Anticoagulation Flashcards
What are anticoagulants?
Anticoagulants are medications that PREVENT blood clots from forming - they do NOT breakdown clots.
*Fibrinolytics breakdown existing clots.
*Antiplatelets interferes with platelet binding to each other.
When are anticoagulants used?
1) For the prevention and treatment of Venous Thromboembolism (VTE):
-DVT: Deep Vein Thrombosis
-PE: Pulmonary Embolism
2) Immediate treatment of STEMI and NSTEMI
3) Prevention of cardio-embolic stroke (This is where the clot forms in the heart)
4) Any other situation where there is an increased risk of clot formation (blood disorders)
What is the body’s natural anticoagulant?
Anti-thrombin
General Mechanisms of Action of Anticoagulants
1) Heparins (UFH & LMWH-Enoxaparin, Dalteparin): Indirectly inhibits factors Xa and IIa (thrombin) via. Antithrombin.
2) Factor Xa Inhibitors:
Direct inhibitions (RIvaroxaban, Apixaban, Edoxaban)
Indirect Inhibition (Fondaparinux)
3) Direct Thrombin Inhibitors (Argatroban, Bivalirudin, Dabigatran)
4) Vitamin K antagonist (Warfarin): Inhibits factors 2,7,9,10
Dosing of Unfractionated Heparin (UFH)
1) VTE Prophylaxis: 5000U SubQ q8-12h
2) VTE Treatment: 80 U/kg IV bolus; 18 U/kg/hr infusion
3) ACS/STEMI Treatment: 60 U/kg IV bolus; 12 U/kg/hr infusion
Reversal Agent: Protamine
*It is important to monitor platelets for thrombocytopenia
*Monitor via aPTT levels
What are the Low Molecular Weight Heparins (LMWH)?
1) Enoxaparin (Lovenox)
2) Dalteparin
Enoxaparin Dosing
1) VTE Prophylaxis: 30 mg subQ q12h or 40 mg daily
CrCl < 30: 30 mg subQ daily
2) VTE and Unstable Angina and NSTEMI Treatment: 1 mg/kg subQ q12h or 1.5 mg/kg subQ daily
CrCl < 30: 1 mg/kg subQ daily
3) STEMI Treatment (< 75 y.o.): 30 mg IV bolus plus a 1 mg/kg subQ dose followed by 1 mg/kg q12h
CrCl < 30: 30 mg IV bolus plus a 1 mg/kg dose, followed by 1 mg/kg subQ daily
4) STEMI Treatment (> 75 y.o.): 0.75 mg/kg subQ q12h (no bolus)
CrCl < 30: 1 mg/kg subQ daily
*Enoxaparin is renally excreted
Reversal Agent: Protamine
Contraindications of Heparin (UFH & LMWH)
1) Uncontrolled active bleed
2) History of HIT
3) Hypersensitivity to pork products
What is HIT?
Heparin-Induced Thrombocytopenia is an immune mediated IgG drug interaction. This leads the platelet activation and platelet aggregation, and increases the risk of clotting.
Diagnosis of HIT
4T Score:
1) Thrombocytopenia (> 50% drop in platelets)
2) Timing of platelet count fall
3) Thrombosis
4) Other causes of thrombocytopenia
*After, we can confirm that the patient has HIT by Labs: ELISA
Once the patient is diagnosed with HIT, we then stop all heparin products, and we reverse warfarin with vitamin K
-Start a non-heparin anticoagulant for patient
What are the Factor Xa inhibitors?
1) Apixaban (Eliquis)
2) Rivaroxaban (Xarelto)
3) Edoxaban
4) Fondaparinux (This is the only injectable, and it works INDIRECTLY by Antithrombin)
These DIRECTLY inhibit Factor Xa, except Fondaparinux.
Fondaparinux is contraindicated in CrCl < 30!
Apixaban (Eliquis) Dosing
1) Stroke prophylaxis in Non-valvular Atrial Fibrillation: 5 mg PO BID
*IF the patient has at least 2 of the following, dose 2.5 mg PO BID:
- Age >= 80 y.o.
-Weight <= 60 kg
-Serum Creatinine >= 1.5 mg/dL
2) VTE Treatment:
Initial: 10 mg PO BID x 7 days, followed by 5 mg PO BID
Rivaroxaban (Xarelto) dosing
Creatinine Clearance dependent!
