Anticoagulants

Question 1

Describe risk assessment for NOACS

Answer 1

Noacs are potent anticoagulants agents and overdose with any amount could result in clinically signifiacnt bleeding
-Classic coagulation test correlate poorly with the anticoagulant effect of these agents and have a limited role in refining risk assessment

Question 2

Describe TM and TK of DOACS

Answer 2

TM

• Dabigatrin is a direct competitive inhibitor of both free and firbin bound thrombin
• Rivaroxaban and apixaban are direct factor 10a inhbitors

TK
DABI - bioavailability of only 6% following oral admin but this is inreased to 75% if the granules are removed from the capsule prior to ingestion. Peak concentration at 2-4 hour. Metabolised by the live to form active mtabolits. VD of 50-70L and protein binding of 35%/ Elimination is predominantly renal with a terminal half life of 12-24 hours.

Apixaban and rivoxaban - bioavailability is >50% following oral admin. Peak conentration 3-4 hours. VD is small <50L and they are highly protein bound.l Elimination is renal and hepatic with terminal elimination half lives of 5-14 hours.

Question 3

Discuss effects of Noacs on coagulation profile

Answer 3

1) INR
- Dabi mild prolongation
- Factor Xa - variable

2) aPTT
- Dabi - prolonged but poor correlation with drug concentration, aPTT >90 suggest a high drug level, normal aPTT suggest minimal drug level
- Xa - variable

3) THrombin clotting time (TT, TCT)
- dabi - very sensitive, normal values excludes presence of drug, Exceeds measurement time of coagulometer at high concentration
- Xa - not usueful

4) Factor Xa assay
- dabi - not useful
- Xa- good correlation with levels.

NOTES

1) combination of INR >2 and aPTT >90 seconds suggest high plasma levels of dabi
2) Normal INR and aPTT suggest low plasma levels of dabigatran
3) Combination of PT and aPTT suggest low plasma levels of apixaban and rivaroxaban
4) Factor 2a, Xa and Haemoclot assays are available in few hospitals and can take more than 24 hours to perform
5) TEG is effective at measuring anticoagulant activity of NOACS but specific assays have not yet been developed

Question 4

Discuss management of DOACs

Answer 4

RESUS

1) active bleeding
- apply local control measures - compression suturing
- Institute HD support including fluid resus to maintain a good UO
- Give blood products as indicated
- admin coag factors

D: - charcoal within 4 hours

E: dabi is effectively removed via dialysis, dialysis is not useful for 10a inhibitors

A: Idarucizumab 5grams for dabi - can consider FFP, recombinant factor 7, txa and FFP if life threatening haemorrhage