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Pharmacotherapy II > VTE Weber Exam 4 > Flashcards

VTE Weber Exam 4 Flashcards

1
Q

When and where are venous thrombi formed?

A

In areas of slow or disturbed blood flow in veins, leading to obstructed flow, vascular tissue inflammation, or embolus travels to other portion of body.

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2
Q

What is an embolus?

A

A piece of a clot that has broken off and travels somewhere else to become lodged (pulmonary embolism in lungs)

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3
Q

What are the three components of Virchow’s Triad of VTE causes?

A

Hypercoagulable state (malignancy, factor V leiden, pregnancy), endothelial injury (atherosclerosis, orthopedic injury), and circulatory stasis (immobility, paralysis, varicose veins)

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4
Q

Why are the legs the most common site of DVT?

A

Blood flow in the legs is opposed by gravity. The popliteal vein is especially common.

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5
Q

Name the physiologic anticoagulants.

A

Antithrombin III, protein C, protein S, tissue factor pathway inhibitor, and tissue plasminogen activator

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6
Q

Which clotting pathway is the “spark” that gets the clotting cascade started? Which clotting pathway helps to amplify the initial clotting stimulus?

A

Spark: Extrinsic pathway
Amplification: Intrinsic pathway

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7
Q

What is the long-term complication of DVT? What does this cause?

A

Post-thrombotic syndrome; damage to venous valves causes venous obstruction, venous hypertension, chronic pain and swelling, stasis ulcers, and development of infection

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8
Q

What conditions put a patient at risk for a DVT?

A

Heart failure, immobilization, malignancy, MI, obesity, paralysis, postoperative state (3 mos), pregnancy, varicose, veins, and orthopedic injury.

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9
Q

What patient history or demographics put a patient at risk for DVT?

A

Age >40 years, family history of DVT, OC/estrogen use, postoperative state (3 mos), history of prior DVT.

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10
Q

What are appropriate nonpharmacologic treatment options for DVT?

A

Bed rest (if on appropriate anticoagulation), elevation of feet, pain management, compression stockings

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11
Q

What are appropriate nonpharmacologic treatment options for PE?

A

Oxygen, mechanical ventilation, and compression stockings

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12
Q

What are the goals of DVT treatment?

A

To stabilize the clot, prevent worsening/growing, prevent risk of embolism, and prevent another clot.

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13
Q

What is the mechanism of action of unfractionated heparin (UFH)? What factors does it inhibit?

A

Binds to ATIII, improving its ability to inhibit thrombin, factor VII, IX, X, XI, XII, and plasmin

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14
Q

What is the pharmacokinetic reason for aPTT monitoring?

A

Non-linear kinetics and variable dose response

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15
Q

What is a therapeutic range for aPTT on heparin?

A

1.5 - 2.5 x normal range

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16
Q

By what route can heparin be dosed?

A

IV or SQ (NOT IM)

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17
Q

How often is aPTT monitored on heparin?

A

At baseline, 6 hours after dose and after each dosage change, daily after one day stable on dose.

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18
Q

What are potential adverse effects of heparin?

A

Bleeding, osteoporosis, hypersensitivity, HAT, HIT

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19
Q

How often are platelet counts monitored on heparin?

A

Every other day until day 14

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20
Q

What is the half life of UFH when given IV?

A

30-90 minutes (caution about discontinuing)

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21
Q

What route of administration of heparin puts a patient at higher bleeding risk?

A

IV

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22
Q

What factors put a patient at high bleeding risk?

A

Age >65, h/o GI bleed or PUD, renal failure, EtOH use, malignancy, cerebrovascular disease, surgery, major trauma, concurrent medications like inhibitors and other anticoagulants

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23
Q

What parameters are monitored for bleeding on heparin?

A

CBC – HGB, HCT – and BP

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24
Q

How long does protamine persist when given to neutralize heparin? What is the half life? When should you check aPTT after protamine administration?

A

Persists 2 hours but half life 7 minutes. Check aPTT in 30 minutes.

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25
Q

If a patient has received a dose of heparin in the last 30 minutes, how should protamine be dosed to neutralize it?

A

1 - 1.5 mg protamine per 100 units of UFH given

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26
Q

If a patient has received a dose of heparin within 30 - 120 minutes, how should protamine be dosed?

A

0.5 - 0.75 mg protamine per 100 units of UFH given

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27
Q

If a patient has received a dose of heparin more than 2 hours ago, how should protamine be dosed?

A

0.25 - 0.375 mg protamine per 100 units of UFH given

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28
Q

What are potential adverse effects of protamine that must be weighed? How can these be controlled?

