Thrombotic disorders

Question 1

what is the main presentation of DVT and why is this?

Answer 1

leg swelling due to reduced venous return

Question 2

what location is a DVT usually found?

Answer 2

Above the knee - in the iliac or femoral vein

Question 3

what is the location of clots in a DVT that are silent?

Answer 3

below the knee (popliteal or tibial vein) and have high risk of PE

Question 4

what is the main test for DVT?

Answer 4

D-Dimer

Question 5

what test would be done for DVT if D dimers are raised?

Answer 5

US of leg to look at venous blood flow using a doppler

Question 6

what are differential diagnoses for DVT?

Answer 6

cellulitis, bakers cyst behind the knee or muscular pain

Question 7

name 6 thrombotic risk factors

Answer 7

post operative, long term bed rest, cancer, pregnancy/oral contraceptive, long haul flights, obesity, IV drug use

Question 8

what kind of picture is produced by US?

Answer 8

a real time 2D image of soft tissue structures

Question 9

which two tests are used together to assess likelihood of DVT and what do these indicate?

Answer 9

D dimers and wells risk score

• D dimers show activation of the clotting cascade
• wells score assesses risk factors that indicate the likelihood of having a DVT

Question 10

what is the initial treatment for DVT?

Answer 10

anti-coagulation with LMW heparin eg tinzaparin or enoxaparin

Question 11

what is a requirement to administer LMW heparin?

Answer 11

good renal function (creatinine clearance > 30ml/min)

Question 12

how would a patient with poor renal function be anti coagulated?

Answer 12

using IV unfractionated heparin (not LMW) and ensure APTT is maintained

Question 13

what is the subsequent treatment for DVT?

Answer 13

load patients with oral warfarin for 3-5 days

Question 14

when is LMW heparin stopped?

Answer 14

when INR (clotting) is more than 2 for 2 days

Question 15

what would be the long term treatment for a first DVT?

Answer 15

6 months of warfarin

Question 16

what would be the treatment for a second DVT/PE?

Answer 16

llifelong warfarin

Question 17

what does a PE cause in relation to VQ?

Answer 17

VQ mismatch

Question 18

micro emboli in a PE may be asymptomatic but what symptom can they cause?

Answer 18

dyspnoea

Question 19

how will PE patients present O/E?

Answer 19

tachycardia, tachypnoeic (rapid RR) and hypotensive, shock

Question 20

what would someone presenting with a PE and shock be urgently treated with?

Answer 20

thrombolytics and IV heparin

Question 21

what are the three main symptoms of an acute PE?

Answer 21

pleuritic pain, dyspnoea and haemoptysis

Question 22

what are the three main symptoms of a severe PE?

Answer 22

syncope, death, signs of shock (hypotension and acute dyspnoea)

Question 23

what is the gold standard test for a PE?

Answer 23

CT pulmonary angiogram to look for filling defects

Question 24

what is a saddle embolism?

Answer 24

blockage at the bifurcation of the pulmonary trunk

Question 25

after a CTPA what other investigations can be done for a PE?

Answer 25

- VQ scan (inject and inhale a radioisotope to examine air and blood flow in the lungs) - ECG - look for sinus tachycardia (increased pulse rate), AF, right heart strain due to right bundle branch block - CXR - usually normal (rarely see linear atelectasis or small effusions)

Question 26

what is a limitation of a VQ scan for PE?

Answer 26

most patients have underlying lung disease so cant be done

Question 27

apart from LMW heparin and warfarin what other treatments can be given for PE?

Answer 27

- IVC filters to prevent embolisation to lungs | - direct oral anti coagulants (DOACs) eg dabigatran and rivoroxaban

Question 28

What drug treatment for PE is the most safe in pregnancy and cancer?

Answer 28

LMW heparin

Question 29

how many deaths per year are due to PE?

Answer 29

25,000

Question 30

what condition do young patients get a thrombophilia screen for?

Answer 30

venous thrombo embolism

Question 31

what inherited factors will be looked for in a thrombophilia screen?

Answer 31

- Factor V leiden (increases likelihood of clots) - prothrombin gene variant - anti thrombin deficiency - protein C or protein S deficiency

Question 32

what is the role of protein S and protein C and what would a deficiency in them lead to?

