34. Anticoagulation Flashcards
T/F: Anticoagulants break down clots
False - they prevent blood clots from forming and keeping existing clots from getting bigger but do not break down clots
What can cause blood clots for form?
Blood vessel injury, blood stasis (stopping/slowing of blood flow) and prothrombotic conditions
What part of the coagulation cascade do UFH/LMWH (enoxaparin, dalteparin) work on?
Xa and thrombin IIa via antithrombin
UFH: equal anti-Xa and anti-thrombin IIa activity
LMWH: most anti-Xa activity than IIa
What part of the coagulation cascade does warfarin work on?
Inhibits factors II, VII, IX, and X
What part of the coagulation cascade do rivaroxaban, apixaban, edoxaban work on?
Xa (direct inhibitor)
What part of the coagulation cascade does argatroban (IV), bivalirudin (IV), dabigatran (PO) work on?
Thrombin IIa
What part of the coagulation cascade does fondaparinux work on?
Xa (indirect inhibitor) via antithrombin
DOACs are generally preferred for stroke prevention in Afib but if _______, use warfarin
mod-severe mitral stenosis or mechanical heart valve
DOACs are generally preferred for VTE treatment but if _____, use warfarin
antiphospholipid syndrome or mechanical heart valve
Compare DOACs vs warfarin in terms of DDIs, bleeding risk, and duration of action
DOACs have less DDIs, less or comparable bleeding risk, and shorter duration of action compared to warfarin
_____ do not cross-react with heparin-induced thrombocytopenia (HIT) antibodies
IV direct thrombin inhibitors (argatroban, bivalirudin)
T/F: all anticoagulants can cause significant bleeding and are classified as “high-alert” meds by ISMP
True
An acute drop in ___ (e.g. ≥ 2g/dL) could signify that bleeding is occurring (visible or not)
Hgb
UFH MOA
binds to antithrombin and accelerates its ability to inactivate thrombin (factor IIa) and factor Xa and prevents conversion of fibrinogen to fibrin
UFH dosing for VTE ppx
5000 units SC Q8-12H
UFH dosing for VTE treatment
80 units/kg IV bolus; 18 units/kg/hr infusion
Note: use TBW for dosing
UFH dosing for ACS/STEMI
60 units/kg IV bolus; 12 units/kg/hr infusion
Note: use TBW for dosing
Side effects of UFH
bleeding, thrombocytopenia, HIT, hyperkalemia, osteoporosis (long-term use), alopecia
Monitoring for UFH
aPPTT or anti-Xa level - check 6 hrs after initiation and q6h after therapeutic
aPPT therapeutic range is 1.5-2.5x control (depends on institution)
Platelets, Hgb, Hct at baseline and daily (decrease in platelets >50% from baseline suggests possible HIT)
Note: aPTT and anti-Xa monitoring not required for SC (VTE ppx)
Antidote of UFH
Protamine
Why is UFH continuous IV infusions common for treating VTE and ACS?
Short half-life (1.5hrs)
Why should UFH not be given IM?
hematoma risk
Heaprin lock-flushes (HepFlush) are only used to ___. Fatal errors, especially in neonates have occured when incorrect heparin strength (higher conc) was chosen.
Heparin injection 10,000 units/mL vs flushes 10 or 100 units/mL.