A

Risk for hypotension, bradycardia, and anaphylaxis
Check if pt history vasectomy, fish sensitivity, received protamine-containing insulin
Infuse protamine over 1-3 minutes, MAX 50mg over 10 mins

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29
Q

What differentiates HIT from HAT?

A

HIT is immune mediated, occurs later (7-14 days after heparin start), and is associated with a larger drop in platelets (>50% from baseline or

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30
Q

True or false: Due to the drop in platelets, patients experiencing HIT need to discontinue all anticoagulants immediately.

A

False – although heparin products DO need to be stopped immediately, they must be put on an alternative due to the higher risk for thrombosis

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31
Q

What lab tests can confirm a diagnosis of HIT?

A

HIPA, serotonin release assay, or heparin-PF4 Ab ELISA

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32
Q

When can warfarin be used for HIT?

A

After platelet count is >150 and when patient stable on direct antithrombin already.

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33
Q

In pregnant patients with HIT, what agent is preferred?

A

Danaparoid (fondaparinux only if danaparoid not availble)

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34
Q

What factor do the LMWHs preferentially inhibit?

A

Factor Xa

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35
Q

LMWHs are smaller than heparin and have reduced protein binding, longer half life, less effect on platelets, and predictable dose response. Based on these, what are the advantages to using LMWH?

A

Predictable dose response allows for fixed or weight-based dosing and removes monitoring requirement. Better SQ bioavalability, reduced HIT incidence, and longer dosing intervals possible.

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36
Q

What is the mechanism for LMWH elimination?

A

Renally – adjust for decrease in renal function CrCl

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37
Q

What are the upper weight limits that the LMWHs have been studied at?

A

Enoxaparin 144kg
Dalteparin 190kg
Tinzaparin 165kg

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38
Q

What parameters should be monitored for LMWHs?

A

CBC with plt, SCr, and fecal occult blood

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39
Q

What patients may need anti-Xa level monitoring when on LMWH?

A

Children, severe kidney failure, obesity, long courses, and pregnancy

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40
Q

What black box warning do all LMWH products carry?

A

Use with neural anesthesia or spinal puncture can lead to increased risk of spinal hematoma leading to paralysis

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41
Q

What adverse effects are associated with LMWHs?

A

Bleeding, thrombocytopenia, delayed hypersensitivity skin reactions

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42
Q

If protamine must be administered for LMWH-induced bleeding, how is it dosed within 8 hours of receiving LMWH?

A

1mg protamine/ 1mg enoxaparin

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43
Q

If protamine must be administered for LMWH-induced bleeding, how is it dosed after 8 hours of receiving LMWH?

A

0.5mg protamine / 1mg enoxaparin

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44
Q

What conditions is fondaparinux approved for?

A

Prophylaxis following THA, TKA, and abdominal surgery (NOT acutely ill pts) and treatment of DVT/PE

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45
Q

If a patient is

A

They can receive it for DVT/PE treatment, but not for prophylaxis

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46
Q

True or false: Fondaparinux must be renally adjusted for CrCl

A

False – do NOT use if CrCl

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47
Q

What factor does fondaparinux inhibit?

A

Factor Xa

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48
Q

What should be monitored for fondaparinux?

A

Bleeding, SCr, potentially monitor Xa (not ideal)

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49
Q

What four conditions is rivaroxaban approved for?

A

DVT prophylaxis, DVT/PE treatment, NV afib, secondary prevention of recurrent DVT/PE

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50
Q

When is rivaroxaban initiated when used for DVT prophylaxis?

A

6-10 hours post surgery (confirmed hemostasis)

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51
Q

How long should rivaroxaban be continued in prophylaxis?

A

THA: 35 days
TKA: 12 days

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52
Q

What reversal agent may be helpful for rivaroxaban?

A

PCC

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53
Q

What is the brand name for rivaroxaban?

A

Xarelto

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54
Q

What conditions should rivaroxaban be avoided in?

A

CrCl

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55
Q

How is warfarin transitioned to rivaroxaban?

A

Stop warfarin and start rivaroxaban when INR

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56
Q

For rivaroxaban, apixaban, and edoxaban, how do you convert to warfarin?

A

Start warfarin and stop the NOAC 3 days later. (Can also stop NOAC and start warfarin with LMWH concurrently like normal initiation)

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57
Q

What are the two black box warnings for all NOACs?

A

Neural anesthesia or spinal puncture with NOAC can lead to epidural or spinal hematoma.
Premature discontinuation increases the risk of thrombotic event.

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58
Q

What is the brand name for edoxaban?

A

Savaysa

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59
Q

What is edoxaban approved for?

