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NAPLEX Review > Anticoagulation > Flashcards

Anticoagulation Flashcards

1
Q

What are anticoagulants used for?

A

Anticoagulants are used to prevent blood clots from forming and to keep existing clots from becoming larger

*They do not break down clots

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2
Q

What conditions are anticoagulants commonly used for?

A

Acute coronary syndromes, prevention of cardioembolic stroke and prevention/treatment of VTE (DVT and/or PE)

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3
Q

What is the most common side effect of anticoagulants?

A

Bleeding which can be fatal

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4
Q

What is coagulation?

A

Coagulation is the process by which blood clots form

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5
Q

What are some factors that can lead to activation of the coagulation process?

A

Blood vessel injury, blood stasis (stopping or slowing of blood flow) and pro-thrombotic conditions

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6
Q

What does coagulation involve?

A

Coagulation involves activation of platelets and the clotting cascade

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7
Q

Where are clotting factors made?

A

Clotting factors are proteins made primarily by the liver

*All the clotting factors have an inactive and an active form

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8
Q

What happens when a clotting factor is activated?

A

Once activated, a clotting factor will activate the next clotting factor in the sequence until fibrin is formed

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9
Q

What are the two pathways of the coagulation cascade that leads to fibrin formation?

A

The contact activation pathway (or the intrinsic pathway) and the tissue factor pathway (or the extrinsic pathway)

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10
Q

What do anticoagulants do in the coagulation cascade?

A

Anticoagulants inhibit the coagulation cascade and prevent (or reduce) clot formation

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11
Q

How and what are anticoagulants used for?

A

Injectable anticoagulants are used for ACS and VTE (treatment and prevention), while oral anticoagulants are used mainly for VTE (treatment and prevention) and stroke prevention in patients with atrial fibrillation

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12
Q

What are different types of oral anticoagulants?

A

Warfarin, factor Xa inhibitors and thrombin inhibitors (DOACs)

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13
Q

Why are DOACs preferred to warfarin?

A
  • DOACs have less drug-drug interactions, less or comparable bleeding and a shorter half life compared to warfarin
  • DOAC dosing is based on the indication and kidney/liver function (no need to adjust the dose based on the INR
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14
Q

What are the exceptions where DOACs are not preferred?

A
  • For stroke prophylaxis in Afib if there is moderate to severe mitral stenosis or mechanical heart valve (USE WARFARIN)
  • For VTE treatment, if the patient has cancer (USE LMWH)
  • For VTE treatment, if the patient has antiphospholipid syndrome (USE WARFARIN)
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15
Q

What is the MOA of Warfarin?

A

Warfarin is a vitamin K antagonist that inhibits factors II, VII, IX, X

*Without adequate vitamin K, the liver produces the clotting factors, but they have reduced coagulant activity

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16
Q

What is an important note about Warfarin?

A

Warfarin has a narrow therapeutic range and requires careful monitoring of the INR, which is affected by many drugs and changes in dietary vitamin K

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17
Q

What is antithrombin (AT)?

A

Antithrombin is one of the body’s natural anticoagulants which inactivates thrombin (factor IIa) and other proteases (like factor Xa) involved in blood clotting

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18
Q

How does unfractioned heparin, LMWHs and fondaparinux work?

A

They work by binding to AT and causing a conformational change which increases AT activity 1000 fold

  • LMWHs inhibit factor Xa more specifically than unfractioned heparin
  • Fondaparinux binds to AT, resulting in selective inhibition of factor Xa
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19
Q

What are some examples of medications that work by inhibiting factor Xa directly?

A

Apixaban, edocaban and rivaroxaban

*Taken once or twice daily and require no laboratory monitoring efficacy

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20
Q

How does UFH and LMWH work?

A

UFH and LMWH indirectly inhibit thrombin and Factor Xa through AT binding

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21
Q

How do direct thrombin inhibitors work?

A

DTIs block thrombin directly, decreasing the amount of fibrin available for clot formation

*IV DTIs are important clinically since they do not cross react with heparin-induced thrombocytopenia antibodies

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22
Q

What is the drug of choice once HIT develops in the hospital?

A

Argatroban

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23
Q

What is an oral direct thrombin inhibitor?

A

Dabigatran (Pradaxa)

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24
Q

How do fibrinolytics work and what are they used for?

A

Fibrinolytics break down existing clots but are associated with a very high risk of bleeding and are used for STEMI and acute ischemic stroke when the patient could die without rapid restoration of blood flow

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25
Q

What are antiplatelets used mainly for?

A

Antiplatelet drugs are used mainly for ACS and to prevent stroke/TIA (not sufficient for treating DVT/PE)

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26
Q

What is DAPT?

A

Dual antiplatelet refers to using both aspriin and a P2Y12 inhibitor together which is very common in patients who have had an ACS

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27
Q

What are oral anticoagulants primarily used for?

