Anticoagulation Flashcards
1
Q
How do anticoagulants work?
A
prevent clots from forming and to keep existing clots from becoming larger; they DO NOT break down clots
2
Q
What 3 main factors contribute to thrombosis (blood clots) forming (Virchow’s triad)?
A
- blood vessel (endothelial) injury
- blood stasis (stopping/slowing of blood flow)
- pro-thrombotic conditions (hypercoagulability)
3
Q
What conditions are anticoagulants used to prevent?
A
- venous thromboembolism (VTE)
–> DVT/ PE - cardioembolic stroke
4
Q
What conditions are anticoagulants used to treat?
A
- immediate treatment of acute coronary syndrome (ACS)
- venous thromboembolism (VTE)
–> DVT/ PE
5
Q
Where do blood clots form?
A
anywhere in the body
6
Q
When do blood clots become dangerous?
A
when they become an embolus (a clot/ piece of clot that travels somewhere), blocking blood flow to the lungs, heart, or brain
7
Q
Where are coagulation (clotting) factors made?
A
liver
8
Q
Which clotting factors are vitamin K dependent?
A
II (2)
VII (7)
IX (9)
X (10)
9
Q
At which factor do the intrinsic and extrinsic pathways meet?
A
X (10)
10
Q
What is the outcome of clotting factor activation beginning from either pathway?
A
activate the next clotting factor in the cascade until fibrin is formed
11
Q
What is the body’s natural, endogenous anticoagulant?
A
Antithrombin
12
Q
Which anticoagulants inhibit the clotting cascade indirectly via antithrombin?
A
- Fondaparinux
- LMWHs
- UFH
13
Q
What factors does heparin inhibit?
A
IIa (thrombin)
Xa
14
Q
What factors do LMWHs inhibit?
A
Xa > IIa (thrombin)
15
Q
Which medications directly inhibit factor Xa?
A
- apixaban (Eliquis)
- edoxaban (Savaysa)
- rivaroxaban (Xarelto)
16
Q
What is the MOA of warfarin?
A
vitamin K antagonist; coagulation factors are still made but have reduced coagulation activity
17
Q
What medications are DOACs (direct-acting oral anticoagulants)?
A
- apixaban
- rivaroxaban
- edoxaban
- dabigatran (direct thrombin inhibitor)
18
Q
When is warfarin preferred over DOACs?
A
- stroke prevention in Afib WITH moderate to severe mitral stenosis or mechanical heart valve
- VTE treatment in patients WITH triple-positive antiphospholipid syndrome or mechanical heart valve
19
Q
What agents directly inhibit thrombin, decreasing the amount of fibrin available for clot formation?
A
- Argatroban (IV)
- Bivalirudin (IV)
- Dabigatran (PO)
20
Q
What conditions require more anti-platelet action vs. anticoagulation?
A
- coronary artery disease
- acute coronary syndromes
- PREVENTION of ischemic stroke/ TIA
21
Q
What conditions are fibrinolytics appropriate for?
A
- acute ischemic stroke
- STEMI
22
Q
What is the biggest side effect of anticoagulants?
A
bleeding
23
Q
A drop ≥2 g/dL in what lab value could signify internal or external bleeding?
A
Hemoglobin
24
Q
What can cause epistaxis (nose bleeds)?
A
- drugs
- dry nasal mucosa
- nose blowing
25
What can cause bleeding gums?
1. new or worse than usual gingivitis
--> counsel patients to use soft toothbrushes
26
What can cause bruising?
1. drugs (chronic steroids)
2. thrombocytopenia/ clotting disorder
3. Cushing's syndrome
4. malnutrition
5. fracture/sprain
6. infection
7. physical abuse
27
What can cause hematoma (internal bleeding from broken blood vessels; deep bruise)?
1. can occur on the abdomen from LMWH injection that was rubbed
2. epidural/spinal hematomas can occur in patients using LMWH or DOACs getting neuraxial anesthesia or spinal puncture
28
What can cause hematuria (blood in urine)?
1. UTIs
2. kidney stones
3. prostatitis
4. kidney disease
29
What can cause hematemesis (blood in the vomit)?
1. esophageal (varices, chronic reflux)
2. stomach/ duodenum (ulcer)
30
What can cause hematochezia (blood from the anus)?
1. esophageal (varices, chronic reflux)
2. stomach/ duodenum (ulcer)
3. rectum (hemorrhoid, rectal tear)
4. diverticulosis
5. colon cancer
6. IBD
7. colon polyps
31
What infections can cause bloody diarrhea (dysentery)?
1. C. diff
2. Shigella
3. Entamoeba hitsolytica
32
How can we tell where a GI bleed might be based on visual appearance?
the darker the bleeding site is away from the anus, the darker the stool; rectal bleeding from polyps might be occult; need fecal occult test to identify
33
Which medications do not cross-react with HIT antibodies?
IV direct thrombin inhibitors
34
What is the MOA of unfractionated heparin?
binds to antithrombin and potentiates its ability to inactivate thrombin (IIa), Xa, and other clotting factors (IXa, XIa, XIIa, and plasmin); prevents conversion of fibrinogen to fibrin
35
What is the dosing of heparin for VTE prophylaxis?
5000 units SQ Q8-12H
36
What is the dosing of heparin for VTE treatment?
80 units/kg IV bolus --> 18 units/kg/h
37
What is the dosing of heparin for ACS/STEMI?
