anticoags Flashcards Preview

Summer pharm 4 > anticoags > Flashcards

Flashcards in anticoags Deck (76):

Explain thrombus formation

activated platelets adhere to vascular endothelium and express P-selectin
microparticles accumulate and bind to platelets and the p selectin
tissue factor leads to thrombin generation which leads to fibrin clot formation


What receptors are at the platelet membrane and what do they bind

GP Ia: binds collagen
GP Ib: binds vWF
GP IIb/IIIa: fibrinogen and other molecules


Explain the clotting mechanism at the site of vascular wall injury

Platelet membrane receptors bind clotting factors
Antiplatelet prostacyclin is released
Aggregating substances from degranulating platelet are released (ADP, thromboxane A2, and 5-HT)


What is hemostasis

maintains integrity of circulatory system after blood vessel injury
hemostatic clots stay localized to vessel wall and do not impair blood flow
pathologic clots causing VTE do result in impaired blood flow
-this is followed by fibrinolysis (clot degradation)


What are some clotting factors and what affects them

Prothrombin: heparin, dabigatran, warfarin
Proconvertin (factor VII): warfarin
PTC (factor IX): warfarin
Factor X: heparin, rivaroxiban, apixaban, edoxaban, warfarin
Protein C&S: warfarin
Plasminogen: thrombolytic enzymes, aminocaproic acid


What is the goal in treating with anticoags

prevent VTE in high risk by:
prevent thrombus extension and embolization
reduce recurrence risk
prevent long term complications (post thrombotic syndrome, chronic thromboembolic pulm HTN)


What are the different anticoag therapies available

Aspirin: anti-platelet
Warfarin: vitamin K antagonist
Heparin: antithrombin (inactivates factor Xa)
LMWH: indirect antithrombin w/ factor Xa inhibitor
Fondaparinux: indirect factor Xa inhibitor
DOAC: direct Xa inhibitors
Dabigatran: Direct thrombin inhibitor


What are Chest guidelines on patients with DVT of leg or PE and no cancer

for long term (first 3 months) anticoag therapy, Dabigatran, Rivaroxiban, apixaban, or edoxaban should be used over vitamin K antagonists


How do you incorporate initial parenteral anticoagulation

Give it before dabigatran and edoxaban
do NOT give it before rivaroxiban and apixaban
Overlap it with VKA therapy


How is heparin dosed

weight based! and admin as continuous IV infusion


How does heparin work

binds endothelial cells and macrophages, and plasma proteins
Neutralize platelet factor 4 released from active platelets
Reduce capacity of heparin-antithrombin comples to inhibit factor Xa bound to active platelets


What are the limitations of heparin

poor bioavailability at low dose
dose dependent clearance
variable anticoag response
reduced activity in vicinity of platelet rich thrombi
limited activity against factor Xa incorporated in the prothrombinase complex, and thrombin bound to fibrin


What are the ADE of heparin

MC: bleeding!
thrombocytopenia (PLT <100k or 50% decrease)
elevated transaminases


How do you monitor heparin

activated PTT or anti-factor Xa level


How do you reverse heparin's effect

IV protamine sulfate neutralized heparin
-mix of basic polypeptides isolated from salmon sperm that bind heparin with high affinity and result in protamine heparin complexes that are cleared


What are features of heparin induced thrombocytopenia

PLT levels fall 5-10 days after starting heparin
MC with unfractionated heparin, less common with LMWH
MC in surgical pts and those with cancer


How do you manage heparin induced thrombocytopenia

Stop heparin!!
Give a diff anticoag (lepirudin, argatroban, bivalirudin, fondaparinux, rivaroxiban)
Do not give PLT transfusions
Do not give warfarin until PLT count returns to baseline
Eval for thrombosis, esp. DVT


How does LMWH work

Same as heparin!
Binds AT-III which inactivates thrombin, factor IXa, Xa, and XIIa


What are LMWH agents

Enoxaparin (lovenox)
Dalteparin (fragmin): surgical prophylaxis, extended cancer VTE Tx
Fondaparinux (Arixta): AT-III mediated selective inhibition of factor Xa


What is the principle difference in the activity of UFH and LMWH

Relative inhibition of factor Xa and thrombin!
UFH: anti Xa:IIa ratio is 1:1
LMWH: anti Xa:IIa ratio is 4:1 - 2:1


What are advantages of LMWH

Predictable anticoag dose response= can be given subQ QD-BID as prophylaxis and Tx
Lower incidence of thrombocytipenia= safer for short or long term admin
Reduced need for routine monitoring: safer for extended admin


Initiating anticoag therapy with Lovenox is

Weight based!
but all basically 1mg/kg q12 hrs?