A

Oral anticoagulants are used mainly in Afib (for stroke prevention) and for DVT/PE (treatment and prevention)

*Oral medications like Xarelto or Eliquis are not indicated for ACS when platelet aggregation is the main target of drug therapy

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28
Q

Why are all anticoagulants classified as high alert medications

A

All anticoagulants can cause significant bleeding

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29
Q

What does the Joint Commission’s National Patient Safety Goals require with anticoagulation therapy?

A

They require policies and protocols to properly initiate and manage anticoagulant therapy

*Patients receiving anticoagulants should receive individualized care through a defined process that includes standardized ordering, dispensing, administration, monitoring and patient/caregiver education

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30
Q

What is a lab value that could signify bleeding is occurring?

A

An acute drop in hemoglobin

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31
Q

Where can bleeding occur?

A

Epistaxis, gums, bruising, hematoma, hematuria, blood in emesis, blood from anus

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32
Q

What is the MOA of UFH?

A

UFH binds to antithrombin, which then inactivates thrombin (factor IIa) and factor Xa (as well as factors IXa, XIa, XIIa, and plasmin) and prevents the conversion of fibrinogen to fibrin

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33
Q

What are some contraindications of UFH?

A

Uncontrolled active bleed (intracranial hemorrhage), severe thrombocytopenia, history of HIT, hypersensitivity to pork products

*Some products contain benzyl alcohol as a preservative (do not use in neonates, infants, pregnancy and breastfeeding)

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34
Q

What are some warnings associated with UFH?

A

Fatal medication errors; verify the correct concentration is chosen

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35
Q

What are some side effects associated with UFH?

A

Bleeding, thrombocytopenia, HIT, hyperkalemia and osteoporosis (with long term use), alopecia

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36
Q

What are some monitoring parameters of UFH?

A
  • aPTT or anti-Xa level: check 6 hours after initiation and every 6 hours until therapeutic, then every 24 hours and with every dosage change
  • aPTT therapeutic range is 1.5-2.5 xcontrol, anti-Xa therapeutic range typically 0.3-0.7 units/mL
  • aPTT and anti-Xa monitoring are not required for SC (prophylactic dosing)
  • Platelets, Hgb, Hct at baseline and daily (decrease in platelets > 50% from baseline suggests possible HIT)
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37
Q

What are some notes about UFH?

A
  • Antidote: protamine
  • Unpredictable anticoagulant response
  • Continuous IV infusions are common for treating VTE and ACS because of the very short half life
  • Do not give IM due to hematoma risk
  • Heparin lock-flushes are only used to keep IV lines open (Fatal errors, especially in neonates, occurred when the incorrect heparin strength (higher dose) was chosen
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38
Q

What is the exact MOA of LMWH?

A

LMWHs bind to AT, which inactivates factor Xa and factor IIa with anti-factor Xa activity is much greater than the anti-factor IIa activity

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39
Q

What are some examples of LMWHs?

A

Enoxaparin and Dalteparin

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40
Q

What are the boxed warnings associated with LMWH?

A

Patients receiving neuraxial anesthesia (epidural, spinal) or underging spinal puncture are at risk of hematomas and subsequent paralysis

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41
Q

What are some contraindications of LMWH?

A

History of HIT, active major bleed, hypersensitivity to pork

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42
Q

What are some side effects of LMWH?

A

Bleeding, anemia, injection site reactions, decreased platelets (thrombocytopenia)

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43
Q

What are some monitoring parameters of LMWH?

A
  • Platelets, Hgb, Hct, SCr
  • More predictable anticoagulant response and does not require anti-Xa level monitoring in most cases
  • Anti-Xa level monitoring is recommended in pregnancy
  • Monitoring may be done in obesity, low body weight, pediatrics, elderly or renal insufficiency
  • aPTT is not used
  • Obtain peak anti-Xa levels 4 hours post SC dose
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44
Q

What are some important notes about LMWH?

A
  • Antidote: protamine
  • Do not expel air bubble from syringe prior to injection (can cause loss of drug)
  • Do not administer IM
  • Store at room temperature
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45
Q

What are some drug interactions associated with UFH/LMWH?

A

Most drug interactions are due to additive effects with other drugs that can increase bleeding risk (other anticoagulants, antiplatelet drugs, some herbal supplements, NSAIDs, SSRIs, SRNIs, thrombolytics)

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46
Q

What is heparin-induced thrombocytopenia (HIT)?

A

HIT is an immune-mediated IgG drug reaction that has a high risk of venous and arterial thrombosis where the immune system forms antibodies against heparin bound to platelet factor 4 and antibodies then join with heparin and PF4 to create a complex, and this complex bind to the Fc receptors on platelets

*This causes platelet activation and a release of pro-coagulant microparticles

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47
Q

What are some complications of HIT?

A

If left untreated, HIT can lead to a prothrombotic state causing many complications including heparin-induced thrombocytopenia and thrombosis (HITT)

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48
Q

What are some complications of HITT?

