemia

Answer 27

Deep Vein Thrombosis Clinical Features Symptoms/signs Calf swelling (>3cm vs other calf) Erythema, warmth, pitting oedema Tenderness to palpation, particularly along the deep venous system, pain on foot dorsiflexion History of Risk Factors Malignancy Bedridden > 3 days Major surgery in last 3 months Immobilisation of limb - paralysis, plaster etc. History of VTE

Answer 28

Assessment of DVT Wells score 2 or more = likely Wells score 1 or less = unlikely Likely DVT (Wells 2+) Offer a proximal leg vein ultrasound scan within 4 hours If this cannot be performed within 4hrs: Check the d-dimer and offer interim anticoagulation, and ensure US scan is performed within 24hrs Unlikely DVT (Wells 1-) Offer a d-dimer test If this cannot be performed within 4hrs, offer interim anticoagulation

Answer 29

Interim anticoagulation Apixaban and rivaroxaban are now 1st line (previously LMWH) If not appropriate, offer LMWH for at least 5 days, followed by long-term anticoagulation (continue LMWH until INR >2) Pregnancy - LMWH ESRF - Warfarin

Answer 30

Haemoglobinopathies Sickle cell disease Genetics and pathophysiology Inheritance: Autosomal recessive Mutation in the genes encoding the B-globin chain on Chromosome 11 Hydrophilic glutamate is substituted for hydrophobic VALINE at codon 6 The abnormal form of Hb is known as HbS When HbS exists in a deoxygenated state (venous capillaries/ hypoxia), it polymerises, and changes into an abnormal sickle shape. The sickle red cells are: Fragile – breakdown leads to haemolytic anaemia Obstructive – block blood vessels resulting in ischaemia/infarct

Answer 31

Investigations Most cases are diagnosed during newborn screening FBC: Normocytic, normochromic anaemia Blood film: Reflects hyposplenism – howell jolly bodies, target cells Reticulocytosis Gold standard: Haemoglobin electrophoresis Management

Answer 32

Hydroxycarbamide (prev. hydroxyurea) – increases HbF levels, and reduces vaso-occlusive crises Pneumococcal vaccine every 5 yrs Prophylactic phenoxymethylpenicillin

Answer 33

Vaso-occlusive / thrombotic crisis (Acute painful crisis) Sickle cells obstruct capillaries causing ischaemia, and resulting in painful infarcts of the spleen, lungs, hands and feet (hand-foot syndrome), bone (avascular necrosis of the hip) and brain causing stroke. Clinical features: Pain, stroke, end-organ damage, hyposplenism, necrosis Triggers: dehydration; hypoxia; infection Management: Analgesia (opiates), hydration, transfusion if required

Answer 34

Sequestration crisis Sickling within organs (spleen, lungs) is followed by pooling of blood Clinical features: severe anaemia +/- hypovolaemic shock Acute chest syndrome Clinical features: shortness of breath, chest pain, hypoxia Investigations: CXR demonstrates new infiltrates The most common cause of death

Answer 35

Aplastic crises A sudden drop in haemoglobin count due to reduced bone marrow production Trigger: parvovirus B19 infection Bloods: LOW reticulocyte count, anaemia Management: transfusion Hyposplenism Splenic sequestration results in functional hyposplenism in most sickle cell patients This results in significant risk of infection with encapsulated organisms including e.coli, neisseria meningitidis, klebsiella, haemophilus influenzae, pseudomonas. Management: Prophylactic phenoxymethylpenicillin (pen v) for life

Answer 36

Genetic mutations result in defective synthesis of the globin chains Normally, each haemoglobin molecule consists of four polypeptide chains - alpha chains, beta chains, delta chains etc. Common subtypes of haemoglobin include HbA, HbA2 and HbF.

