Anticoagulation Flashcards
What are the three factors in Virchow’s Triad that can cause thrombosis?
Altered blood flow (stasis)
Endothelial damage (trauma)
Hypercoagulable state
Which factors are Vitamin K dependent?
factor II
factor VII
factor IX
factor X
what are the contact activation and tissue factor pathways of the coagulation cascade?
Tissue Factor - initiated by trauma occurring outside of the blood vessel
Contact activation - intrinsic
These pathways come together at factor X, which begins the “Common pathway” that results in factor IIA (thrombin) and converting fibrinogen to fibrin
What is antithrombin?
Antithrombin is a natural anticoagulant. It targets Xa and IIa
What is the MOA of unfractionated heparin? How is the LMWH MOA different?
The unfractionated heparin has a long chain and binds to antithrombin, which causes a conformational change. After this change, thrombin and factor Xa can’t bind. It effects factor Xa and factor IIa (thrombin) in a 1:1 ratio.
LMWH often have shorter chains than the UFH, which results in a stronger activity towards factor Xa (inhibits factor IIa and Xa in ~1:2 ratio).
What is the dosing of unfractionated heparin for prophylaxis of VTE, treatment of VTE, and treatment of ACS/STEMI? What body weight do you use to dose?
VTE ppx: 5000 units SQ q8-12h
treatment of VTE: use TBW
- 80 units/kg IV bolus
- 18 units/kg/hr infusion
treatment of ACS/STEMI: use TBW
- 60 units/kg IV bolus
- 12 units/kg/hr infusion
Unfractionated heparin - contraindications (3), monitoring (2), antidote?
Contraindications:
- uncontrolled active bleed
- hx of HIT
- hypersensitivity to pork products
Monitoring:
- aPTT or anti Xa level - at baseline, 6 hours after initiation, and every 6 hours until therapeutic; aPTT therapeutic range is 1.5-2.5x control
- platelets, Hbg, Hct (decrease in plt >50% from baseline suggests possible HIT)
Antidote: Protamine
What is the dosing of enoxaparin for prophylaxis of VTE, treatment of VTE and unstable angina/NSTEMI, treatment of STEMI in pts < 75yo, and treatment of STEMI in pts ≥ 75yo?
What body weight do you use to dose?
VTE ppx:
- 30mg SC q12h or 40mg SC daily
- if CrCl < 30mL/min: 30mg SC daily
Treatment of VTE and unstable angina/NSTEMI: use TBW
- 1mg/kg SC q12h or 1.5mg/kg SC daily
- if CrCl < 30mL/min: 1mg/kg daily
Treatment of STEMI in pts <75yo: use TBW
- 30mg IV bolus PLUS 1mg/kg SC followed by 1mg/kg q12h
- if CrCl < 30mL/min: same as above except maintenance is 1mg/kg SC daily
Treatment of STEMI in pts > 75yo: use TBW
- 0.75mg/kg SC q12h (with no bolus)
- if CrCl < 30mL/min: 1mg/kg SC daily
enoxaparin - boxed warning, contraindications (3), monitoring (when to monitor anti Xa?), what is the reversal agent?
Boxed warning: pts receiving neuraxial anesthesia (epidural or spinal) are at risk of hematomas and subsequent paralysis
Contraindications: same at UFH
- uncontrolled active bleed
- hx of HIT
- hypersensitivity to pork products
Monitoring:
- platelets, hbg, hct, SCr
- anti Xa if extremes of body weight, reduced kidney function, pregnancy (draw peak 4 hours post SC dose)
Antidote: Protamine
What is HIT?
heparin induced thrombocytopenia - Immune mediate IgG drug reaction, which increases the risk for venous and arterial thrombosis
- leads to platelet activation and procoagulant microparticle release -> thrombosis
- at the same time, splenic macrophages are removing the platelet complexes & platelets are being consumed, resulting in thrombocytopenia
What are the components of the 4T score?
- Thrombocytopenia (>50% drop in plt)
- Time of platelet count fall (5-10 days usually or hours if heparin was received in past 3 months)
- Thrombosis
- oTher causes of thrombocytopenia
How do we manage HIT?
once HIT is suspected
- stop all heparin products
- reverse warfarin with vitamin K
- start a non-heparin anticoagulant (pt at increased risk of clot), bivalirudin preferred if urgent cardiac surgery or PCI
do not start/restart warfarin until plt ≥ 150k
Apixaban - dosing for stroke ppx in nonvalvular A fib? What is the dose reduction criteria? dosing for treatment of VTE?
Stoke ppx in AF:
- 5mg BID
- 2.5mg BID if 2/3: ≥ 80yo, ≤ 60kg, SCr ≥ 1.5
VTE treatment:
- 10mg BID for 7 days, then 5mg BID
rivaroxaban - dosing for stroke ppx in AF with CrCl dose adjustments? dosing for treatment of VTE w/ CrCl info?
