Lecture 7 Pharm - Anticoagulants

How long do we treat subsequent blood clots?

indefinitely

What are some important characteristics of unfractionated heparin?

-*MOA:* 1. binds to the natural anticoagulant antithrombin (AT) and accelerates its enzymatic activity 2. complex inhibits thrombin (AKA factor IIa) as well as other clotting factors (Xa, IXa, XIa, and XIIa) -*pharmacokinetics:* (a) short half life (30-90 minutes) (b) eliminated via enzymatic degradation as well as renally (c) d/t regular monitoring, often preferred parenteral agent with renal impairment -lab monitoring: (a) close monitoring required (b) *activated partial thromboplastin test (aPTT)* (c) 1.5-2.5 x normal control = therapeutic range for anticoagulation -*ADRs:* 1. bleeding 2. osteoporosis (with long-term use) 3. hypersensitivity 4. heparin induced thrombocytopenia (HIT) -*heparin antidote:* (a) *protamine sulfate* --> cationic protein that binds to anionic heparin (b) neutralizes heparin in 5 minutes and effects last for 2 hours

What is fondaparinux (Arixtra)?

-*MOA:* indirect factor Xa inhibitor -labeled uses: often seen in patients with concern for/hx of *HIT* 1. prophylaxis following THA, TKA, or abdominal surgery 2. DVT or PE tx 3. ACS: off-label use -prophylaxis dosing: 2.5mg subQ once daily -tx dosing: (a) <50kg: 5 mg subQ once daily (b) 50-100kg: 7.5 mg subQ once daily (c) >100kg: 10 mg subQ once daily -*ADRs:* 1. bleeding 2. black box warning: use with *neural anesthesia or spinal puncture* can lead to increased risk of *spinal hematoma and paralysis* -renal elimination (a) will accumulate in renal impairment (b) contraindicated with CrCl < 30 ml/min or dialysis patients (c) should also not be used for prophylaxis in patients <50kg -no method of monitoring -no reversal agent -pregnancy category B

What are the AHA/ACC guidelines regarding Afib and coagulation therapy?

-2+ in men = oral anticoagulation -3+ in women = oral anticoagulation -DOACs are recommended over warfarin in eligible patients (without mod-severe mitral heart valve or mitral stenosis)

How do anticoagulants work?

-all work by blocking one or more clotting factors and in turn, prolong time to clot -newer oral anticoagulants target specific points in the coagulation cascade (a) *factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban):* target factor Xa, preventing the conversion of prothrombin to thrombin (b) *direct thrombin inhibitors (dabigatran):* target thrombin (factor IIa) --> block conversion of fibrinogen to fibrin (c) *vitamin K antagonists (warfarin):* inhibit synthesis of vit K-dependent clotting factors made in the liver --> II, VII, IX and X and proteins C and S

How should you monitor warfarin?

-challenges associated with warfarin therapy: 1. narrow therapeutic window 2. considerable inter-subject variability 3. drug, diet, and disease state interactions 4. requires thorough understanding by both provider and patient -INR goals: (a) A-fib, prevention/treatment of VTE: *2.0-3.0* (b) mechanical heart valve in mitral position: *2.5-3.5* -effects take *36-72 hours* to occur (often 5+ days for full therapeutic effect) (a) INR typically checked after 2-3 doses (b) if initial start in inpatient setting: 1. check daily until INR therapeutic --> weekly until 2 consecutive INRs therapeutic --> every 2 weeks --> monthly as long as INRs remain therapeutic 2. CHEST guidelines --> may extend monitoring to up to every 12 weeks -important to consider reasons *why* INR may be out of range 1. new start - delayed action 2. changes in clinical condition (infection, CHF exacerbation) 3. new drugs added (especially antibiotics) 4. drugs discontinued 5. N/V 6. changes in diet (vitamin K rich foods) PRN med use (NSAIDs, aspirin, acetaminophen) 7. medication compliance

How do you treat DVT/PE with coagulation therapy?

-choice of anticoagulant (per CHEST guidelines) (a) DOAC or warfarin preferred if no cancer --> may consider DOAC above warfarin (b) in cancer patients with VTE --> LMWH preferred treatment option, extended duration of therapy -duration of anticoagulation (per CHEST guidelines) (a) DVT or PE provoked by surgery or other transient risk factor --> 3 mo tx (b) 1st unprovoked DVT or PE 1. *low bleed risk* --> extended anticoagulant therapy 2. *high bleed risk* --> 3 mo tx (c) 2nd unprovoked VTE 1. *low-moderate bleed risk* --> extended anticoagulant therapy 2. *high bleed risk* --> 3 mo tx

How should you monitor a patient who is on LMWH?

-routine efficacy monitoring is not recommended (a) anti-factor Xa levels are the most accurate method to monitor efficacy --monitor peak level 4 hrs post dose at steady state (b) patients to consider anti-factor Xa level monitoring: 1. weight > 150 kg or < 50 kg 2. CrCl < 30 ml/min 3. pediatric patients 4. pregnant patients 5. long duration of use (c) still carries risk of HIT --> monitor platelets

What are some important considerations with direct oral anticoagulants (DOACs)?