keep IV lines open
LMWH MOA
bind to antithrombin and accelerate ability to inactivate factor Xa and IIa
Anti-factor Xa activity»_space;» anti-factor IIa activity
Enoxaparin (Lovenox) dosing for VTE ppx
30 mg SC Q12H or 40mg SC daily
CrCl < 30: 30 mg SC daily
Note: use TBW for dosing
Enoxaparin (Lovenox) dosing for VTE treatment and UA/NSTEMI
1mg/kg SC Q12H or 1.5 mg/kgSC daily (only for inpatient VTE treatment)
CrCl < 30: 1mg/kg SC daily
Note: use TBW for dosing
Enoxaparin (Lovenox) dosing for STEMI treatment in pts <75 yo
30 mg IV bolus + 1mg/kg SC dose followed by 1 mg/kg SC Q12H (max 100mg for first 2 SC doses only)
CrCl < 30: 30mg IV bolus + 1mg/kg SC dose, followed by 1mg/kg SC daily
Note: use TBW for dosing
Enoxaparin (Lovenox) dosing for STEMI treatment in pts ≥75 yo
No bolus, 0.75mg/kg SC Q12H - max 75mg for first 2 SC doses only
CrCl < 30: 1mg/kg/ SC daily, no bolus
Note: use TBW for dosing
Boxed warnings for enoxaparin (Lovenox)
Pts receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
Contraindications for enoxaparin (Lovenox)
Hx of HIT, active major bleed, hypersensitivity to pork
Side effects for enoxaparin (Lovenox)
bleeding, anemia, injection site reactions (e.g. pain, bruising, hematomas), decreased platelets (thrombocytopenia, including HIT)
Monitoring for enoxaparin (Lovenox)
Platelets, Hgb, Hct, SCr
More predictable anticoag response than UFH
Does not require anti-Xa level monitoring in most cases but recommended in pregnancy
May be useful to monitor in renal insufficiency, obestiy, low body weight, peds, elderly
Optain peak anti-Xa levels 4 hrs post SC dose
Antidote for enoxaparin (Lovenox)
Protamine
T/F: before self-administering Lovenox, you should expel the air bubble from syringe to reduce pain from injecting
False - do not expel air bubble for syringe prior to injection (can cause loss of drug)
T/F: Lovenox should be refrigerated
False - room temp
What kind of reaction is HIT?
Immune-mediated IgG drug reaction
The immune system forms antibodies against heparin bound to platelet factor 4 (PF4) »_space; antibodies join and creates complex > complex binds to the Fc receptors on platelets»_space; platelet activation
HIT is a ____ state and if left untreated, can cause many complications including heparin-induced thrombocytopenia and thrombosis (HITT). Can lead to amputations, post-thrombotic syndrome and/or death
prothrombotic
Probability of HIT can be assessed by calculating 4 Ts score which is based on ____
Thrombocytopenia: unexplained >50% drop in platelet count from baseline
Timing of platelet count drop: typical onset of HIT is 5-10 days after start of heparin or within hrs if pt has been exposed to heparin within past 3 months
Thrombosis
Other causes: ruling out other probable causes of HIT increases likelihood of diagnosis
If HIT is suspected or confirmed, what should you do?
Stop all forms of heparin and LMWH (including heparin flushes and heparin-coated catheters)
If pt is on warfarin and d/x with HIT, warfarin should be d/c and vit K should be administered
For immediate tx of HIT, rapid-acting non-heparin anticoag (e.g. ___) are to be used
Argatroban
After HIT is suspected/confirm, do not start warfarin therapy until the platelets have recovered to ≥ _____. Warfarin should be initiated at lower doses (5mg max) and overlap with non-heparin anticoag for minimum of ______ and until INR is within target range for at least _____
150,000 cells/mm3
5 days
24 hrs
If HIT is suspected/confirmed and urgent cardiac surgery or PCI is required, ___ is preferred anticoag
Bivalirudin
Apixaban (Eliquis) dose for nonvalvular AFib (stroke ppx)
5mg PO BID
If pt has at least 2 of the folloiwng: age ≥80 yo, weight ≤60kg, or SCr ≥1.5, then give 2.5mg BID
Apixaban (Eliquis) dose for DVT/PE treatment
Initial 10mg PO BID x 7 days then 5mg PO BID
Rivaroxaban (Xarelto) doses ≥ ___ hsould be taken with food
15mg
Rivaroxaban (Xarelto) dose for nonvalvular Afib (stroke ppx)
CrCl > 50: 20mg PO daily with evening meal
CrCl 15-50 :15mg PO daily with evening meal
CrCl < 15: avoid use
Rivaroxaban (Xarelto) dose for DVT/PE Treatment
Initial: 15mg PO BID x21 days, then 20 mg PO daily with food
CrCl <30: avoid use
Pt is on rivaroxaban (Xarelto) 15mg BID but missed their dose. What do you recommend?
