M103 T2 L7

Question 1

What are the thrombotic risk factors?

Answer 1

Post-operative, especially orthopaedic
Hospitalisation
Cancer
Pregnancy
OCP
Long-haul flights
Obesity
i.v. drug abuse

Question 2

How does DVT present?

Answer 2

Can be no symptoms at all – clinically silent
Unilateral calf swelling/ heat/ pain/ redness/ hardness
Potentially fatal if missed

Question 3

What is the function of a doppler ultrasound?

Answer 3

shows the flow / lack of flow in a blood vessel

Question 4

What is the initial treatment for DVT?

Answer 4

Therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)

Question 5

How is the initial treatment of DVT administered / calculated?

Answer 5

Dosing is according to patient’s weight
No monitoring is required
patient needs to have adequate renal function

Question 6

What is the patient treated with for DVt if they have renal impairment?

Answer 6

anti-coagulate with i.v. unfractionated heparin instead (maintain APTT 1.5-2.0)
only if the creatinine clearance of the kidney is less than 30ml/min

Question 7

How is the patient treated after the initial treatment for DVT?

Answer 7

Load patient with oral warfarin for 3-5 days
warfarin levels monitored with INR tests
Stop LMW heparin once INR > 2.0 for 2 days
the first clot would be treated for six months - 1st DVT (femoral or iliac) - 6 months’ warfarin
the second DVT/PE: lifelong warfarin
Maintain INR between 2.0-3.0 (target 2.5)

Question 8

What are the classical symptoms of DVT?

Answer 8

pleuritic pain - pain on inspiration
dyspnoea - difficulty breathing
haemoptysis - coughing up blood

Question 9

What are the severe symptoms of DVT?

Answer 9

syncope

death

Question 10

What are other conditions DVT patients might have?

Answer 10

O/E
tachycardic
tachypnoeic
hypotension

Question 11

What are some statistics for DVT?

Answer 11

5% mortality with treatment
Cause of death in 10-30% of in-patient post mortems
Up to 60% have micro-emboli at post mortem

Question 12

What is the treatment for DVT?

Answer 12

LMW heparin injections (better for cancer patients)
warfarin for 6 months
no oral contraceptive pill if associated with
IVC filter
DOAC / NOAC

Question 13

Which age group would you consider doing a thrombophilia screen and why?

Answer 13

Sometimes done in younger patients with VTE to check for inherited risk factors

Question 14

What are inherited risk factors for DVT?

Answer 14

deficiencies of anti-thrombin, Protein C and S
Prothrombin gene variant
Factor V Leiden

Question 15

What is the function of warfarin?

Answer 15

Vitamin K antagonist - prevents post-translational modification / γ-carboxylation of factors II, VII, IX, X
in so doing it prolongs the extrinsic pathway (which is tested by measuring the prothrombin time)

Question 16

What are the target INRs for warfarin patients?

Answer 16

Target INR for warfarin patients usually 2.5 for DVT/PE and AF
Target 3.5 for recurrent VTE or metal heart valves

Question 17

How does warfarin work?

Answer 17

inhibits vitamin k reductase
it’s metabolized by p450
it prevents the formation of factors II, VII, IX, X

Question 18

Why does it take warfarin a few days to work?

Answer 18

the different factors (II, VII, IX, X) have different half lives
so it takes 3-5 days to reach adequate levels of anti-coagulation for patients started on warfarin

Question 19

Which four factors does warfarin affect?

Answer 19

II
VII
IX
X

Question 20

How does warfarin affect the patient outside of the treatment?

Answer 20

warfarin also inhibits the formation of natural coagulants - protein C and protein S
bc these have very short half lives, when patients are started on warfarin they become pro-thrombotic before they become anti-coagulated bc their anti-coagulants are being depleted
Fall in protein C and S occurs within hours and can result in a temporary pro-coagulant state

Question 21

How is warfarin prescribed?

Answer 21

Patient usually loaded with more warfarin then they need
then the level is brought down on day 3 to a maintanance level
warfarin is overlapped with LMW heparin until the INR is within the therapeutic range, above 2.0 for 2 consecutive days

Question 22

What is the typical loading regime of warfarin?

Answer 22

10mg, 10mg, 5mg

Question 23

What is a dangerous feature of warfarin?

Answer 23

patients have different levels of sensitivity to warfarin

Question 24

Can warfarin be prescribed without checking for other drugs?

Answer 24

no, need to be aware of interactions between warfarin and other drugs that are metabolized by the same enzyme in the liver as warfarin is - p450
those drugs that inhibit p450 will potentiate the action of warfarin
conversely those drugs that induce p450 will inhibit the action of warfarin

Question 25

What is the most important drug that interacts with warfarin and why?

Answer 25

alcohol problem for alcoholics will lead to high INR and high risk of bleeds

Question 26

What are the side-effects of warfarin?