A

DVT/PE treament and NVAF (if CrCl 15-95 mL/min)

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60
Q

True or false: Edoxaban should be started immediately to treat DVT or PE.

A

False – only started after 5-10 days of parenteral anticoagulant

61
Q

What are the major sources of drug interactions with the NOACs?

A

CYP3A4 and Pgp

62
Q

When should edoxaban, apixaban, and dabigatran be started when transitioning from warfarin?

A

When INR

63
Q

What is the brand name for apixaban?

A

Eliquis

64
Q

What is apixaban approved for?

A

DVT prophylaxis, DVT/PE treatment, and NVAF

65
Q

True or false: Apixaban should be started immediately when treating DVT or PE.

A

True – apixaban does not require parenteral coagulant first

66
Q

What is the only pregnancy class B NOAC?

A

Apixaban (Eliquis)

67
Q

What is the only NOAC that is a direct thrombin inhibitor?

A

Dabigatran (Pradaxa)

68
Q

What direct thrombin inhibitor is often used as a UFH alternative during PCI?

A

Bivalrudin (Angiomax)

69
Q

What is the brand name of dabigatran?

A

Pradaxa

70
Q

What is dabigatran approved for?

A

DVT/PE treatment and NVAF

71
Q

True or false: When treating PE or DVT, dabigatran should be started right away.

A

False – started after 5-10 days of parenteral anticoagulation

72
Q

With what patient population is dabigatran not recommended?

A

Extreme caution with patients 80 years and older

73
Q

What are two unique counseling points with dabigatran among the other NOACs?

A

Keep in manufacturer bottle, may cause dyspepsia.

74
Q

True or false: The dabigatran dose is adjusted for renal function in DVT/PE treatment.

A

False – do not use if CrCl

75
Q

In a patient with CrCl >50mL/min, dabigatran should be stopped ___ days later when transitioning to warfarin.

A

3 days after warfarin start
2 days if CrCl 31-50
1 day if CrCl 15-30

76
Q

True or false: NOACs are dosed differently when used for prophylaxis in mechanical heart valve.

A

False – use of NOACs is contraindicated with mechanical heart valve.

77
Q

What is the only NOAC to have a reversal agent?

A

Pradaxa – Praxbind antibody

78
Q

What is the thrombolytic that can potentially be used for acute pulmonary embolism?

A

Alteplase

79
Q

What are the available strengths of warfarin?

A

1, 2, 2.5, 3, 4, 5, 6, 7.5, and 10mg tablets (all scored)

80
Q

What is warfarin indicated for?

A

Prophylaxis and treatment of thromboembolic disorders and embolic complications from atrial fibrillation or valve replacement, adjunct to reduce risk of embolism after MI

81
Q

True or false: All warfarin products (generic, Coumadin, Jantoven) are roughly equivalent and can be exchanged easily.

A

False! Pt needs to get same one each time.

82
Q

What clotting factors are inhibited by warfarin?

A

Factor II, VII, IX, and X in addition to protein C and S

83
Q

When can effect from warfarin first be seen? When does the effect peak?

A

Effect within 24 hours but peak in 3-4 days

84
Q

What isomer of warfarin is more potent? What enzyme degrades this isomer?

A

S isomer 5 times more potent; degraded by CYP 2C9, 2C19, 2C18 (genetic variability!)

85
Q

What pregnancy category is warfarin? Is it safe for breastfeeding?

A

Pregnancy X but safe for breastfeeding

86
Q

What genetic variant of CYP2C9 leads to an 80% lower dose requirement?

A

3/3 (lowest possible warfarin clearance)

87
Q

What genetic variation of CYP2C9 is more common in Asians and African Americans?

A

*8: lower dose requirement

88
Q

What variations of vitamin K oxide reductase gene (VKORC1) may lead to warfarin resistance and higher dose requirement? Which population has this more commonly?

A

VKORC1 GG: African Americans

89
Q

What variation of VKORC1 leads to higher warfarin sensitivity and lower dose requirement? Which population has this more commonly?

A

VKORC1 AA: Asians

90
Q

What three criteria must a patient meet in order to receive warfarin genetic testing?

A

Must be warfarin naive, at high risk of bleeding if elevated INR, and able to get test results before sixth dose.

91
Q

What patients have an INR goal of 2.5 - 3.5?

A

Those with a mitral, caged ball, or high risk mechanical heart valve.

92
Q

True or false: Once a patient reaches a stable dose, they are generally stable on that dose for the rest of their life.

A

False – warfarin dosing is variable over time.

93
Q

How long should LMWH/UFH/Xa therapy be overlapped when starting warfarin?