A

HITT leads to amputation, post-thrombotic syndrome and/or death

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49
Q

What is the estimated incidence and duration of HIT?

A

Estimated incidence of HIT is ~3% of patients exposed to heparin for more than 4 days and typical onset occurs 5-14 days after the start of heparin or within hours if a patient has been exposed to heparin within the past 3 months

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50
Q

How is a diagnosis of HIT made?

A

A diagnosis is made by a compatible clinical picture, an unexplained drop in platelet count (defined as >50% drop from baseline and laboratory confirmation of antibodies (ELISA test and confirmatory serotonin release assay) or platelet activation by heparin

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51
Q

Describe the management of HIT complicated by thrombosis (HITT)?

A
  • If HIT is suspected, stop all forms of heparin and LMWH
  • If patient is on warfarin and diagnosed with HIT, warfarin should be discontinued and vitamin K should be administered
  • In patients with HIT, non-heparin anticoagulants are recommended (in particular, argatroban)
  • Do not start warfarin therapy until the platelets have recovered to > 150,000/mm3 and should be initiated at lower doses with bridging in the first 5 days
  • If urgent cardiac surgery or PCI is required, bivalirudin is the preferred anticoagulant
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52
Q

What are some examples of direct oral factor Xa inhibitors?

A

Apixaban (Eliquis), Rivaroxaban (Xarelto), Edoxaban (Savaysa)

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53
Q

What are some boxed warnings of direct factor Xa inhibitors?

A
  • All: patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
  • Apixaban, edoxaban and rivaroxaban: premature discontinuation increases risk of thrombotic events
  • Edoxaban: reduced efficacy in nonvalvular AFib patients with CrCl > 95 L/min (do not use)
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54
Q

What is a contraindication of direct factor Xa inhibitors?

A

Active pathological bleeding

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55
Q

What are some warnings associated with direct factor Xa inhibitors?

A

Not recommended with prosthetic heart valves or antiphospholipid syndrome, avoid in patients with moderate to severe hepatic impairment

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56
Q

What are some side effects associated with direct factor Xa inhibitors?

A

Generally well-tolerated, unless bleeding occurs

*Edoxaban: rash, increased LFTs

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57
Q

What are some monitoring parameters of direct factor Xa inhibitors?

A

Hgg, Hct, SCr, LFTs

*No monitoring of efficacy required

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58
Q

What are some notes about direct factor Xa inhibitors?

A
  • Antidote for apixaban and rivaroxaban: andexanet alfa (Andexxa)
  • Can be crushed and put on applesauce, crushed and mixed in water, D5W or apple juice (apixaban), or suspended in water to administer by NG tube (apixaban, edoxaban, rivaroxaban)
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59
Q

What do you do with direct factor Xa inhibitors when there is elective surgery?

A
  • Discontinue 24 hours prior to elective surgery (rivaroxaban, edoxaban)
  • Discontinue 48 hours prior to elective surgery with moderate-high bleeding risk or 24 hours prior with a low bleeding risk (apixaban)
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60
Q

What is an example of an injectable indirect factor Xa inhibitor?

A

Fondaparinux (Arixtra)

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61
Q

What is the boxed warning associated with Fondaparinux?

A

Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis

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62
Q

What is a contraindication of Fondaparinux?

A

Severe renal impairment (CrCl < 30 mL/min), active major bleed, bacterial endocarditis, thrombocytopenia with positive test for anti-platelet antibodies in presence of fondaparinux

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63
Q

What are some side effects associated with Fondaparinux?

A

Bleeding, anemia, local injection site reactions, thrombocytopenia, hypokalemia, hypotension

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64
Q

What are some monitoring parameters of Fondaparinux?

A

Anti-Xa levels (3 hours post dose), platelets, Hgb, Hct, SCr

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65
Q

What are some notes about Fondaparinux?

A
  • Do not expel air bubble
  • No antidote
  • Do not administer IM
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66
Q

What is something in general that should be avoided with factor Xa inhibitors?

A

Avoid using with other anticoagulants (unless benefit outweighs risk) and monitor for additive effects with other drugs that can increase bleeding risk (antiplatelet drugs, some herbals, NSAIDs, SSRIs, SNRIs, thrombolytics)

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67
Q

What should be avoided with the use of Apixaban?

A

Apixaban is a substrate of CYP3A4 and P-gp so avoid use with strong dual inducers of CYP3A4 and P-gp (e.g. CBZ, phenytoin, rifampin, St. John’s Wort)

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68
Q

What are some recommendations for a patient taking apixaban and strong dual inducers of CYP3A4 and P-gp?

A
  • For patients receiving doses > 2.5 mg BID, the dose of apixaban should be decreased by 50% when coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp
  • For patients taking 2.5 mg BID, avoid these strong dual inhibitors
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69
Q

What should be avoided with use of Rivaroxaban?

