Anticoagulation Flashcards
Who needs anticoagulation?
Atrial fibrillation Mechanical heart valves Tissue heart valves 3 months Cardiomyopathy MI (Anterior MI with LV dysfunction) Coagulopathy DVT and prophylaxis of venous thrombosis in high risk surgery Pulmonary Emboli Post op orthopedics
Virchow’s Triad
Hypercoagulable State
Endothelial Injury
Circulatory Stasis
Prothrombin Time
Needed to measure extrinsic pathway
Historically, a most reliable and “relied upon” clinical test
However:
Proliferation of thromboplastin reagents with widely varying sensitivities to reduced levels of vitamin K-dependent clotting factors has occurred
Concept of correct “intensity” of anticoagulant therapy has changed significantly (low intensity)
Problem addressed by use of INR (International Normalized Ratio)
Partial Thromboplastin Time/Activated Partial Thromboplastin Time (PTT or aPTT)
Needed to measure intrinsic pathway
PTT-Used as part of an investigation of a bleeding or thrombotic episode; to monitor unfractionated (standard) heparin anticoagulant therapy
This test measures the integrity of the intrinsic pathways of coagulation
The aPTT now measures the clotting time of plasma, from the activation of factor XII by a reagent (a negatively charged activator such as silica and a phospholipid) through the formation of a fibrin clot.
aPTT has replaced PTT, basically the same thing.
International Normalized Ratio
ratio calculated from the PT
The INR is calculated from the PT and is intended to allow valid comparisons of results regardless of the type of PT reagent used among different laboratories (INR = [patient PT / mean normal PT]).
The INR is a method of standardizing the PT for coumadin anticoagulation. Before the INR, different labs using different reagents had different controls and widely differing PT value ranges.
An INR of 1 means the blood clots “normally” for that pt. The greater the INR, the longer it takes the blood to clot.
Drugs that Decrease INR
American Ginseng (No effect on Warfarin with Asian Ginseng) Barbiturates Binding Resins Tegretol Oral Contraceptives PCN Rifampin St. Johns Wort Vitamin K
Drugs that Increase INR
Acetaminophen Alcohol Amiodarone Anabolic Steroids Antifungal Medications Aspirin Cephalosporin Chloral Hydrate Cimetidine Cranberry Juice Clofibrate Danazol Diflunisal Disulfram –anabuse Fluvoxamine Ginkgo Biloba Heparin HMG CoA Reductase inhibitors INH Macrolides Metronidazole Nalidixic Acid NSAIDS Paroxetine Penicillin Proafenone Quinidine Quinolones Sulfinpyrazone (Anturane) Tamoxifen Tetracycline Thyroid Hormone Trimethoprim-Sulfamethoxazole Vitamin E
Prolonged APTT in Non-heparinized individuals
Salicylates Inherited or acquired intrinsic clotting factor deficiency or abnormality (XII, XI, X, IX, VII, V, II, I) Massive blood replacement Hemophilia A Lupus anticoagulant Excessive coumadin dosage
Causes of Decreased APTT
Digitalis Tetracyclines Antihistamines Nicotine Elevated factor VIII Tissue inflammation or trauma
Bleeding Time
It addresses how well platelets interact with blood vessel walls to form blood clots following a wound or trauma.
A prolonged BT may indicate a vascular defect, a platelet function defect or thrombocytopenia.
The normal range can vary depending on the method used but is typically between 2 and 9 minutes.
BT is longer in women and in persons over 50 years of age.
Causes of a Prolonged Bleeding Time
Thrombocytopenia Disseminated intravascular coagulation Functional platelet disorders Capillary wall abnormalities Von Williebrand disease Medications: dextran, indomethacin, and salicylates (including aspirin).