A

For at least 5 days and until INR therapeutic

94
Q

What patients may need a starting warfarin dose lower than 5mg daily?

A

Patients >60yo, debilitated, malnourished, CHF, liver disease, concomitant medications, high bleeding risk, genetic factors (AA or 3/3)

95
Q

In the flexible initiation (“loading”) warfarin initiation method, how often should INR be checked?

A

Daily through day 4, then within 3-5 days

96
Q

In the average daily dosing method, how often should INR be checked?

A

Within 3-5 days, then within 1 week

97
Q

How soon should INR be checked after hospital discharge if stable? If unstable?

A

Stable: 3-5 days
Unstable: 1-3 days

98
Q

How often should warfarin be checked during the first month of therapy?

A

At least weekly

99
Q

If a warfarin dose must be held, when should you next check the patient’s warfarin?

A

Within 1-2 days

100
Q

If a warfarin dose was changed, when should you next check the patient’s warfarin?

A

Within 1-2 weeks

101
Q

If a patient’s warfarin dose was changed up to 2 weeks ago, when should the INR next be checked?

A

In 2-4 weeks

102
Q

For an unstable patient on warfarin, how often should routine INR follow up occur?

A

Every 1-2 weeks

103
Q

For a stable patient on warfarin, how often should INR follow up occur?

A

Every 4-6 weeks

104
Q

For a patient consistently stable on warfarin, what is the longest you can wait before checking INR?

A

12 weeks (3 months)

105
Q

What patients may be eligible to self adjust their warfarin doses?

A

Patients anticoagulated >3 months with good cognitive skills, dexterity, and communication and ability to use a POC INR test.

106
Q

What are the 5 D’s + B&B of a warfarin patient interview?

A 
Drugs (change in meds/OTCs/herbals)
Diseases (change in condition/treatment)
Doses (missed doses)
Diet (changes in diet, esp green leafy veggies)
Drink (EtOH consumption)
Bruising & bleeding
107
Q

What is the duration of therapy if a patient had an identifiable risk factor for their DVT?

A

3 months

108
Q

What is an appropriate duration of therapy if a patient had an idiopathic DVT?

A

At least 3 months, then re-evaluate. Extended therapy up to 1 year.

109
Q

How long should a cancer patient who experienced DVT be on therapy?

A

LMWH for 3-6 months, then warfarin or LMWH indefinitely or cancer resolves.

110
Q

How long should a patient with a history of multiple DVTs be on therapy?

A

Lifelong

111
Q

What medications require an empiric (25-50%) decrease in warfarin dose due to interaction?

A

Metronidazole, amiodarone, ciprofloxacin, fluconazole, and bactrim

112
Q

What medication requires an empiric increase in warfarin dose due to interaction?

A

Rifampin

113
Q

Do cholestyramine, carbamazepine, vitamin K foods, and chronic alcohol use increase or decrease INR? (when on warfarin)

A

Decrease INR

114
Q

Do erythromycin, cimetidine, anabolic steroids, acute alcohol use, isoniazid, and propafenone increase or decrease INR? (when on warfarin)

A

Increase INR

115
Q

True or false: Use of aspirin and other NSAIDS with warfarin may increase INR.

A

False – increases bleeding risk but no change in INR.

116
Q

Which condition may require a decrease in warfarin dose: chronic alcohol abuse with liver damage or without liver damage?

A

Chronic alcohol abuse with liver damage – increased anticoagulant effect. Chronic alcohol abuse with normal liver actually induces hepatic enzymes that clear warfarin.

117
Q

At what time of day is warfarin usually dosed?

A

In evening – allows for good INR measurement in morning.

118
Q

What should a patient be instructed to do in case of a missed dose?

A

When you remember, you can take it if it is within 12 hours of when you normally take it. If you are closer to the next dose than the one you missed, just skip it. Do not double up.

119
Q

What should be a patient be counseled on regarding bleeding?

A

If you experience unexplained bruising or bruising that gets worse over time or bleeds that make you uncomfortable, seek medical help. Wear a medical ID bracelet just in case!

120
Q

What dietary counseling points should you cover with a warfarin patient?

A

Keep vitamin K intake consistent (Boost shakes, green leafy vegetables) and no more than 1 drink of alcohol per day for women, 2 for men.

121
Q

How and when is oral vitamin K given?

A

Given as a 5mg tablet if INR >10 and no evidence of bleeding. Acts in 24 hours.

122
Q

If a patient has an INR of 6 and no evidence of bleeding, what should you do?

A

Hold warfarin doses and let INR come back slowly. Avoid vitamin K.

123
Q

How is parenteral vitamin K dosed? How fast does it work?