60 units/kg IV bolus --> 12 units/kg/h
38
Heparin treatments are dosed off of which weight in kg?
total body weight
39
Why should heparin not be administered IM?
hematoma risk
40
What are CIs to heparin?
1. uncontrolled active bleed (intracranial hemorrhage)
2. severe thrombocytopenia (low platelets)
3. history of HIT
4. benzyl alcohol formulations in neonates, pregnancy, breastfeeding, and infants
5. pork containing products in those with pork hypersensitivity
41
What are the warnings with heparin?
fatal medication errors; verify the correct concentration is chosen
42
What are SEs with heparin?
1. bleeding (epistaxis, bruising, gingival, GI)
2. thrombocytopenia
3. HIT
4. hyperkalemia
5. alopecia
6. osteoporosis (long-term use)
43
What should be monitored while on heparin treatment?
1. aPTT or anti-Xa level (Q6H until therapeutic, at every dose change, and daily)
2. platelets (baseline and daily)
3. Hgb (baseline and daily)
4. Hct ( baseline and daily)
44
What should be monitored while on VTE prophylaxis with SQ heparin?
1. platelets (baseline and daily)
2. Hgb (baseline and daily)
3. Hct ( baseline and daily)
45
What is a therapeutic aPTT range while on heparin?
1.5 -2.5x control (per specific institutional protocol
46
What is a therapeutic anti-Xa range while on heparin?
0.3-0.7 units/mL
47
What lab value suggests HIT?
a drop in platelets >50% from baseline
48
Why is heparin dosed IV for VTE and ACS treatment?
rapid onset and short half life (1.5h)
49
Why is heparin dosed SQ for VTE prophyaxis?
longer onset (20-30 minutes) vs. IV administration
50
What dosage form of heparin is only used to keep IV lines open?
heparin lock-flushes (HepFlush)
51
Which dosages of heparin are look alike and sound alike and has been fatal especially in neonates?
heparin injection (10,000 units/mL)
and heparin flushes (10-100 units/mL)
52
What is the MOA of LMWHs?
binds to antithrombin and potentiates its ability to inactivate thrombin (IIa) and Xa; prevents the conversion of fibrinogen to fibrin; factor Xa inhibition is much greater than IIa
53
What is the antidote for UFH and LMWHs?
protamine
54
What is the dosing of enoxaparin for VTE prophylaxis in those with normal renal function?
1. 30mg SQ BID
2. 40mg SQ QD
55
What is the dosing of enoxaparin for VTE prophylaxis when CrCl <30 ml/min?
30mg SQ QD
56
What is the dosing of enoxaparin for VTE, unstable angina, and NSTEMI treatment?
1. 1 mg/kg SQ Q12H
2. 1.5 mg/kg SQ QD (only for inpatient VTE treatment)
3. CrCl <30 ml/min: 1 mg/kg SQ QD
57
What is the dosing of enoxaparin for STEMI in patients <75 y/o?
1. 30mg IV bolus + 1 mg/kg SQ dose (MAX 100mg for the first IV+SQ doses only), followed by 1 mg/kg SQ Q12H
2. CrCl <30: 30mg IV bolus + 1 mg/kg SQ dose followed by 1 mg/kg SQ QD
58
What is the dosing of enoxaparin for STEMI in patients >75 y/o?
1. 0.75 mg/kg SQ Q12H (no bolus); (MAX 75mg for first 2 SQ doses)
2. CrCl <30: 1 mg/kg SQ QD (no bolus)
59
LMWHs are dosed based off of which weight in kg?
total body weight
60
What is the dosing of dalteparin for VTE prophylaxis?
2500-5000 units SQ QD
61
What is the dosing of dalteparin for unstable angina/NSTEMI treatment?
120 units/kg SQ Q12H (MAX 10,000 units)
62
What are boxed warnings for LMWHs?
patients undergoing neuraxial anesthesia (epidural/spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
63
What are CIs to using LMWHs?
1. Hx of HIT
2. active major bleed
3. hypersensitivity to pork
64
What should be monitored on LMWHs?
1. platelets
2. Hgb
3. Hct
4. SCr
65
In what populations is it recommended that anti-Xa levels for LMWHs be monitored?
1. pregnancy
2. renal insufficiency
3. obesity
4. low body weight
66
When should anti-Xa levels be obtained in special populations taking LMWHs?
peak anti-Xa levels 4 hours post-SQ dose
67
What are important storage and administration requirements for LMWHs?
1. store at room temperature
2. do not administer in patients with HIT, antibodies will cross-react
3. do not expel air bubble prior to administration (can cause loss of drug)
4. do not administer IM
68
What drugs interact with LMWHs?
drugs that can increase bleeding risk:
1. NSAIDs
2. SSRIs/SNRIs
3. fibrinolytics
4. anticoagulants/antiplatelets
5. some herbal supplements
69
Enoxaparin
Lovenox
70
Dalteparin
Fragmin
71
What is the MOA of HIT?
1. the immune system forms IgG antibodies against heparin bound to platelet factor 4
2. the antibodies join with heparin and PF4 to make a complex
3. complex binds to Fc receptors on platelets
4. platelet activation band release of pro-coagulant microparticles
5. pro-thrombotic state
72
How is the probability of HIT assessed?
4 Ts:
1. Thrombocytopenia
2. Timing of platelet drop (hours up to 5-10 days after starting heparin)
3. Thrombosis (or skin lesions that are necrotizing or non-necrotizing)
4. oTher causes
73
How is HIT confirmed?
