Anticoag Flashcards by Jimmy Hayden

Where are DVTs most commonly found?

Deep veins in the legs (underlined) - also thighs and pelvis

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A number of factors can lead to activation of the coagulation process such as…

blood vessel injury, blood stasis, and pro-thrombotic conditions

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True or false: all of the clotting factors have an active and inactive form

True

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Once activated, the clotting factor will serve to activate the next clotting factor in the sequence until _____ is formed

fibrin

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How do UFH, LMWH, and fondaparinux work?

Bind antirhrombin (AT)
Causes an increase in AT activity 1000-fold
AT inactivates thrombin and other proteases involved in blood clotting, including factor Xa

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Difference between UFH and LMWH

LMWHs inhibit factor Xa more specifically than UFH

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How is fondaparinux different from UFH/LMWHs

Synthetic pentasaccharide that requires AT binding to selectively inhibit factor Xa

Considered an indirect factor Xa inhibitor vs eliquis/xarelto/savaysa/bevyxxa which are direct factor Xa inhibitors

LMWH and UFH inhibit factor Xa on their own

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What factors does warfarin inhibit

II, VII, IX, and X

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Which factors are vitamin K dependent

II, VII, IX, and X

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Where do direct thrombin inhibitors work?

Block thrombin directly, decreasing the amount of fibrin available for clot formation

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Role of IV direct thrombin inhibitors, name one

Used when HIT develops in a hospital setting
IV DTI’s do not cross react with heparin-induced thrombocytopenia antibodies

Argatroban = drug of choice in heparin induced thrombocytopenia

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Patients receiving anticoagulants should receive individualized care through a defined process that includes…

standardized ordering, dispensing, administration, monitoring, and patient/caregiver education

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UFH moa

Binds to antithrombin (AT) which inactivates thrombin (factor IIa) and factor Xa and prevents conversion of fibrinogen to fibrin

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UFH dose VTE prophylaxis, VTE treatment, ACS/STEMI
Side effects
Monitoring

VTE prophylaxis: 5000 units SC q8-12h
VTE tx: 80 units/kg IV bolus followed by 18 units/kg/hr infusion
Treatment of ACS/STEMI: 60 units/kg IV bolus (max 4000 units), 12 units/kg/hr infusion (max 1000 units/hr)

Use ACTUAL body weight for dosing

Side effects = bleeding, thrombocytopenia, HIT, hyperkalemia, osteoporosis (long-term use)

Monitor aPTT, therapeutic range 1.5-2.5 x pt’s baseline; take 6 hours after initiation then every 24 hours
Monitor platelets, Hgb, Hct baseline and daily

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UFH antidote

Protamine
1 mg protamine reverses ~100 units of heparin
Max dose 50 mg

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Heparin injection vs heparin flushes

Heparin flushes are used to keep IV lines open
Heparin flush dose = 10 or 100 units/mL
Heparin injection doses are 10,000 units/mL
Look and sound alike = fatal errors

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Enoxaparin VTE ppx dosing, VTE tx dosing, UA/NSTEMI dosing, STEMI tx dosing
Boxed warning
Contraindications
Side effects
Monitoring

PPx VTE: 30 mg SC q12h or 40 mg SC daily
Tx VTE: 1 mg/kg SC q12h or 1.5 mg/kg SC daily for inpatient tx
UA/NSTEMI: 1 mg/kg SC q12h
STEMI:
–Age < 75: 30 mg IV bolus + 1 mg/kg loading dose followed by 1 mg/kg SC q12h maintenance (max 100 mg for first 2 SC doses)
–Age >75: 0.75 mg/kg SC q12h, no bolus - max 75 mg for first 2 doses

—->CrCL < 30: 1 mg/kg SC daily (not q12h)

Boxed warnings: risk of hematomas, subsequent paralysis (pts undergoing neuraxial anesthesia or spinal puncture)

Contraindications: Hx of HIT, active major bleed

Side effects: Bleeding, anemia, inc LFTs, thrombocytopenia, hyperkalemia

Monitoring: platelets, Hgb, Hct, SCr
Anti-Xa levels in pregnancy (obtain 4 hrs post dose)

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What is heparin induced thrombocytopenia?

Unexplained drop in platelet count (> 50% drop in baseline), laboratory confirmation of antibodies or platelet activation by heparin
Can lead to a prothrombic state, can lead to thrombosis

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How to treat HIT?