A

Rivaroxaban is a substrate of CYP3A4 and P-gp so avoid use with drugs that are combined P-gp and strong CYP3A4 inducers or combined P-gp and strong CYP3A4 inhibitors

*benefit must outweigh the potential risks in these situations: CrCl 15-80 mL/min who are receiving combined P-gp and moderate CYP3A4 inhibitors

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70
Q

What should be avoided with use of edoxaban?

A

Edoxaban is a substrate of P-gp so avoid use with rifampin

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71
Q

What are some recommendations of concomitant use of Edoxaban and substrates of P-gp?

A

When treating with DVT/PE, reduce dose to 30 mg daily with verapamil, macrolides, and oral itraconazole or ketoconazole

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72
Q

What are some other medications to avoid with Rivaroxaban?

A

Cobicistat (Tybost), Stribild and Genvoya

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73
Q

When do you initiate another oral anticoagulant when converting from warfarin?

A
  • Rivaroxaban when INR is < 3
  • Edoxaban when INR is < 2.5
  • Apixaban when INR is < 2
  • Dabigatran when INR is < 2
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74
Q

What is the process of converting from oral Xa inhibitors to warfarin?

A

Overlap Xa inhibitor with warfarin until INR therapeutic

75
Q

How do you convert from dabigatran to warfarin?

A

Start warfarin 1-3 days before stopping dabigatran (determined by renal function)

76
Q

What is the MOA of Dabigatran?

A

Directly inhibit thrombin (factor IIa) by binding to active thrombin site of free and clot-associated thrombin

77
Q

What is a boxed warning of Dabigatran?

A

Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis

*Premature discontinuation increases risk of thrombotic events

78
Q

What are contraindications of Dabigatran?

A

Active pathological bleeding, treatment of patients with mechanical prosthetic heart valves

79
Q

What are some warnings associated with Dabigatran?

A

Not recommended for antiphospholipid syndrome

80
Q

What are some side effects of Dabigatran?

A

Dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding)

81
Q

What are some monitoring parameters of Dabigatran?

A

Hgb, Hct, SCr, no monitoring efficacy required

82
Q

What are some notes associated with Dabigatran?

A
  • Antidote: idarucizumab (Praxbind)
  • Protect from moisture: dispense in original container and discard 4 months after opening
  • Blister packs are good until the date on the pack
  • Swallow capsules whole and do not administer by NG tube
  • Can increase aPTT, PT/INR
  • Discontinue if undergoing invasive surgery (1-2 days before if CrCl > 50 mL/min, 3-5 days before if CrCl < 50 mL/min)
83
Q

What are some examples of injectable direct thrombin inhibitors?

A

Argatroban and Bivalirudin

84
Q

What are some contraindications of IV direct thrombin inhibitors?

A

Active major bleeding

85
Q

What are some side effects associated with IV direct thrombin inhibitors?

A

Bleeding (mild to severe), anemia

86
Q

What are some monitoring parameters of IV direct thrombin inhibitors?

A

aPTT and/or activated clotting time (for bivalirudin), platelets, Hgb, Hct, renal function

87
Q

What are some counseling points associated with IV direct thrombin inhibitors?

A
  • Safe with history of HIT; no cross reaction with HIT antibodies
  • No antidote
  • Argatroban can increase INR; if starting on warfarin concurrently, dose cautiously and do not use a loading dose of warfarin
88
Q

What are some medications to avoid with Dabigatran?

A
  • Avoid using with other anticoagulants, monitor for additive effects with other drugs that can increase bleeding risk
  • Substrate of P-gp so avoid use with rifampin and possibly Cobicistat, Stribild and Genvoya
89
Q

What are some dosage adjustment recommendations associated with Dabigatran and nonvalvular AFib?

A

If CrCl 30-50 mL/min and patient is taking P-gp inhibitors, reduce dose to 75 mg BID

*In severe renal impairment (CrCl 15-30 mL/min), avoid use with any P-gp inhibitors

90
Q

What is a dosage adjustment recommendation of Dabigatran with other indications?

A

Other indications: avoid use with P-gp inhibitors in patients with CrCl < 50 mL/min

91
Q

What is the MOA of Warfarin?

A

Warfarin competitively inhibits the C1 subunit of the multi-unit vitamin K epoxidase reductase enzyme complex which reduces the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and proteins C and S

92
Q

What is a boxed warning of Warfarin?

A

Major or fatal bleeding

93
Q

What are contraindications of Warfarin?

A

Pregnancy (except with mechanical heart valves at high risk for thromboembolism), hemorrhagic tendencies, blood dyscrasias, uncontrolled hypertension, noncompliance, recent or potential surgery of the eye or CNS, major regional lumbar block anesthesia or traumatic surgery resulting in large open surfaces, pericarditis or pericardial effusion, bacterial endocarditis, preeclampsia/eclampsia, possible miscarriage

94
Q

What are some warnings associated with Warfarin?