1. heparin-PF4 antibody enzyme-linked immunosorbent assay (ELISA) test
2. functional assay (serotonin release assay or heparin-induced platelet aggregation assay)
74
How is HIT managed/treated?
1. stop all forms of heparin and LMWH (if on warfarin D/C and administer vitamin K)
2. immediately treat with non-heparin anticoagulants (Argatroban)
3. DO NOT start warfarin therapy until platelets ≥ 150,000 cells/mm3 and should be initiated at lower doses
4. overlap warfarin with a non-heparin anticoagulant for at least 5 days and after the INR is in target for >24 hours
5. if urgent cardiac surgery or PCI is required use Bivalrudin
75
What is the MOA of PO factor Xa inhibitors?
directly inhibit factor Xa
76
What is the MOA of Fondaparinux (SQ factor Xa inhibitor)?
injectible synthetic pentasaccharide that selectively and indirectly inhibits factor Xa by binding to anti-thrombin
77
What are boxed warnings with PO factor Xa inhibitors?
1. patients undergoing neuraxial anesthesia (epidural/spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
2. premature discontinuation increases risk of thrombotic events
78
What are boxed warnings unique to edoxaban?
reduced efficacy in nonvalvular AF patients with CrCl >95 ; DO NOT USE
79
What are CIs with PO factor Xa inhibitors?
active pathological bleeding
80
What are general warnings with PO factor Xa inhibitors?
1. not recommended with prosthetic heart valves or triple-positive antiphospholipid syndrome (all 3 antibodies positive)
2. avoid in patients with moderate to severe hepatic impairment
81
What are SEs with PO factor Xa inhibitors?
generally well tolerated unless bleeding occurs
82
What are unique SEs with edoxaban?
1. rash
2. elevated LFTs
83
What is monitored with PO factor Xa inhibitors?
1. Hgb
2. Hct
3. SCr
4. LFTs
84
How can PO factor Xa inhibitors be administered if patients have trouble swallowing or have an NG tube?
all can be crushed and put on applesauce or suspended in water
85
How can apixaban be administered if patients have trouble swallowing or have an NG tube?
can be crushed and mixed with D5W, water, or applesauce
86
How long before elective surgery shoud PO factor Xa inhibitors be discontinued?
rivaroxiban: 24 hours prior
edoxaban: 24 hours prior
apixaban: 48 hours prior with mod-high bleeding risk; 24 hours prior with low bleeding risk
87
What is the dosing of apixaban for nonvalvular AF (stroke prophylaxis)?
1. 5mg PO BID
2. if 2/3 conditions met (≥80 y/o, ≤60mg TBW, SCr ≥1.5); 2.5mg PO BID
88
What is the dosing of apixaban for DVT/PE treatment?
Initial: 10mg PO BID x 7days, then 5mg PO BID (Eliquis DVT/PE started pack)
Extended (≥ 6 months of initial treatment): 2.5 mg PO BID
89
What is the dosing of apixaban for DVT prophylaxis post hip/knee replacement?
Knee: 2.5mg PO BD x 12 days; give first dose 12-24 hours after surgery
Hip: 2.5mg Po BID x 35 days ; give first dose 12-24 hours after surgeryv
90
What should a patient do if they miss a dose of apixaban?
take immediately on the same day, then resume BID dosing; DO NOT double the dose to make up for a missed dose
91
Which PO Xa-inhibitor is available as a suspension?
rivaroxaban
92
What should doses of rivaroxiban ≥15 mg be administered with?
food
93
What is dosing of rivaroxaban for nonvalvular AF (stroke prophylaxis)?
CrCl>50: 20mg PO QD with evening meal
CrCl 15-50: 15mg PO QD with evening meal
CrCl <15: 15 mg PO QD (per manufacturer, but limited data)
94
What is the dosing of rivaroxaban for DVT/PE treatment?
Initial: 15mg PO BID x 21 days, then 20mg PO QD with food
Extended (≥ 6 months of initial treatment): 10mg PO QD
CrCl 15-30: use caution
CrCl<15: DO NOT USE
95
What is dosing of rivaroxaban for DVT prophylaxis (after hip/knee replacement) and VTE prophylaxis in acutely ill medical patients)?
knee: 10mg PO QD x 12 days
hip: 10mg PO QD x 35 days
acutely ill: 10mg PO QD x 31-39 days
CrCl 15-30: use caution
CrCl<15: DO NOT USE
96
What is dosing of rivaroxaban for risk reduction of major CVD events in PAD/CAD?
2.5 mg PO BIS in combination with low dose aspirin
CrCl< 15: 15mg PO QD (per manufacturer)
97
What should be done if a dose of rivaroxaban is missed?
If taking 15mg BID: take immediately to ensure intake of 30mg/day (2 tablets can be taken at once) then resume regular schedule the following day
If taking 10,15,20mg QD: take immediately on the same day, otherwise skip (DO NOT DOUBLE UP)
98
What is andexanet alfa (Andexxa) an antidote for?
apixaban and rivaroxaban
99
What is the dosing of edoxaban for nonvalvular AF (stroke prevention) ?
CrCl> 95: DO NOT USE
CrCl 51-95: 60mg PO QD
CrCl: 15-50: 30mg PO QD
CrCl< 15: not recommended
100
What is the dosing of edoxaban for the treatment of DVT/PE?