Answer 37

1 gene deletion – silent carrier 2 gene deletion – alpha-thalassaemia trait (microcytosis) 3 gene deletion – Haemoglobin H disease – Hypochromic, microcytic anaemia + splenomegaly 4 gene deletion – hydrops fetalis, Barts disease – death in utero

Answer 38

Beta thalassaemia trait / Beta thalassaemia minor Genetics: typically one normal gene (B), and one affected gene B+ or B0 as above Classically have a significant microcytosis, which is disproportionate to the level of anaemia. Beta thalassaemia intermedia Genetics: Both genes affected, but some b-globin chain production Generally asymptomatic but may become increasingly anaemic during pregnancy. Beta thalassaemia major Genetics: No normal B-globin chain production Clinical Features: Presentation usually occurs between 6-24 months with failure to thrive, feeding problems and growth failure Significant microcytic anaemia develops If untreated patients develop symptoms including: Hepatosplenomegaly - abdominal enlargement Failure to thrive Features of Extramedullary haematopoiesis: skull bossing, bone marrow expansion Haemolysis - pallor, jaundice, fatigue

Answer 39

Management Regular blood transfusions (complicated by iatrogenic iron overload) Subcutaneous desferrioxamine infusions - Chelation of the iron to treat iatrogenic iron overload

Answer 40

Blood tests Elevated bilirubin Reticulocytosis and therefore elevated MCV LDH raised Direct coombs test Detects antibodies & complement proteins on the surface of RBCs A positive direct coombs test indicates autoimmune haemolysis Indirect coombs test Detects the presence of free & unbound antibodies present in the serum, against specific antigens (e.g. before blood transfusion)

Answer 41

Schumm test: Increased methemalbumin Free haemoglobin usually binds to haptoglobin. However when haptoglobin becomes saturated (during increased haemolysis), the haemoglobin binds to albumin forming methemalbumin. If methemalbumin is elevated this indicates intravascular haemolysis

Answer 42

Investigation findings Increased bilirubin Positive schumm (i.e. elevated methemalbumin) Causes of Intravascular Haemolysis Cold autoimmune haemolytic anaemia - IgM mediated Acute haemolytic transfusion reaction Paroxysmal nocturnal haemoglobinuria G6PD deficiency Fragmentation of RBCs: Valvular heart disease, haemolytic uraemic syndrome etc.

Answer 43

Causes: Abnormalities of RBC shape: Sickle cell disease Thalassaemia Hereditary spherocytosis Haemolytic disease of the newborn Warm autoimmune haemolytic anaemia - IgG mediated

Answer 44

Examination findings Splenomegaly Causes Drugs: penicillin, cephalosporins, methyldopa SLE Lymphoma

Answer 45

Investigations DCT positive (autoimmune) Schumm positive (intravascular) Causes Lymphoma Infections: EBV, mycoplasma pneumoniae

Answer 46

Clinical features Symptoms of anaemia Jaundice Gallstones - RUQ pain Diagnosis DCT negative (not autoimmune) Schumm positive (intravascular) Blood Film: Spherocytes HEINZ BODIES present on film, bite cells Gold standard: G6PD enzyme assay

Answer 47

Fava / broad beans Antimalarials Ciprofloxacin Sulfonamides - inc. co-trimoxazole

Answer 48

Clinical Features Failure to thrive Jaundice Gallstones Splenomegaly Crisis: Parvovirus B19 can trigger an acute aplastic crisis

Answer 49

Investigations DCT negative (not autoimmune) Schumm negative (extravascular) Diagnosis can be made on the basis of typical features such as raised MCH, reticulocytosis, a family history, and the presence of spherocytes on the blood film Hb electrophoresis is the investigation of choice if uncertain diagnosis/atypical Management Folic acid, splenectomy to reduce extravascular haemolysis

Answer 50

Bloods DCT positive (autoimmune) Schumm positive (intravascular) Anaemia/leukopenia/thrombocytopenia Clinical Features 'Dark urine' (haemoglobinuria) typically in the morning Thrombosis - lack of surface CD59 - Budd-Chiari syndrome, DVT et . Diagnosis Gold standard - Flow cytometry for cell surface CD59/CD 55 Ham's test positive - acid induced haemolysis Management Anticoagulation to reduce thrombotic risk Transfusions if required for anaemia Stem cell transplant

Answer 51

Pathophysiology An autosomal recessively inherited disease Mutation of HFE gene on chromosome 6 disrupts iron regulation, causing increased absorption from the diet. Over time, this results in iron overload, as the body has no efficient way to excrete excess iron. The excess iron is deposited in various organs, causing oxidative damage and functional impairment.