Take immediately to ensure intake of 30mg/day (two 15mg tabs may be taken at once) then resume regular schedule on the following day
Pt is on rivaroxaban (Xarelto) 10, 15, or 20mg daily but missed their dose. What do you recommend?
take immediately on the same day, otherwise skip
Which oral direct factor Xa inhibitor should not be used for nonvalvular afib (stroke ppx) if CrCl > 95?
Edoxaban (Savaysa)
Edoxaban (Savaysa) dose for DVT/PE treatment
60mg daily - start after 5-10 days of parenteral anticoagulation
Boxed warnings for oral direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)
Pts receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
Premature d/c increases risk of thrombotic events
Edoxaban only: reduced efficacy in nonvalvular afib pts with CrCl > 95 (do not use)
Contraindications for oral direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)
active pathological bleeding
Monitoring for oral direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)
Hgb, Hct, SCr, LFTs
No monitoring of efficacy required
Antidote for apixaban (Eliquis) and rivaroxaban (Xarelto)
andexanet alfa (Andexxa)
Contraindications of fondaparinux (Arixtra)
Severe renal impairment CrCl <30
Others: active major bleed, bacterial endocarditis, thrombocytopenia with positive test for anti-platelet antibodies in presence of fondaprinux
Apixaban is a substrate of CYP3A4 and P-gp. Avoid use with strong dual inducers of CYP3A4 and P-gp such as ___
carbamazepine, phenytoin, rifampin, St. John’s wort
Apixaban is a substrate of CYP3A4 and P-gp. Avoid use with strong dual inducers of CYP3A4 and P-gp such as ___ or combined P-gp and strong CYP3A4 inhibtors such as ____
carbamazepine, phenytoin, rifampin, St. John’s wort
ketoconazole, itraconazole, lopinavir/ritonavir, tironavir, conivaptan
If switching from warfarin to rivaroxaban, stop warfarin and switch when INR is ____
INR < 3
If switching from warfarin to edoxaban, stop warfarin and switch when INR is ____
INR ≤ 2.5
If switching from warfarin to apixaban, stop warfarin and switch when INR is ____
<2
If switching from warfarin to dabigatran, stop warfarin and switch when INR is ____
<2
If switching from oral Xa inhibitors (apixaban, rivaroxaban, edoxaban) to warfarin, what should you do?
Stop Xa inhibitor. start parenteral anticoag and warfarin at next scheduled dose
Edoxaban only: refer to package labeling for conversion recs
If switching from dabigatran to warfarin, what should you do?
start warfarin 1-3 days before stopping dabigatran (determined by renal function, refer to dabigatran labeling)
Dabigatran (Pradaxa) dose for DVT/PE treatment and reduction in risk of recurrent DVT/PE
150mg BID, start after 5-10 days of parenteral anticoagulation
Antidote for dabigatran (Pradaxa)
Idarucizumab (Praxbind)
Which PO anticoag must be dispensed in original container and discard 4 months after opening?
Dabigatran (Pradaxa)
T/F: dabigatran can be crushed and administered by NG tube if necessary
False - swallow capsules whole (do not break, chew, crush, or open) // do not administer by NG tube
Dabigatran (Pradaxa) side effects
dyspepsia, gastritis-like symptoms, bleeding (including GI bleeding)
Contraindications of dabigatrain (Pradaxa)
Active pathological bleeding, tx of pts with mechanical prosthetic heart valves
What is the antidote for IV direct thrombin inhibitors (argatroban, bivalirudin (Angiomax))
No antidote
What anticoag have boxed warning for pts receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture d/t risk of hematomas and subsequent paralysis?