60mg QD after 5-10 days of parenteral anticoagulation
CrCl 15-50, TBW ≤60kg, or certain P-gp inhibitors: 30mg QD
CrCl<15: not recommended
101
What should be done if a dose of edoxaban is missed?
take immediately on the same day; DO NOT DOUBLE UP
102
Apixaban
Eliquis
103
Rivaroxaban
Xarelto
104
Edoxaban
Savaysa
105
What are boxed warnings for fondaparinux?
neuraxial analgesia (epidural/spinal) or spinal puncture are at increased risk of hematomas and subsequent paralysis
105
Fondaparinux
Atraxia
106
What are CIs to using fondaparinux?
1. CrCl<30ml/min
2. active major bleed
3. bacterial endocarditis
4. thrombocytopenia with a positive test for anti-platelet antibodies in the presence of fondaparinux
107
What are SEs with fondaparinux?
1. bleeding (epistaxis, bruising, gingival, GI)
2. anemia
3. local injection site reactions (rash, pruritus, bruising)
4. thrombocytopenia
108
What is the dosing of fondaparinux for VTE prophylaxis?
≥50kg: 2.5mg SQ QD
<50kg: contraindicated
109
What is the dosage of fondaparinux for VTE prophylaxis?
<50kg: 5mg SQ QD
50-100kg: 7.5mg SQ QD
>100kg: 10mg SC QD
110
What are warnings with fondaparinux?
1. CrCl 30-50mL/min: use caution
2. do not expel air bubble from syringe prior to the dose
3. Do not administer IM
4, No antidote (indirect inhibition)
111
What is monitored on fondaparinux?
1. platelets
2. Hgb
3. Scr
4. anti-Xa levels (one time 3 hours post-dose; does not have to be routine)
112
How should fondaparinux pre-filled syringes be stored?
room temperature
113
What drugs interact with all factor Xa inhibitors?
medications that increase bleeding risk:
NSAIDs
antiplatelet drugs
SSRI/SNRIs
fibronolytics
Cobicistat-containing products can increase exposure of factor Xa inhibitors:
Tybost
Stribild
Genvoya
114
What drugs should be avoided with apixaban (major CYP3A4 and P-gp substrate) due to drug interaction?
strong dual CYP3A4 and P-gp inducers:
1. carbamazepine
2. phenytoin
3. rifampin
4. st.johns wart
115
What drugs interact with apixaban requiring doses >2.5 mg BID to be reduced by 50% AND should be voided in those taking 2.5mg BID (major CYP3A4 and P-gp substrate)?
strong dual CYP3A4 and P-gp inhibitors:
1. itraconazole
2. ketoconazole
3. ritonavir
116
What drugs should be avoided with rivaroxaban (major CYP3A4 and P-gp substrate) due to drug interaction?
strong dual CYP3A4 and P-gp inducers:
1. carbamazepine
2. phenytoin
3. rifampin
4. st.johns wart
strong dual CYP3A4 and P-gp inhibitors:
1. itraconazole
2. ketoconazole
3. ritonavir
117
What drugs must provide benefit over risk in patients taking rivaroxaban (major CYP3A4 and P-gp substrate) due to drug interaction??
patients with CrCl 15-80 and receiving combined P-gp and moderate CYP3A4 inhibitors:
1. diltiazem
2. verapamil
3. dronedarone
4. erythromycin
118
What medication should be avoided with edoxaban? (P-gp substrate)
rifampin
119
What drugs interact with edoxaban requiring dose reduction to 30mg QD when treating DVT/PE?
1. verapamil
2. macrolides (azithromycin, clarithromycin, erythromycin)
3. oral itraconazole/ketoconazole
120
How is warfarin converted to other oral anticoagulants?
D/C warfarin and start other when:
Rivaroxaban when INR<3
Edoxaban when INR≤2.5
Apixaban when INR <2
Dabigatran when INR <2
121
How are rivaroxiban and apixiban converted to warfarin?
1. stop factor Xa inhibitor
2. start parenteral anticoagulant and warfarin at next scheduled dose
122
How is edoxaban converted to warfarin?
refer to package labeling for conversion recommendations
123
How is dabigitran converted to warfarin?
start warfarin 1-3 days before stopping dabigatran (determined by renal function- refer to dabigatran labeling)
124
What is the MOA of direct thrombin inhibitors?
directly inhibit thrombin ( factor IIa); bind to active site of free and clot-associated thrombin
125
What are boxed warnings for dabigatran?
1. patients reciving neuraxial anesthesia (epidural/spinal) or spinal puncture are at risk of hematomas and subsequent paralysis
2. premature discontinuation increases risk of thrombotic events
126
What are CIs wth dabigatran?
1. active pathological bleeding
2. treatment of patients with mechanical heart valve
127
What are the warnings with dabigitran?
1. not recommended for triple-positive antiphospholipid syndrome
2. can increase aPTT, PT/INR
3. discontinue if undergoing invasive surgery (1-2 days if CrCl≥50 or 3-5 days of CrCl<50)
128
What are SEs with dabigitran?
1. dyspepsia
2. gastritis-like symptoms
3. bleeding (including GI bleeding)
129
What is the dosing of dabigitran for nonvalvular AF?
150mg BID
CrCl15-30: 75mg BID
CrCl<15 avoid use
130
What is the dosing of dabigatran for the treatment and prevention of recurrent DVT/PE?
