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Flashcards in Anticoagulation Deck (29)

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


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


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

1. Stop all forms of heparin and LMWH including heparin flushes
2. Argatroban is recommended over the further use of heparin products or the initiation or continuation of warfarin
3. Do not start warfarin until the platelets have a covered to it least 150,000 per mm^3
4. 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:
1. If 15 mg twice daily: take immediately to ensure intake of 30 mg daily
2. 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)



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


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


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

CYP2C9*2 and CYP2C9*3 and polymorphisms to the VKORC gene increase the risk of bleeding with warfarin


Warfarin drug interactions

1. Highly protein-bound: highly protein-bound may displace warfarin such as phenytoin, valproic acid, furosemide, bumetanide, spironolactone, metolazone, doxycycline, glipizide, glyburide, ibuprofen, naproxen, diphenhydramine
2. Substrate of CYP2C9: inducers well decrease INR and inhibitors may increase INR
3. Antibiotics: penicillins, fluoroquinolones, macrolides, bactrim and tetracyclines may enhance the anticoagulant effect of warfarin
4. When starting amiodarone, decrease the dose of warfarin by 30 to 50%
5. Increased risk of bleeding: use with NSAIDs, antiplatelet agents, other anticoagulants, SSRIs and SNRIs
6. Diet: a consistent because the more vitamin K that is consumed the lower the INR
7. 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

1. Oral: 2.5-5 mg preferred in pts w/out major bleed
2. SC: should be avoided due to slower onset and variable response
3. IM: use with caution do to risk of hematoma formation
4. IV: using patients experiencing serious bleeding (infuse slowly due to risk of anaphylaxis)


Vitamin K use

1. INR less than 4.5: reduce or skip warfarin dose and monitor INR
2. 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.
3. INR >10 without bleeding: hold warfarin and give 2.5-5mg oral vitamin K
4. Major bleeding: hold warfarin and give vitamin K 5 to 10 mg by slow IV infusion and PCC


Perioperative management of patients on warfarin

1. Stop approximately five days before major surgery but bridge patients who are at high risk with LMWH or UFH (stop 24 hours prior to surgery)
2. See warfarin therapy 12 to 24 hours after surgery
3. And continue warfarin and patients undergoing minor dental or dermatologic surgery


Chronic anticoagulation for patients in chronic atrial fibrillation


A-age >75
S-prior stroke/TIA (2pts)

0pts: no therapy or aspirin 81 mg daily
1pt: oral anticoagulation for aspirin or a combination therapy of aspirin and plavix
2pts: anticoagulation


Counseling for all anticoagulants

Watch for other drugs that increase risk of bleeding, do not stop medication without talking to your physician, signs and symptoms of bleeding or clotting


Counseling for enoxaparin

1. Wash and dry hands and choose a spot on the right or left side of your abdomen at least 2 inches from the belly button
2. Clean the injection site with an alcohol swab and let dry
3. Prepare a needle do not expel that air bubble in the syringe prior to injection
4. Pinch an inch of the cleansed area and inject at a 90° angle press the plunger with your phone and pull the needle straight out the same angle


Rivaroxaban counseling

1. Not for patients with artificial heart valves
2. If taking for atrial fibrillation take once a day with your evening meal
3. If taking for blood clots then take once or twice a day as prescribed with food
4. Taking for hip or knee replacement can take with or without food