Anticoagulants Flashcards
What is the source of heparin?
- bovine lung
- porcine intestinal mucosa
What is heparin’s mechanism of action?
- increases the rate of the thrombin-antithrombin III reaction at least 1000-fold by being a catalyst in template that binds antithrombin III and protease bind
- heparin induces conformational change in antithrombin III that makes the reactive site more accessible to protease
- after thrombin is bound to antithrombin III heparin molecule is released
What are indications for use of heparin?
- acute MI
- anticoagulation during arterial/cardiac surgery
- diagnosis and treatment of DIC
- non Q-wave MI
- percutaneous coronary intervention
- pregnancy complications
- prophylaxis of postoperative DVT and PE
- prophylaxis and treatment of VTE
- prophylaxis and treatment of of peripheral arterial embolism
- unstable angina
What is heparin’s onset?
- IV: immediate
- SQ: 1-2 hours
What is the half life of heparin?
- 100 units/kg = 1 hour
- 400 units/kg = 2.5 hours
- 800 units/kg = 5 hours
How is heparin metabolized?
- cleared by the reticuloendothelial system
True or False
Heparin crosses the placenta.
- false
- heparin does not cross the placenta
What types of factors does heparin work on?
- only acts on unbound factors
What causes heparin resistance?
- accelerated clearance of drug with massive PE
- acquired antithrombin III deficiency in patients with cirrhosis, nephrotic syndrome or DIC
- increased concentration of factor VIII
- ## inherited antithrombin III deficiency
How can you treat heparin resistance caused by an acquired antithrombin III deficiency?
- administer 2 units of FFP to provide antithrombin III
- antithrombin III concentrate
What are signs and symptoms of heparin toxicity?
- abnormal LFTs
- bleeding
- osteoporosis
- spontaneous vertebral fractures
- thrombocytopenia
What is the occurrence of major bleeds caused by heparin?
- 1-33% of patients
What lab values are associated with heparin induced thrombocytopenia (HITT)?
- platelets < 100,000
- 7-14 days after initiate of full or low dose heparin therapy (including heparin flush solution).
- can occur earlier if patient has been previously exposed to platelets
What causes HITT?
- heparin dependent antiplatelet IgG antibiotics or a direct nonimmunogenic effect on platelets
How is HITT treated?
- stop the heparin
What is the reversal agent of heparin?
- protamine sulfate
- acts as a heparin antagonist by creating complex with strongly acidic and anionic heparin to form a stable salt
- removed by the reticuloendothelial system
What are indications for use of protamine sulfate?
- neutralize heparin after CPB procedures or other procedures where higher molecular weight heparin was used
What type of heparin is not as susceptible to protamine antagonism?
- low molecular weight heparin’s (anti-factor Xa agents).
- emergency reversal needed = protamine will neutralize about 65% of anti-xa activity of LMWHs
What is the dose of protamine for reversal of heparin?
- 1-1.5mg of protamine for every 100 unites of heparin.
What are the adverse effects of protamine sulfate?
- acute histamine-related hypotension
- bradycardia
- dyspnea
- pulmonary hypertension
- transient flushing
What should be monitored when administering protamine sulfate by rapid IV injection?
- airway pressures (wheezing)
- blood pressure
- PA pressures
What types factors can increase hypersensitivity to protamine sulfate?
- hypersensitive to fish
- previous protamine reversal of heparin
- previous vasectomy
- protamine containing insulin (NPH)
What is the pretreatment for a patient with a potential hypersensitivity to protamine sulfate?
- antihistamine
- corticosteroid
What can occur with an overdose of protamine sulfate?
- bleeding (theoretically) because it has anticoagulant and anti-platelet effects when given alone or in excess of heparin
When does heparin rebound occur after administration of protamine?
- patient re-anticoagulation after protamine is administered
- usually 8-9 hours
What medications are classified as low molecular weight heparin’s?
- dalteparin
- enoxaparin
- tinzaparin
What is low molecular weight heparin’s mechanism of action?
- inhibition of factor Xa by antithrombin
- some factor IIa inhibition effect
What monitoring is indicated with LMWH?
- anti-factor Xa levels
- aPTT and PT are relatively insensitive with LMWH therapy
What are indications for use of LMWH?
- atrial fibrillation
- non Q-wave MI
- prevention of post-op DVT/thromboembolism
- recurrent DVT
What is an adverse side effect of LMWH?
