Anti-Coagulation Pre-Lecture Flashcards
DVT Risk factors
- obesity
- > 40
- family history of DVT
- Immobilization > 10 days
- heart failure
- malignancy
- MI
- orthopedic injury
- oral contraceptive/estrogen use
- paralysis
- postoperative state
- pregnancy
- prior DVT
- varicose veins
UFH Key points
- rapid
- parenteral
- goal aPTT = 1.5 - 2.5 x control (46 - 70 seconds)
- Dosing (IV bolus = 80 U/kg, IV infusion = 18U/Kg/hr)
- AE= bleeding, thrombocytopenia
- rapid, variable
- commonly a continuous infusion
HIT management
- stop heparin
- dont start warfarin until platelets >150,000
- give alternate LMWH (levirubin, bivalirubin, argatroban, fondaparinux)
- dont give platelet infusion
- evaluate for thrombosis
Benefits of LMWH
- good bioavailability = reduced protein bioavailability
- good predictability
- smaller molecule = good subQ absorption
- long t1/2 = once or twice daily dosing
- less effects on platelets = reduced thrombosis
Enoxaparin Brand
Levonox
Enoxaparin (Levonox) Prophylactic Dose Surgery
30 mg subQ q12h (surgery)
Enoxaparin (Levonox) Prophylactic Dose Medical
40 mg subQ daily (medical)
Enoxaparin (Levonox) Treatment Doses
- 1.0 mg/kg q12h
- 1.5 mg/kg daily
Enoxaparin (Levonox) Key Point
Can be used with renal dysfunction (< 30ml/min)
Enoxaparin (Levonox) Renal Dysfunction Doses
- 30 mg subQ DAILY (prophylactic)
- 1.0 mg/kg subQ DAILY (treatment)
Dalteparin (Fragmin) Key Points
- Less common
- Treatment dose common for VTE cancer patients
Dalteparin (Fragmin) prophylactic dose
2500 - 5000 U subQ daily
Dalteparin (Fragmin) treatment dose
200 U subQ x 30 days QD, 150 U subQ daily (cancer treatment)
Monitoring anti Xa levels for LMWH
-consider for children, pregnant, severe kidney dysfunction, obese
- tx:
- **BID dosing 0.6 - 1.0 U/ml obtained 4 hours post dose
- **QD dosing 0.1 - 0.3 U/ml obtained as a trough (checked prior to second dose)
Is monitoring anti Xa levels of LMWH recommended?
NOOOOOOO
Fondaparinux Labeled Uses
- TKA
- THA
- Hip replacement
- Abdominal surgery
- TREATMENT OF DVT OR PE (OFTEN 1ST MED A PT CAN USE)
Fondaparinux prophylactic dose
2.5 mg subQ once daily (hip, knee or abdominal surgery)
Fondaparinux treatment dose
- < 50 kg = 5mg subQ QD
- 50 - 100 kg = 7.5mg subQ QD
- > 100 kg = 10mg subQ QD
If pt has renal dysfunction < 30ml/min, can a pt use fondaparinux?
NOOOOOOOO
Fondaparinux can NOT be used prophylactically in patients with
low body weight < 50 kg. Can be used to treat pts < 50 kg
Can Fondaparinux be used to treat HIT
YESSSS
Routine monitoring of fondaparinux levels?