Answer 52

Clinical features Symptoms typically manifest after the age of 40-50, once significant iron accumulation has occurred. Key clinical features include: Skin discolouration: Bronze or dark grey colour. Endocrine Dysfunction: Erectile dysfunction, loss of sex drive Diabetes mellitus. Musculoskeletal Issues: Joint pains due to osteoarthritis Often with chondrocalcinosis seen on X-rays. Liver Disease: Deranged liver function tests (LFTs), fibrosis, and cirrhosis. Hypogonadism: Reduced function of the gonads, leading to decreased hormone production. Cardiac Problems: Heart failure due to dilated cardiomyopathy. General Symptoms: Weakness, lethargy, and an increased risk of infection.

Answer 53

Investigations General Screening: In the general population, the first-line investigation is to measure transferrin saturation, with values >55% in men and >50% in women indicating possible iron overload. Family History: If hereditary haemochromatosis is suspected due to family history, HFE gene testing for common mutations (C282Y and H63D) is recommended. X-rays: These may show chondrocalcinosis, indicating joint involvement.

Answer 54

Complications Increases risk of infection from encapsulated organisms Management Vaccinations: Pneumococcal booster - every 5 years Haemophilus influenzae B - 2 weeks before or after splenectomy Meningococcal C - 2 weeks before or after splenectomy Influenza - annual Antibiotic prophylaxis: BD penicillin/amoxicillin/macrolides (i.e. azithromycin)

Answer 55

Haemolytic Warm haemolytic anaemia Thalassaemia Neoplastic / myeloproliferative CLL/CML/AML Lymphoma Myelofibrosis Hereditary spherocytosis Infiltrative Amyloidosis Gaucher’s disease Infective Malaria Visceral leishmaniasis Splenic trauma Congestive disorders Splenic vein thrombosis Thrombotic thrombocytopenia purpura not responding to plasmapheresis/ immunosuppression Immune thrombocytopenic purpura not responding to steroids

Answer 56

Causes Dietary deficiency Malabsorption - coeliac disease, IBD Blood loss GI - most common in adult men and postmenopausal women Menstrual blood loss - most common in premenopausal women Clinical features Symptoms Shortness of breath Tiredness all the time Dizziness Other - weakness, palpitations, evidence of heart failure

Answer 57

Treatment and monitoring Oral iron (ferrous fumarate/sulfate) - one tablet once daily until 3 months after correction of iron deficiency to replenish stores. Consider ongoing prophylactic treatment if likely to recur (e.g. menorrhagia) Recheck Hb within 4 weeks of iron treatment - Hb should increase by approx. 20g/L

Answer 58

Clinical Features Typically occurs in a child between 2-5 yrs of age Bone marrow crowding with resultant BM failure - fatigue, pallor, infections, bruising, weight loss Lymphadenopathy Hepatosplenomegaly Investigations Labs: leukocytosis Diagnosis: Bone marrow biopsy Management Chemotherapy

Answer 59

Investigations Bloods: Lymphocytosis, anaemia, thrombocytopenia Blood film: SMUDGE cells Diagnostic: flow cytometry / immunophenotyping --> CD19+ , CD5, CD23 Management CLL can be managed conservatively, unless specific indications are present for chemotherapy. These include: Bone marrow failure Lymphadenopathy > 10cm Splenomegaly >6cm Lymphocytosis increase by 50% or more in 2 months Systemic symptoms affecting QOL Chemotherapy - FCR regimen commonly used

Answer 60

Investigations Bloods High WBC - increased granulocytes present at different stages of maturity - basophilia, eosinophilia etc. Thrombocytosis - plts tend to be elevated during chronic phase Leukocyte ALP is low Genetics: Philadelphia chromosome confirms diagnosis (PCR/FISH/Cytogenetics used) Bone marrow biopsy: Increased cellularity with increased myeloid to erythroid ratio Management 1st line: IMATINIB - tyrosine kinase inhibitor Others: hydroxyurea, IFN-alpha, BM transplant

Answer 61

Clinical Features Average age of diagnosis is 65-70 yrs of age Symptoms are related to the failure of production of normal cells: Symptoms of anaemia - pallor, fatigue Recurrent infections (WCC is high, but cells are dysfunctional) Thrombocytopenia - bleeding/ bruising Bone pain Mild splenomegaly Night sweats, weight loss Investigations + Diagnosis Blood film: Auer rods (eosinophilic needle inclusions visible within the myeloblast cytoplasm) FBC: typically high levels of immature white cells, bone marrow failure - anaemia, thrombocytopenia BM biopsy: >30% blasts present in BM Management Chemotherapy, allogeneic stem cell transplant if high risk of relapse.

