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Anticoagulants
Steven R. Kayser, PharmDProfessor Emeritus
Department of Clinical PharmacyUCSF
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Anticoagulants‐Definition
• A substance that hinders the clotting of blood
• Sometimes referred to as “blood thinners”
– Is this accurate?
• Many different types of drugs can alter clotting
• What do they really do?
• What are “clot busters?”
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When are blood clots GOOD?
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Where and why do blood clots occur?
• Economy class syndrome
– Clots in the legs
• Lungs‐pulmonary embolus
• Brain‐stroke
• Atrial fibrillation‐stroke
• Any condition with
– Stasis, injury, ↑coag
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When are Blood Clots BAD?• When they block the flow of blood
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Blood clotting
• A complex series of events
• Balance clotting with bleeding
• Balance clotting with tissue damage
• Evolution of a bruise– Trauma
– Bleeding
– Clotting
• Natural elements in the body maintain this balance
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Bleeding Clotting
Types of Anticoagulants
• Injections versus Oral Medications• Medications which affect platelets, ASA• Heparin• Enoxaparin or Lovenox®• Warfarin or Coumadin®• Dabigatran or Pradaxa®• Rivaroxaban or Xarelto®• Apixaban or Eliquis®• tPA or Activase®
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Warfarin‐Coumadin®• 1920’s prairies of Canada and Northern Plains
• Previous healthy cattle started dying from internal bleeding
• Devastating economic blow to farmers
• Discovered that cattle fed damp sweet clover hay which normally would have been discarded
• 10 years later a local farmer went to Karl Link who was able after a few years to crystallize the active substance
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Wisconsin Alumni Research Foundation(WARF)
WARFARIN
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Warfarin
• 1941‐patent rights for first anticoagulant
• 1948‐first promoted as a rodenticide
• 1954‐approved for human use
• 1955‐Dwight Eisenhower received warfarin after heart attack, “What was good for a war hero and the President of the United States must be good for all, despite being a rat poison”
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Why is my dosage of warfarin so different
from Joe’s or Mary’s?
Warfarin DosingWhat influences the dose?
• Must be individualized!
• What about my diet?
• How do we manage complicated medication regimens and avoid drug interactions?
• What to look for? Age, sex, weight, smoking?
• What about travel?
• What about activities?
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Warfarin and GeneticsIn search of personalized medicine
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Warfarin and Genetics
• Genetics accounts for about 40% of dose prediction
• Weight and age account for 16%
• Other factors make up the rest
• If the average dose for a Caucasian is 5 mg
– The dose for an Asian patient is 2.5 mg
– The dose for an African American is 7.5 mg
• Not routinely useful to genotype
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Diet and Warfarin
• Do not need to avoid vitamin K containing foods
– They are good for you!
– We can adjust the warfarin dose if necessary
– Maintain “relative” consistency
– Do not weigh or measure portions
• Biggest dietary influence is not eating anything due to an illness
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Interactions with Warfarin
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Drug Interactions with Warfarin
• 1 + 1 ≠ 2 (one plus one does not always = two)
• Some drugs make warfarin work too much
• Some drugs do not allow warfarin to work
• Timing can be different‐when an interaction occurs can be different for different medicines
• Influence of other factors
– Stomach irritation, ulcers
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Most common drug interactions
• Antibiotics and other anti‐infective drugs
• NSAIDs‐non steroidal anti‐inflammatory drugs
– Advil® (ibuprofen), Alleve®(naproxen)
• Heart Medicines, for example Cordarone®
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How to manage interactions?• Avoid them!
– Nutritional supplements
– Herbal medications
– Over the counter medications (OTC)
• Ask lots of questions!– Pharmacist
• Use an alternative agent that does not interact
• Monitor more closely and change dose of warfarin if needed
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Warfarin Monitoring
• Laboratory
• Physician Office
• Anticoagulation Clinic
• Home Testing
• Home Monitoring
• Frequency of monitoring
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Point‐of‐care INR testing
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Warfarin and Bleeding
• Warfarin does not cause bleeding!
• Requires some type of injury– Trauma
– Irritation
• Direct pressure
• Ice for bruises
• Call 911 if does not stop
• MedicAlert
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Pros and Cons of Warfarin
• Pros– Able to monitor– Lots of experience– Antidote (vit K)– Inexpensive– Very effective– Few side effects– Well absorbed– Long duration of action– Once daily
• Cons– Need to monitor– Drug interactions– Food interactions– Bleeding– Care with surgery– Avoid in pregnancy
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“Clot Busters”
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New Anticoagulants
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New Anticoagulants
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Use of new anticoagulantsDrug Atrial
fibrillation Treatment DVT/PE
Prevention of DVT/PE during
surgery
Eliquis®apixaban
√ √
Pradaxa®rivaroxaban
√ √
Xarelto®dabigatran
√ √ √
New Anticoagulants
• Pros– No monitoring
– Fewer drug interactions
– Few diet interactions
– Short duration of action
– Effective and better than warfarin for some
• Cons– Expensive
– Unable to measure
– Short duration of action, risk if miss a dose
– No antidote
– Dangerous with kidney problems
– Bleeding in stomach (Pradaxa®, Xarelto®)
– Avoid in pregnancy
– Twice daily (Pradaxa®, Eliquis®)
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Natural anticoagulants?
• Garlic
• Ginseng
• Fish oils
• Vitamin E
• Ginger
• Dong quai
• Feverfew
• Most are reported to have an effect on platelets
• Some are reported to influence warfarin and INR
• Different formulations make generalized conclusions difficult
Approaches to Anticoagulant Therapy
Platelet Adherence Aggregation
Platelet Inhibitors
Vascular Injury Risk Factor Reduction
Coagulation Activation Thrombin Generation Fibrin
Formation
Anticoagulants
Plasmin Generation Fibrinolysis
Thrombolytics
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Resources
• ClotConnect http://www.clotconnect.org/
• ClotCare http://www.clotcare.com/
• American Heart Association http://www.heart.org/HEARTORG/
• National Blood Clot Alliance http://www.stoptheclot.org/learn_more/learn_more.htm
• Individual health plans, e.g. Kaiser Foundation
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