NOOOOO, but can choose to monitor anti-10a levels similar to LMWH
Fondaparinux safe for pregnancy
YES. Category B
IV direct thrombin inhibitors should be associated with
USE IN HIT
IV direct thrombin inhibitors
- argatroban
- bivalirubin (angiomax)
- levirubin
Bivalirubin Brand
Angiomax
Argatroban KEY points
- if pt has liver dysfunction, adjust dose:
- **normal dose = 2 mcg/kg/min
- **hepatic dysfunction dose = 0.5 mcg/kg/min
- Causes a false elevation of INR
- **overlap with warfarin until INR of 4 (most meds overlap until INR of 2)
-this medicine can cause hepatic dysfunction
For lepirubin, reduce dose
if CrCl is < 60 ml/min
LIST ALL NOACS/DOACS
-direct thrombin inhibitor = dabigatran (Pradaxa)
- Factor Xa inhibitors:
- **rivaroxaban (xarelto)
- **apixaban (eliquis)
- **edoxaban (savaysa)
- **betrixaban (bevyxxa)
KEY THING TO REMEMBER ABOUT NOACS/DOACS
WHAT ARE THEY F-ING INDICATED FOR
Postoperative Prophylaxis
prevention of a postoperative DVT to PE in pts undergoing knee or hip surgery
Non valvular atrial fibrillation
- THIS PIECE OF INFORMATION MUST BE GIVEN TO YOU
- general prevention of stroke and systemic embolism in pts with non-valvular atrial fibrillation
Indefinite anticoagulation (secondary prevention of recurrent DVT and/or PE)
- reduction in the risk of a recurrent DVT and/or PE following initial 6 months of treatment
- continuing an anti-coag after a pt has been on one for months
VTE prophylaxis
-prophylaxis of VTE in adults hospitalized for an acute medical illness who are at risk for thromboembolic complications due to immobility and other VTE risk factors
DABIGATRAN INDICATIONS
- POST OPERATIVE PROPHYLAXIS (Hip)
- NON-VALVULAR ATRIAL FIBRILLATION
- DVT/PE TX
RIVAROXABAN INDICATIONS
EVERYTHING
- POST OPERATIVE PROPHYLAXIS (Hip)
- NON-VALVULAR ATRIAL FIBRILLATION
- DVT/PE TX
- SECONDARY PREVENTION OF RECURRENT DVT/PE
- VTE PROPHYLAXIS
APIXABAN INDICATIONS
- POST OPERATIVE PROPHYLAXIS (Hip)
- NON-VALVULAR ATRIAL FIBRILLATION
- DVT/PE TX
- SECONDARY PREVENTION OF RECURRENT DVT/PE
EDOXABAN INDICATIONS
- NON-VALVULAR ATRIAL FIBRILLATION
- DVT/PE TX
BETRIXABAN INDICATIONS
-VTE PROPHYLAXIS
Rivaroxaban also approved for
reduction of risk of major CV events in pts with CAD or PAD
Betrixaban other risk factors
- great than or equal to 75 yoa
- 60 - 74 yoa with D-dimers >/= 2 ULN
- 40 - 59 yoa with D-dimers >/= 2 ULN and a history of VTE or cancer
Warfarin Brands
- coumadin
- jantoven
Warfarin color is
CONSISTENT
Warfarin challenges
- drug drug interactions
- narrow therapeutic window
- drug and diet interactions
- intersubject variablity
- difficult to standardize labs
- Good PK/PD understanding by both pt/provider
Warfarin inhibits the synthesis of vitamin k dependent clotting factors
- 2, 7, 9, 10
- Protein C + S
Warfarin specifically inhibits the
enzyme responsible for cyclic conversion of vitamin K (vitamin K reductase)
Warfarin anti-coag effect in
24 hours
Warfarin peak effect
72 - 96 hours
Warfarin duration of action from a single dose
2 - 5 days
Warfarin S enantiomer hepatically metabolized by
2C9, 2C19, 2C18
Warfarin R enantiomer hepatically metabolized by
1A2 and 3A4
Factor t1/2 considerations
- Factor II (prothrombin) = 60 -100 h
- Factor 7 = 4 - 6 h
- Factor 9 = 20 - 30 h
- Factor 10 = 24 - 40 h
VKORC1
reductase enzyme that forms the vitamin K which is converted to clotting factors
Who should be tested for warfarin
ALL THREE THINGS NEED TO BE MET:
- Insulin naiive
- Will get results back before 6th dose
- Pt is at a high risk of bleeding (for example on meds that increase bleeding risk)
HIGHER THE INR
HIGHER THE BLEEDING RISK
Drugs that increase INR
- amiodarone
- fluconazole