D/C heparin and LMWH

If on warfarin d/c warfarin and give vitamin K. Do not restart warfarin until platelets have recovered to at least 150,000

Give argatroban for anticoagulation

Fondaparinux often used off label in clinical practice for HIT

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Eliquis generic, dosing, boxed warnings, monitoring

Afib: 5 mg BID unless pt has at least 2 of the following (>80 yo, body wt < 60 kg, SCr >1.5) then give 2.5 mg bid

tx of DVT/PE: 10 mg BID x 7 days, then 5 mg PO bid x 6 months?

DVT ppx after knee/hip: 2.5 mg PO BID for 12 days after knee or 35 days after hip, first dose 12-24 hours after surgery

Boxed warnings: spinal puncture/neuraxial anesthesia at risk of hematomas, subsequent paralysis

Contraindications: active bleeding

Warnings: not recommended w prosthetic heart valves

Side effects: bleeding

Monitoring: No monitoring of efficacy required

Bevyxxa generic, dose, boxed warnings, monitoring

Betrixaban
PPx of DVT in hospital: 160 mg x 1 dose then 80 mg PO daily with food, duration 35-42 days

Boxed warnings: spinal puncture/neuraxial anesthesia at risk of hematomas, subsequent paralysis

Contraindications: active bleeding

Warnings: not recommended w prosthetic heart valves

Side effects: bleeding

Monitoring: No monitoring of efficacy required

Savaysa generic, dose, boxed warnings, monitoring

CrCL > 95 mL/min: DO NOT USE
CrCL 51-95: 60 mg daily
CrCL 15-50: 30 mg daily
CrCL < 15: not recommended

Tx of DVT/PE: 60 mg daily, start after 5-10 days of parenteral anticoagulation

Boxed warnings: spinal puncture/neuraxial anesthesia at risk of hematomas, subsequent paralysis, edoxaban do not use if CrCL > 95 mL/min

Contraindications: active bleeding

Warnings: not recommended w prosthetic heart valves

Side effects: bleeding

Monitoring: No monitoring of efficacy required

When to DC factor Xa inhibitors for elective surgery?

Rivaroxaban, edoxaban: 24 hours prior

Apixaban: 48 hours prior

Xarelto generic, dose, boxed warnings, monitoring

Rivaroxaban
Nonvalv afib: CrCL > 50 20 mg PO daily w evening meal
CrCL 15-50: 15 mg PO daily w evening meal
Avoid CrCL < 15

Tx of DVT/PE:
15 mg PO BID x 21 days then 20 mg PO daily (w food)

Missed doses:
If taking 15 mg BID, take immediately to ensure intake of 30 mg/day. Can take 2 15 mg tabs at once.
If taking 10, 15, or 20 mg once day, take immediately on the same day otherwise skip

Boxed warnings: spinal puncture/neuraxial anesthesia at risk of hematomas, subsequent paralysis, edoxaban do not use if CrCL > 95 mL/min

Contraindications: active bleeding

Warnings: not recommended w prosthetic heart valves

Side effects: bleeding

Monitoring: No monitoring of efficacy required

Factor Xa inhibitor drug interactions

Apixaban and rivaroxaban are substrates of 3A4 and Pgp Avoid inducers (carbamazepime, phenytoin, rifampin, St Johns wort) Avoid combo 3A4/P-gp inhibitors (ketoconazole, itraconazole, lopinavir/ritonavir, indinavir, conivaptan)

Conversion from warfarin to Xa inhibs/dabigatran

Rivaroxaban when INR < 3 Edoxaban wen INR < 2.5 Apixaban when INR < 2 Dabigatran when INR < 2 Note: conversion between warfarin and betrixaban shouldn't be required bc they dont have the same indications

Conversion from Xa inhibs/dabigatran to warfarin

Stop Xa inhib Start parenteral anticoag and warfarin at next scheduled dose of Xa Dabigatran to warfarin Start warfarin 1-3 days before stopping dabigatran

Pradaxa generic, dose, boxed warnings, contraindications, side effects, monitoring

Dabigatran Factor IIa (thrombin) inhibitor Dose Nonvalv afib: 150 mg BID (reduce to 75 mg BID CrCL 15-30 mL/min) Tx of DVT/PE: 150 mg BID, start 5-10 days after parenteral anticoag Take w full glass of water (dyspepsia SE). Swallow capsules whole. Do not break, chew, crush, or open Boxed warnings: Boxed warnings: spinal puncture/neuraxial anesthesia at risk of hematomas, subsequent paralysis Contraindications: pts w mechanical prosthetic heart valve(s) Side effects: Dyspepsia, gastritis-like symptoms, bleeding (more GI bleeding) Monitoring: Hgb, Hct, SCr - no efficacy monitoring KEEP IN ORIGINAL CONTAINER. Discard 4 months after opening. Do not administer via NG tube.