Antidote for Coumadin
Vitamin K Onset 6-8 hours Dose/Routes of Administration 1mg IV (allergic reactions common) 1mg subcut (may delay onset) 1 mg po ( you can use the IV solution)
Antidote for Heparim
Protamine Sulfate
Warfarin Indications
Prophylaxis of venous thrombosis (high-risk surgery)
Treatment of venous thrombosis
Treatment of PE
Prevention of systemic embolism
Tissue heart valves
AMI (to prevent systemic embolism)
Atrial fibrillation
Mechanical prosthetic valves (high risk)
Certain patients with thrombosis and the anti-phospholipid syndrome
AMI (to prevent recurrent AMI)
Bileaflet mechanical valve in aortic position, NSR
Starting Warfarin
Loading dose for Warfarin is not needed
Indications for starting with concurrent Heparin
Thrombophilic state (e.g. known protein C deficiency)
Thromboembolism
Indications for starting Warfarin without Heparin
Chronic stable A Fib
Starting dose of Warfarin Usual: 5 mg PO qd (anticipate therapeutic by day 4-5) High Dose: 7.5 to 10 mg qd If urgency to reach therapeutic level Study: 10 mg start was therapeutic 1.4 days earlier Low dose: 2.5 mg PO qd Elderly Liver disease High risk of bleeding
Starting Warfarin in the Elderly
Therapeutic INR achieved within 6-7 days
Initial Dose: 4 mg daily for first 3 days
Dosing protocol after day 3 based on daily INR
INR <1.3: Warfarin 5 mg
INR 1.3-1.4: Warfarin 4 mg
INR 1.5-1.6: Warfarin 3 mg
INR 1.7-1.8: Warfarin 2 mg
INR 1.9-2.4: Warfarin 1 mg
INR >2.4: Hold Warfarin, check INR daily
INR Monitoring
Monitor INR
Daily Protime with INR
Stop Heparin when 2 consecutive INRs therapeutic
Monitor INR 2-3 times per week for 1-2 weeks
Monitor INR every 2-4 weeks when stable
INR 2.2 to 2.3 associated with lowest overall mortality
INR 2-3 for DVT, A Fib, Most Valvular Problems
To Get To An INR 2-3
INR less than 2
Increase weekly Warfarin dose by 5 to 20%
INR 3 to 3.5
Decrease weekly Warfarin dose by 5 to 15% or
Maintain same dose and recheck in 7 days
INR 3.6 to 5.0
Consider withholding one Warfarin dose
Decrease weekly Warfarin dose by 10 to 15%
Scary INRs
INR 5.0 to 10.0
Withhold 1 to 2 Warfarin doses
Decrease weekly Warfarin dose by 10 to 20%
Indications for Vitamin K
Risk of bleeding: Vitamin K 1 to 2.5 mg PO x1 dose
Surgery in 24 hours: Vitamin K 2 to 4 mg PO x1 dose
INR exceeds 10.0
Hold Warfarin
Vitamin K 3 to 5 mg PO x1 dose
Monitor INR daily and consider repeating Vitamin K
Anticipate significantly lower INR within 24-48 hours
Serious or Life-threatening bleeding (esp. INR >20)
Replace clotting factors (first-line)
Fresh Frozen Plasma (FFP) 15 ml/kg
Reverse Warfarin effect
Vitamin K 10 mg by slow IV infusion
Anticipate Warfarin resistance after dose
Avoid in valve replacement
Anticipate 16 hour delay in effect
Consider repeat INR at that time
Consider repeating Vitamin K at 12 hours
Other
Prothrombin Complex Concentrate (PCC) 50 U/kg
INR Too High
Decrease Dosing by 20% (27.5 mg per week)
Warfarin 2.5 mg PO on Monday, Wednesday, Friday
Warfarin 5 mg PO all other days
Decrease Dosing by 15% (30 mg per week)
Warfarin 2.5 mg PO on Monday and Friday
Warfarin 5 mg PO all other days
Decrease Dosing by 5% (32.5 mg per week)
Warfarin 2.5 mg PO on Monday
Warfarin 5 mg PO all other days
INR Too Low
Increase Dosing by 5% (37.5 mg per week)
Warfarin 7.5 mg PO on Monday
Warfarin 5 mg PO all other days
Increase Dosing by 15% (40 mg per week)
Warfarin 7.5 mg PO on Monday and Friday
Warfarin 5 mg PO all other days
Increase Dosing by 20% (42.5 mg per week)
Warfarin 7.5 mg PO on Monday, Wednesday, Friday
Warfarin 5 mg PO all other days
Pradaxa/Dabigatran
Indications
Non-valvular AF
Treatment of DVT and PE
CHADS2 > or = 2
Direct thrombin inhibitor that prevent thrombus development
Inhibits both free and clot bound thrombin and thrombin induced platelet aggregation.
150mg bid with normal creatinine clearance
Creatinine clearance 15-30 75mg bid
If less than 15 not recommended
Converting to or from Pradaxa/Coumadin
- Conversion from warfarin to dabigatran:
- Discontinue warfarin
- Start dabigatran once international normalized ratio (INR) is < 2
- Conversion from dabigatran to warfarin:
- CrCl ≥50 mL/min: Start warfarin 3 days before stopping dabigatran
- CrCl 30-50 mL/min: Start warfarin 2 days before stopping dabigatran
- CrCl 15-30 mL/min: Start warfarin 1 day before stopping dabigatran
- CrCl <15 mL/min: No recommendations
Dabigatran [package insert] 3/1/2012
Xarelto/Rivaroxaban
Indications
Prevention of stroke in non valvular atrial fibrillation
Prevention of venous thromboembolism in
Perioperative/Post op mainly in orthopedics
Treatment DVT and pulmonary emboli
Mechanism of Action
Inhibits platelet activation and fibrin clot formation via direct and selective and reversible inhibitation of factor Xa in both the intrinsic and extrinsic coagulation pathways
Dose
20mg po daily
Avoid if Creatinine Clearance less than 15
Post op 10mg daily in orthopedic patients.