1) Stroke Prophylaxis in Non-valve Atrial Fibrillation:
CrCl > 50: 20 mg PO daily
CrCl 15-50: 15 mg PO daily
CrCl < 15: AVOID
2) VTE Treatment:
Initial: 15 mg PO BID x 21 days, then 20 mg PO daily with food
CrCl < 30: AVOID
What is the antidote for Apixaban and Xarelto?
Andexanet alfa (Andexxa)
What medications causes an additive bleed risk when given with Factor Xa inhibitors?
1) Anticoagulants
2) Antiplatelets
3) NSAIDs
4) SSRIs
5) SNRIs
What to do when converting from a Xa inhibitor to Warfarin?
1) Stop Xa inhibitor
2) Start parenteral anticoagulant
3) Start warfarin at next scheduled dose
INR Level indication
Higher INR —> thinner the blood
Lower INR —> thicker the blood
How often should we adjust warfarin dose?
Every 5 days
What is the usual starting dose of warfarin?
Most patients are initiated on 5 mg of warfarin daily. However, there are times where we initiate at a lower dose:
-Elderly
-Liver disease
-Malnourished
-Heart Failure
-Taking CYP Inhibitors
-Taking select antibiotics (Penicillins, Cephalosporins, Quinolones, Tetracyclines)
Contraindications and Warnings of Warfarin
Contraindications: Pregnancy
Warnings: Can cause HIT!
Warfarin make-up
Warfarin is a mixture of 2 enantiomers:
S-Warfarin - more potent (Metabolized by CYP2C9)
R-Warfarin
What are some foods that are high in vitamin K?
1) Spinach (cooked)
2) Broccoli
3) Brussels sprouts
4) Collard greens
5) Kale
6) Turnip greens
7) Swiss chard
8) Parsley
When would we consider reversing Warfarin?
If INR > 10: Hold warfarin and administer 2.5-5 mg oral Vitamin K, if there is no bleeding
If there is bleeding, we hold warfarin and administer IV Vitamin K 5-10 mg and give PCC.
*PCC: 4-factor Prothrombin Complex Concentrate (Kcentra). This contains factors 2,7,9,10 and Protein C & S.
What is the alternative name of Vitamin K?
Phytonadione
*Only administer IV (NO IM or SC)
What are the Direct Thrombin Inhibitors?
1) Dabigatran (Pradaxa) (PO)
2) Argatroban (IV)
3) Bivalirudin (IV)
What is the antidote of Dabigatran?
Idarucizumab (Praxbind)
When is Argatroban used?
Treatment of HIT
Antidote for Heparins
Protamine
-Protamine reverses the UFH given in the last 2-2.5 hours
-1 mg of Protamine reverses ~100 units heparin (MAX 50 mg)
-Protamine is less effective at reversal of LMWH
-Reverses the Enoxaparin given in the last 8 hours
-1 mg of Protamine is given per 1 mg of Enoxaparin
Antidote for Apixaban & Rivaroxaban
Andexanet alfa (Andexxa)
What is the confirmatory test for a VTE (DVT & PE)?
D-dimer
Atrial Fibrillation and Atrial Flutter treatment
DOAC or Warfarin is preferred in Non-Valvular AF.
For patients with mechanical heart valves, use Warfarin.
VTE Treatment
For patients without cancer, we treat with Oral Xa inhibitor & dabigatran for the first 3 months
For patients with cancer, Oral Xa inhibitors are preferred, along with other oral anticoagulants and LMWHs
Anticoagulation in patients undergoing Cardioversion
AF <= 48 hours: Initiate AC at the time of diagnoses and continue for 4 weeks after CV.
AF > 48 hours: AC for 3 weeks prior to CV, and continue for 4 weeks after CV.
CHA2DS2-VASc Score
C - Congestive Heart Failure (1)
H - Hypertension (1)
A2 - Age >= 75 years (2)
D - Diabetes
S2 - Prior stroke/TIA/Thromboembolism (2)
V - Vascular disease (prior MI, PAD) (1)
A - Age 65-74 years (1)
S - Sex: Female (1)
After adding up the score, oral anticoagulation (DOAC preferred) is recommended if:
>= 2 Males
>= 3 Females
*This scoring system helps to predict the risk of Stroke, and their need for anticoagulation in AF.
HAS-BLED Score
H - Hypertension (1)
A - Abnormal liver/Kidney function (1-2)
S - Stroke (1)
B - Bleeding tendency or predisposition (1)
L - Labile INR (if on Warfarin) (1)
E - Elderly (> 65)
D - Drugs (ASA, NSAIDs) or excessive alcohol use (1-2)
*This scoring system helps to assess the bleed risk in AF.