150mg BID starts after 5-10 days anticoagulation
CrCl≤30 mL/min avoid use
131
What is the dosing of dabigatran for DVT/PE prophylaxis after hip replacement?
110mg on day 1 then 220mg daily
CrCl≤30 mL/min avoid use
132
What should the patient do if they miss a dose of dabigatran?
take it immediately unless within 6 hours of the next scheduled dose; do not double the dose to make up for it
133
What are important counseling points for the storage and administration of dabigatran?
1. dispense in original container (protects capsules from moisture) and dispose of the container 4 months after opening
2. blister packs are good until the date on the pack
3. swallow capsules whole
4. do not administer capsules or pellets via NG/OG tube (increases bioavailability by 75%)
134
What is the antidote for dabigatran?
idarucizumab (Praxbind)
135
What are CIs to IV direct thrombin inhibitors (argatroban, bivalirudin)?
active major bleed
136
What are SEs with IV direct thrombin inhibitors (argatroban, bivalirudin)?
1. bleeding (mild to severe)
2. anemia
137
What is monitored with IV direct thrombin inhibitors (argatroban, bivalirudin)?
1. aPTT and/or activated clotting factor (efficacy)
2. platelets
3. Hgb
4. Hct
5. renal function
138
What is the approved indication for argatroban?
patients with HIT
139
What is the approved indication for bivalirudin?
patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI)
140
How is argatroban dosed for HIT?
initiate 2 mcg/kg/min then titrate to a goal aPTT
MAX: 10mcg/kg/min
141
How is bivalirudin dosed for HIT (or suspected)?
IV bolus followed by infusion; all weight based dosing
142
What dosage adjustments are required for renal/hepatic impairment in IV direct thrombin inhibitors (argatroban, bivalirudin)?
argatroban: decrease dose in hepatic impairment
bivalirudin: decrease dose when CrCl<30
143
What are drug interactions with dabigitran (P-gp substrate)?
1. avoid use with rifampin (or any P-gp inhibitor if CrCl<50 (CrCl<30 in nonvalvular Afib)
2. reduce dose to 75mg BID if CrCl 30-50 in nonvalvular A fib and concurrent use of dronedarone nor systemic ketoconazole
144
What is the outcome of P-gp inducers interacting with anticoagulants that are substrates of P-gp?
increased transport of drug to intestinal lumen for excretion in the feces; decreased anticoagulation effect; subtherapeutic
145
What is the outcome of P-gp inhibitors interacting with anticoagulants that are substrates of P-gp?
decreased transport of drug to intestinal lumen for excretion in the feces; increased anticoagulation effect; supratherapeutic
146
What is the outcome of P-gp and CYP3A4 inducers interacting with anticoagulants that are substrates of both enzymes?
1. increased transport of drug to be excreted in feces
2. increased CYP enzyme available to breakdown the drug
3. decreased anticoagulation effect; subtherapeutic
147
What is the outcome of P-gp and CYP3A4 inhibitors interacting with anticoagulants that are substrates of both enzymes?
1. decreased transport of drug to be excreted in feces
2. decreased CYP enzyme available to breakdown the drug
3. increased anticoagulation effect; supratherapeutic
148
What medications can increase exposure to dabigatran?
Cobicistat-containing products:
1. Tybost
2. Stribild
3. Genvoya
149
What is the MOA of warfarin?
competitively inhibits the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex --> decreases the production of active clotting factors (II, VII,IX, and X) and natural anticoagulants protein C and protein S
150
What are boxed warnings for warfarin?
major or fatal bleeding
151
What are CIs to using warfarin?
1. pregnancy (except with mechanical heart valve at risk for thromboembolism)
2. hemorrhagic tendencies
3. blood dyscrasias
4. malignant HTN
5. non compliance
6. recent or potential surgery of eyes or CNS
7. major regional lumbar block analgesia or trauma surgery resulting in large open surfaces
8. pericarditis or pericardial effusion
9. bacterial endocarditis
10. preeclampsia/eclampsia
11. possible miscarrige
152
What are warnings with warfarin?
1. tissue necrosis/gangrene
2. HIT (CI as monotherapy in initial treatment of active HIT)
3. systemic arhtroemboli and cholesterol microemboli (PURPLE TOE SYNDROME)
4. presence of CYP2C9 *2 or *3 alleles and /or polymorphism of VKORC1 gene may increase bleeding risk
153
What are SEs with warfarin?
1. bleeding/bruising
2. skin necrosis
154
What are the monitoring parameters for warfarin?
1. INR monitoring after the initial 2-3 doses, if chronic then every 4-12 weeks
2. HCT
3. Hgb
4.signs of bleeding
155
What conditions have a goal INR 2-3 (target 2.5)?
most indications:
1. VTE
2. AF
3. bioprosthetic mitral valve
4. mechanical aortic valve
5. antiphospholipid syndrome
156
What conditions have a goal INR of 2.5-3.5 (target 3)?
1. mechanical mitral valve
2. 2 mechanical heart valves
3. mechanical aortic valve with 1 additional risk factor (hx DVT, AF, hypercoagulable state)
157
Which 3x more potent enantiomer of warfarin is a substrate of CYP2C9 responsible for most drug interactions?
S-warfarin
158
What medications are CYP2C9 inhibitors that increase the INR?
1. amiodarone
2. fluconazole (other azole antifungals)
3. metronidazole
4. Bactrim
5. capecitabine
6. cimetidine
7. fluvastatin
8. tigecycline
158
What medications are CYP2C9 inhibitors that decrease the NR?
