Anticoagulants. Anticoagulants Definition. When are blood clots GOOD? Where and why do blood clots occur? 6/12/2014

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1 Anticoagulants Steven R. Kayser, PharmD Professor Emeritus Department of Clinical Pharmacy UCSF 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? 1 2 When are blood clots GOOD? 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 3 4 1

2 When are Blood Clots BAD? When they block the flow of blood Blood clotting A complex series of events Balance clotting with bleeding Balance clotting with tissue damage Evolution of a bruise Trauma Bleeding Clotting Bleeding Clotting Natural elements in the body maintain this balance 5 6 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 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 7 8 2

3 Wisconsin Alumni Research Foundation(WARF) WARFARIN 9 10 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 11 3

4 Why is my dosage of warfarin so different from Joe s or Mary s? Warfarin Dosing What 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? Warfarin and Genetics In search of personalized medicine

5 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 Diet and Warfarin Interactions with 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

6 Drug Interactions with Warfarin (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 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 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

7 Warfarin Monitoring Laboratory Physician Office Anticoagulation Clinic Home Testing Home Monitoring Point of care INR testing Frequency of monitoring 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

8 Pros and Cons of Warfarin Clot Busters 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 New Anticoagulants New Anticoagulants

9 Use of new anticoagulants Drug Eliquis apixaban Pradaxa rivaroxaban Xarelto dabigatran Atrial fibrillation Treatment DVT/PE Prevention of DVT/PE during surgery 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 ) 35 9

10 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 Vascular Injury Risk Factor Reduction Platelet Adherence Aggregation Platelet Inhibitors Coagulation Activation Thrombin Generation Fibrin Formation Anticoagulants Plasmin Generation Fibrinolysis Thrombolytics 40 10

11 Resources ClotConnect ClotCare American Heart Association National Blood Clot Alliance _more.htm Individual health plans, e.g. Kaiser Foundation 41 11

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