A

Max rate of 1mg/min; works in 4-6 hours.

124
Q

How is fresh frozen plasma dosed?

A

10-15 mL/kg

125
Q

How is prothrombin complex concentrate dosed?

A

30 IU/kg

126
Q

How can you achieve rapid (10-15 minute) reversal of warfarin?

A

PCC + IV vitamin K (FFP may also be used in addition)

127
Q

What is the recommended VTE prophylaxis in patients who are ambulatory and undergoing minor surgery?

A

Just early, aggressive walking! No pharmacologic therapy recommended

128
Q

What VTE risk are non-orthopedic surgery or acutely ill medical patients at?

A

Moderate – VTE risk 10-40%

129
Q

What are pharmacologic options for VTE prophylaxis for general surgery patients? How long should they be continued?

A

UFH, LMWH, and fondaparinux all options – continue at prophylactic doses up to 28 days after discharge.

130
Q

What are pharmacologic options for VTE prophylaxis for acutely ill medical patients (moderate risk)?

A

UFH, LMWH, and fondaparinux. Increased VTE risk d/t early discharge and immobility, but no specific recommendation for duration. Can stop anticoag on discharge.

131
Q

What patients are at highest VTE risk?

A

Patients undergoing orthopedic surgery or who have experienced major trauma or spinal cord injury.

132
Q

What six agents are approved for VTE prophylaxis in orthopedic surgery patients?

A

LMWH, fondaparinux, rivaroxaban, apixaban, UFH, or warfarin

133
Q

In patients with high bleeding risk, what are VTE prophylaxis options?

A

Intermittent pneumatic compression devices, venous foot pumps, graduated compression stockings

134
Q

What PE patients are most likely to benefit from a thrombolytic?

A

If PE associated with hypotension and a low bleeding risk

135
Q

When using parenteral anticoagulation and warfarin to treat a VTE, when should warfarin be initiated?

A

Initiate warfarin on day 1-2 of treatment with LMWH/UFH/fondaparinux. Overlap at least 5 days and until INR >2.0 for 24 hours.

136
Q

What CHAD2DS2-VASc score in a patient with NV atrial fibrillation warrants oral anticoagulants?

A

Score of 2 or greater

137
Q

At what CHAD2DS2-VASc score in a NVAF patient can aspirin or anticoagulant be considered?

A

Score of 1

138
Q

What are the criteria for the CHA2DS2-VASc scoring system?

A 
1 - Congestive HF
1 - Hypertension
2 - Age 75 or greater
1 - Diabetes mellitus
2 - Stroke/TIA/TE 
1 - Vascular disease (MI, PAD, aortic plaque)
1 - Age 65-74yo
1 - Female gender
139
Q

Generally, what doses of anticoagulants do we use in NVAF?

A

Although anticoagulant is being used for prophylaxis, need to use treatment-like doses.

140
Q

For the oral direct Xa inhibitors (rivaroxaban, apixaban, edoxaban), how long should they be stopped before a high bleeding risk procedure? For a low risk procedure?

A

Low bleeding risk: stop at least 24 hours before (36 hours if CrCl under 30)
High bleeding risk: stop at least 48 hours before
same for dabigatran if CrCl 80 or greater

141
Q

If a patient is on dabigatran and needs to stop it for a high risk surgery and their CrCl is 35, how long before the surgery should they stop?

A

96 hours (4 days) before

142
Q

When bridging any patient on warfarin therapy over a surgical procedure, when should warfarin be stopped?

A

5 days before surgery

143
Q

When bridging a patient, when should LMWH be stopped before the procedure? UFH?

A

Stop LMWH 24 hours before procedure

Stop IV UFH 4-6 hours before

144
Q

When should warfarin be resumed after surgery?

A

12-24 hours after (if adequate hemostasis)

145
Q

True or false: LMWH should be used when bridging the NOACs.

A

False – don’t need to bridge NOACs

146
Q

What dose of enoxaparin should be used for bridging – prophylaxis or treatment doses?

A

Treatment doses – only exception is optional prophylaxis doses in 2 days after surgery.

147
Q

When LMWH is dosed daily in bridging, what must the last dose before surgery be?

A

Last dose must be 24 hours before surgery and 50% of normal daily dose.

148
Q

What anticoagulant should a patient receive in the day after their last warfarin dose in bridging?

A

None – start LMWH in day after that.

149
Q

When on dabigatran, rivaroaban, or apixaban, SCr, CBC, and PT/INR (direct Xa) or aPTT (dabigatran) should be monitored at least every ___ months.

A

3 months

Pharmacotherapy II (15 decks)

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