Haematology

• What is a Pulmonary Embolism (PE), and explain its pathophysiology and how may it affect the ventricles of the heart Obstruction of pulmonary vasculature, due to an embolus (unattached mass that travels through blood) - these emboli typically originate in lower extermities (DVT in calf), which travel through R side of heart before lodging into and obstructing the pulmonary arterial system PE causes strain on R Ventricle due to increased pulmonary vascular resistance as a result of the obstruction - a massive PE may result in Cor pulmonale and death
• What are the key clinical features of a PE Textbook triad of pleuritic chest pain, dyspnoea and haemoptysis - only present in 10% of patients Symptoms: • Pleuritic chest pain • Dyspnoea • Haemoptysis Signs: • Tachycardia (>100) • Tachypnoea (>16) - most common clinical feature • Pyrexia • Hypoxia • Hypotension (<90mmHg) - suggests massive PE • Elevated JVP - suggests Cor pulmonale Tachycardia and tachypnoea with no other signs - think PE
• What investigations would you perform in a patient with suspected PE (general) • History • Examination • CXR - to exclude other pathology
• What diagnostic pathway should be followed if clinical suspicion of PE is low Pulmonary Embolism Rule-out Criteria (PERC) - all of criteria must be absent to have negative PERC result ⤷ Only done if suspicion of PE is low, which is only 15% of cases (so therefore not routinely done) PERC factors (don't think you need to know this) - HADCLOTS: • Hormone/oestrogen use - COCP, HRT • Age ≥50 • DVT or PE history • Coughing up blood - haemoptysis • Leg swelling - unilateral • O2 saturation ≤94% • Tachcardia - HR ≥100 • Surgery or trauma in last month
• What diagnostic pathway should be followed if clinical suspicion of PE is high Wells 2-Level PE score - 7 parameters below (with points): • Clinical signs and symptoms of DVT (leg swelling, pain with deep palpation) - 3 • Alternative diagnosis is less likely than PE - 3 • Tachycardia (>100) - 1.5 • Previous DVT/PE - 1.5 • Immobilisation for >3 days, or surgery in past month - 1.5 • Haemoptysis - 1 • Malignancy, with treatment in past 6 months or palliative - 1 Results: • >4 - PE likely • ≤4 - PE unlikely
• What investigations are performed if Wells 2-Level PE score is >4 points, and then what are the subsequent courses of action Immediate CTPA (CT Pulmonary Angiogram) - if there is a delay in this, give intermin DOACs (Apixaban, Rivaroxaban) until scan is performed ⤷ If allergic to contrast, pregnant or renal impairment - perform V/Q scan Outcome: • Positive CTPA - diagnosis of PE • Negative CTPA - perform proximal leg vein USS if DVT is suspected
• What investigations are performed if Wells 2-Level PE score is ≤4 points, and then what are the subsequent courses of action D-dimer test (measures amount of D-dimer, which is a protein the body makes to break down blood clots) - if there is a delay in this, give intermin DOACs until test is performed Outcome: • Positive (raised) D-dimer test - arrange immediate CTPA • Negative D-dimer test - PE unlikely, so stop anticoagulation and consider alternative diagnosis
• When do we perform a CTPA vs V/Q scan as 1st-line investigation of PE CTPA is the recommended 1st-line modality for non-massive PE - it is quicker, easier to use, reduces need for further imaging and provides alternative diagnoses if PE is excluded V/Q scan may be used if CXR is normal and there is no symptomatic concurrent cardiopulmonary disease - also investigation of choice if there is renal impairment (does not use contrast)
• Describe the sensitivity and specificity of D-dimers test Good sensitivity (95-98%) but poor specificity - therefore useful as a rule-out investigation, rather than rule-in (SPIN & SNOUT) Age-adjusted D-dimer tests should be considered in those >50
• What ECG changes would you see in PE • Sinus tachycardia - most common finding • S1Q3T3 - large S wave in lead I; large Q wave in lead III; inverted T wave in lead III ⤷ Only seen in 20% of patients • RBBB and R axis deviation - suggest R heart strain
• What CXR changes would you see in a PE Typically normal - possible findings include a wedge-shaped opacification ⤷ CXR usually done for exclusion purposes
• Describe the sensitivity and specificity of V/Q scans Sensitivity of 75% and specificity of 97% - but mismatch in V/Q can also present with old PE, AV malformations, vasculitis, previous radiotherapy... ⤷ COPD gives matched defects
• Give a key disadvantage of CTPA Peripheral emboli affecting sub-segmental arteries may be missed
• Describe the presentation of a PE on CTPA Saddle embolus typically seen - embolism that saddles bifurcation of pulmonary trunk, extending into left and right pulmonary arteries
• What is management of a normal/non-massive PE (haemodynamically stable) DOAC (Apixaban/Rivaroxaban) 1st-line - if not suitable/available, offer: • LMWH, followed by Dabigatran/Edoxaban OR • LMWH, followed by a VitK antagonist (Warfarin)
• When should DOACs be started in a non-massive PE Once diagnosis is suspected - continue same DOAC if diagnosis is confirmed
• What is management of a non-massive PE if patient has active cancer DOAC - unless contraindicated
• What is management of a non-massive PE if patient has renal impairment 1 of the following (no DOAC) if severe renal impariment (<15ml/min): • LMWH • UFH (UnFractionated Heparin) • LMWH or UFH, followed by Warfarin
• What is management of a non-massive PE if patient has anti-phospholipid syndrome LMWH followed by VitK antagonist (Warfarin) - specifically if it is 'triple positive' syndrome
• How long should DOACs be given for in a non-massive PE All patients to have DOACs for 3 months - continuing after this is based on if VTE was provoked or unprovoked: • Provoked VTE is due to an obvious event (immobilisation following major surgery) - as event is no longer occuring, implication is that patient is no longer at risk of PE ⤷ Therefore stop DOACs after 3 months (total = 3 months) • Unprovoked VTE occurs in the absence of an event - this means there is a possibility of unknown risk factors (mild thrombophilia - abnormal tendency to develop blood clots), meaning they are still at ris...