Answer 62

Management: Chemotherapy Chemotherapy in BL can be complicated by tumour lysis syndrome, so rasburicase should be given prophylactically.

Answer 63

An important subtype of AML Genetics: t(15;17) - results in the formation of the PML:RAR-alpha fusion gene Clinical Features Disseminated intravascular coagulation (DIC) Gum swelling, bleeding Thrombocytopenia Recurrent chest infections Management: Chemotherapy + ATRA (all trans retinoic acid) - ATRA activates the RAR-alpha gene, which stimulates WBC differentiation from blast cells.

Answer 64

Clinical features Acute kidney injury Cardiac arrhythmia Seizures Bloods Hyperkalaemia Hyperphosphataemia Uric acid increased HypOcalcaemia Acute kidney injury Prevention Good hydration (inc. IV fluids) and either of the following: IV rasburicase – a recombinant urate oxidase - uric acid is converted into allantoin for excretion IV allopurinol - a xanthine oxidase inhibitor

Answer 65

Clinical features Progressive peripheral lymphadenopathy Hepatosplenomegaly Non-Hodgkin lymphomas may present with extra-nodal features including: AKI secondary to obstructive hydronephrosis (due to retroperitoneal lymphadenopathy) Testicular mass Weight loss Diagnosis Lymph node biopsy Staging Ann Arbour staging Management Chemotherapy

Answer 66

Clinical Features Bimodal age distribution, affecting patients in their 30's and then again around their 70's. Lymphadenopathy - enlarged, but otherwise asymptomatic LN - commonly in anterior cervical chain / supraclavicular Classically LNs become painful shortly after drinking alcohol (pathognomonic of HL) , but reported in only 1/10 cases Beta symptoms Weight loss > 10% over 6 months Pyrexial - T > 38.3 Drenching night sweats Diagnosis Lymph node biopsy - presence of reed-sternberg cell

Answer 67

Management Usually a combination of radiotherapy and chemotherapy Patients with HL who require transfusion must have irradiated blood products for the rest of their lives.

Answer 68

Investigations Serial full blood counts demonstrate worsening bone marrow failure, with progressively lower cell counts Bone marrow biopsy: Increased cellularity Complications 30% of patients with myelodysplasia go on to develop acute myeloid leukaemia (AML)

Answer 69

Bloods FBC: Anaemia, leukopenia (or leukocytosis), thrombocytopenia (or thrombocytosis) Increased cell turnover - high LDH, high urate Blood film: Tear drop poikilocytes (dacrocytes) Leukoerythroblasts Bone marrow biopsy to confirm diagnosis - collagen fibrosis and megakaryocytes Management 1st line: Ruxolitinib (Jakafi) - targets the JAK-2 mutation Chemotherapy, splenectomy Allogeneic stem cell transplantation is the only curative treatment

Answer 70

MGUS A dyscrasia of plasma cells resulting in an asymptomatic paraproteinaemia with no clinical features of myeloma Widely considered as a premalignant stage of myeloma - 1% of cases progress to myeloma or related malignancy each year Normal B2 microglobulin

Answer 71

Waldenstrom's Macroglobulinaemia Pathophysiology A haematological malignancy affecting plasma and lymphoplasmacytoid cells resulting in a Monoclonal IgM Paraproteinaemia Considered an indolent lymphoma, sharing characteristics with non-hodgkins lymphoma Often preceded by IgM MGUS Clinical features Average age: 70 years Symptoms Extreme fatigue, weight loss, lethargy Recurrent or prolonged infections Bone marrow suppression by LPL cells Anaemia - TATT, SOB Thrombocytopenia - nose/gum bleeding, bruising Lymphadenopathy Hepatosplenomegaly Hyperviscosity due to IgM paraproteinaemia Blurred vision Tinnitus Headache Management Rituximab, chemo, steroids