Stroke ppx:
- CrCl > 50mL/min: 20mg QD w/ evening meal
- CrCl 15-50mL/min: 15mg PO w/ evening meal
- CrCl < 15mL/min: AVOID
treatment of VTE:
- 15mg BID x21 days, then 20mg QD w/ food
- CrCl <30: AVOID
edoxaban - when not to use for stroke ppx in AF? Dose in VTE treatment?
Stroke ppx in AF:
- CrCl > 95mL/min: DO NOT USE
VTE treatment:
- start 60mg PO daily AFTER 5-10 days of parenteral anticoagulation
What should patients do in they miss a dose of apixaban, edoxaban, and rivaroxaban?
apixaban/edoxaban - take missed dose immediately, then resume the schedule
- don’t double up doses at one time tho
rivaroxaban -
- 15mg BID: take immediately, CAN double up
- 10, 15, or 20mg QD: take immediately on the same day, otherwise SKIP
DOACs - boxed warnings (2), antidote for apixavan/rivaroxavan
Boxed warnings
- risk of hematoma/paralysis if receiving neuraxial anesthesia or spinal puncture
- premature discontinuation increases risk of thrombotic events
Antidote for apixavan/rivaroxaban: andexanet alfa (Andexxa)
Fondaparinux - MOA, boxed warning (1), contraindication (1)?
MOA - injectable indirect factor Xa inhibitor
Boxed warning
- risk of hematoma/paralysis if receiving neuraxial anesthesia
Contraindication
- severe renal impairment (CrCl < 30 mL/min)
What are two major drug enzyme interactions that we need to be cautious of with apixaban and rivaroxaban
CYP 450
- inducers: carbamezapine, st johns wort, rifampin
- inhibitors: azoles; may need to decrease dose or avoid all together
Pgp
How do we convert between anticoagulants -
- warfarin -> DOAC
- DOAC -> warfarin
- dabigatran -> warfarin
Warfarin -> DOAC: stop warfarin and convert to (READ)
- Rivaroxaban when INR <3
- Edoxaban when INR ≤ 2.5
- Apixaban when INR < 2
- Dabigatran when INR < 2
DOAC -> warfarin
- stop Xa inhibitor
- start parenteral anticoagulant and warfarin at next scheduled dose
dabigatran -> warfarin
- start warfarin 1-3 days before stopping dabigatran
What are the direct thrombin inhibitors? What are they indicated for?
PO: dabigatran
- treatment and prevention of VTE (after 5-10 days of parenteral anticoagulation)
- stroke ppx in non-valvular AF
- ppx of DVT/PE
IV: argatroban
- heparin-induced thrombocytopenia (HIT)
- in patients with or at risk for HIT that are undergoing PCI
IV: bivalirudin
- patients undergoing PCI, including those at risk for HIT
What are side effects of dabigatran (3)? What is the reversal agent for dabigatran? How is it dispensed? Can it be crushed? What if you miss a dose?
Side effects:
- dyspepsia
- gastritis-like symptoms
- bleeding
Antidote: idarucizumab (Praxbind)
Note
- dispense in original container and discard the bottle 4 months after opening
- swallow capsule whole (do NOT crush), can’t be used in NG tube
- take missed dose immediately unless it’s within 6 hour of the next dose
argatroban, bivalirudin - monitoring (2)? antidote?
Monitoring:
- aPTT
- kidney function (esp. bivalirudin)
Antidote: NONE
*yes, is safe for HIT
What is the MOA of warfarin? What is the order of half lives of the factors that warfarin indirectly inhibits?
- warfarin competitively inhibits epoxide reductase, which inhibits vitamin K from being activated
- without activated vit K, factors II, VII, IX, and X cannot be activated
Factor half life: (SN0T)
- 7 < 9 < 10 < 2
- proteins C & S have a shorter half life that some of the factors, which is why pts are at thrombotic risk when initiating warfarin
What types of patients should be initiated on lower doses of warfarin (<5mg)? (6)
- elderly: decreased liver function/production of vit K clotting factors
- liver disease: decreased liver function/production of vit K clotting factors
- malnourished: decreased intake of vit K
- heart failure: liver congestion, decreased clotting factor synthesis
- taking CYP inhibitors: increased warfarin serum levels
- taking select antibiotics (penicillins, cephalosporins, quinolones, tetracyclines): alteration of intestinal flora
warfarin - contraindication (1), warnings (2), side effects (2), antidote
Contraindications
- pregnancy (except if mechanical heart valve at high risk for VTE)
Warnings
- tissue necrosis/gangrene
- if pt has HIT, need to wait until plt > 150k before restarting warfarin
Side effects
- skin necrosis
- purple toe syndrome
Antidote: vitamin K
How is warfarin metabolized? What are the major inducers(5)/inhibitors(3) that interact with warfarin?
S-warfarin: CYP2C9
R-warfarin: CYP3A4, CYP1A2, CYP2C19
*S-warfarin is much more potent!!