Initiating anticoag therapy with Fondaparinux is

weight based! <50 kg= 5mg qd. 50-100kg= 7.5mg qd
Start warfarin on 2nd day of Tx, but continue Fonda until INR >2 (at least 24 hours)


What meds are affected by pork allergy

LMWH (EXCEPT fondaparinux!!)


What should Enoxaparin NOT be used in

patients with cancer
-it can be used as prophylaxis in hip/knee replacement, abd surgery, acute med illness, and DVT Tx


What should Dalteparin NOT be used in

DVT/PE treatment
Knee replacement surgery
-can be used in hip replacement, abd surgery, acute med illness, and VTE cancer prophylaxis


What are properties of heparins

Large acidic polysaccharide polymers
Parenteral admin
site of action: blood
Onset: rapid, minutes
MOA: binds AT-III and inactivates factor IXa, Xa, XII
Monitoring: aPTT for UFH
Antidote: protamine IV for UFH
Use: acute, over days
Use in pregnancy: yes!


What are properties of warfarin

Small lipid soluble molecule
site: Liver
Onset: slow (days); limited by halflives of normal factors
MOA: interferes w/ synthesis of vitamin K dependent clotting factors (II, VII, IX, X)
Monitor: PT/INR
Antidote: vitamin K if Sx. plasma
Use: chronic, wk-mo
Pregnancy: No! it is teratogenic*


What is warfarin also known as

rat poison!


What is the MOA of warfarin

Inhibits VK poxide reductase= interferes with synthesis of functional VK= No VK dependent clotting factors
-Used in VTE, PE, preventing clots in AFIB or cardiac valve replacement
PO has delayed onset and offset activity


What are ADE of Warfarin

Bleeding! can use VK to reverse effects
thrombosis early in therapy is 2/2 protein C deficiency
*Monitor PT/INR


What drugs does warfarin interact with

CYP450 inducers: decreases effect
CYP450 inhibitors: increases effect


What clotting protein does vitamin K block first

Factor VII!!! (4-6 hour half life)
Then protein C (9 hour half life)
Lastly Protein S (60 hr half life)


What are some contraindications to warfarin

Hemorrhagic tendencies
recent eye surgery or CNS
lumbar block anesthesia or traumatic surgery
malignant HTN
Adherence concerns (need to monitor)


What are the DOACs

Apixaban (eliquis)
Rivaroxaban (xarelto)- most bioavailable (80%)
Dabigatran: prodrug! converted in liver to active form. most renally excreted drug (80%)


How do DOACs work

Bind active site of Factor Xa and inhibit enzyme action
-Used for VTE, PE, preventing stroke in AFib pts
Fixed PO dose


ADE of DOACs are

bleeding! no specific reversal agent
Do not need to monitor these patients or dose adjust, but can check factor Xa test


What DOACs should NOT be used in VTE prophylaxis after *orthopedic* surgery

Dabigatran (pradaxa)
Edoxaban (also do NOT use this in extended VTE Tx; >6 months)


What is important to note about administering Rivroxiban

When using for extended VTE Tx (>6 months), give the dose WITH food!
The only time you have the option, w/ or w/o food, is short term VTE prophylaxis after ortho surgery


What DOAC is good to use in ESRD

It has the lowest renal excretion, at only 25%


What do current guidelines say about long term DVT and PE prevention

Full dose anticoag therapy is recommended for min. 3 months after DVT or PE
Patients at high risk may benefit from extended Tx
Low dose DOAC is safer than full dose traditional anticoag for extended Tx
*Consider low dose DOAC for patients requiring long term VTE prevention after 3-6 months of acute Tx


What are reversal agents for DOACs

Dabigatran: Praxbind
Rivaroxiban, Apixaban, LMWH: Andexanet (FDA approved)
Ciraparantag: UFH, LMWH, Rivaroxaban, Apixaban, Edoxaban, Dabigatran


What is the VTE treatment PO only strategy

Day 0-7: Apixaban high dose
Wk 2-6 mo: Apixaban med dose
>6 months: Apixiban low dose
Day 0-21: Rivaroxaban 15mg
Day 22->6 mo: Rivaroxaban 20mg