Argatroban indication, notes

Used in patients with a history of HIT | No cross-reaction with HIT antibodies, no antidote

Bivalirudin brand, indication, notes

Used in patients with history of HIT Direct thrombin inhibitor No cross creativity with HIT antibodies

Warfarin is a racemic mixture. Which is more potent?

S enantiomer is 2.7 to 3.8 times more potent

Normal starting dose of warfarin? When do you start lower doses of warfarin initially?

Normal dose: 10 mg daily x 2 days then adjust based on INR Elderly, malnourished, taking drugs that can increase warfarin levels, liver disease, heart failure, high risk of bleeding When starting amiodarone dec warfarin dose by 30-50% initially

Warfarin contraindications, warnings, side effects, monitoring, notes

CI: Pregnancy (except with mechanical heart valves at high risk for thromboembolism) Warnings: Tissue necrosis/gangrene, HIT, presence of 2C9*2 or *3 alleles and/or polymorphisms of VKORC1 gene may increase bleeding risk Side effects: bleeding, skin necrosis, purple toe syndrome Monitoring: Goal INR 2-3, 2.5-3.5 for mechanical mitral or 2 mechanical heart valves Antidote: vit K

What drugs can decrease INR?

2C9 inducers: | Rifampin, carbamazepine, phenobarbital, phenytoin, St John's Wort

Which drugs can increase INR?

2C9 inhibitors: | amiodarone, fluconazole, metronidazole, bactrim

Natural products that can increase risk bleeding risk w warfarin

``` 5 G's: Garlic Ginger Ginkgo Ginseng Glucosamine ```

Warfarin colors/strengths

Please Leg Greg Brown Bring Peaches To Your Wedding ``` Pink (1) Lavender (2) Green (2.5) Brown/Tan (3) Blue (4) Peach (5) Teal (6) Yellow (7.5) White (10) ```

How long do you continue parenteral anticoag when treating acute DVT/PE?

Continue at least 5 days and until INR is > 2 for at least 24 hours.

How is vitamin K administered for warfarin reversal? When do we use different dose forms?

PO or IV only SC not recommended because of variable absorption IM not recommended due to risk of hematoma Po pref'd when patients don't have significant or major bleeding IV should be used only when patient has major bleeding; IV injection is associated with anaphylaxis so infused slowly. Give PO when INR > 10 if not bleeding, if INR between 4.5-10 and not bleeding just hold warfarin rather than give vitamin K.

KCentra works on what factors?

``` II VII IX X Protein C Protein S Give WITH vitamin K ```

What to do if a patient is on warfarin and has a scheduled surgery?

Stop 5 days before major surgery Bridge with heparin in patients with a mechanical heart valve, AFib, or VTE at high risk for thromboembolism Bridging not required for low risk patients

Risk factors for development of VTE

``` Surgery Major trauma Immobility Cancer Previous VTE Pregnancy Estrogen containing meds or selective estrogem receptor modulators Erythropoiesis stimulating agents ```

VTE guidelines for patients without cancer...

Dabigatran and factor Xa inhibitors preferred over warfarin for first 3 months of treatment for a DVT in the leg or PE

VTE guidelines for patients with cancer

LMWH preferred over all oral anticoagulants

When is anticoag required in afib?

Mechanical heart valves = highest risk , treated with warfarin only Non-valvular afib = based on CHA2DS2VASc score (> or equal to 2=oral anticoag)

CHA2DS2VASc scoring system

``` C CHF H HTN A Age >/= 75 yrs (2 pts) D Diabetes S2 Prior stroke/TIA (2 points) V Vascular disease Age 65-74 S Sex category, female ``` All the others are 1 point each

Enoxaparin injection counseling - air bubble

Do not expel air bubble in the syringe prior to injection

Dabigatran counseling

Take with a full glass of water, do not swallow whole Keep in original bottle or blister package If you miss a dose and your next dose is less than 6 hours away, skip the missed dose

Xarelto counseling

Take with evening meal If twice daily take with food at the same time each day If you miss a dose you may take 2 at the same time if taking 15 mg twice daily