1. carbamazepine
2. phenobarbital
3. phenytoin
4. rifampin (large decrease)
5. St.John's wort
159
What medication should be avoided with warfarin?
1. tamoxifen
2. SERMs
3. estrogens
4. drugs that increase clotting risk
160
How much should the warfarin dose be reduced when starting amiodarone?
30-50%
161
What other medications can increase the effect of the anticoagulant effect of warfarin?
1. PCNs
2. quinolones
3. tetracyclines
4. some cephalosporins
162
What are pharmacodynamic drug interactions with warfarin?
1. NSAIDs, antiplatelet agents, other anticoagulants, SSRI/SNRI may increase bleeding risk without increasing INR
2. drugs that increase clotting risk should be avoided when possible (estrogen, SERMs)
3. drugs that are highly protein bound may displace warfarin
163
What natural/ herbal supplements can increase bleeding risk without increasing INR?
1. 5Gs (garlic, ginger, ginkgo, ginseng, glucosamine)
2. Vitamin E
3. chondroitin
4. dong quai
5. high doses of fish oils
6. Willow bark (a plant salicylate)
164
What natural/herbal supplements decrease the effectiveness of warfarin?
1. St. John's wort
2. coenzyme Q10
3. green tea
165
What foods are high in vitamin K?
1. spinach (cooked)
2. broccoli
3. brussel sprouts
4. collard greens
5. kale
6. green onion
7. parsley
8. swiss chard
9. turnip greens
10. endive
166
What warfarin tablet color corresponds to what dose?
pink (1 mg)
lavender (2mg)
green (2.5)
brown (3mg)
blue (4mg)
peach (5mg)
teal (6mg)
yellow (7.5mg)
white (10mg)
167
What is typical dosing of warfarin for healthy outpatients?
≤10mg QD for the first 2 days then adjust based on INR
168
In what patients should lower starting doses ≤ 5mg of warfarin be used?
1. elderly
2. malnourished
3. liver disease
4. HF
5. high risk of bleeding/other drugs that increase bleeding risk
169
When should warfarin be started when a patient is being bridged from a parenteral anticoagulant for DVT/ PE treatment?
start warfarin while the patient is still on a parenteral anticoagulant; continue both anticoagulants for a minimum of 5 days and until the INR ≥2 for at least 24 hours
170
If a patient with a stable therapeutic INR has a single low INR what should and should not be done?
Should: continue current dose and obtain repeat INR in 1-2 weeks if ≤0.5 below or above the therapeutic range
Should not: bridge with UFH or LMWH
171
What dental procedure can be done without D/C warfarin?
1. general cleaning
2. single tooth extraction
172
Why would anticoagulation need to be reversed?
1. life-threatening bleed
2. surgery
173
What is the MOA of protamine for heparin and LMWH reversal?
protamine binds to highly acidic heparin to form a stable salt complex, neutralizing the anticoagulation effect
174
What is the antidote for UFH/LMWH?
protamine
175
What is the dosing of protamine for IV UFH reversal?
1mg protamine --> reverses ~100 units heparin; reverse the amount of heparin given within the last 2-2.5 hours due to short half-life
MAX dose 50mg
176
What is the dosing of protamine for LMWHs?
1. enoxaparin given within 8 hours: 1mg protamine --> 1mg enoxaparin
2. enoxaparin given >8 hours ago: 0.5mg protamine per 1mg enoxaparin
3. 1 mg protamine per 100 anti-xa units of dalteparin
177
What are boxed warnings for protamine sulfate?
1. hypersensitivity
2. hypotension
3. cardiovascular collapse
4. non-cardiogenic pulmonary edema
5. pulmonary vasoconstriction
178
what are SEs with protamine sulfate?
1. hypotension
2. bradycardia
3. flushing
4. anaphylaxis
179
What are important administration warnings with protamine?
rapid IV infusion causes hypotension; administer slow IV push (max rate 50mg over 10 min)
180
What is used for the reversal of rivaroxaban and apixaban (and off-label for other Xa inhibitors)?
Andexanet alfa (Andexxa)
181
What are boxed warnings with Andexxa?
1. thromboembolic risk
2. ischemic events
3. cardiac arrest
4. sudden death
182
What are SEswith Andexxa?
1. injection site reactions
2. UTI
3. pneumonia
4. antibody development
183
What is the reversal agent for dabigatran?
idarucizumab (praxbind)
184
What are boxed warnings with idarucizumab?
1. thromboembolic risk
2. adverse reactions from sorbitol excipient
185
What are SEs with idarucizumab?
1. headache
2. constipation
3. hypersensitivity reaction
186
What is dosing for idarucizumab?
5 g IV (given as two separate 2.5mg doses no more than 15 minutes apart)
187
What are reversal agents for warfarin?
1. Vitamin K/phytonadione
2. Four factor Prothrombin complex concentrate
3. Factor VII Recombinant (off-label)
4. three factor prothrombin complex concentrate (off-label)
188
What is dosing of Vitamin K for warfarin reversal?
1-10mg PO/IV
189
Vitamin K / Phytonadione
Mephton
190
Four Factor Prothrombin Complex Concentrate (human)
Kcentra, Balfaxar
191
Three Factor Prothrombin Complex Concentrate (human)
Profilnine
192
Factor VIIa Recombinant
NovoSeven RT, Sevenfact
193
What are boxed warnings for vitamin K (phytonadione)?
severe reactions resembling hypersensitivity reactions have occurred rarely during or immediately after IV (even with proper dilution and rate of administration <1mg/min)
194
What are SEs with vitamin K (phytonadione)?