PO direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)
enoxaparin
Fondaparinux
Dabigatran (Pradaxa)
Warfarin MOA
competitively inhibits the C1 subunit of the multi-unit vit K epoxide reductase (VKORC1) enzyme complex»_space; reduces regeneration of vit K epoxide and causes depletion of active clotting factors II, VII, IX, and X and anticoagulants protein C and S
Warfarin (Jantoven, Coumadin) dosing
Health outpatients ≤ 10mg daily for first 2 days, then adjust dose per INR
Lower doses (≤ 5mg) for elderly, malnourished, taking drugs which can increased warfarin levels, liver disease, Hf, or high risk of bleeding
Warfarin (Jantoven, Coumadin) is contraindicated in pregnancy except with ____
mechanic heart valves at high risk for thromboembolism
Warfarin (Jantoven, Coumadin) and presence of CYP2C9 ____ alleles and/or polymorphism of ____ gene may increase bleeding risk
*2 or *3
VKORC1 gene
Side effects of warfarin (Jantoven, Coumadin)
bleeding/bruising (mild to severe), skin necrosis, purple toe syndrome
Goal INR is 2-3 (target 2.5) for most indications. INR 2.5-3.5 (target 3) is for high-risk indications such as ____
mechanical mitral valve
2 mechanical heart valves or mechanical aortic valve with 1 additional risk factor (e.g. previous DVT, Afib, hyper-coagulable state)
S-warfarin is primarily metabolized via CYP ___ and R-warfarin is primarily metabolized via CYP___.
S-warfarin: CYP2C9
R-warfarin: CYP3A4
Which enantiomer is 3-5x more potent than the other enantiomer?
S-warfarin > R-warfarin
Hence why DDIs with CYP2C9 has greater impact on anticoag effect
Antidote of warfarin (Jantoven, Coumadin)
vit K
CYP2C9 inducers that can decrease INR include ___
carbamazepine, phenobarbital, phenytoin, rifampin (large drop in INR) and St. John’s wort
CYP2C9 inhibitors that increase INR include ____
amiodarone, azole antifungals (e.g. fluconazole, keotoconaozle, voriconazole), capcitabine, cimetidine, fluvastatin, fluvoxamine, metronidazole, tamoxifen, igecycline, TMP/SMX and zafirlukast
When starting amiodarone, dose of warfarin should be decreased by ___
30-50%
T/F: Use of NSAIDs, antiplatelet agents, other anticoags, SSRI/SNRIs can increase INR (therefore bleeding risk)
False - they increase bleeding risk but may not increase INR
When using warfarin, drugs that increase clotting risk such as ___ should be d/c if possible
Estrogen and SERMs
What dietary supplements can increase bleeding risk when used with warfarin?
Chamomile, chondroitin, dong quai, high doses of fish oils, 5 Gs (garlic, ginger, ginkgo, ginseng, glucosamine), vit E, and willow bark
What foods have high vit K and cause decrease in INR?
spinach (cooked), broccoli, brussel sprouts, collard greens, kale, turnip greens, green onion, swiss chard, endive, parsley
Others: asparagus, cabbage, canola oil, cauliflower, coleslaw, lettuce (red leaf or butterhead), watercress, some teas
Warfarin tablet colors
Please Let Greg Brown Bring Peaches To Your Wedding
Pink - 1mg
Lavender - 2mg
Green - 2.5mg
Brown/Tan - 3mg
Blue - 4mg
Peach - 5mg
Teal - 6mg
Yellow - 7.5mg
White - 10mg
Pt has acute DVT/PE and doctor wants to start warfarin. What do you recommend?
