thrombosis

Question 1

name 4 deep veins? 4

Answer 1

• iliac vein
• femoral vein
• popliteal vein
• tibial vein

Question 2

what is virchow’s triad and what does it show?

Answer 2

• factors clinically important in the development of a thrombosis
• circulatory stasis
• endothelial injury
• hypercoagulable state

Question 3

what are the thrombotic risk factors? 8

Answer 3

• post-operative, especially orthopaedic
• hospitalisation
• cancer
• pregnancy
• OCP (oral contraceptive pill)
• long-haul flights
• obesity
• intravenous drug abuse

Question 4

how can DVT be presented? 4

Answer 4

• can be clinically silent (no symptoms)
• unilateral calf swelling/ heat/ pain/redness/ hardness
• differential diagnosis= cellulitis, bakers cyst, muscular pain
• potentially fatal if missed

Question 5

what is the investigation of choice for DVT? 4

Answer 5

• doppler ultrasound
• ultrasound transducer produces a real-time two dimensional image of soft tissue structure
• colour duplex shows velocity and direction of blood flow
• veins are non-compressible by probe

Question 6

what is the D-dimer test? 4

Answer 6

• likelihood of having a DVT can be assessed using the Wells risk score and doing a D-dimer test
• indicate activation of the clotting cascade
• low Wells score and negative D-dimer test have a high negative predictive value
• if high wells score or positive D-dimer then proceed to ultrasound scan to confirm DVT

Question 7

what is initial treatment for above the knee DVT? 3

Answer 7

• therapeutic anticoagulation using sub-cut LMW (low molecular weight) heparin (anti-coagulant)
• dose of LMW heparin according to patient’s weight
• no monitoring required

Question 8

what happens when we switch patients to warfarin? 6

Answer 8

• load patient with oral warfarin for 3-5 days
• stop LMV heparin once INR (internationalised normal ratio) is lower than 2 for 2 days
• 1st DVT= anticoagulation for 6 months
• 2nd DVT/ PE= lifelong anticoagulation
• want to maintain INR between 2 and 3
• monitor INR every 3 weeks

Question 9

describe the clinical spectrum of Pulmonary Embolism? 8

Answer 9

• micro-emboli= asymptomatic
• pleuritic pain
• dyspnoea
• haemoptysis
• massive PE= syncope, death
• tachycardia
• tachypnoea
• hypotension

Question 10

what is a CTPA scan?

Answer 10

CT pulmonary angiogram

Question 11

what does a V/Q scan for PE show? 2

Answer 11

• underperfusion~ V/Q mismatch

- limitation= underlying lung disease

Question 12

what does an ECG for pulmonary embolism show? 4

Answer 12

• sinus tachycardia
• atrial fibrillation
• right heart strain (RBBB)
• classic SI, QIII, TIII (rare)

Question 13

what does a CXR (chest x-ray) for a pulmonary embolism show? 3

Answer 13

• usually normal
• linear atelectasis
• small effusions

Question 14

what are the outcomes of PE? 5

Answer 14

• 5% mortality rate despite treatment
• 4% develop pulmonary hypertension
• cause of death in 10-30% of in-patient post mortems
• up to 60% have micro-emboli at post mortem
• a leading cause of ‘preventable death’

Question 15

what are the treatments of a massive PE? 3

Answer 15

• thrombolysis with tPA (Alteplase)
• tissue plasminogen activator (fibrinolytic) 2-6% risk of serious bleeding
• iv unfractionated heparin (monitor with APTR (Activated Partial Thromboplastin Time Ratio))

Question 16

what is the standard treatment for PE? 6

Answer 16

• LMW (low molecular weight) heparin injections
• warfarin for 6 months
• consider underlying causes
• LMW heparin is better if there is underlying cancer
• IVC filter (inferior vena cava filter)
• consider a DOAC as an alternative

Question 17

when do we do a thrombophilia screen? 3

Answer 17

• consider in young patients with a spontaneous venous thromboembolism
• inherited causes: factor V leiden, deficiency of natural anticoagulants, antithrombin deficiency, protein C and protein S deficiency
• acquired causes: antiphospholipid syndrome (tests for lupus anticoagulant (DRVVT))

