Anticoagulation

Question 1

What are anticoagulants?

Answer 1

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.

Question 2

When are anticoagulants used?

Answer 2

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)

Question 3

What is the body’s natural anticoagulant?

Answer 3

Anti-thrombin

Question 4

General Mechanisms of Action of Anticoagulants

Answer 4

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

Question 5

Dosing of Unfractionated Heparin (UFH)

Answer 5

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

Question 6

What are the Low Molecular Weight Heparins (LMWH)?

Answer 6

1) Enoxaparin (Lovenox)
2) Dalteparin

Question 7

Enoxaparin Dosing

Answer 7

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

Question 8

Contraindications of Heparin (UFH & LMWH)

Answer 8

1) Uncontrolled active bleed
2) History of HIT
3) Hypersensitivity to pork products

Question 9

What is HIT?

Answer 9

Heparin-Induced Thrombocytopenia is an immune mediated IgG drug interaction. This leads the platelet activation and platelet aggregation, and increases the risk of clotting.

Question 10

Diagnosis of HIT

Answer 10

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

Question 11

What are the Factor Xa inhibitors?

Answer 11

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!

Question 12

Apixaban (Eliquis) Dosing

Answer 12

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

Question 13

Rivaroxaban (Xarelto) dosing

Answer 13

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

Question 14

What is the antidote for Apixaban and Xarelto?

Answer 14

Andexanet alfa (Andexxa)

Question 15

What medications causes an additive bleed risk when given with Factor Xa inhibitors?

Answer 15

1) Anticoagulants
2) Antiplatelets
3) NSAIDs
4) SSRIs
5) SNRIs

Question 16

What to do when converting from a Xa inhibitor to Warfarin?

Answer 16

1) Stop Xa inhibitor
2) Start parenteral anticoagulant
3) Start warfarin at next scheduled dose

Question 17

INR Level indication

Answer 17

Higher INR —> thinner the blood
Lower INR —> thicker the blood

Question 18

How often should we adjust warfarin dose?

Answer 18

Every 5 days

Question 19

What is the usual starting dose of warfarin?

Answer 19

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)

Question 20

Contraindications and Warnings of Warfarin

Answer 20

Contraindications: Pregnancy

Warnings: Can cause HIT!

Question 21

Warfarin make-up

Answer 21

Warfarin is a mixture of 2 enantiomers:
S-Warfarin - more potent (Metabolized by CYP2C9)
R-Warfarin

Question 22

What are some foods that are high in vitamin K?

Answer 22

1) Spinach (cooked)
2) Broccoli
3) Brussels sprouts
4) Collard greens
5) Kale
6) Turnip greens
7) Swiss chard
8) Parsley

Question 23

When would we consider reversing Warfarin?

Answer 23

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.

Question 24

What is the alternative name of Vitamin K?

Answer 24

Phytonadione

*Only administer IV (NO IM or SC)

Question 25

What are the Direct Thrombin Inhibitors?

Answer 25

1) Dabigatran (Pradaxa) (PO)
2) Argatroban (IV)
3) Bivalirudin (IV)

Question 26

What is the antidote of Dabigatran?

Answer 26

Idarucizumab (Praxbind)

Question 27

When is Argatroban used?

Answer 27

Treatment of HIT

Question 28

Antidote for Heparins

Answer 28

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

Question 29

Antidote for Apixaban & Rivaroxaban

Answer 29

Andexanet alfa (Andexxa)

Question 30

What is the confirmatory test for a VTE (DVT & PE)?

Answer 30

D-dimer

Question 31

Atrial Fibrillation and Atrial Flutter treatment

Answer 31

DOAC or Warfarin is preferred in Non-Valvular AF.

For patients with mechanical heart valves, use Warfarin.

Question 32

VTE Treatment

Answer 32

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

Question 33

Anticoagulation in patients undergoing Cardioversion

Answer 33

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.

Question 34

CHA2DS2-VASc Score

Answer 34

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.

Question 35

HAS-BLED Score

Answer 35

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.