Anticoagulants Flashcards
What clotting factors require vitamin K to be produced?
II, VII, IX, X
What does plasmin do?
- It is the enzyme that breaks down a fibrin enriched clot
- *plasmin medications are dangerous to give because they will break down clots everywhere, not just the one clot that may be causing a problem.
For what reasons are anti-coagulants most commonly given?
- in peri-op setting for CV procedures
- to prevent DVT (10-40% of surgical patients)
- to pts with chronic atrial fibrillation
How do the different types of anticuagulanst effect clots?
anticoagulants?
anti-platelet drugs?
Thrombolytic drugs?
- Anticoagulants- decrease the production of fibrin
- Anti-platelet drugs- reduce platelet aggregation/function
- Thrombolytic drugs- promote clot lysis/fibrinolysis
What are the anticoagulant drugs that decrease the production of fibrin?
- Warfarin (Coumadin)
- Heparin
- Low molecular weight heparin
- lovenox
- Xa inhibitors
- Direct thrombin inhibitors
- Argatroban
- Dabigatran
Warfarin
Use
origination
- Used for long term thrombosis prophylaxis
- DVT
- afib
- prosthetic heart valves
- recurrent TIA/MI
- Originally marketed as a rat poison, but in a much higher dose
If you are dealing with arterial clotting issues, you would use ___________ therapy.
If you are dealing with venous (hemostasis) issues, you would use _________ therapy.
anti-platelet
Anticoagulant
Warfarin (Coumadin) MOA?
Why do the effects differ so much from patient to patient?
- Inhibits vitamin K epoxide reductase complex I (VKORC1), preventing the synthesis of vitamin K
- decrease in vitamin K will decrease production of the clotting factors that require vit K (II, VII, IX, X)
- The effects of this drug differ so greatly between patients because everybody has a different amount of epoxide reductase and also a different amount of the enzyme that breaks down warfarin
Warfarin:
absorption
peak effect
E1/2t
Pb
dosing
- Absorbed in 1-2 hours, but no effect until the clotting factors you already have are depleted
- Peak effect delayed 36-72 hours
- E1/2t = 24-36 hours
- 97% PB
- Very narrow therapeutic index, but doses can range from 0.5 mg to 30 mg/day
How is INR calculated?
What would INR be for a pt not on warfarin?
What would INR be for pt with DVT, Afib, or PE?
- (Pt’s PT/normal PT)ISI
- ISI= international sensitivity index that is given with each batch of thromboplastin
- Pt NOT on Warfarin = 0.8-1.2
- Pts with DVT, Afib, or PE = 2.0-3.0
What is pregnancy category for Warfarin?
What are adverse reactions to Warfarin
- Category X
- Do not take while breastfeeding
- Adverse reactions?
- bruising
- bloody nose
- bleeding when brushing teeth
- blood in urine and stool
- pelvic pain
- HA
- dizziness
- low BP
- Tachycardia
- **pts should wear a medical alert bracelet
How can dietary intake affect Warfarin?
How can medications interfere?
- Foods with vit K antagonize the effect of warfarin;
- have a consistent diet
- Medications can increase or decrease the anticoagulation effects of Warfarin
- alter protein binding
- alter function of CYP enzymes
- Acetaminophen increases risk of bleeding
- several anti-sz medication
- Alter the synthesis or function of clotting factors and/or platelets
- heparin, NSAIDS, ASA, clopidogrel
- Alter absorption of warfarin
How far before surgery should you have the pt discontinue their warfarin?
When should you assess how this affects them?
How can warfarin be reversed for emergent procedure
- d/c at least 5 days before elective procedure
- Assess INR 1-2 days prior to surgery
- if >1.5, consider 1-2 mg oral Vit K
- Reversal for urgent procedure: 2.5-5 mg oral or IV vitamin K or FFP
What is the best way to reverse warfarin if INR is high?
- If INR is above range but less than 6.0, hold 1-2 doses of warfarin
- If INR is higher or pt is showing signs of bleeding, administer Vit K
- Low doses via oral route is best
- IV may be used in pts with absorption issues
Unfractionated Heparin
structure?
- Highly sulfated glycosaminoglycans
- Potency varies so it is always prescribed in units
Heparin function is very variable, what factors cause the variablility?
Molecule size/shape?