A

Tissue necrosis/gangrene, HIT (contraindicated as monotherapy in the initial treatment of active HIT), systemic atheroemboli and cholesterol microemboli, presence of CYP2C9*2 or *3 alleles and/or polymorphism of VKORC1 gene may incrrease bleeding risk

95
Q

What are some side effects of Warfarin?

A

Bleeding/bruising (mild to severe), skin necrosis, purple toe syndrome

96
Q

What are some monitoring parameters of Warfarin?

A
  • Goal INR 2-3: most indications
  • Goal INR 2.5-3.5: high risk indications such as mechanical mitral valve or 2 mechanic heart valves
  • Begin INR monitoring after the initial 2 or 3 doses or if on a chronic, stable dose of warfarin, monitor every 4-12 weeks
  • Hct, Hgb, signs of bleeding
97
Q

What are some notes about Warfarin?

A
  • Antidote: Vitamin K
  • Dental cleanings and single tooth extraction do not generally require a change in warfarin dosing, if INR is in therapeutic range
98
Q

Why does Warfarin have so many drug interactions?

A

Warfarin is a substrate of CYP2C9, 1A2 and 3A4 and an inhibitor of CYP2C9 and 2C19

*avoid use with tamoxifen

99
Q

What are some examples of CYP2C9 inducers that can increase INR?

A

Aprepitant, Bosentan, CBZ, Phenobarbital, Phenytoin, Primidone, Rifampin (large decrease in INR), licorice and St. John’s Wort

100
Q

What are some examples of CYP2C9 inhibitors that can increase INR?

A

Amiodarone, azole antifungals, capecitabine, fluvastatin, fluvoxamine, metronidazole, tigecycline, TMP/SMX and zafirlukast

*when starting amiodarone, decrease the dose of warfarin by 30-50%

101
Q

What was some antibiotics that can affect INR?

A

Penicillins, some cephalosporins, quinolones and tetracyclines

102
Q

What are some drugs that increase bleeding risk with concomitant use of Warfarin?

A

NSAIDs, antiplatelet agents, other anticoagulants, SSRIs and SNRIs

103
Q

What are some dietary supplements that increase bleeding risk with Warfarin?

A

Garlic, ginger, ginkgo, ginseng, glucosamine, bromelain, dong quai, vitamin E, evening primrose oil, high doses of fish oils, goldenseal, grapefruit, policosanol, willow bark and wintergreen oil

104
Q

What are some dietary supplements that decrease effectiveness of Warfarin?

A

CoQ10, St. John’s Work, American ginseng

105
Q

What are some food supplements that can decrease INR?

A

Vitamin K

106
Q

What are some counseling points associated with Vitamin K use and Warfarin?

A
  • Stay consistent with the amount of vitamin K in the diet

- Tube feeds should be held one hour before and after Warfarin

107
Q

What are some food high in Vitamin K?

A

Spinach, broccoli, brussel sprouts, cabbage, beef liver, kale, mustard greens, swiss chard, collard greens, parsley

108
Q

What is the initial starting dose of Warfarin?

A

The initial starting dose of Warfarin should be 10 mg daily for the first 2 days, then adjust per INR values

109
Q

What is the recommendation for patients with acute DVT/PE who are starting Warfarin?

A

In patients with acute DVT/PE, start warfarin on the same day as the parenteral anticoagulant and continue both anticoagulants for a minimum of 5 days and until the INR is > 2 for at least 24 hours (both criteria must be met)

110
Q

What are some routine things that are not recommended with use of Warfarin?

A
  • Routine pharmacogenomic testing is not recommended
  • Routine use of vitamin K supplementation is not recommended in patients taking Warfarin
  • For patients with stable therapeutic INRs presenting with a single subtherapeutic (low) INR value, routinely bridging with UFH or LMWH is not recommended
111
Q

How often should INR be tested on patients taking Warfarin?

A
  • For patients with previously stable therapeutic INRs who present with a single out-of-range INR of < 0.5 below or above the therapeutic range, continue current dose and obtain another INR within 1-2 weeks
  • For patients with consistently stable INRs on warfarin therapy, INR testing can be done up to every 12 weeks rather than every 4 weeks
112
Q

What is a counseling point associated with Warfarin?

A

Warfarin is highly protein bound so caution is advised with other highly protein bound drugs that may displace warfarin such as phenytoin, valproic acid and others

113
Q

What is the MOA of Protamine?

A

Protamine combines with strongly acidic heparin to form a stable salt complex, neutralizing the anticoagulant activity of UFH and LMWH

114
Q

What is Kcentra indicated for?

A

For the urgent reversal of Warfarin

115
Q

What is the antidote for UFH/LMWH?

A

Protamine Sulfate

116
Q

What are some boxed warnings associated with Protamine?

A

Hypersensitivity; hypotension, cardiovascular collapse, non-cardiogenic pulmonary edema, pulmonary vasoconstriction

117
Q

What are some side effects of Protamine?