Conversion to and From Warfarin/Rivaroxaban
Discontinue warfarin •Initiate rivaroxaban once INR is < 3 •Rivaroxaban to warfarin: •No clinical trials available •Possibility of discontinuing rivaroxaban and starting an injectable anticoagulant then converting to warfarin
Apixaban/Eliquis
Indications
Prevention of stroke in non-valvular atrial fibrillation
Prevention of DVT perioperative
5 mg PO BID
Dosage Modifications
Coadministration with strong dual inhibitors of CYP3A4 and P-gp: Decrease dose to 2.5 mg PO BID; in patients already taking 2.5 mg BID, avoid coadministration with strong dual inhibitors
Decrease dose to 2.5 mg PO BID in patients with at least 2 of the following characteristics: age ≥80 years, weight ≤60 kg, or Serum creatinine ≥1.5 mg/dL
Renal impairment
Mild-to-moderate: No dosage adjustment required
Serum creatinine ≥1.5 mg/dL: Decrease dose to 2.5 mg BID if patient has 1 additional characteristic of age ≥80 years or weight ≤60 kg
CrCl, 15 mL/min or dialysis: No data are available; not recommended
Conversion to and from Warfarin/apixaban
Switching between apixaban and anticoagulants other than warfarin: Discontinue one being taken, and begin the other at the next scheduled dose
Switching from warfarin to apixaban: Discontinue warfarin and initiate apixaban when INR <2.0
Switching from apixaban to warfarin
Apixaban affects INR, so measurements during coadministration with warfarin may not determine appropriate warfarin dose
If continuous anticoagulation is necessary, discontinue apixaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of apixaban would have been taken
Discontinue parenteral anticoagulant when INR reaches an acceptable level
Surgery/procedures
Discontinue at least 48 hr before elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding
Discontinue at least 24 hr before elective surgery or invasive procedures with a low risk of unacceptable or where the bleeding would be noncritical in location and easily controlled
Reversal Agents Apixaban/Rivaroxaban
May 7, 2018 — The U.S. Food and Drug Administration (FDA) has approved Portola Pharmaceuticals’ Andexxa, the first factor Xa inhibitor antidote indicated for patients treated withrivaroxaban (Xarelto) and apixaban (Eliquis) when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
Praxbind
PRAXBIND is a specific reversal agent for PRADAXA, with no impact on the effect of other anticoagulant or antithrombotic therapies.
For emergency surgery/urgent procedures
In life-threatening or uncontrolled bleeding
PRAXBIND specifically binds to dabigatran (Pradaxa) and its acylglucuronide metabolites and reverses their anticoagulant effect immediately after administration.
For intravenous use only. The recommended dose of PRAXBIND is 5g, provided as two separate vials, each containing 2.5g/50mL of PRAXBIND. Two vials constitute one complete dose administered intravenously, as two consecutive infusions, or bolus injections by injecting both vials consecutively one after another via syringe
PRADAXA treatment can be re‑initiated 24 hours after administration of PRAXBIND.
Heparin
Sulphated carbohydrate
Derived from canine liver cells
Administration - parenteral- Do not inject IM - only IV or deep s.c.
Half-life 1 - 5 hrs - monitor aPTT, Anti-XA
Adverse effect: hemorrhage
Antidote : protamine sulfate
Lovenox
Indications
Enoxaparin is a low molecular weight heparin. It is an anticoagulant used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. Its use is evolving in acute coronary syndromes (ACS).
Mechanism of Action: Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. The anticoagulant effect of enoxaparin can be directly correlated to its ability to inhibit factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so enoxaparin’s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.
Pharmokinetics
Anti-factor Xa levels can be measured, and are generally used to monitor enoxaparin activity in certain subgroups of patients. Anti-factor Xa levels may be recommended in underweight, obese, pregnant, or renally impaired patients. Anti-Xa levels should be checked at their peak at 4 hours after dosing (both q12 and q24 variations).
Protamine is less effective at reversing enoxaparin compared to heparin, with a maximum neutralisation of approximately 60% of the anti-factor Xa effect
Anticoagulation in Pregnancy
Women who require anticoagulation and become pregnant need to take special precautions. Warfarin poses significant risk to the fetus, especially in the first trimester. Many women on warfarin are switched to heparin during the first weeks of pregnancy. Some may then stay on heparin throughout the pregnancy and delivery. Others may be started back on warfarin during the middle of the pregnancy, then switched back to heparin for the delivery.
It’s critical to discuss management of anticoagulation during pregnancy with your cardiologist and obstetrician. The care must be tailored for each woman.
Watchman
The WATCHMAN Implant fits right into your LAA. It’s designed to permanently close it off and keep those blood clots from escaping.
WATCHMAN is about the size of a quarter and made from very light and compact materials commonly used in many other medical implants.
WATCHMAN is implanted into your heart in a one-time procedure. It’s a permanent device that doesn’t have to be replaced and can’t be seen outside the body.
To implant WATCHMAN, small cut in your upper leg and insert a narrow tube, as done in a standard stent procedure. The doctor then guides WATCHMAN into the left atrial appendage (LAA) of the heart. The procedure is done under general anesthesia and takes about an hour. Patients commonly stay in the hospital overnight and leave the next day.
Due to the risk of having a medical procedure, patients should not be considered for WATCHMAN if they are doing well and expect to continue doing well on blood thinners.