Answer 32

they are natural anti-coagulants that keep clotting in check - deficiency leads to more prone to clotting

Question 33

what acquired syndromes will be looked fora on a thrombophilia screen?

Answer 33

anti phospholipid syndromes (phospholipid is required in prothombinase)

Question 34

what is the mechanism of action of warfarin?

Answer 34

- antagonises vitamin K - prevents gamma carboxylation of factors II, VII, IX and X - inhibits protein C and protein S

Question 35

how is warfarin monitored

Answer 35

using the INR - how long it takes blood to clot

Question 36

what is the target INR for DVT, PE and AF?

Answer 36

2.5

Question 37

what is the target INR for recurrent venousthrombo embolism or metal heart valves?

Answer 37

3.5

Question 38

what is warfarin metabolised by and where?

Answer 38

metabolised by P450 in the liver

Question 39

what is patient usually loaded with before prescribing warfarin?

Answer 39

LMW heparin

Question 40

what effect do cytochrome P450 inhibitors have on warfarin?

Answer 40

increase its power

Question 41

what are some examples of P450 inhibitors?

Answer 41

carbamazepine, azathioprine, allopurinol, erythromycin, fluconazole

Question 42

what effect do P450 enhancers have on warfarin and why?

Answer 42

inhibit warfarin as P450 breaks down warfarin in the liver

Question 43

what are some examples of P450 enhancers?

Answer 43

rifampicin, amiodarone, citalopram

Question 44

what are five side effects of warfarin?

Answer 44

teratogenic (use LMW heparin instead), risk of haemmorhage, minor bleeding, skin necrosis and alopecia

Question 45

in what situation would warfarin need to be rapidly reversed and how is this done?

Answer 45

needs to be reversed in rapid bleeding by giving vitamin K | - if bleed is life threatening then give octaplex (prothrombin complex) or fresh frozen plasma

Question 46

what is octaplex and when it is it given?

Answer 46

a prothrombin complex containing factors II, VII, IX and X | - given in a bleeding emergency to reverse warfarin as vitamin K wouldn't work fast enough

Question 47

what is the mechanism of action of heparin?

Answer 47

- promotes anti-thrombin - irreversibly inactivates factors IIa (thrombin) and Xa - this means no fibrinogen to fibrin and no clotting

Question 48

how is heparin administered?

Answer 48

Parenterally (any way but oral so bypasses GI tract) - LMW even as a sc injection - unfractionated given as IV infusion

Question 49

how is unfrationated heparin monitored and how can it be partially reversed ?

Answer 49

monitored using APTT and can be part reversed by protamine sulphate

Question 50

what are rare complications of using unfractionated heparin and what can they result in?

Answer 50

thrombocytopenia and WTE which results in heparin induced thrombocytopenia

Question 51

what is LMW heparin prescribed according to?

Answer 51

patients weight

Question 52

does LMW heparin need to be monitored using APTT?

Answer 52

no - but can be monitored by an anti Xa assay

Question 53

what drug were NOACs developed as an alternative to?

Answer 53

warfarin

Question 54

what are three advantages of NOACs?

Answer 54

orally available, no monitoring needed and good safety profile

Question 55

give examples of two NOACs and their action

Answer 55

1) dabigatran - direct thrombin inhibitor (factor IIa) | 2) rivoroxaban - direct factor Xa inhibitor

Question 56

does rivaroxaban require good renal function?

Answer 56

yes

Question 57

name four anti plat drugs and their mechanism of action

Answer 57

1) Aspirin - cox inhibitor which prevents plat aggregation 2) prostacyclin prevent formation of cAMP therefore no plat aggregation 3) clopidogrel - ADP receptor blocker (P2Y inhibitor) 3) glycoprotein IIb/IIIa inhibitors - prevent clots in patients with cardiac stents

Question 58

how do fibrinolytic agents work and when are they given?

Answer 58

- convert plasminogen to plasmin - given systemically in acute MI, recent PE, thrombotic stroke, major PE or iliofemoral thrombosis - given in stroke to minimise neurological damage but must be given within 6 hours

Question 59

give two examples of fibrinolytic agents

Answer 59

tissue plasminogen activator (alteplase) and streptokinase