Start warfarin on the same day as parenteral anticoag (e.g. enoxaparin or UFH) and continue both anticoags for minimum of 5 days and until INR is ≥2 for at least 24h (2 consecutive days)
For pts with consistently stable INRs on warfarin, INR testing can be up to every ____ instead of monthly
every 12 weeks
For IV UFH reversal, what is the dose of protamine
1mg protamine will reverse ~100 units of heparin
Since UFH has very short half-life, reverse amt of heparin given in the last 2-2.5 hrs
Max dose: 50mg
What is the max dose of protamine
50mg
For LMWH reversal, what is the dose of protamine
Enoxaparin given within last 8 hrs: 1mg protamine per 1 mg of enoxaparin
Enoxaparin given >8 hrs ago: 0.5mg protamine per 1 mg of enoxaparin
Vit K or phytonadione (Mephyton) formulations
PO or IV
SC not recommended d/t variable absorption
IM not recommended d/t risk of hematoma
Side effects of Vit K or phytonadione (Mephyton) for warfarin reversal
anaphylaxis, flushing, rash, dizziness
Boxed warnings of Vit K or phytonadione (Mephyton) for warfarin reversal
severe reactions resembling hypersensitivity reactions (e.g. anaphylaxis) - rare
Four factor prothrombin complex concentrate (Human) (KCentra) should be administered with ___
vit K
Four factor prothrombin complex concentrate (Human) (KCentra) works on ___
factors II, VII, IX, X, protein C and S
What are off label options for warfarin reversal?
Three factor prothrombin complex concentrate (Human) (Profilnine)
Factor VIIa recombinant (NovoSeven RT, Sevenfact)
What formulation of vit K is preferred for reversal in pts without significant or major bleeding?
Oral vit K (generally doses of 2.5-5mg)
IV vit K should only be used if pt is experiencing serious bleeding
Infuse slowly d/t risk of anaphylaxis
Pt on warfarin INR is above therapeutic range but < 4.5 without bleeding. What do you do?
Reduce or skip warfarin dose. Monitor INR
Pt on warfarin INR is supratherapeutic 4.5-10 without bleeding. What do you do?
Hold 1-2 doses of warfarin. monitor INR
Routine use of vit K is not recommended if no evidence of bleeding
Pt on warfarin INR >10 without bleeding. What do you do?
Hold warfarin
Give oral vit K 2.5-5mg even if not bleeding
Monitor INR, resume warfarin at lower dose when INR therapeutic
Pt on warfarin experiencing major bleeding. What do you do?
Hold warfarin
Give IV vit K 5-10mg by slow injection and four-factor prothrombin complex concentrate (PCC)
PCC suggested over fresh frozen plasma (FFP) d/t risk of allergic reactions, infection transmission, longer prep time, slower onset, and higher volume
Stop warfarin ____ before major surgery
~5 days
Pt is on warfarin and has mechanical heart valve, Afib, or VTE at high risk of thromboembolism, ___ is recommended when stopping warfarin for surgery.
LMWH or UFH (bridge)
D/C therapeutic-dose SC LMWH ___ before surgery
24 hrs
Note: UFH IV thearpy can be stopped 4-6 hr before surgery
T/F: All pts d/c warfarin prior to surgery should be bridged with LMWH or UFH d/t clotting risk
False - not required for pts at low risk of thromboembolism
Symptoms of DVT
pain in affected limb and unilateral lower extremity swelling
DVTs can be diagnosed with ___
ultrasound (or MRI or venography in some cases)
D-dimer lab test can aid in diagnosis
PE suspected = pulmonary CT angiogram can dx
Modifiable risk factors for venous thromboembolism
Acute medical illness
Immobility
Medications (e.g. SERMs, drugs containing estrogen, ESAs)
Obesity (BMI ≥30)
Pregnancy and postpartum period
Recent surgery or major trauma
Non-modifiable risk factors for VTE
Increasing age
Cancer or chemotherapy
Previous VTE
Inherited or acquired thrombophilia (e.g. antithrombin deficiency, factor V Leiden, antiphospholipid syndrome, protein C or S deficiency)
Certain disease states (e.g. HF, nephrotic syndrome, respiratory failure)
If pts have contraindication to anticoags (such as active bleed) or have high risk for bleeding, what are non-drug alternatives to prevent VTE?