• What do NICE state that a patient's anticoagulation timeframe should be based on Balance Risk of VTE recurrence (from PE) vs Risk of bleeding (from anticoagulation) for those in the 3-6 month window: ⤷ ORBIT score used to determine bleeding risk Generally, patients are better off continuing anticoagulation for a total of 6 months
• What is management of a massive PE Massive PE presents with haemodynamic instability (SBP <90mmHg): • Thrombolysis (Alteplase) - 1st-line ⤷ Other invasive approaches (open pulmonary embolectomy) are alternatives - may be considered if appropriate facilities exist
• What is management for those who have repeat PEs despite anticoagulation therapy IVC filters - stops the clots formed in deep veins of leg from moving to pulmonary arteries
• When should a PE patient be treated as an outpatient, rather than being an inpatient admission into hospital Low-risk PE patient (typically newly diagnosed) - a 'validated risk stratification tool' must be used to determine suitability of outpatient treatment, which BTS recommends is Pulmonary Embolism Severity Index Score (PESI) PESI - key requirements include: • Haemodynamic stability • Lack of comorbidities • Support at home
• Should D-dimers be used in pregnant patients No - D-Dimer normally rises during gestation so can give false positives
• What is the imaging modality of choice for pregnant patients with a suspected PE V/Q scan ⤷ CTPA contraindicated due to high radiation doses
• What are risk factors for PE Characterised by Virchow's triad: • Vessel wall damage - trauma, previous DVT, venous harvest/surgery • Venous stasis - DVT, recent surgery, >40, significant immobility (hospitalisation, paralysis), long-haul travel, obesity • Hypercoagulability - cancer, high-oestrogen states (COCP, HRT), nephrotic syndrome, sepsis, thrombophilia (Factor V Leiden mutation, Protein C/S deficiency)
• 4fe665d6454b44bca47238439730c65b-oa-1 Clotting cascade Warfarin = VitK antagonist ⤷ VitK clotting factors = 2, 7, 9, 10 Intrinsic (in-blood) pathway 1) Following surface contact, F12 is converted to F12A 2) F12A allows for conversion of F11 to F11A 3) F11A allows for conversion of F9 to F9A 4) F9A allows for conversion of F10 to F10A, by combining with F8, Phospholipids and Ca2+ to form the F10A complex Extrinsic (out-blood) pathway 1) Following tissue damage, tissue factor is released 2) This allows for conversion of F7 to F7A 3) F7A allows for conversion of F10 to F10A, by incorpora...
• What is Acute Lymphoblastic Leukaemia (ALL) Rapid proliferation/replication of lymphoblasts, mainly of B cell lineage, which end up replacing the normal bone marrow - therefore there is a drop in other cell lineages (RBCs, WBCs, platelets...) ⤷ Most common acute leukaemia in children (80%)
• What are the most common cytogenic abnormalities in both children and adults that cause ALL Children t(12;21) Adults t(9;22) - Philadelphia chromosome ⤷ Produces BCR-ABL fusion product, which results in a constitutively active receptor tyrosine kinase
• Which type of leukemia is the Philadelphia chromosome mostly associated with CML (rather than ALL)
• efdfb8bcb38746e0b32bcd44239c68a6-ao-1 ALL classification: B-cell ALL maturity 75% • Pro-B ALL • Common ALL • Precursor-B ALL • Mature-B ALL
• efdfb8bcb38746e0b32bcd44239c68a6-ao-2 ALL classification: T-cell ALL maturity 25% • Pro-T ALL • Intermediate-T ALL • Mature-T ALL
• efdfb8bcb38746e0b32bcd44239c68a6-ao-3 ALL classification: B-cell ALL cell surface markers • TdT • CD10 (B cell pre-marker) • CD19
• efdfb8bcb38746e0b32bcd44239c68a6-ao-4 ALL classification: T-cell ALL cell surface markers • TdT • CD2-CD8
• What is the peak incidence of ALL 2-5 Boys affected slightly more commonly than girls
• What are some risk factors for the development of ALL • Family history • Down's syndrome • Previous chemotherapy/radiotherapy • Benzene - paint/rubber industry
• What are some clinical features of ALL Related to bone marrow failure: • Anaemia - pallor, lethargy, weakness • Neutropenia - recurrent infections • Thrombocytopenia - bleeding, bruising • Testicular swelling - as lymphoblasts can invade into testicles • CNS involvement (meningism) - as lymphoblasts can invade into CNS • Hepatosplenomegaly • Bone pain • Anorexia • Weight loss
• What are some investigations you would carry out in a case of ALL • FBC - lymphocytosis, thrombocytopenia, anaemia with low reticulocyte count ⤷ Neutropenia may be present too • Blood film - lymphoblasts • Bone marrow aspirate and biopsy - >20% lymphoblasts is diagnostic • Molecular studies/immunophenotyping - t(12;21), t(9;22), cell surface markers (CD10 for B-ALL)
• Describe the management of ALL Complicated, but involves: • Chemotherapy • Corticosteroids • Bone marrow transplantation Don't need to know it