1. anaphylaxis
2. flushing
3. rash
4. dizziness
195
What is important with vitamin K (phytonadione) administration?
1. requires light protection during administration
2. SQ route not recommended due to variable absorption
3. IM not recommended due to hematoma risk
4. orlistat and mineral oil decrease oral vit K concentrations
196
What is contained in Four Factor Prothrombin Complex Concentrate (human)?
1. factor II
2. factor VII
3. factor IX
4. factor X
5. protein S
6. protein C
197
What are boxed warnings with Four Factor Prothrombin Complex Concentrate (human)?
arterial and venous thromboembolic complications have been reported
198
What are CIs with Four Factor Prothrombin Complex Concentrate (human)?
1. known HIT (contains heparin)
2. disseminated intrvascualr coagulation (DIC with Kcentra only)
3. IgA deficiency with antibodies to IgA (Balfaxar only)
199
What are SEs with Four Factor Prothrombin Complex Concentrate (human)?
1. headache
2. N/V/D
3. asthenia
4. hypotension
5. hypokalemia
6. thrombotic events
200
What is important about administration of Four Factor Prothrombin Complex Concentrate (human)?
1. administer with vitamin K
2. do not let drug back up into line it will clot
3. allow to reach room temperature prior to administration if refrigerated
4. each vial can have a different potency of multiple coagulation factors; actual potency stated in vial
201
What are warnings with Three Factor Prothrombin Complex Concentrate (human)?
1. contains factors II, IX, and X but low or nontherapeutic levels of VII and should not be confused with Kcentra that contains therapeutic amounts of VII
2. made from human blood and may carry risk for transmitting infectious agents (virus)
202
What are SEs with Three Factor Prothrombin Complex Concentrate (human)?
1. chills
2. fever
3. flushing
4. nausea
5. headache
6. risk of thrombosis
203
What is important with administration of Three Factor Prothrombin Complex Concentrate (human)?
1. administer with vitamin K
2. administer via slow infusion and give antihistamine to minimize SEs
3. given with fresh frozen plasma or factor VIIa
204
What are boxed warnings for factor VIIa recombinant?
serious thrombotic events are associated with the use of factor VIIa
205
What should be done if INR is above the therapeutic range but <4.5 without bleeding?
reduce or skip warfarin dose; resume when INR is therapeutic
206
What should be done if INR is 4.5-10 without active bleeding?
routine use of vitamin K not recommended; hold 1-2 warfarin doses and monitor INR; resume at lower dose
Oral vitamin K can be used if urgent surgery is needed(≤5mg then 1-2mg in 24 hours prn) or bleeding risk is high (1-2.5mg)
207
What should be done if INR> 10 without bleeding?
hold warfarin, give oral vitamin K 2.5-5mg, and monitor INR; resume at lower dose
208
What should be done if INR> 10 with bleeding?
hold warfarin, give vitamin K 5-10mg slow IV injection and four-factor prothrombin complex concentrate (PCC)
209
Why is four-factor prothrombin complex concentrate (PCC) preferred over fresh frozen plasma for warfarin reversal?
1. less allergic reaction
2. less infection risk
3. less preparation time
4. quicker onset
5. lower volume
210
How long before major surgery should warfarin be stopped?
5 days
211
Which patients should have bridge therapy with therapeutic UFH or LMWH while off warfarin prior to surgery and after restarting warfarin for 5 days?
1. mechanical heart valve
2. atrial fibrillation
3. VTE
4. at high risk for thromboembolism
212
How long before surgery should therapeutic doses of SQ LMWH be discontinued?
24 hours
213
How long before surgery should therapeutic doses of IV heparin be discontinued?
4-6 hours
214
When should warfarin be restarted after surgery?
12-24 hours after surgery or adequate hemostasis
215
What should be done if INR is elevated 1-2 days before surgery?
give low dose vitamin K 1-2 mg
216
What should be done if an urgent reversal of warfarin is required for a procedure?
give low dose 2.5-5mg vitamin K PO/IV
217
What are symptoms of DVT?
1. pain
2. unilateral leg swelling
218
What are symptoms of a PE?
1. chest pain
2. shortness of breath
219
How is DVT diagnosed?
1. ultrasound/ MRI/venography
2. D-dimer
220
How is PE diagnosed?
pulmonary CT angiogram
221
What are modifiable VTE risk factors?
1. acute medical illness
2. immobility
3. medications (SERMs, ESA, estrogen)
4. obesity (BMI≥30)
5. pregnancy/postpartum
6. recent surgery/trauma
222
What are non-modifiable risk factors?
1. increasing age (>40 surgical, >70nonsugical)
2. cancer/chemo
3. previous VTE
4. inherited or acquired thrombophilia
5. disease states (HF, nephrotic syndrome respiratory failure)
223
What are non-drug alternatives to prevent VTE?
1. intermittent pneumatic compression (IPC devices)
2. graduated compression stockings
224
What is recommended for long-distance travelers to prevent VTE?
1. frequent ambulation
2. calf muscle exercises
3. sitting in the aisle seat
4. use graded compression stockings with 15-30 mmHg at the ankle during travel
225
How long should full-dose treatment of VTE last?