Intermittent pneumatic compression (IPC) devices or graduated compression stockings
What are some recommendations for long-distance travels at risk for VTE?
Frequent ambulation
calf muscle exercises
sitting in aisle seat
using graduated compression stockings with 15-30 mmHg pressure at the ankle during travel
Note: aspirin or anticoag should NOT be used just for traveling
Any VTE that is caused by surgery or a reversible risk factor should be treated for ___
3 months
VTE that is unprovoked (unknown cause) should be treated for ___
usually longer than 3 months as long as bleeding risk is low-moderate
T/F: Estrogen-containing meds and selective estrogen receptor modulators (SERMs) are contraindicated in pts with hx of or current VTE and should be d/c
True
For pts without cancer, ___ anticoag are preferred for the first 3 months of treatment for DVT
dabigatran and oral factor Xa inhibitors»_space; warfarin
For pts with cancer, ___ anticoag are preferred
oral factor Xa inhibitors are preferred over other oral anticaogs and LMWH
If Afib > 48 hrs or unknown duration: anticoag for at least ___ prior to and after cardioversion (when normal sinus rhythm is restored)
If using warfarin, target INR of ___
3 weeks
4 weeks
INR goal 2-3
If Afib ≤ 48 hrs and undergoing elective cardioversion: start full therapeutic anticoagulation at presentation, perform cardioversion, and continue full anticoag for at least ____ while pt is in normal sinus rhythm
4 weeks
What types of patients have highest risk for clotting/strokes?
Pts with Afib and mechanical heart valves - treat with warfarin only
Factor Xa inhibitors and DTIs are not approved for this population
If CHA2DS2-VASC score is 0 (males) or 1 (females), what do you recommend for afib stroke ppx therapy
Risk of stroke is low
No anticoag recommended
If CHA2DS2-VASC score is ≥ 1(males) or ≥ 2 (females), what do you recommend for afib stroke ppx therapy
Risk of stroke is moderate
Oral anticoag may be considered
If CHA2DS2-VASC score is ≥ 2 (males) or ≥ 3 (females), what do you recommend for
afib stroke ppx therapy
Risk of stroke is high
Oral anticoag recommended (DOAC (apixaban, rivaroxaban, edoxaban, dabigatran) > warfarin)
What is CHA2DS2-VASC score based on?
C - CHF
H - HTN
A2 - Age ≥75 yo (worth 2 points)
D - DM
S2 - prior Stroke/TIA (worth 2 points)
V - vascular disease (prior MI, PAD, aortic plaque)
A - age 65-74 yo
Sc - sex category, female
Every category worth 1 point except Age ≥75yo and prior stroke/TIA (worth 2 points)
What is HAS-BLED score based on?
H - HTN (SBP > 160)
A - abnormal liver or kidney function (worth 1-2 points)
S - prior stroke
B - bleeding tendnecy or predisposition
L - labile INR (if on warfarin)
E - elderly (age > 65)
D - drugs (aspirin, NSAIDs), excess use of alcohol (worth 1-2 points)
Every category worth 1 point except abnormal live or kidney function and drugs (aspirin, NSAIDs) or excess use of alcohol (worth 1-2 points)
For ppx and tx of VTE in pregnant women, ___ is preferred
LMWH
Since warfarin is teratogenic, women who require chronic warfarin therapy for mechanical heart valves or inherited thrombophilias are generally converted to ___ during pregnancy. They may be switched back to warfarin after ___ week of pregnancy and then back to LMWH closer to delivery
LMWH
13th (after 1st trimester)
When LMWH is used in pregnancy, ____ monitoring is recommended
anti Xa
Where can enoxaparin SC be administered?
Right or left side of your abdomen, at least 2 inches from belly button
T/F: after administering enoxaparin you should rub the site of injection to ensure proper absorption
false - can lead to bruising, do not rub