A

Hypotension, bradycardia, flushing, anaphylaxis

118
Q

What are some monitoring parameters for Protamine?

A

aPTT, anti-Xa levels, cardiac monitoring (ECG, BP, HR)

119
Q

What are some notes associated with Protamine?

A
  • Rapid IV infusion causes hypotension
  • Administer slow IV push (50 mg over 10 minutes)
  • Inject without further dilution over 1-3 minutes
120
Q

What is the antidote for Dabigatran?

A

Idarucizumab (Praxbind)

121
Q

What are some warnings associated with Idarucizumab?

A

Thromboembolic risk, risk of serious adverse reactions due to sorbitol excipient

122
Q

What are some side effects associated with Idarucizumab?

A

HA, decreased K, delirium, constipation, fever

123
Q

What is an important counseling point associated with Idarucizumab?

A

Do not confuse with IDArubicin

124
Q

What is the antidote for Apixaban and Rivaroxaban?

A

Andexanet alfa (Andexxa)

125
Q

What are some boxed warnings associated with Andexanet alfa?

A

Thromboembolic risks, ischemic events, cardiac arrest, sudden death

126
Q

What are some side effects of Andexanet alfa?

A

Injection site reaction, DVT, ischemic stroke, UTI, pneumonia

127
Q

What is an important note about Andexanet alfa?

A

Not indicated for reversal of factor Xa inhibitors other than apixaban and rivaroxaban

128
Q

What are the antidotes for Warfarin?

A

Vitamin K or phytonadione (Mephyton) and Four Factor Prothrombin Complex Concentrate (Kcentra)

129
Q

What are some off-label antidotes of Warfarin?

A

Three Factor Prothrombin Complex Concentrate (Profilnine), Factor VIIa Recombinant (NovoSeven RT)

130
Q

What are some boxed warnings associated with Mephyton?

A

Severe reactions resembling hypersensitivity reactions (e.g. anaphylaxis) have occurred rarely during or immediately after IV administration (even with proper dilution and rate of administration)

*Some patients had no previous exposure to phytonadione

131
Q

What are some side effects of Mephyton?

A

Anaphylaxis, flushing, rash, dizziness

132
Q

What are some notes associated with Mephyton?

A
  • Requires light protection during administration
  • SC route not recommended due to variable absorption; IM route not recommended due to risk of hematoma
  • Orlistat and mineral oil decreases absorption of oral vitamin K
133
Q

What is a boxed warning associated with Kcentra?

A

Arterial and venous thromboembolic complications have been reported

134
Q

What are contraindications of Kcentra?

A

Disseminated intravascular coagulation (DIC) and known HIT (contains heparin)

135
Q

What are some warnings associated with Kcentra?

A

Made from human blood and may carry risk of transmitting infectious agents

136
Q

What are some side effects of Kcentra?

A

HA, N/V/D, arthralgia, hypotension, decreased K, thrombotic events

137
Q

What are some important notes associated with Kcentra?

A
  • Administer with Vitamin K
  • Do not let drug back-up into line (will clot)
  • Refrigerate; allow to reach room temperature prior to administration
  • Each vial can have a different potency of multiple coagulation factors (actual potency is stated on the vial)
138
Q

What are some warnings associated with Profilnine?

A
  • Contains factors II, IX and X but low or nontherapeutic levels of factor VII and should not be confused with Kcentra, which contains therapeutic levels of factor VII
  • Made from human blood and may carry risk of transmitting infectious agents
139
Q

What are some side effects associated with Profilnine?

A

Chills, fever, flushing, nausea, headache, risk of thrombosis

140
Q

What are some notes associated with Profilnine?

A
  • Slow infusion and give antihistamine to minimize side effects
  • Administer with Vitamin K
141
Q

What is a boxed warning associated with NovoSeven RT?

A

Serious thrombotic events are associated with the use of factor VIIa

142
Q

What is preferred for reversal of Warfarin in patients without significant or major bleeding?

A

Oral formulations of vitamin K generally at doses of 2.5 - 5 mg

143
Q

Why should you avoid SC injections of Vitamin K for warfarin reversal?

A

Vitamin K given subcutaneously has a slow onset and a variable response

144
Q

Why should you avoid IM injections of Vitamin K for warfarin reversal?

A

Avoid the intramuscular route due to the risk of hematoma formation

145
Q

When should intravenous Vitamin K be used for?

A

IV Vitamin K should be used only when the patient is experiencing serious bleeding

146
Q

Why does Vitamin K need to be infused slowly?

A

IV injection is reported to cause anaphylaxis in 3 out of 100,000 patients

147
Q

What is the recommendation when INR is above therapeutic range but < 4.5 without bleeding?

A

Reduce or skip warfarin dose and monitor INR. Resume warfarin when INR is therapeutic

*Dose reduction may not be needed if only slightly above therapeutic range

148
Q

What is the recommendation when there is supratherapeutic INR of 4.5-10 without bleeding?

