ABCs of anticoagulation, bleeding & clotting

Question 1

INR and APTT look at which pathways (and which factors)?

Answer 1

INR: extrinsic pathway (II, V, VII, X)
APTT: intrinsic pathway (all factors aside from factor XIII and VII)

Question 2

Warfarin
- MOA
- Major anticoagulant effect (which factor?)
- Half life?
- Why bridge?

Answer 2

• Warfarin is a Vitamin K epoxide reductase inhibitor. VitK dependent coag factors need reduced VitK to properly carboxylate… Interferes with this.
• Major effect: reduces prothrombin (factor II)
• Half life 60 hours
• Warfarin inhibits protein C and S (natural anticoagulants). Given its 60 hour half life, it takes its sweet time with the anticoagulation, but gets rid of the protein C and S quickly. This makes it initially pro-thrombotic, hence why you need to bridge.

Question 3

Which patients get warfarin induced skin necrosis?

Answer 3

Patients with protein C and S deficiency… Already have low protein C/S levels, warfarin inhibits further –> microvascular thromboses –> warfarin skin necrosis

Question 4

Heparin
- MOA
- Metabolism
- Half life
- Monitoring
- Reversal agent

Answer 4

• Works VIA effects on antithrombin –> inactivates thrombin (Fact IIa) and factor X
• Hepatic metabolism
• Short half life 1 - 2.5 hours
• Monitored by APTT
• Full reversal with protamine

Question 5

You have a patient who, no matter what you do, you can’t get their APTT therapeutic on a heparin infusion…
Why?

Answer 5

A. They have antithrombin deficiency (heparin works VIA antithrombin - completely dependent on its presence)

OR

B. They get a big Factor VIII response as an acute phase response which brings the APTT back down into range…. Check a Xa level (you’ll get a much more accurate measure)

Question 6

LWMH
- Difference cf heparin
- Predominant action
- Monitoring
- Downsides cf heparin

Answer 6

• Derived from UFH but chemically synthesised into small molecules. Reduced risk of HITs and osteopenia
• Has predominantly anti- factor Xa activity (skips the need for action via antithrombin)
• No monitoring: more predictable anticoagulation given less junk in it
• Downsides: renally excreted, cannot fully reverse

Question 7

DOACs
- Direct thrombin inhibitors (3)
- Direct Xa inhibitors (2)
- Proven efficacy in which situations

Answer 7

• DTIs: dabigatran (PO), lepirudin (IV), bivalirudin (IV)
  -Direct Xa inhibitors: rivaroxaban, apixaban
• Proven efficacy: rx VTE, prevention of stroke in AF and VTE prevention post THR/TKR

Question 8

Which DOAC is the best for renal impairment

Answer 8

Apixaban!!
Only 25% renally excreted cf 66% (riv) and 88% (dabig)

Question 9

Dabigatran monitoring

Answer 9

• INR and PT has not relation
• Thrombin clotting time (TCT) is VERY sensitive to dabigatran… If there is ANY level of dabigatran in the blood, the TCT will be prolonged. Can’t infer level of anticoagulation.

Can ask for a derived dabigatran level using the TCT but data is lacking on what is a good level

Question 10

Which patients on warfarin do you need to bridge before surgery?

Answer 10

HIGH RISK for clotting:

Mechanical heart valve:
1. Any mitral valve prosthesis
2. Specific types of aortic valve prosthesis
3. Mech valve with recent stroke or TIA (past 6/12)

AF:
1. AF with CHADSVASC of >5
2. AF with recent stroke or TIA (past 3/12)
3. Rheumatic valvular heart disease

VTE:
1;. VTE within past 3/12
2. Severe thrombophilia

Question 11

Perioperative management of warfarin for patients at high risk of thrombosis - 3 options prior to surgery

Answer 11

OPTION 1 - Bridge:
- Withhold warf 4-5 days prior to OT. Once INR <2, start clexane 1.5mg/kg daily or 1mg/kg BD. Last dose 24 hours prior to OT.

OPTION 2 - Vitamin K:
- If INR 2-3 in the preceding 2-4/52, administer vit K 3mg IV the night before surgery. If INR <1.5 day of surgery, OT can proceed. If >1.5, give prothrombinex (or FFP second line), or defer OT

OPTION 3 (rarely used)
- Check INR prior to surgery and administer prothrombinex according to table

Question 12

What does prothrombinex contain?

Answer 12

Factor II, Factor IX and factor X
And a little heparin (avoid in Phx HITS)

I.e. doesn’t contain factor VII. Note that FFP given in critical bleeding as well as PTX BECAUSE it contains factor VII. Do we actually need it? Jury is still out

Question 13

Why avoid PTX in a patient with a PHx HIT?

Answer 13

PTX actually contains a little heparin… avoid where you can if PHx HIT

Question 14

How many half-lives of a drug pass before the drug is eliminated?

Answer 14

4-5 half lives (provided normal renal fn)

Multiple a DOACs half life by 4-5 and you can almost guarantee the drug is gone (practical implication - high risk bleeding procedures)

Question 15

Classic pattern of coag derangement in CLD

Answer 15

• Prolonged INR
• Prolonged APTT
• Low fibrinogen

Note that this is a compensatory response to various changes in procoagulants and anticoagulants in CLD –> doesn’t necessarily actually confer and increased risk of bleeding

Question 16

You have a pre-op patient who has an isolated prolonged APTT on routine coags… What do you do?

Answer 16

Ask the lab to do mixing studies (mix plasma with normal reference plasma)

• If the APTT corrects: patient has a clotting factor deficiency (commonly factor XII deficiency…. Note this is NOT associated with bleeding risk IRL and so you can just crack on with the surgery)
• If it does APPT does not correct: they have an inhibitor of coagulation (i.e. lupus anticoagulant)