Question 18

name some antithrombotic drugs? 6

Answer 18

• warfarin
• heparin (unfractionated heparin, LMW heparin)
• newer agents- dabgatran (oral direct thrombin inhibitor)- rivaroxaban/ apixaban (oral direct factor Xa inhibitors)
• anti-platelet drugs
• fibrinolytic agents

Question 19

what is warfarin and what does it do? 5

Answer 19

• vitamin K antagonist
• prevents gamma-carboxylation of factors, II, VII, IX, X
• required for functional maturation of these factors
• prolongs the extrinsic pathway
• monitored by INR

Question 20

how long can warfarin take to achieve therapeutic levels?

Answer 20

over 3 days

Question 21

what warfarin interactions should we beware? 2

Answer 21

• drug interactions due to cytochrome P450 (enzyme inhibitors potentiate warfarin, enzyme inducers inhibit warfarin)
• interaction with alcohol, binge drinking can potentiate warfarin and chronic alcoholism can inhibit warfarin

Question 22

what can warfarin control be affected by? 4

Answer 22

• binding to albumin
• absorption of vitamin K from GI tract
• synthesis of vitamin K factor by liver
• hereditary resistance

Question 23

what are the side effects of warfarin? 5

Answer 23

• teratogenic (may cause birth defects)
• significant haemorrhage risk
• minor bleeding
• skin necrosis
• alopecia

Question 24

how do we reverse warfarin? 3

Answer 24

• if life threatening bleed, give activated prothrombin complex (octaplex or beriplex) which contains vitamin K dependent factors II, VII, IX, X
• dose is 25-50 units per kg depending on INR level
• give vitamin K 2-10mg depending on INR level

Question 25

what is heparin? 6

Answer 25

• mucopolysaccharide that works by potentiating anti-thrombin
• irreversibly inactivates factor Ia (thrombin) and factor Xa
• injected
• unfractionated heparin (iv infusion)
• LMW heparin (sc injections)
• safe in pregnancy

Question 26

what is unfractionated heparin used? 4

Answer 26

• not often due to inconvenience of administration
• safe in renal failure as unfractionated heparin is metabolised by the liver and not renally excreted
• if bleeding , protamine sulphate can partially reverse heparin
• heparin-induced thrombocytopenia (HIT) is a rare complication of heparin (suspect if platelet count falls on heparin, this is a prothrombotic condition which can cause VTE)

Question 27

when is low molecular weight heparin used? 4

Answer 27

• very convenient due to once daily injections
• prescribed according to weight
• not usually monitored
• used for thromboprophylaxis for hospital inpatients

Question 28

when are direct oral anticoagulants used? 6

Answer 28

• developed as oral alternatives to warfarin
• no monitoring required
• direct thrombin (IIa) inhibitor
• direct factor Xa inhibitor
• trials show clinical non-inferiority of DOACs when compared to warfarin and LMW heparin
• should not be used for cardiac valves as here it is inferior to heparin

Question 29

what is rivaroxaban? 6

Answer 29

• direct factor Xa inhibitor
• causes irreversible anticoagulation
• VTE prophylaxis
• used for DVT and PE treatment
• stroke prevention in AF
• apixaban is an alternative anti Xa drug and is less affected by renal function

Question 30

what is dabigatran? 4

Answer 30

• a direct thrombin inhibitor - VTE prophylaxis
• treats DVT and PE
• stroke prevention in AF
• can be reversed by Prabind

Question 31

name some types of antiplatelet drugs? 5

Answer 31

• aspirin (cyclooxygenase inhibitor)
• clopidogrel (ADP receptor blocker)
• Dipyridamole (inhibits phosphodiesterase)
• prostacyclin (stimulates adenylate cyclase)
• glycoprotein IIb/IIIa inhibitors used in angioplasty procedures

Question 32

what are fibrinolytic agents? 5

Answer 32

• thrombolytic agents used to lyse fresh thrombi by converting plasminogen to plasmin
• tissue plasminogen activator (tPA)
• streptokinase and urokinase
• administered systemically in acute MI, recent thrombotic stroke , major PE and massive iliofemoral thrombosis
• need to look at risk-benefit ratio