Thrombosis

Question 1

What is Factor V leiden?
What is the epidemiology?

Answer 1

Pathophysiology:
DNA mutation leadigng to **Activated protein C resistance ** –> increased clotting

Most common cause of inherited thrombophilia, 5% of caucasian are heterozygous (3x increase in thrombosis if heterozygous), <1% homozygaos

Question 2

What is the lupus anticoagulant?

Answer 2

Autoantiody against phospholipids

In lab settings: anticoagulant (explains the name). but clinically increases coagulability

Question 3

What is antiphospholipid syndrome?

What are it’s aetiologies?

Answer 3

Antiphospholipid syndrome (APS) is an autoimmune disease associated with increased risk of thrombosis due to the presence of procoagulatory antibodies (e.g. lupus anticoagulatn = antiphosphoplipid auto-antibodies)

Aetiology
1. Primary = idiopathic
2. Secondary associated with SLE (most common cause) or other autoimmune diseases (eg. RA)

Question 4

What is a typical presentation of Antiphospholipid syndrome?

Answer 4

Venous or arterial thrombosis + recurrent miscarriages

Question 5

How would antiphospholipid syndrome be diagnosed?

Answer 5

Usually on clotting tests have increased APTT

There are several antibodies (Lupus anticoagulant) antibodies involved.
Including

1. anticardiolipin (cardiolipin = phospholipid), not very sensitive
2. anti-beta 2 glycoprotein I antibodies: have pro-thrombotic effect

Question 6

What is the MOA of heparins?

Answer 6

Heparin forms a complex with antithrombin and potentiates its effect –> inhibition of Factors II, X, IX and XI

Question 7

Are heparins safe to use during pregnancy + breastfeeding?

Answer 7

Yes - do not cross placenta or are secreted in breast milk

Question 8

What are the indications of use of unfractonated heparin?

How long does it last? How is it monitored?

Answer 8

Administered IV –> then immediate effect, usually lasting around 6h

Indications
* immediate anticoagulation required
* reversal may be necessary (can be donw tih protamine sulphate)
* anticoagulation of choice in end-stage renal failure

Dost-adjustment via APTT time and

Question 9

How long should anticoagulant therapy be continued in a clearly provoked DVT?

Answer 9

3 months (but can be longer due to clinical picture / if trigger not removed yet)

Question 10

How are DVTs usually prevented?

Answer 10

Daily subcutaneous LMWH (prophylactic dose), TED stockings

Some DOACs are now licensed for DVT prophylaxis e.g. in post-op ortho patients

Question 11

How are DVT/ PEs usually treated?

Answer 11

First line: apixaban or rivaroxaban

if not suitable
1. LMWH (treatment dose 5 days) followed by Warfarin or Apixaban/Rivaroxaban/Edoxaban (DOACs)
2. LMWH stopped once INR in therapeutic range (2-3) (with some DOACs LMWH can be stopped immediately)

Reason for continuing LMWH while warfarin started: Warfarin also affects protein C/S and often leads to procoagulant state in the first few days before anticoagulant effect

Question 12

How do LMWH differ from Heparin in their

1. MOA
2. Duration of Action
3. Reversibility

Answer 12

1. MOA: higher Factor X activity
2. Duration of Action longer than UFH
3. But less reversible

Question 13

How can the anticoagulant effect of Warfarin be reveres?

How long does each method take?

Answer 13

1. IV vitamin K (Takes 6 hours)
2. Prothrombin complex concentrate or FFP (Octaplex/Beriplex - takes 30 mins)

Question 14

What are common INR target ranges for a patient on warfarin for
1. VTE treatment
2. prosthetic cardiac valve /recurrent thrombosis

Answer 14

1. VTE treatment (2-3)
2. Prosthetic cardiac valve / recurrent thrombosis (2.5-4)

Question 15

What MOA odes Dabigatran have?
How can it be reversed?

Answer 15

Dabigatran (direct thrombin inhibitor)

Can be reversed by– idracizumabcan be used to reverse depending on local
availability

Question 16

What are the advantages of usuing a doac over warfarin?

Answer 16

Overall similar efficiancy with less risk + less monitoring required

However, shorter half-life and good complicance more importnant

Question 17

How frequently should a patient be monitored when starting Warfarin?

Answer 17

1. Daily, or on alternate days, until it is within the therapeutic range (usually between 2–3, ideally 2.5) on two consecutive occasions (first resuls only after 3-4 days
2. Then, twice weekly for 1–2 weeks, followed by weekly measurements until at least two INR measurements are within the therapeutic range
3. Thereafter, depending on the stability of the INR, at longer intervals (for example, up to every 12 weeks) if agreed locally. then often stable dose

Question 18

How frequenttly should INR be measured in people taking DOAC (e.g. apixaban)

Answer 18

No monitoring required

Question 19

How frequently should someone started on unfractionated heparin have their APTT monitored?

Answer 19

Initially every 6h