PB
Metabolism
Indications
- Variability:
- Baseline antithrombin activity can influence pt response
- Temperature dep: more active at higher temps
- Size/shape:
- Higly polar and large molecular weight (3,000-30,000 daltons- does not cross biologic membranes)
- IV/SQ only
- Good choice in pregnancy and breast feeding
- Higly polar and large molecular weight (3,000-30,000 daltons- does not cross biologic membranes)
- Non-specific protein binding = variable free drug/unpredictable dose response
- Metabolism:
- Onset in minutes; 1-2 hours SQ
- 1/2 live about 1 hour; mechanism unclear, renal excretion
- Indications:
- PE, DVT (&prevention) acute MI, stroke, dialysis, cardiopulm bypass, DIC
Heparin MOA?
- Heparin binds to antithrombin, a normally circulating anti-coagulant, once bound to heparin, the antithrombin’s effect is enhanced about 1,000x
- Antithrombin/heparin inactivate: thrombin, IX, X, XI, XII
What test is used to measure the efficacy of heparin?
What is the goal?
- aPTT
- goal: 1.5-2x normal (normal = 30-35 seconds)
- ACT used for higher doses
- get baseline, then check 3-5 minutes after administration, then every 30 minutes
What are the adverse effects of Heparin?
- Hemorrhage
- HIT (heparin induced thrombocytopenia)
- 50% decrease in plt count with thrombosis
- Osteoporosis
- hypersensitivity- d/t being extracted from animals
What is the reversal agent for heparin?
How does it work?
DOA?
dose?
SE?
- Protamine
- Protamine is alkaline with + charge and heparine is acidic wth - charge, so they are very attracted to each other, together they have no anticoagulant effects
- removed by macrophages
- DOA: 2 hours (may need to redose)
- Dose: 1 mg protamin per 100 units heparin
- give slowly!
- consider how much of the dosed heparin has already been metabolized
- SE:
- anaphylaxis (made from fish, in insulin)
How is Heparin induced thrombocytopenia caused?
- Platelets produce/release platelet factor 4, which the heparin can bind to
- This creates a new surface that antibodies might bind to, forming a heparin-PF4-antibody complex
- The antibody will then bind to the Fc receptor on platelets
- this activates the release of more PF4, further enhancing the aggregation
- These platelets form clots that are removed by the spleen, causing thrombocytopenia
When is heparin contraindicated or should be used cautiously?
- liver and kidney disease
- indwelling epidural catheter
- traumatic placement of epidural or spinal anesthetic
- other anti-platelet or anti-coagulation medications
- peri-surgical: eye, brain or spinal cord
- patients at high risk of bleeding
- hemophilia, aneurysm, severe HTN, GI bleed, thrombocytopenia
How does the relative risk of spinal hematoma change with these situations? (table)
- No heparin
- no trauma
- trauma
- ASA
- Heparin
- no trauma
- trauma
- heparin > 1 hr after puncture
- heparin < 1 hour after puncture
- ASA
Low molecular weight heparins:
prototype?
use?
efficacy?
- Enoxaparin
- Use
- 1st line therapy for DVT prophylaxis and tx
- unstable angina, MI, coronary ischemia
- efficacy:
- equal with heparin- inactivates 10a
- not as effective in inactivating thrombin
LMWH pharmacokinetics?
compared to heparin
- Higher bioavailability
- longer half life (up to 6x longer)
- No aPTT monitoring required
- no hospitalizatin required
LMWH
adverse effects?
Contraindications?
- adverse effects:
- bleeding- lower risk than with unfractionated hep
- HIT
- Contraindicatins:
- effect greatly prolonged in renal failure- use unfractionated heparin instead
- spinal or epidural- hold for 24 hours
- Anti-pld or anti-coagulant drugs
- delay surgery 12 hours after last dose
How does Fondaparinux (Arixtra) work?
Half life?
- Exclusively inactivates Xa by enhancing antithrombin III activity
- no direct effect on thrombin activity
- Chemically identical to the 5 sugar active site of heparin and LMWH, but much smaller than them
- Half life is over 3x longer than LMWH
- E1/2 t = 15 hours
- effect onset 2 hours, lasts 2-4 days after last dose
- eliminated unchanged in kidneys
Fondaparinux
reversal agent?
Contraindications?
Caution?
- No reversal agent
- Contraindications:
- severe renal impairment (CrCL <30ml/min)
- Weight <50 kg for pts undergoing hip fracture, hip replacement, or knee replacement surgery
- Caution:
- HIT does not occur but thrombocytopenia does (3%)
- elderly
- CrCl 30-50 ml/min
- epidural or spinal (d/t long half life)