A

Routine use of vitamin K is not recommended if no evidence of bleeding. Hold 1-2 doses of warfarin. Monitor INR. Resume warfarin at lower dose when INR therapeutic. Vitamin K can be used if urgent surgery needed (<5 mg, with additional 1-2 mg in 24 hours if needed) or bleeding risk is high (1-2.5 mg)

149
Q

What is the recommendation when INR > 10 without bleeding?

A

Hold warfarin. Give oral vitamin K 2.5-5 mg even if not bleeding. Monitor INR. Resume warfarin at a lower dose when INR is therapeutic.

150
Q

What is the recommendation for patients on warfarin undergoing major bleeding?

A

Hold warfarin. Give vitamin K 5-10 mg by slow IV injection and four-factor prothrombin complex concentrate (PCC). PCC suggested over fresh frozen plasma (FFP) due to risks of allergic reactions, infection transmission, longer preparation time, slower onset and higher volume

151
Q

What is the recommendation of perioperative management of patients on warfarin?

A
  • Stop warfarin therapy approximately 5 days before major surgery
  • In patients with a mechanical heart valve, Afib or VTE at high risk for thromboembolism, bridging therapy with LMWH or UFH is recommended
  • Discontinue therapeutic dose SC LMWH 24 hours before surgery
  • Patients at low risk for thromboembolism do not require bridging (stop warfarin and restart after surgery when hemostasis is achieved)
152
Q

What is the recommendation when INR is still elevated 1-2 days before surgery?

A

Give low dose Vitamin K (1-2 mg)

153
Q

What are symptoms of DVT?

A

Pain in the affected limb and unilateral lower extremity swelling

154
Q

How can DVT be diagnosed?

A

DVTs can be diagnosed with an ultrasound (or MRI or venography, in some cases). A D-dimer (a lab test) can aid in the diagnosis

155
Q

How can a PE be diagnosed?

A

If a PE is suspected, it is diagnosed with pulmonary CT angiogram

156
Q

What are the risk factors for the development of VTE?

A

Surgery, major trauma or lower extremity injury, immobility, cancer or chemotherapy, previous VTE, pregnancy and postpartum period, estrogen-containing medications or SERMs, erythropoiesis-stimulating agents, increasing age, obesity, inherited or acquired thrombophilia, acute medical illness, venous compression, inflammatory bowel disease, nephrotic syndrome, myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, central venous catheterization

157
Q

What medications are approved for VTE prophylaxis?

A

UFH, LMWHs, fondaparinux, rivaroxaban, apixaban, and dabigatran are all approved for VTE prophylaxis

158
Q

What are some alternatives for patients who have a contraindication to anticoagulants or have a high risk for bleeding?

A

Intermittent pneumatic compression (IPC) devices or graduated compression stockings

159
Q

What are some other recommendations to decrease VTE risk for long-distance travelers?

A

Frequent ambulation, calf muscle exercises, sitting in an aisle seat and using graduated compression stockings with 15-30 mmHg of pressure at the ankle during travel

*Aspirin or anticoagulants should not be used

160
Q

What is the duration of therapy for VTE treatment?

A
  • Any VTE that is caused by surgery or a reversible risk factor should be treated for three months
  • If VTE is unprovoked, extending therapy longer than three months is recommended, as long as the patient’s bleeding risk is low-to-moderate
  • If the risk of bleeding is high, limit the treatment to three months
  • If a patient has two unprovoked VTE episodes, long-term treatment can be considered
161
Q

What medications are contraindicated in patients with a history of, or current, VTE?

A

Estrogen-containing medications and selective estrogen receptor modulators (SERMs) are contraindicated in patients with history of, or current, VTE and should be discontinued

162
Q

What VTE treatment is recommended for patients without cancer?

A

For patients without cancer, dabigatran and the oral factor Xa are preferred over warfarin for the first three months of treatment for a DVT in the leg or a PE

163
Q

What is the preferred VTE treatment for patients with cancer?

A

For patients with cancer, LMWH is preferred over all oral anticoagulants (including warfarin)

164
Q

What is the recommendation for patients with an unprovoked DVT or PE who are stopping anticoagulation?

A

Aspirin is recommended to prevent recurrence (if there are no contraindications)

165
Q

What are some complications associated with atrial fibrillation or atrial flutter?

A

It can form clots in the heart that can be ejected from the heart which can travel to the brain and cause a stroke or transient ischemic attack

166
Q

What are some possible solutions for patients with afib or aflutter and heart valve problems?

A

Some of these patients require valve replacement surgery and involves replacing the damaged valve with a mechanical (prosthetic) or animal (sometimes called a bioprosthetic) valve

167
Q

What is the only medication that patients with mechanical heart valves can use?

A

Patients with mechanical heart valves have the highest risk for clotting/strokes and are treated with warfarin only

168
Q

What medications are not approved in patients with mechanical heart valves?