Answer 72

I: Infections: Dysfunctional antibodies results in immunodeficiency Clinical feature: Frequent infections - CAP, pyelonephritis etc. C: Calcium: Hypercalcaemia: Excess bone breakdown +/- PTH-related peptide release Clinical features: Vomiting, confusion, thirst, polyuria, abdominal pain, depression, constipation R: Renal: Excess immunoglobulins and free light chains are filtered by the kidneys and precipitate renal failure. Clinical feature: Acute renal failure A: Anaemia: Overcrowding of the bone marrow by infiltrating tumour cells suppresses normal haematopoietic processes - results in a normochromic, normocytic anaemia and thrombocytopenia Clinical features: Tiredness all the time, shortness of breath, bruising/bleeding. B: Bone: Overactivation of osteoclasts results in excess, abnormal bone resorption Clinical features: Bone pain (70% patients), lytic ‘punched-out’ lesions, and fragility fractures (vertebral collapse etc.)

Answer 73

2WW-Referral Criteria If serum or urine electrophoresis are suggestive of myeloma, arrange a 2WW urgent (suspected cancer pathway) referral to haematology. Nb. Serum/urine electrophoresis can be negative in 5% of patients who have a non-secretory form of myeloma Other investigations to consider: Blood film: Rouleaux - suggests paraproteinaemia UE: Renal impairment Uric acid - high due to inc. cell turnover X-rays of focal bone pain - osteolytic lesions/pathological fractures

Answer 74

Secondary care investigations include: Serum and urine immunofixation to confirm presence of paraproteinaemia BM aspirate MRI whole body - Gold standard to assess skeletal involvement Management Chemotherapy - cyclophosphamide, doxorubicin etc. Steroids - e.g. dexamethasone Bisphosphonates - reduce bone pain/disease Stem cell transplant Transfusions for anaemia/ thrombocytopenia etc.

Answer 75

True polycythaemia Primary: Polycythaemia rubra vera (PRV) Secondary: Chronic hypoxia - COPD / OSA Elevated EPO levels - cerebellar haemangioma / hypernephroma

Answer 76

Clinical Features Classically occurs in men aged 50-75 yrs who present with symptoms of: Hyperviscosity - headache, pulsatile tinnitus, visual disturbance Pruritus - often following a warm bath Erythromelalgia - peripheries appear purple and are painful - caused by cell aggregation - treat with aspirin Examination findings: Hypertension Splenomegaly Bloods Elevated Hb +/- leukocytosis, thrombocytosis High haematocrit (typically >0.52 in men, >0.48 in women) Low levels of EPO (negative feedback) In secondary polycythaemia EPO levels are elevated

Answer 77

Management 1st Line Venesection - to maintain haematocrit at < 0.45 Aspirin - especially for erythromelalgia Hydroxycarbamide - for patients at high risk of thrombosis (age > 60 or hx thrombosis), (alternatives IFN-alfa or ruxolitinib if HC is not tolerated/ineffective/CId) Complications Thrombosis Approx. 10% of patients will develop myelofibrosis as bone marrow is replaced by fibrous bands of reticulin -- > Progressive cytopenias. Approx. 10% of patients will develop acute myeloid leukaemia

Answer 78

Clinical Features Darrier’s sign - Rubbing or scratching the skin causes local wheal and flare reactions due to mast cell degranulation. Flushing - Episodes of sudden skin redness and warmth, often triggered by stress or certain foods. Abdominal pain resulting from mast cell infiltration of the GI tract. Investigations Blood Film: Often reveals monocytosis, reflecting increased mast cell presence in the bone marrow. Biochemical Markers: Elevated levels of serum tryptase and urinary histamine indicate mast cell activation.

Answer 79

Clinical features Typically an asymptomatic, progressive thrombocytopenia which occurs 5-14 days after commencing heparin. Investigations 1st Line - HIT antibodies Management Stop heparin Fondaparinux or Argatroban (direct thrombin inhibitor)

Answer 80

Clinical features Petechial, purpuric rash Fluctuating neurological signs - drowsiness, confusion, headaches, stroke, seizure Fever Acute renal failure Thrombocytopenia Management - 1st line: Plasma exchange

Answer 81

Disease course ITP can follow an acute or chronic course Acute Most common in children following an infection Generally self-limiting and resolves after 2-3 weeks Chronic More common in adults Follows a relapsing/remitting course of symptoms Management 1st Line: Oral prednisolone 2nd Line: IV Immunoglobulins 3rd line: Splenectomy