- thrombocytopenia
When should you now use LMWH?
- patients with HIT
- need to decrease the dose in patients with chronic renal insufficiency
What are advantages of Arixtra (Fondaparinux)
- fixed dose
- once daily SQ administration
- not associated with HIT (but should stop if platelet count drops below 100,000)
What is Arixtra’s mechanism of action?
- synthetic indirect inhibitor of factor Xa
- Antithrombin III mediated
- no effect on factor IIa
- no effect on platelet function
What are indications for use of arixtra?
- prevention of post-op DVT/thromboembolism
- treatment of DVT or PE
What are the indications for use of Bevyxxa?
- prophylaxis of VTE for adults in hospital with acute medical illness
- similar to lovenox
Is there more or less risk of a spinal or epidural hematoma with use of fondaparinux?
- same amount of risk as with use of LMWH
What type of medication is danaparoid sodium?
- heparinoid (not a LMWH or true heparin_
- almost exclusively anti-Xa activity
- relatively loss cross reactivity for patients with a history of HIT (but can still cause HIT).
Name 3 oral Xa inhibitors.
- rivaroxaban (xarelto)
- apixaban (eliquis)
- edoxaban (savaysa)
When can warfarin be resumed after surgery?
- 12-24 hours post-op
When can oral anti-Xa agents be resumed after surgery?
- as soon as adequate hemostasis has been established
When should apixaban (Eliquis) be stopped before surgery?
- high/moderate risk procedure: 48 hours
- low risk procedure: 24 hours
When should xarelto be stopped before surgery?
- 24 hours
When should pradaxa be stopped prior to surgery?
- CrCl > 50: 1-2 days
- CrCl < 50: 3-5 days
What actions can be taken to reverse an oral factor Xa inhibitor?
- activated charcoal (if medication taken within 2 hours)
- discontinue medication
- FEIBA
- mechanical compression
- PCC
- recombinant factor VIIa
- surgical hemostasis
- transfusion support
Are there any approved reversal agents for anti-Xa inhibitors?
- not currently, two pending approval
- andexanet
- ciraparantag
How does andexanet alpha work?
- binds competitively to factor Xa inhibitors for complete reversal
How does ciraparantag work?
- binds to anticoagulants through a hydrogen bond
- reverses Xa inhibitors, IIa inhibitors, fondaparinux and heparin
What medications are classified as direct thrombin inhibitors?
- argatroban
- bivalirudin (angiomax)
- hirudin
- lepirudin (refludin)
- dabigatran (pradaxa)
What polypeptide is responsible for the anticoagulant properties of the salvia in leeches?
- hirudin
What is the indication for use of argatroban?
- prevention and treatment of thrombosis in patients with HIT or HITTS
How does argatroban affect lab values?
- produces dose dependent increases in aPTT, ACT, PT and TT
- goal: aPTT 1.5-3x baseline (< 100 seconds)
Is there a reversal agent for argatroban?
- no
Hirudin is indicated for treatment of _____________.
- thrombosis associated with HIT
How are hirudin analogs excreted?
- excreted by kidneys and dose should be adjusted in renal impairment to
How do hirudin analogs work?
- bind irreversibly to active catalytic and substrate-recognition sites of both circulating and clot-bound thrombin (factor IIa).
Is there a reversal agent for hirudin analogs?
- no
How should bleeding be managed in a patient who is on dabigatran?
- activated charcoal (if medication taken within 2 hours)
- discontinue drug
- HD will remove 62-68% of circulating medication
- mechanical compression
- PCC
- recombinant factor VIIa
- specific antidotes: idarucizumab, ciraparantag)
- surgical hemostasis
- transfusion support
How does idarucizumab (Praxbind) work to reverse dabigatran?
- humanized antibody fragment
- non-competitive binding to dabigatran with 350x more affinity than thrombin
What were the results of the reverse AD trial?
- elderly multi morbidity patients with life-threatening emergencies required reversal of anticoagulation because of uncontrolled bleeding or need for emergency surgery or invasive procedure
- median time from reversal to procedure was 1.6 hours for invasive procedures
- median time to investigator reported hemostasis was 2.5 hours
What is warfarin’s mechanism of action?
- indirect anticoagulant
- alters synthesis of vitamin K dependent coagulation factors (II, VII, IX and X) by interfering with actions of vitamin K
Vitamin K should never be administered via what route?
