VTE and Stroke

Question 1

Oral Anticoagulants
(Warfarin)

Answer 1

MOA: Vitamin K antagonist, inhibits vitamin K dependent clotting factors (2, 9, 7, 10) and the antithrombotic factors protein C and S

Indicated: prevent and treatment of VTE, Ischemic stroke

Side effects: Bleeding

Precautions: high vitamin K foods can cancel the affect of warfarin (a lot of greens) so minimise intake. Drugs that are strong inhibitors or inducer of CYP2C9

Counsel
- Keep alcohol consumption to 1-2 standard drinks
Take same brand and around the same time every day
- Avoid large amounts of cranberry juice as it increase effects of warfarin

Pregnancy: Cat D = avoid
Target INR is 2-3 in non-valvular AF

Question 2

Direct Oral Anticoagulants (DOAC)
Ending in ‘an’ - Dabigatran

Answer 2

MOA: Reversibly inhibit both free and fibrin bound thrombin, preventing conversion of fibrinogen to fibrin, preventing thrombus formation. Thrombin-induced platelet aggregation is also inhibited

Indicated: prevent and treatment of VTE, non valvular AF

Side effect: GI bleeding, gastritis, dyspepsia

Contraindicated: CrCl <30mL/min
precaution:
- Use with caution with renal/liver failure (>2x ULN)
-strong P-GP inhibitor or inducers

Counsel
- Swallow whole with a glass of water with food. Do not open capsules/chew/crush the pellets as this will increase risk of bleeding
- Not to be kept in a DAA unless it is in its original packaging affects bioavailability

Question 3

Factor Xa Inhibitors
Ending in ‘ban’ - Apixaban, rivaroxaban

Answer 3

MOA: selectively inhibit factor Xa (10a), blocking thrombin production, conversion of fibrinogen to fibrin and thrombus development

Indicated: prevent and treatment of VTE, non-valvular AF, CAD or PAD

Contraindicated: in severe bleeding, or renal failure

Side effects: bleeding

Counsel
- There is no monitoring required for INR as it has a short half life.
They are metabolised by CYP3A4 and are substrates of P-GP

Rivaroxaban is taken once daily
Apixaban is taken twice daily

Question 4

Heparin

Answer 4

MOA: Inactive clotting factors IIa (thrombin) and Xa by binding to antithrombin III:

Indicate: Prevent and treatment of VTE

Side effect: bleeding, hyperkalemia, bruising at injection site, mild reversible thrombocytopenia

LMWH should be switched to heparin 36 hours before planned delivery, heparin should be stopped 4-6 hours before delivery

Question 5

Low Molecular weight Heparins (LMWH)
- Dalteparin, Enoxaparin, Danaparoid

Answer 5

MOA: Inactive clotting factors IIa (thrombin) and Xa by binding to antithrombin III. LMWH have a much greater effect on factor Xa than on thrombin. Danaparoid is more selective inhibitor of factor Xa than LMWH

Indicate: Prevent and treatment of VTE, cancer

Side effect: bleeding, hyperkalemia, bruising at injection site, mild reversible thrombocytopenia

Pregnancy: Heparin and LMWH are used to treat or prevent thromboembolism during pregnancy, safe in BF

Notes: Shorter half life than warfarin but has a quick onset therefore prophylactic dose is preferred for bridging before warfarin is use

• Prevention: LMWH have longer half life 3-6 hours than heparin 60minutes therefore only require once daily. LMWH is safer and effective and associated with a lower incidence of heparin induced thrombocytopenia

Question 6

Reperfusion therapy rt-PA

Answer 6

MOA: binding to a fibrin meshwork and converts plasminogen to plasmin (protease which converts insoluble fibrin to soluble fibrin degradation product) breaking down the clot

Effectiveness decreases with time after stroke

Precaution: Risk of bleeding

ADR: bleeding, transient hypotension