What is the VTE Tx Switch strategy

Day 0-5: UFH, LMWH, or Fondaparinux
Day 5- >6mo: Dabigatran or Edoxaban


What is the VTE Tx overlap strategy

Day 0-6: UFH, LMWH, or Fondaparinux
Day 0- >6mo: Warfarin PO daily


What is appropriate duration of VTE Tx

Initial duration to effectively treat acute 1st episode of VTE: 3 months
This reduced recurrent VTE risk


What is INR goal range for warfarin therapy

Except if with a mechanical valve: 2.5-3.5 (lifelong therapy)


What is the way to remember the color of warfarin tabs

Please Let Granny Brown Bring Peaches To Your Wedding
Pink -1
Lavender -2
Green -2.5
Brown -3
Blue -4
Peach -5
Teal -6
Yellow -7.5
White -10


How do you start warfarin therapy

Day 1: 5mg
2-3 days later: if INR <1.5, continue at 5. >3, hold and recheck next day
5-7 days later: if INR <1.5, increase to 7.5-10. If >3, reduce to 0-.25mg


How frequently do you check INR when initiating warfarin therapy

Every 2-3 days until INR in therapeutic range on 2 consecutive checks
Every week until 2+ checks in therapeutic range
Every 2 weeks until 2+ checks in therapeutic range
Every 4 weeks when dose is stable


What is a basic way you can adjust warfarin dose based on INR (if goal is 2-3)

<1.5: increase 10-20% TWD
1.5-1.9: increase 5-10% total weekly
2-3: no change
3-1.4: decrease 5-10% total weekly
4.1-5: hold 1-2 doses and decrease 10% total weekly
-If goal is 2.5-3.5, hold 1-2 doses and decrease 10% if INR is 4.6-5


How frequently do you check warfarin when maintaining warfarin therapy

After 1 week if starting or stopping interacting med, changing diet or activity level
Every 1-2 wks if 5-10% dose adjustment needed
Every 4 wks if maintained on same stable dose <3 mo.
Every 6-8 weeks if pt on same stable dose 3+ mo
Every 12 weeks if pt on same stable dose for 6+ mo


What factors indicate warfarin sensitivity

Increased INR response
Baseline INR >1.5
65+ y/o
ABW <45kg (actual < ideal)
Malnourished/NPO >3 days
Chronic diarrhea
Significant dug interactions
Decompensated HF
Increased bleeding risk
Cirrhosis/total bili >2.4
Hx alcohol abuse
GI bleed in past 30 days
Surgery in the past 2 weeks
IC bleed in past 30 days


What are key concepts in managing warfarin

dose adjustments should be made on current total weekly dose
consider trends in INR when making management decisions
consider pt ht, wt, age with dose requirements
Consider repeating INR in same day if value is very diff. than expected
Consider no dose adjustments for INR on low end or high end, retest in 1-2 weeks
Consider no dose adjustments for INR above or below therapeutic range by 0.5 or less. retest in 1-2 wks
Monitor more frequently in first month of initiation
Consider extending monitoring more frequently in first 3 mo. of in-range INR
CoaguCheck XS machine is only accurate for INR 0.8-8


If pt INR is 5-10 (supratherapeutic), how do you proceed

Recommend against use of VK
Hold 1-2 doses, check INR in 24 hrs
Resume lower dose when INR in range


If pt INR is >10 (supratherapeutic), how do you proceed

Give VK 2.5-5mg
Hold 2 doses, check INR in 24 hrs
Repeat VK prn
Resume lower dose of warfarin when INR is in range


Pearl on holding warfarin

Holding warfarin 1 dose drops INR by appx. 1


How do you transition from LMWH to warfarin

Need min. 5 days of warfarin therapy and pt INR in goal range for min 24 hours before you can d/c Lovenox
day 1: initiate lovenox and warfairn
day 4: check INR. cont or adjust dose if needed
day 6: check INR. cont or adjust dose if needed
day 7: check INR. dc lovenox if INR in goal range for 24 hrs, or continue lovenox until it occurs


What procedures are high risk for bleed

heart valve replacement
neuro, urologic, head/neck, abd, or breast cancer
kidney biopsy
transurethral prostate resection
polypectomy, variceal Tx, biliary sphincterotomy, pneumatic dilation
PEG placement
EGD guided FNA
multiple tooth extractions
vascular and general surgery
Any major op lasting >45 min