- subcutaneous
Is warfarin safe in pregnancy?
- no
- category X
What drugs can interact with warfarin?
- acetaminophen
- antibiotics
- antiepileptics
- blood thinners
- NSAIDs
- supplements (garlic, ginkgo, ginger)
What do the CHADS2-Vasc guidelines calculate?
- calculates stroke risk if patient is not on an anticoagulant
What does the HAS-BLED scale calculate?
- calculates bleeding risk
True or False
Most new oral anticoagulants do not require bridge therapy as they are only held for 24-48 hours prior to surgery.
- true
What types of procedures are considered low/minor risk for bleeding?
- cardiac catheterization
- cardiac device implantation
- cataract removal
- catheter ablation for afib
- dental extraction
- dermatology
- GI endoscopy
What types of procedures are consider major/high risk for bleeding?
- intraabdominal surgery
- intrathoracic surgery
- major orthopedic surgery
- peripheral arterial revascularization
- urologic surgery
What patients are considered high risk for bridge therapy?
- mechanical heart valves (aortic and mitral valve replacements, stroke or TIA within 6 months)
- atrial fibrillation (stroke or TIA within 3 months, rheumatic valvular heart disease)
- VTE (VTE within 3 months, severe thrombophilia)
What patients are considered moderate risk for bridge therapy?
- mechanical heart valve (bileaflet aortic valve prosthesis with either afib, prior stroke/TIA, HTN, diabetes, CHF or > 75)
- atrial fibrillation
- VTE (within 2-12 months)
What patients are considered low risk for bridge therapy?
- atrial fibrillation (with no previous stroke/TIA)
- VTE (single VTE over 12 months ago with no other risk factors)
- mechanical heart valve (bileaflet aortic valve replacement without afib and no other risk factors for stroke)
When should bridge therapy be resumed after surgery?
- LMWH: within 24-72 hours
- unfractionated heparin: within 24 hours
When should bridge therapy be held preoperatively?
- LMWH: 24 hours pre-procedure (recommend using 50% of regular dose for last pre-procedure dose)
- unfractionated heparin: 4 hours pre-procedure
What does the 2017 update demonstrate regarding bridge therapy?
- questionable benefit to bridge therapy
- no reduction in thromboembolic events and increase risk of bleeding
- 40-60% of anticoagulant interruptions may be unnecessary
- continue medications if bleeding risk is very low
What types of procedures have a high risk of perioperative bleeding?
- major cardiac, neurological, orthopedic, urologic or vascular surgeries
- major cancer treatments
- kidney biopsy
- endoscopically guided fine needle aspiration
- major surgery with duration greater than 45 minutes
What types of procedures have a low risk of perioperative bleeding?
- abdominal hernia repair
- abdominal hysterectomy
- cholecystectomy
- GI endoscopy
- minor gynecological procedures
- minor dental procedures
- minor orthopedic procedures
- minor plastic surgery
- pacer/defibrillation insertion
What types of medications are not associated with an increased risk of epidural hematoma?
- aspirin
- NSAIDs
When can you place or remove an epidural atheter when a patient is on low dose Coumadin?
- place or remove catheter with INR < 1.5
True or False
There is no contraindication to the use of neuraxial technique in patients who have received subcutaneous heparin.
- true
- no contraindication
- delay injection until after the block
- patients on heparin more than 4 days should have a platelet count checked to rule out HIT
What it’s he risk of epidural hematoma after neuraxial blockade in patients treating with LMWH or fondaparinux?
- significant risk
- antiplatelet medications co-administered with LMWH may increase risk of spinal hematoma
What are recommendations for neuraxial anesthesia in patients being treated with direct oral anticoagulants?
- all medications currently have black box warning for use with neuraxial anesthesia
- medications should be discontinued prior to procedure
- can be restarted 24 hours post procedure for low bleed risk and 48-72 hours for high bleed risk
When can needle placement for neuraxial anesthesia occur in patients receiving LMWH?
- should occur at least 10-12 hours after last LMWH
- high doses of LMWH require a delay of at least 24 hours
- epidural should be placed 6-8 hours prior to any dose of postoperative LMWH (once a day dosing)
- twice daily dosing of LMWH should be delayed until 24 hours post-operative
- removal should be done 2-4 hours before a dose of LMWH
- removal should occur 10-12 hours after any dose