CYP2C9 inducers (RPPCS)
- Rifampin
- Phenytoin
- Phenobarbital
- Carbamazepine
- St John’s Wort
CYP2C9 inhibitors (AAA)
- amiodardone
- Azole antifungals
- anti-infectives (metronidazole, bactrim)
What supplements can increase bleeding risk with warfarin?
chamomile
chondroitin
dong quai
high doses of fish oils
vitamin E
willow bark
5Gs: garlic, ginger, ginko, glucosamine, ginseng
What are the different warfarin tablet colors/strengths? (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
when should we reverse warfarin? When do we not need reversal?
if no bleeding:
- INR < 4.5: hold or decrease dose, resume when INR is therapeutic
- INR 4.5-10: hold 1-2 doses, resume warfarin at lower dose when INR is therapeutic
- INR > 10: hold warfarin, adminsiter 2.5-5mg PO vit K, resume warfarin at lower dose when INR is therapeutic
major bleeding: any INR
- hold warfarin
- administer IV vit K 5-10mg and 4-PCC (Kcentra)
What factors does 4-PCC contain? What is the dosing based off of?
4 factor prothrombin complex concentrate (Kcentra, Balfaxar)
factors VII, IX, X, II, protein C, and protein S
Dosing: IV dose is based on units of factor IX, the patient’s weight, and INR
- each vial has different potency of coagulation factors
**given with vit K, since the 4-PCC factors will go away eventually
vitamin K/phytonadione: boxed warnings (1), notes about administration (3)
Can be given PO or IV depending on severity
Boxed warnings
- severe reaction resembling hypersensitivity reactions after IV administration
Notes:
- SC route not recommended due to variable absorption
- IM should not be used due to risk of hematoma
- should be protected from light
When to stop LMWH or UFH bridge prior to surgery?
Stop warfarin 5 days before surgery
Stop LMWH 24 hours before surgery
Stop UFH 6hrs before surgery
Restart warfarin after surgery once bleeding has stopped
protamine - what does it reverse? how many units does 1mg of protamine reverse? How much reversal agent do we use? Max dose?
For IV UFH reversal
- 1mg protamine with reverse ~100units of heparin
- reverse the amount of heparin given in the last 2-2.5 hours
- Max dose: 50mg
For LMWH reversal
- 1mg protamine per 1mg of enoxaparin
- reverses the enoxaparin given in the last 8 hours
what is the MOA of andexanet alfa? What does it reverse?
MOA - recombinant modified human factor Xa protein. It increases the availability of factor Xa by binding to apixaban and rivaroxaban
- reverses apixaban and rivaroxaban
what is the MOA of idarucizumab? What does it reverse?
MOA - humanized monoclonal antibody fragment that binds to and reverses the effects of dabigatran
What lab test (1) and imaging (3) do we use to diagnose VTE?
lab test: D-dimer (to help rule OUT a blood clot)
imaging: ultrasound, MRI venography, pulmonary CT angiogram
How do we treat VTE?
Provoked VTE: treat for 3mo with an anticoagulant
- w/o cancer: DOACs or dabigatran preferred for the first 3 months
- w/ cancer: DOACs preferred
Discontinue estrogen containing meds, SERMS
How do we prevent VTE in pregnancy? How do we treat?
Prevention
- non-pharm: intermittent pneumatic compression devices
- pharmacologic: LMWH preferred due to favorable safety profile and can check anti Xa
Treatment:
- LMWH preferred, monitor w/ anti-Xa levels
- DOACs/direct thombin inhibitors NOT recommended
How do we manage a pregnancy patient who was on chronic anticoagulation with warfarin?
Warfarin is a teratogen, so once we see a positive pregnancy test, STOP warfarin and START LMWH
After 13 weeks, some people may restart warfarin
Close to delivery, switch back to LMWH (esp if pt may require C-section)
What do we do with anticoagulation if the patient needs to be cardioverted?
If pt has been in AF for ≤ 48 hours, cardiovert and initiate anticoagulation -> continue AC for 4 weeks
If pt has been in AF for > 48 hours, anticoagulate for 3 weeks, THEN cardiovert -> continue AC for 4 more weeks
What are the components of the CHA2DS2-VASc scoring system? When is anticoagulation recommended?
Congestive heart failure
Heart failure
Age (2 if 75+)
Diabetes
Stroke/TIA/thromboembolism (2 if yes)
Vascular disease (prior MI, PAD, aortic plaque)
Age 65-74
Sex (1 for females)
AC recommended if males ≥ 2 or females ≥ 3
- may be considered if males = 1 or females = 2
What are the components of the HAS-BLED scoring system?
Uncontrolled hypertension (>160 SBP)
Abnormal liver or kidney function
Prior stroke
Bleeding tendency/predisposition
Labile INR (if on warfarin)
Elderly (age > 65yo)
Drugs (aspirin, NSAIDS), excess alcohol use
The higher the score, the higher the risk of bleeding
