Anticoagulation Flashcards
Risk factors for the development of venous thromboembolism
Surgery, major trauma, immobility, cancer, previous thrombus, age, pregnancy, estrogen containing medications or SER ends, erythropoietin stimulating agents come inflammatory bowel disease, obesity, central venous catheterization and acquired traits
Clotting cascade
Intrinsic pathway clotting factors: 12, 11, 9, 8
Extrinsic pathway: tissue factor and 7
Meet at 10 and 5A
10 goes to 10 a
Then goes to prothrombin which goes to fibrinogen which goes to fibrin
New Joint commission patient safety goals around anticoagulation
Patient should receive individualized care through a process that includes standardized ordering, dispensing, administration, monitoring and patient caregiver education
Heparin-induced thrombocytopenia or HIT
Immune mediated IgG reaction against heparin that is associated with a high-risk of venous and arterial thrombosis
If left untreated the patient will be in a pro thrombotic state causing many complications such as thrombosis resulting in amputations, post thrombotic syndrome and/or death.
Typically occurs with long duration of heparin therapy (>4 days)
Diagnosis: unexplained drop in platelet count defined as more than 50% drop from baseline and a laboratory confirmation of antibodies for platelet activation by heparin
Management of HIT Complicated by Thrombosis
- Stop all forms of heparin and LMWH including heparin flushes
- Argatroban is recommended over the further use of heparin products or the initiation or continuation of warfarin
- Do not start warfarin until the platelets have a covered to it least 150,000 per mm^3
- If patients require urgent cardiac surgery, bivalirudin is the preferred anticoagulant
Unfractionated heparin
Protamine: 1 mg or verse 100 units of heparin but infuse slowly over 10 minutes to decrease risk of hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, pulmonary vasoconstriction and pulmonary hypertension
MOA: finds to anti-thrombin and inactivates thrombin factor to eight and factor Xa as well as factors IXa, XIA, XIIa and plasmin prevents conversion of fibrinogen to fibrin
Prophylaxis of VTE: 5000 units SC q8-12 hours
Treatment of VTE: 5000 units IV bolus followed by 1000 units per hour infusion
Treatment of ACS/STEMI: 60 units per kilogram (actual bodyweight) IV bolus then 12 units per kilogram per hour infusion
Antidote: protamine 1 mg will reverse approximately 100 units of heparin
Blackbox warning: some contain benzyl alcohol as a preservative and use of these products is contraindicated in neonate and infants
Contraindications: uncontrolled actively, severe thrombocytopenia, history of hit, hypersensitivity to pork products
Side effects: bleeding, thrombocytopenia, heparin induced thrombocytopenia, hyperkalemia and osteoporosis
Monitoring: aPTT, platelet count, hemoglobin, hematocrit
Pregnancy category C
Low molecular weight heparin (LMWH)
MOA: similar to heparin except that inhibition is much greater for factor Xa than factor IIa
Drugs: Enoxaparin (Lovenox), dalteparin (Fragmin)
Blackbox warning: patients undergoing spinal procedures including punctures or anesthesia are at risk of hematomas and subsequent paralysis
Contraindications: history of hit, active major bleed, hypersensitivity to pork
Side effects: bleeding, thrombocytopenia, hyper Kaylee Mia, anemia, injection site reactions
Monitoring: anti-Xa levels can be used to monitor but not routine. Monitoring is recommended and pregnancy in patients with mechanical heart valves (OBTAIN PEAK ANTI-XA LEVELS FOUR HOURS POST DOSE)
Notes: injected into the abdomen, pregnancy category D, do not expel air bubble from syringe fire gel injection
Enoxaparin (Lovenox)
Prophylaxis of VTE: 30 mg SC every 12 hours or 40 mg SC daily (CrCl <30: 1 mg per kilogram SC daily)
Factor XA inhibitors
Drugs: fondaparinux (Arixtra), rivaroxaban (Xarelto), apixaban (Eliquis)
Fondaparinux (Arixtra)
Prophylaxis: 2.5 mg SC daily
Treatment: 100 kg is 10 mg SC daily
Blackbox warning: at risk of hematoma with spinal puncture or anesthesia
Contraindications: severe renal impairment less than 30 mls/minute, active major bleed, bacterial endocarditis, thrombocytopenia or bodyweight less than 50 kg
Note: pregnancy category B, do not expel air bubble before syringe injection, no antidote, store room temperature
Rivaroxaban (Xarelto)
Indications: nonvalvular atrophic relation, treatment of DVT/PE, prophylaxis for DVT
Blackbox warning: hematoma with spinal procedure; premature discontinuation increases the risk of thrombotic events
Contraindications: active major bleed, avoid using in patients with moderate to severe hepatic impairment or with any degree associated with coagulopathy; avoid using in severe renal impairment; avoid use in prosthetic heart valves
Most doses range between 15 and 20 mg daily with food
Missed doses:
- If 15 mg twice daily: take immediately to ensure intake of 30 mg daily
- If 20, 15 or 10 mg once daily: take the Mistowes as soon as possible on the same day otherwise skip
Apixaban (Eliquis)
Indicated for nonvalvular atrophic relation only
Blackbox warning: discontinuing in patients without adequate continuous anticoagulation increases risk of stroke
Contraindications: bleed, severe hepatic impairment, prosthetic heart valves
Notes: pregnancy category B, no antidote, no monitoring of efficacy required
Direct thrombin inhibitors (IV AND SC)
MOA: directly inhibit thrombin or factor IIa; they bind to the active thrombin side of free and clot associated thrombin
DRUGS: Argatroban, bivalirudin (angiomax), desirudin (iprivask)
Argatroban
Use: hit with thrombosis and patients undergoing PCI who are at risk for hit
Reduce dose and hepatic impairment
Contraindications: major active bleed
Side effects: bleeding, anemia, hematoma
Monitoring: APTT, platelets, hemoglobin, hematocrit, serum creatinine
Notes: pregnancy category B, no cross-reaction with HIT, no antidote
Can increase the INR; if starting on warfarin can currently do not use a loading dose of warfarin
Bivalirudin (Angiomax)
Used: for patients with ACS undergoing PTCA ended our risk for HIT
REDUCED DOSE IN RENAL IMPAIRMENT
contraindication: active bleed
Monitoring: APTT and or ACET, platelets, hemoglobin, hematocrit, SCr
Direct Thrombin Inhibitor (Oral)
Drug: dabigatran (Pradaxa)
Used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
Dose: 150 mg b.i.d. or 75 mg b.i.d. if CrCl 15 to 30 ml/min
Swallow whole. Do not break crush chew or open. Do not put down an NG tube
KEEP AN ORIGINAL CONTAINER. DISCARD FOUR MONTHS AFTER OPENING THE ORIGINAL CONTAINER. KEEP BOTTLE TIGHTLY CLOSE TO PROTECT FROM MOISTURE.
