Pharm - Anticoagulation Flashcards
Can you tell me about novel anticoagulant agents?
Novel anticoagulants (NOACs) are a group of new drugs whose mechanism of action do not rely on vitamin K-dependent pathways. They show more predicable activity, require less monitoring and have a more rapid onset compared with conventional anticoagulation with coumarins. There are several
subtypes:
1 Direct thrombin inhibitors, e.g. dabigatran (oral, bd)
– Uses:
i Equivalent to LMWH for thromboprophylaxis after primary total hip
replacement (THR) and total knee replacement (TKR)
ii Equivalent to warfarin for treatment of DVT
iii Superior to warfarin for prophylaxis of stroke in AF
– Bioavailability is variable: enteric-coated capsule (if broken, 10 times drug
dose released)
– Compliance is poor due to tablet size
– New reversal agent: monoclonal antibody to immediately reverse action,
Idacaruzumab
2 Direct factor Xa inhibitors, e.g. rivaroxaban, apixaban (oral)
– Uses:
i Superior to LMWH in thromboprophylaxis after primary THR and TKR
ii Treatment of VTE
iii Prevention of thromboembolic complications in AF
– Half-life not prolonged provided creatinine clearance >50 ml/min
3 Indirect factor Xa inhibitors, e.g. fondaparinux (subcutaneous)
– Synthetic heparin pentasaccharide, acts via antithrombin III to inhibit
factor Xa
– Uses:
i Non-ST-elevation MI (NSTEMI) and unstable ACS in patients with high
risk of bleeding (unless PCI planned within 24 hours)
ii Thromboprophylaxis in medical patients, and post THR and TKR
iii Treatment of VTE
– Longer half-life
– Renal clearance
Describe the coagulation pathways?
Intrinsic, extrinsic and common pathway?
Intrinsic - damage to vessel wall, exposure of collagen leading to a cascade of coagulation factor leading to conversion of X to Xa
Extrinsic - damage of tissue outside of the vessel - leakage of tissue factor leading to conversion of 7 to 7a which converts ten tot ten a (common pathway)
Common - X to Xa, Xa causes prothrombin (II) to thrombin (IIa)
Thrombin (IIa) converts fibrinogen to fibrin
How does warfarin work?
Prevents oxidisation of vitamin K which activates clotting factors 10, 9, 7 and 2
Are there any antidotes to anticoagulants?
Warfarin - Vitamin K, PCC and FFP
Heparin - Protamine
Dabigatran - Idarucizumab
Apixaban and Rivaroxaban- Andexanet (a recombinant modified Factor Xa) alpha, PCC
Difference between Prothrombin Complex and Fresh Frozen Plasma?
Prothrombin complex concentrate offers several advantages over FFP, most importantly, the small volume needed to reverse anticoagulation. PCC contains significantly higher amounts of the clotting factors compared to FFP; one dose of PCC equals 8 to 16 units of FFP.