3 months
226
What patients is extended VTE treatment at full or reduced dose of anticoagulants recommended?
1. unprovoked VTE and low bleeding risk
2. ≥ 2 unprovoked VTE episodes
227
What medications are contraindicated in patients with a history of or current VTE?
estrogen-containing medications and SERMS
228
What anticoagulants are preferred for the first 3 months of VTE treatment in patients without cancer?
1. dabigatran
2. oral Xa inhibitors
229
What anticoagulants are preferred for the first 3 months of VTE treatment in patients with cancer?
oral Xa inhibitors
230
What is recommended in patients with unprovoked VTE who are stopping anticoagulation?
aspirin if not CI
231
Why is stroke prevention important in those with AF?
clots in the heart (left atrial thrombus) that can travel to the brain and cause cardioembolic stroke or TIA
232
233
How is the need for chronic anticoagulation for AF determined?
based on stroke risk; CHA2DS2VASc scoring system
233
When is temporary anticoagulation utilized in AF?
patients undergoing cardioversion
234
What is the target INR when using warfarin as anticoagulation prior to cardioversion?
2-3
234
How long do patients with AF ≤ 48 hours undergoing elective cardioversion need anticoagulation?
start full anticoagulation at presentation, perform cardioversion, and continue full anticoagulation for at least 4 weeks while in normal sinus rhythm
234
What AF patients have the highest risk of clotting/stroke?
patients with a mechanical heart valve and AF
234
How long do patients with AF < 48 hours or unknown duration need anticoagulation for cardioversion?
at least 3 weeks prior to and 4 weeks after cardioversion (when normal sinus rhythm is preferred?
235
Which AF patient should only recieve warfarin for anticoagulation?
1. mechanical heart valve
2. mitral stenosis
235
What is the most common type on AF?
nonvalvular; no heart valve involvement
235
How is CHA2DS2VASc score calculated?
C: CHF- 1pt
H: HTN- 1pt
A2: age ≥75- 2pt
D: diabetes- 1pt
S2: prior stroke history- 2pt
V: vascular disease (MI, PAD, aortic plaque)- 1pt
A: age <75- 1pt
Sc: sex category, female sex- 1pt
236
What CHA2DS2VASc score is anticoagulation not recommended?
0- male
1-female
237
What CHA2DS2VASc score is anticoagulation recommended if the patient has additional risk facotrs?
1- male
2- female
238
What CHA2DS2VASc score are DOACs recommended due to high stroke risk?
≥2- male
≥3- female
239
What is the HAS-BLED scoring system used for?
assesses bleeding risk in patients requiring anticoagulation for stroke prevention in AF; should be compared with CHA2DS2VASc score to make a individualized decision to anticoagulant
240
How is HAS-BLED score calculated?
H: HTN (SBP>160)- 1pt
A: abnormal liver/kindey function- 1-2 pt
S: prior stroke- 1pt
B: bleeding tendency/predisposition- 1pt
L: labile INR (if on warfarin)- 1pt
E: elderly age >65- 1pt
D: drugs (aspirin, NSAIDs), excess alcohol use- 1-2 pts
241
What anticoagulant agents are preferred in pregnancy?
LMWH
242
What should be done if warfarin is utilized during pregnancy?
1. can switch from LMWH to warfarin after the 13th week of pregnancy (do not use warfarin during the 1st trimester)
2. switch back to LMWH closer to delivery
243
What is recommended to be monitored during pregnancy when using LMWHs?
anti-Xa levels
244
What agents have not been studied in pregnancy and should not be used?
1. oral factor Xa inhibitors
2. direct thrombin inhibitors
245
What are key counseling points for all anticoagulants?
1. can cause serious/life-threatening bleeding/bruising
2. tell physician/dentist before any procedure is performed
3. call provider if you fall, injury, or hit your head
4. avoid alcohol
5. many drug interactions
246
What are key counseling points for dabigatran?
1. take with a full glass of water, and swallow the capsule whole
2. can cause dyspepsia
3. only open 1 bottle of dabigatran at a time; use within 4 months of opening
4. keep dabigatran in the original bottle or blister package; do not put in pill boxes
5. if your next dose is < 6 hours away, skip the missed dose
247
What are key counseling points for rivaroxaban?
1. AF: take once daily with evening meal
2. blood clots in the veins of the legs or in the lungs : take Qd or BID as prescribed with food at the same time every day
3. if taken twice daily, can double up on missed dose
248
What are key counseling points for SQ administration of enoxaparin?
1. choose an area on the right or left side of your abdomen, at least 2 inches from the belly button
2. wash your hands and clean the site
3. remove the needle cap by pulling straight of the syringe; DO NOT twist the cap, can bend needle
4. DO NOT expel air bubble from the syringe unless advised to do so by healthcare provider
5. hold the syringe like a pencil, pinch an inch of skin fold, insert full length of needle at 90 degree angle
6. press plunger with your thumb until syringe is empty
7. pull needle straight out at the same angle and release skin fold
8. point needle down, away from yourself and push down on the plunger to activate the safety
9. Do NOT rub the site of injection, can lead to brusing
10. place used syringe in sharps container
249
What are key counseling points for warfarin?
1. take at the same time everyday
2. Ask your pharmacist if your tablet looks different
3. can rarely cause purple toe syndrome or death of skin tissue (with pain)
4. frequent blood monitoring required (INR)
5. keep vitamin K intake consistent