Blackbox warning: discontinuation places patient at increased risk of thrombotic event therefore consider the use of another anticoagulant during the time of interruption
Contraindication: active bleed or mechanical heart valve
Side effects: dyspepsia, gastritis, bleeding
Monitoring: renal function
Notes: pregnancy category C, no antidote, store in a cool dry place
Drug interaction: PGP substrate avoid PGP inducers such as rifampin
Warfarin (Coumadin, Jantoven)
MOA: competitively inhibits the subunit of vitamin K epoxide reductase (VKORC1) enzyme complex thereby reducing the regeneration of vitamin K epoxide causing depletion of active clotting factors 7,9,10, 2 and protein C & S
Dosing: start at 10 mg daily for the first 2 days and adjust per INR values (consider only 5 mg if elderly, malnourished, taking drugs which will inc. the INR, liver disease, heart failure or high risk of bleeding)
Blackbox warning: may cause major/fatal bleeding
Contraindication: hemorrhagic tendency, blood dyscrasias, pregnancy, uncontrolled hypertension, a noncompliant patient
Side effects: bleeding, skin necrosis, purple toe syndrome
Monitoring: PT/INR (2-3 for most patients) (2.5-3.5 four high-risk indications such as mechanical mitral valve or mechanical heart valves in both the aortic and mitral position)
Notes: pregnancy category X; antidote is vitamin K
Available warfarin tablets
1mg: pink
2mg: lavender
2. 5mg: green
3mg: tan
4mg: blue
5mg: peach
7. 5mg: yellow
10mg: white
Also available in a 5 mg/ml injection
Warfarin pharmacogenetics
CYP2C92 and CYP2C93 and polymorphisms to the VKORC gene increase the risk of bleeding with warfarin
Warfarin drug interactions
- Highly protein-bound: highly protein-bound may displace warfarin such as phenytoin, valproic acid, furosemide, bumetanide, spironolactone, metolazone, doxycycline, glipizide, glyburide, ibuprofen, naproxen, diphenhydramine
- Substrate of CYP2C9: inducers well decrease INR and inhibitors may increase INR
- Antibiotics: penicillins, fluoroquinolones, macrolides, bactrim and tetracyclines may enhance the anticoagulant effect of warfarin
- When starting amiodarone, decrease the dose of warfarin by 30 to 50%
- Increased risk of bleeding: use with NSAIDs, antiplatelet agents, other anticoagulants, SSRIs and SNRIs
- Diet: a consistent because the more vitamin K that is consumed the lower the INR
- Alcohol will increase INR
Natural products that can affect bleeding risk
Ginkgo increases bleeding risk w/ no effect on INR
Others that increased bleeding risk: vitamin D, evening Primrose oil, echinacea, high-dose fish oils, garlic, glucosamine, grapefruit, Wintergreen oil
Foods high in vitamin K
Broccoli, brussels sprouts, cabbage, cauliflower, chickpeas, collard greens, kale, lettuce, mustard greens, parsley, spinach, tea, turnip greens, Granola/soybean oil
Vitamin K for high INR’s
- Oral: 2.5-5 mg preferred in pts w/out major bleed
- SC: should be avoided due to slower onset and variable response
- IM: use with caution do to risk of hematoma formation
- IV: using patients experiencing serious bleeding (infuse slowly due to risk of anaphylaxis)
Vitamin K use
- INR less than 4.5: reduce or skip warfarin dose and monitor INR
- INR of 4.5 to 10 without bleeding: hold 1 to 2 doses of warfarin and monitor INR. Resume warfarin at lower dose when INR therapeutic.
- INR >10 without bleeding: hold warfarin and give 2.5-5mg oral vitamin K
- Major bleeding: hold warfarin and give vitamin K 5 to 10 mg by slow IV infusion and PCC