Answer 82

Thrombocytosis Background Platelet count > 450 x 10(9) Causes of thrombocytosis: Reactive thrombocytosis (e.g. infection) Malignancy Essential thrombocythaemia

Answer 83

Management Aspirin can be used in low risk cases (e.g. no hx thrombosis, age < 60) Hydroxycarbamide is 1st line in intermediate-high risk (e.g. Age > 60, history of thrombosis). History of thrombosis Venous: Hydroxyurea and systemic anticoagulation Arterial: Hydroxyurea and twice daily aspirin

Answer 84

Function Protein C: A zymogen that, when activated (activated protein C or APC), degrades clotting factors Va and VIIIa to regulate clot formation. Protein S: Acts as a cofactor to protein C, enhancing its activity. Protein C/S deficiency Results in reduced degradation of clotting factors Va and VIIIa, leading to an increased risk of thrombosis.

Answer 85

Factor V Leiden The most common inherited thrombophilia Pathophysiology A gain of function mutation in the factor 5 protein which results in activated protein C resistance. This resistance reduces the degradation of factor Va, contributing to an increased risk of thrombosis. Clinical features DVT/PE in patient < 50 yrs Recurrent DVT/PE Family history of VTE CVST

Answer 86

Pathophysiology Inheritance: autosomal dominant ATIII primarily inhibits thrombin (IIa) and factor Xa; it also has inhibitory effects on factors IXa, XIa, and XIIa. Presentation: Recurrent thrombosis

Answer 87

Blood transfusion reactions encompass a spectrum of adverse effects ranging from mild allergic reactions to severe, life-threatening conditions. Prompt recognition and management are crucial to mitigate complications and ensure patient safety during transfusions.

Answer 88

Minor allergic reaction Pathophysiology: Hypersensitivity reaction to plasma proteins in the transfused blood. Clinical features: Pruritus and urticaria. Management: Antihistamines. Anaphylaxis Pathophysiology: Severe allergic reaction Risk factors: Patients with immunoglobulin A deficiency are particularly at risk, due to anti-IgA antibodies in IgA-deficient patients reacting to IgA in donor blood. Clinical features: Rapid onset angioedema, bronchospasm, hypotension, and shock. Management: Immediate cessation of transfusion, intramuscular adrenaline

Answer 89

Acute hemolytic transfusion reaction Pathophysiology: Blood group incompatability (mismatch). IgM antibodies in the recipient's blood target donor red blood cells, leading to complement-mediated intravascular hemolysis. Clinical features: Acute onset of fever, chills, hypertension, flank or abdominal pain, haemoglobinuria, and renal failure. Investigations: direct Coombs positive, decreased haptoglobin. Management: Immediate cessation of transfusion, supportive care with IV fluids, diuretics to maintain urine output, and monitoring renal function.

Answer 90

Transfusion associated circulatory overload (TACO) Pathophysiology: Excessive transfusion volume or rate overwhelms the circulatory system, especially in patients with compromised cardiac function. Clinical features: SOB, orthopnoea, hypertension, pulmonary oedema, elevated JVP. Key point: Hypertension differentiates TACO from TRALI (which typically features hypotension). Management: Diuretics, provide oxygen therapy, and slow down or stop the transfusion.

Answer 91

Transfusion related acute lung injury (TRALI) Pathophysiology: Rapid onset lung damage and non-cardiogenic pulmonary oedema caused by donor antibodies reacting with recipient leukocytes, leading to inflammatory damage to the pulmonary endothelium. Clinical features: Acute respiratory distress, hypoxia, bilateral pulmonary infiltrates on chest X-ray, fever, hypotension, typically within 6 hours of transfusion. Management: Immediate cessation of transfusion, supportive care with oxygen therapy, and mechanical ventilation if necessary.

Answer 92

Delayed haemolytic transfusion reaction Pathophysiology: IgG antibodies in the recipient's blood target donor red blood cells, leading to extravascular hemolysis. Clinical features: Presents 5-7 days post-transfusion with pyrexia, fatigue, jaundice, and low haemoglobin levels despite transfusion. Investigations: Positive direct Coombs test. Management: Monitor haemoglobin levels, supportive care, and potentially additional transfusions if needed.