- acute alcohol
- metronidazole
- fluconazole
- ciprofloxacin
- bactrim
- liver disease
- erythromycin
Drugs that decrease INR
- chronic use of alcohol
- rifampin
- cholestyramine
- carbamazepine
Aspirin and other NSAIDs impact on INR
-these meds increase bleeding HOWEVER do not increase INR
How does vitamin K impact warfarin
it reverses warfarin activity
Warfarin and chronic alcohol and liver damage
increase in INR
Most common antiplatelets
- COX 1 inhibitor = aspirin
- PDE III inhibitor = dipyridamole
Consider dipyridamole use in VTE with
concomitant use of warfarin with prosthetic valves
Consider ASA in VTE with
CHA2DS2 score 1
Bleeding management steps
- discontinue medication
- apply manual compression
- maintain bp
- surgical or radiological intervention
- blood products +/- PCC +/- targeted antidotes
Consider activated charcoal for bleeding
if there is = 2 hours of bleeding
When pt is bleeding and on hemodialysis
use dabigatran only
UFH, LMWH reversal agent
protamine sulfate
Dabigatran reversal agent
idarucizumab (Praxbind)
Factor Xa inhibitors
Andexanet alfa
UFH infusion antidote directions
1 mg protamine/100 units UFH given over the past 3 hours
LMWH antidote directions
- within 8 hours of last LMWH
- **1 mg per 100 anti-factor Xa units
- **1 mg per 1 mg enoxaparin
- > 8 hours
- **0.5 mg per 100 anti-factor Xa units
- **0.5 mg per 1 mg enoxaparin
Adverse reactions of protamine sulfate antidote
- hypotension
- bradycardia
- How to fix: slow the infusion (over 1 - 3 minutes), max can give is 50 mg over 10 minutes
Idarucizumab (Praxbind) MOA
direct binder to dabigatran (higher affinity than dabigatran to thrombin)
Idarucizumab Dose
- 5g IV
- 2 separate 2.5 g doses no more than 15 minutes apart
Idarucizumab monitoring
Baseline aPTT, repeat in 2 hours, every 12 hours until normal
Andexanet alfa (andexxa) binds and sequesters
rivaroxiban and apixaban
Warfarin Bleeding Management dependent on (2 things)
INR and presence/absence of bleeding
Warfarin bleeding management: Vitamin K
- Oral (PREFERRED): 5 mg tablets
- Parenteral: Don’t exceed 1 mg/min (otherwise will trigger anaphylaxis)
Warfarin bleeding management: Fresh Frozen Plasma (FFP)
10 - 15 ml/kg
Warfarin bleeding management: Prothrombin Complex Concentrate (PCC)
30 IU/kg (check INR before, 30 - 60 minutes after)
Warfarin bleeding management: IF INR 4.5 - 10 AND NO EVIDENCE OF BLEEDING
Avoid vitamin K
Warfarin bleeding management: IF INR > 10 AND NO EVIDENCE OF BLEEDING
PO vitamin K
Warfarin bleeding management: Major bleeding while on warfarin
PCC preferred over FFP. May add vitamin K 5 - 10 mg as well
Warfarin reversal: Rapid (complete, w/in 10 - 15 min)
Prothrombin complex concentrate + IV vitamin K
Warfarin reversal: Fast (partial)
Fresh frozen plasma
Warfarin reversal: Prompt (w/in 4-6 hours)
IV vitamin K
Warfarin reversal: Slow (w/in 24 hours)
PO vitamin K
Warfarin reversal: Very slow (3 - 5 days)
Omit warfarin (no vitamin K)
VTE prophylaxis options
- unfractionated heparin
- LMWH
- Factor Xa inhibitors
- Vitamin K antagonist (warfarin)
Moderate VTE risk
- general surgery pts = UFH, LMWH, Factor Xa inhibitor = continue prophylaxis up to 28 days after hospital discharge
- acutely ill medical patients = UFH, LMWH, fondaparinux, rivaroxaban, *BETRIXABAN = For UFH, LMWH, fondaparinux = No specific recommendations for post discharge
~Specific total tx regiments:
- **rivaroxaban = 31 - 39 days
- **betrixaban = 35 - 42 days
High VTE risk
- orthopedic surgery (TKA or THA)
- LMWH, fondaparinux, rivaroxaban, apixaban, dabigatran (hip), UFH, or vitamin k antagonist - FDA approved
- continue >/= 10 - 14 days post opp (consider up to 35 days)