How do you bridge therapy for high-mod risk of thromboembolism

4 days before surgery: dc warfarin
3 days before surgery: initiate LMWH
2 days before surgery: check INR
1 day before surgery: dc LMWH
1 day after surgery: resume warfarin
2 days after surgery: resume LMWH for low bleed risk procedure
3 days after surgery: resume LMWH for high bleed risk procedure


How do you switch from warfarin to LMWH

dc warfarin and start Dabigatran or Eliquis when INR <2
dc warfarin and start Rivaroxaban when INR <3


How do you switch rom LMWH to warfarin

Rivaroxaban: no data available
CrCl >50, start warfarin 3 days before dc dabigatran
CrCl 30-50, start warfarin 2 days before dc
CrCl 15-30, start warfarin 1 day before dc


When should you assess patients on anticoags

Extended therapy: at periodic intervals (ex. yearly)
w/ leg DVT or PE on warfarin: maintain INR 2-3
w/ leg DVT or PE, no cancer, no DOAC: warfarin preferred


Recommendations for pts with DVT

If home circumstance is adequate, initial Tx at home is better
Early ambulation is suggested over bed rest
Anticoag Tx alone is better than cath thrombolysis if DVT is acute and proximal LE
If acut and Sx leg DVT, do not use compression stockings


What are the thrombolytics

Alteplase, Reteplase


How do thrombolytics work

convert plasminogen to plasmin which causes breakdown of clots
-Good for MI, DVT, PE, and ischemic stroke (t-PA)
Alteplase, Reteplase convert fibrin bound plasminogen targeting clots


Indications for the use of fibrinolytics

Ischemic chest discomfort lasting 20+ min, onset <12 hours
ST elevation in 2 contiguous leads (2+mm in men, 1.5+mm in women in V2-3 -OR- 1+mm in all other leads)


Absolute contraindications to fibrinolytics are

active internal bleeding (not menses)
previous IC hemorrhage
Ischemic stroke w/in 3 mo
known IC neoplasm
known structural cerebral vascular lesion (AVM)
suspected aortic dissection
significant closed head/facial trauma w/in 3 mo
IC or intraspinal surgery w/in 2 mo
severe uncontrolled HTN
Use of streptokinase w/in 6 mo


What should STEMI/NSTEMI management include

*Aspirin! class 1 recc. for both
Clopidogrel in addition to ASA is class 1 recc for both
PCI in both is also a class 1
Prasugrel added to ASA is a class I for both
Can also add Ticagrelor, or Cangrelor to ASA therapy


Warfarin and LMWH therapy recommendations in STEMI/NSTEMI include

UFH is a class I in both
Enoxaparin is a class I in both
Bivalirudin is a class I for both
Fondaparinux is a class I for both


What are fibrinolytic recommendations in STEMI/NSTEMI

Fibrinolytic Tx: STEMI w/in 12 hrs, class I. NSTEMI, class III
GPI inhibitors: NSTEMI class I (for abciximab). STEMI class IIa (for abciximab)
Nitroglycerin: class I for both


Other pharm therapy for STEMI/NSTEMI

BB: class I for both (PO). class III for IV
CCB: NSTEMI class I. Diltiazem for NATEMI/AMI class III
ACE-I: class I for both
ARB: class I for both
Aldosterone antag: class I for both
Morphine: class IIb for both if CP persists after drug Tx
Statins: class I for both


Where do antiplatelet drugs work

ASA: inhibits thromboxane A2 synthesis by irreversibly inhibiting COX-1
Clopidogrel, prasugrel: irreversibly block P2Y12 (ADP receptor on PLT surface)
Cangrelor, ticagrelor: reversibly ind P2Y12 receptor
Abciximab, Eptifibatide, tirofiban: block fibrinogen and vWF binding to GP IIb/IIIa= inhibit final common pathway of platelet aggregation
Vorapaxar: targets PAR-1 (major thrombin receptor) and inhibits thrombin mediated platelet activation


What are the direct thrombin inhibitors and how do they work

Bivalirudin, Desirudin, Argatroban
Bind thrombin's active site and inhibit it's enzymatic action
Used as anticoag in patients w/ heparin induced thrombocytopenia


ADE of direct thrombin inhibitors

monitor aPTT


What is the best direct thrombin inhibitor

Bivalrudin! No renal or liver clearance, and shorter half life so easier to control
-Desirudin is renally cleared, Argatroban has hepatic metabolism