Pharm - Anticoagulants Flashcards
What are the two acronyms to assess for risk of cardio embolic stroke
CHADS2 and CHA2DS2-VASc
What are the components of CHADS2
CHF HTN Age >75 yo Diabetes Stroke/TIA (2 points)
What are the components of CHA2DS2-VASc
CHF HTN Age 65-74 1 point Age >75 2 point Diabetes Stroke/TIA/systemic embolism Vascular disease (MI, PAD, aortic plaque) Gender: Female 1 point
what is the elevated risk associated with a mechanical mitral valve
greater risk for cardioembolism
22% chance/year
what is the elevated risk associated with a bioprostheitc aortic valve
elevated (but not high) risk for cardioembolism
12% chance/year
MoA Heparin
- Heparin binds to antithrombin
- Increases the effect of antithrombin on factors II, IX, X, X,I, and XII by >1000 fold
- Antithrombin inhibits coagulation by lysing thrombin (II) and other factors ultimately hindering formation of fibrin
Contraindications of Heparin for pt with clot medical hx
- Active uncontrollable bleeding
- History of HIT
Routes (2) of admin for UFH
IV
SubQ
When use IV route for UFH
- continuous effusion is best when a rapid and confirmed effect is needed.
- easier to titrate that IV bolus or subq
- use an empiric initial dose followed by titration based on response
UFH - how to use subq route
initial bolus and then maintenance dosing
appropriate monitoring parameter to assess heparin therapy
aPTT
Given a patient’s INR or aPTT result and the target range, identify the result as therapeutic, subtherapeutic, or supratherapeutic
I think we can all do this :)
What are the diagnostic criteria for heparin-induced thrombocytopenia (HIT)
- absolute thrombocytopenia (pat <150,000 OR >50% decrease from baseline)
- Occurs 5-10 days after initiation of heparin (if heparin naive) and can occur within 12 hours after dose if have used heparin in last 3 months.
- initial dx is clinical
- conformational assays drawn for HIT antibodies
Describe pathogenesis of heparin-induced thrombocytopenia
- Heparin forms complex with platelet factor 4 (PF4)
- Body forms antibodies against the heparin-PF4 complex
- Complexes aggregate and are removed from circulation prematurely, resulting in thrombocytopenia
- Venous or arterial thrombosis can occur – likely due to release of procoagulant particles from complex (counterintuitive)
What is the appropriate treatment for heparin-induced thrombocytopenia
- discontinue heparin
- anticoagulant with non-heparin product
- do not start warfarin until thrombocytopenia is resolved
- platelet transfusions are contraindicated, aggravate the problem (add fuel to the fire)
UFH reversal agent
protamine sulfate
MoA LMWH
- Interacts with antithrombin to accelerate inactivation of clotting factor Xa (mostly) and IIa (less so)
- Focus on Xa is major difference from UFH
Indication for LMWH
- Acute treatment of DVT/PE
- Prophylaxis of VTE in acutely ill pts or pts following some ortho procedures
What are the contraindications for LMWH for a pt with DVT
- history of HIT
- hypersensitivity to LMWH, UFH, or pork
- active major bleeding
- spinal puncture (black box!!)
Route for LMWH
subq
Reversal agent LMWH
protamine sulfate
What is the LWMH dosing regimen based on?
weight and renal function
MoA fondaparinux
Synthetic based on structure of heparin. Enhances antithrombin’s effect on Xa but no effect on IIa
MoA Warfarin
Vitamin K antagonist → inhibits the production of clotting factors II, VII, IX, and X (vitamin K dependent factors)
Indications for Warfarin
- Treatment or prevention of VTE
- Prevention of cardioembolic VCVA in pts with afib, left heart thrombus, or prosthetic heart valves
- only oral anticoagulant indicated for prevention of stroke in pts with mechanical heart valves!