Answer 26

teratogenic – therefore LMW heparin is used in pregnancy instead there is a significant haemorrhage risk – intra-cranial bleeds up to 1% per year, increased risk in elderly and with higher INR target Minor bleeding up to 20% per year Skin necrosis Alopecia

Question 27

How is warfarin reversed in a severe bleed?

Answer 27

Give vitamin K 2-10mg intravenously depending on INR level will take 6-12 hours to work because of half life of factors being in excess of six hours Patient can become refractory to re-loading with warfarin

Question 28

How is warfarin reversed in a life-threatening bleed?

Answer 28

vitamin K and Octaplex containing the factors 25-50 units per kg octaplex Fresh frozen plasma (FFP) can also be used

Question 29

Why do we need to know how to reverse warfarin?

Answer 29

if patients come in with severe bleeds

Question 30

How is fresh frozen plasma dosed?

Answer 30

according to the patients' weight and their INR

Question 31

How is heparin administered? Is it safe in pregnancy

Answer 31

always given by injection - parenterally | safe in pregnancy

Question 32

What is the function of heparin and how does it work?

Answer 32

it potentiates the action of anti-thrombin | by irreversibly inactivating factors IIa (thrombin) and Xa

Question 33

What are the two formulations of heparin and how are they administered?

Answer 33

Unfractionated heparin - IV or SC LMW heparin - mostly s.c injections (can be IV but less common sc = subcutaneous

Question 34

What conditions will unfractionated heparin be used in?

Answer 34

not often used due to inconvenience | only used in patients with renal failure

Question 35

Can unfractionated heparin be reversed?

Answer 35

it's not very easy to reverse - can be partially reversed with protamine sulphate

Question 36

How is unfractionated heparin monitored to make sure levels are safe?

Answer 36

looking at the APTT with target range of 1.5-2.5 x normal | have to monitor the platelet count

Question 37

Why is the platelet count monitored in the use of unfractionated heparin?

Answer 37

level of platelets can fall due to development of thrombocytopenia VTE is a rare complication resulting in heparin-induced thrombocytopenia or HIT

Question 38

What is the dosage of unfractionated heparin?

Answer 38

Given i.v. with 5000U bolus and ~1000U/hour infusion

Question 39

How (often) is LMW herparin administered to the patient and how is the dose calculated?

Answer 39

it is very convenient due to once daily subcutaenous injections dosed according to patient’s weight

Question 40

What are the main three LMW heparin formations?

Answer 40

Tinzaparin (Innohep) 175U/kg Enoxaparin (Clexane) 1.5mg/kg Dalteparin (Fragmin)

Question 41

Does LMW heparin need to be monitored?

Answer 41

no, but usual renal function needs to be maintained - patient must have creatinine clearance of over 30ml/minute

Question 42

How are NOACs administerd? How are they monitored? How safe are they?

Answer 42

it is orally available no monitoring good safety profile

Question 43

What are the two classes of NOACs?

Answer 43

Dabigatran – direct thrombin (IIa) inhibitor | Rivaroxaban – direct factor Xa inhibitor

Question 44

How effective are NOACs? What is a disadv?

Answer 44

trials show that they are just effective as warfarin and LMW heparin disadv - the anti-coagulant action is irreversible

Question 45

What is the dosing for dabigatran? How is it monitored and administered?

Answer 45

110mg bd or 150mg bd confirm creatinine clearance > 30ml/min administered orally

Question 46

What is dabigatran and rivaroxaban used for?

Answer 46

used for treatment of DVTs and PEs | stroke prevention in atrial fibrillation

Question 47

What is the dosing for rivaroxaban? How is it administered?

Answer 47

Dosing is 15mg bd for 3 weeks, then 20mg od | or 15mg od if CrCl is 15-50ml/min

Question 48

How does aspirin work as an antiplatelet drug?

Answer 48

inhibits cyclooxygenase is a very effective anti-platelet agent it disables platelet function and activation and aggregation

Question 49

What are the three main glycoprotein IIb/IIIa inhibitors?

Answer 49

Abciximab – monoclonal antibody Eptifibatide – snake venom derivative Tirofiban – blocks platelet aggregation

Question 50

How do fibrinolytic agents work?

Answer 50

lyse fresh thrombi (arterial) by converting plasminogen to plasmin

Question 51

What conditions are fibrinolytic agents used for?

Answer 51

``` acute MI recent thrombotic stroke major PE iliofemoral thrombosis strokes ```

Question 52

Give examples of fibrinolytic agents

Answer 52

Tissue Plasminogen Activator (tPA, Alteplase) | Streptokinase

Question 53

How are fibrinolytic agents administered? Describe the dosage

Answer 53

Administered systemically | Standardized dosage regimens aim to use within 6 hours

Question 54

What are signs of shock?

Answer 54

hypotension, acute dyspnoea, collapse, syncope

Question 55

What medication is used to treat a massive PE?

Answer 55

thrombolysis with tPA (Alteplase) Tissue plasminogen activator (fibrinolytic) iv unfractionated heparin Monitor with APTR