A

Factor Xa inhibitors and DTIs are not approved for this population

169
Q

For patients with Afib > 48 hours or unknown duration who will undergo cardioversion, what is the recommendation?

A

Anticoagulation (if warfarin, target INR 2-3) for at least 3 weeks prior to and 4 weeks after cardioversion (regardless of method - electrical or pharmacologic) when normal sinus rhythm is restored

170
Q

For patients with Afib < 48 hours duration undergoing elective cardioversion, what is the recommendation for anticoagulation?

A

Start full therapeutic anticoagulation at presentation, perform cardioversion, and continue full anticoagulation for at least 4 weeks while patient is normal sinus rhythm

171
Q

What is the recommendation for patients staying in Afib?

A

Chronic anticoagulation therapy may be needed for stroke prevention with treatment depending on risk factors present

172
Q

What does the acronym CHA2DS2VASc stand for and what is the scoring system?

A 
C - CHF (1)
H - HTN (1)
A - Age > 75 years (2)
D - Diabetes (1)
S2 - Prior stroke/TIA (2)
V - Vascular disease (prior MI, PAD, aortic plaque) (1)
A - Age 65-74 years (1)
S - Sex category, Female (1)
173
Q

How do you use the CHA2DS2VASc scoring system?

A

Count the number of risk factors the patient has, then select the recommended therapy. The higher the score, the greater the stroke risk and the more intensive the anticoagulation recommendations

174
Q

What do the different CHA2DS2VASc scores represent?

A
  • Score 0 (males) or 1 (females): no anticoagulation recommended
  • Score > 1 (males) or > 2 (females): oral anticoagulation may be considered
  • Score > 2 (males) or > 3 (females): oral anticoagulation is recommended. Non-vitamin K oral anticoagulation (DOAC) is recommended over warfarin
175
Q

What is the recommendation for prevention and treatment of VTE in pregnant women?

A

LMWH is preferred over UFH

*Pneumatic compression devices can be used alone or with LMWH in select patients

176
Q

What is the recommendation for pregnant women who require chronic warfarin therapy?

A

Since warfarin is teratogenic, women who require chronic warfarin therapy for mechanical heart valves or inherited thrombophilias are generally converted to LMWH during pregnancy. They may be switched back to warfarin after the 13th week of pregnancy, then back to LMWH close to delivery

177
Q

What is a monitoring parameter of use of LMWH in pregnancy?

A

Anti-Xa levels are recommended

178
Q

Which medications have not be adequately studied in pregnancy and are not recommended?

A

The oral factor Ca inhibitors and direct thrombin inhibitors

179
Q

What are key counseling points for all anticoagulants?

A
  • Can cause serious and life-threatening bleeding/bruising
  • Tell physicians and dentists that you are using this medication before any surgery is performed
  • Call your healthcare provider right away if you fall or injure yourself, especially if you hit your head
  • Avoid alcohol
  • Many drug interactions
  • Missed dose: take as soon as possible on the same day and do not take a double dose the next day to make up for a missed dose
180
Q

What are key counseling points for Dabigatran?

A
  • Take with a full glass of water; swallow capsules whole
  • Can cause dyspepsia
  • Only one open bottle of dabigatran at a time. After opening a bottle of dabigatran, use within 4 months
  • Keep dabigatran in the original bottle or blister package. Do not put dabigatran in pill boxes or pill organizers
  • Missed dose: if your next dose is less than six hours away, skip the missed dose
181
Q

What are key counseling points for Rivaroxaban?

A
  • Atrial fibrillation: take once daily with the evening meal
  • Blood clots in the veins of your legs or in the lungs: take once or twice daily as prescribed with food at the same time each day
  • Missed dose: if taken twice daily, can take two doses at the same time to make up for the missed dose
182
Q

What are key counseling points for Enoxaparin?

A
  • Subcutaneous injection; choose an area on the right or left side of your abdomen, at least two inches from the belly button. Wash your hands and clean the site
  • Remove the needle cap by pulling it straight off the syringe. Do not twist the cap off as this can bend the needle
  • Do not expel the air bubble in the syringe prior to injection unless your healthcare provider has advised you to do so
  • Hold the syringe like a pencil. Pinch an inch of skin to make a fold. Insert the full length of the needle straight down at a 90 degree angle into the fold of the skin
  • Press the plunger with your thumb until the syringe is empty
  • Pull the needle straight out at the same angle that it was inserted and release the skin fold
    Point the needle down and away from yourself and others, and push down on the plunger to activate the safety shield
  • Do not rub the site of injection as this can lead to bruising. Place the used syringe in the sharps collector
183
Q

What are some key counseling points of Warfarin?

A
  • Take at the same time every day
  • Ask your pharmacist if your tablet looks different
  • Can rarely cause purple toe syndrome (painful toes and purple discoloration) or death of skin tissue
  • Frequent blood monitoring required (INR)
  • Consistent intake of vitamin K required (mainly found in green, leafy vegetables)

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