- Prevention of secondary CVA
- Prevention of recurrent MI
starting dose of warfarin and the timeframe for monitoring for efficacy
5-10 mg daily for 1-3 days, then measurement of effect (PT/INR)
List the 6 medications that interact with Warfarin
- Fluconazole
- Bactrim
- Metronidazole
- Amiodarone
- Aspirin
- Carbamezepine
What 4 medications that interact with Warfarin increase INR, why?
Fluconazole
Bactrim
Metronidazole
Amiodarone
- inhibit metabolism of Warfarin, Warfarin increases which increases INR
What medication that interacts with Warfarin has no affect on INR
Aspirin
- platelet inhibition
What medication that interacts with Warfarin decreases INR, why?
Carbamezepine
- induces metabolism of Warfarin, Warfarin decreases which decreases INR
Effect of dietary vitamin K on warfarin dosing
- If increase vitamin K intake, INR will decrease, if decrease vitamin k intake, INR will increase
- If eat consistent amt of vitamin K, can titrate to stable INR
Reversal agent for warfarin
vitamin K
MoA of dabigatran
Orally active direct thrombin (II) inhibitor, inhibits conversion of fibrinogen to fibrin
Indications for dabigatran
- Prevention of stroke and systemic embolism in non-valvular afib
- Treatment of actute DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days
- Prevention of recurrent DVT and PE
Contraindications for dabigatran
- Active pathological bleeding
- Prosthetic mechanical heart valve
Reversal agent for dabigatran
Idarucizumab (Praxbind)
MoA of rivaroxaban, apixaban, edoxaban
Selectively block the active site of factor Xa, inhibiting its activation within the intrinsic and extrinsic pathways. Mechanism is independent of antitrhombin (unlike heparin, LMWH, fondaparinux)
Indication for factor Xa inhibitors
- Prevention of cardioembolism in nonvalvular afib
- Treatment of DVT and PE
- Prevention of recurrence of DVT and PE
- Prevention of DVT and PE in patients undergoing knee or hip replacement sx
Contraindications for factor Xa inhibitors
active pathologic bleeding
ID goals of therapy for the treatment of acute venous or arterial thromboembolism
- Prevent PE (venous)
- Prevent extension of thrombus (venous or arterial)
- Prevent post-thrombotic syndrome (venous or arterial)
- Prevent recurrence of thromboembolism (venous or arterial)
Appropriate anticoagulant for a pt with a:
- bioprosthetic mitral valve
- mechanical mitral valve
- bioprosthetic : warfarin for 3 months, then aspirin
2. mechanic: warfarin w/INR target 2.5-3.5
Appropriate anticoagulant for a pt with a:
- bioprosthetic aortic valve
- mechanical aortic valve
- bioprosthetic: aspirin
- mechanical: no additional risk: Warfarin w/INR target 2-3
additional risk: Warfarin with INR 2.5-3.5
If a pt has a mechanical aortic or mitral valve with low bleed risk what med should add to Warfarin
low-dose ASA
What medication should not be used with pts who have heart valve replacements?
direct oral anticoagulants
CHADS2 score of 0 is treated with what
ASA 75-325 mg/day
CHADS2 score of 1 is treated with what
- oral anticoagulant
- ASA 75-325 mg/day is non-anticoagulant alternative
CHADS2 score of 2-6 is treated with what
oral anticoagulant
Patient with a first, provoked DVT/PE
- duration of treatment
- target INR
- 3 months
- INR target 2-3
Acronym for risk of major hemorrhagic event
HAS-BLED
What are the risk factors for HAS-BLED
H: hypertension (BP>160 mmHg) (1 pt)
A: abnormal renal or liver function (1 or 2 pts)
S: stroke hx (1 pt)
B: bleeding hx (1 pt)
L: Labile INRs (1 pt)
E: Elderly (>65) (1 pt)
D: drugs that increase bleeding risk (ASA, NSAIDs, etc.) or alcohol (1 or 2 points)
Appropriate uses for Heparin (6)
- Acute tx or prophylaxis of venous or arterial thrombosis
- DIC
- Venous catheter occlusion
- Atrial fibrillation
- Cardiac surger
- ACS