-like all anticoagulants, DOACs carry a significant risk of bleeding --> contraindicated in *active pathologic bleeding* -increased risk of bleeding when used in combination with *anti-platelets agents* -have relatively short half lives (prolonged in renal impairment) 1. Dabigatran: 14-17 hours 2. Rivaroxaban: 5-9 hours 3. Apixaban: 12 hours 4. Edoxaban: 10-14 hours 5. Betrixaban: 19-27 hours (a) extended compared to others (b) effects persist for >/= 72 hours) --d/t to short half lives --> compliance is especially important! -pregnancy category C - insufficient data

What is the dosing for andexanet alfa (Andexxa)?

-low dose = 400mg IV bolus followed by 4 mg/min IV infusion for up to 120 minutes -high dose = 800mg IV bolus followed by 8 mg/min IV infusion for up to 120 minutes

How do you treat ACS with coagulation therapy?

-parenteral anticoagulation recommended in UA/NSTEMI/STEMI (a) reduces the risk of intracoronary and catheter thrombus formation (b) options include: 1. enoxaparin, unfractionated heparin (with or without PCI) 2. bivalirudin (only to be used if patient is going for PCI) 3. fondaparinux (not recommended as sole anticoagulant to support PCI) -used throughout percutaneous intervention (PCI) -typically discontinued after PCI (a) if no PCI --> typically continued for at least *48 hours* or *until hospital discharge*

What are direct thrombin inhibitors?

-products: 1. argatroban (a) indicated for HIT and patients undergoing PCI who are at risk of HIT 2. bivalirudin (Angiomax) (a) indicated for ACS and patients undergoing PCI (with or w/o hx of HIT) -all are given as continuous infusions --bolus dose followed by weight-based continuous infusion -*no reversal agent* available -argatroban (a) adjust dose with hepatic insufficiency (b) elevates the INR --> overlap with warfarin until INR > 4

What can we do to prevent ADRs with anticoagulants?

-provide patient/caregiver education -assure healthcare professionals have adequate education related to anticoagulants -monitor levels/labs appropriately based on specific anticoagulant patient taking -assure patients are on the correct dose based on indication -assess patient compliance/understanding of dosing regimen -assure optimal care transitions

How do Factor Xa and direct thrombin inhibitors compare to warfarin?

*advantages:* -no routine monitoring -impoved safety profile -rapid onset (may preclude need for induction or bridging) -short half life --> good for invasive procedures or active bleeding -fixed dosing -greater convenience, patient satisfaction, & quality of life -potentially more cost-effective (health system perspective) -fewer drug, dz, and diet interactions *disadvantages:* -no reliable, readily available measurement assay -dose reduction or avoidance in renal impairment & avoidance in moderate to severe hepatic impairment -lack of specific antidote for all agents -short half life (mandates strict adherence) -less flexibility in dosing -fewer studies and approved indications -likely a higher dose acquisition costs for patients -DOAC drug interactions do exist that may preclude use

What is the factor Xa inhibitor reversal drug?

*andexanet alfa (Andexxa)* -approved for the reversal of apixaban or rivaroxaban -potential for use with edoxaban, enoxaparin, fondaparinux (NOT studied) -*MOA:* 1. recombinant modified human factor that acts as a factor Xa decoy protein 2. reversibly binds to the active site and inhibits factor Xa inhibitors and inhibits the pharmacological activity of factor Xa inhibits and thereby allows restoration of thrombin generation and fibrin clot formation -dosing is dependent upon dose of apixaban/rivaroxaban and time since last dose -many institutions are NOT adding for formulary at this time due to unclear risk versus benefit and high cost of medication (a) high dose full duration = $58,000 (b) low dose full duration = $29,000

What are other forms of supportive therapy in bleeding?

*antifibrinolytics* (a) tranexamic acid (b) aminocaproic acid (Amicar) -form a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis -not reversal agents, may be used for: 1. prevention of procedural and post-operative bleeding 2. traumatic bleeding 3. intracranial hemorrhage associated with thrombolytics 4. oral TXA used for heavy menstrual bleeding

How do you manage bleeding with warfarin?

*based on INR and evidence of bleeding* -IM administration should be avoided risk of hematoma -IV administration preferred over subQ --> with subQ, less predictable response -high doses of vit K (>10 mg) may cause prolonged warfarin resistance --> may see resistance ≥1 week

How do you prevent DVT/PE with coagulation therapy?

*based upon risk of VTE development* 1. low risk of VTE --> *no pharmacologic therapy*, *early ambulation* (a) minor surgery: not bed-ridden post-op (b) fully ambulatory medical patients 2. moderate risk of VTE --> *UFH, LMWH, and fondaparinux* (a) non-orthopedic surgery patients (b) medical patients with limited mobility 3. high risk of VTE (a) critically ill patients --> *UFH, LMWH, and fondaparinux* (b) most orthopedic surgery patients LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, UFH, adjusted-dose VKA, aspirin -also must consider bleeding risk --> high bleed risk --> mechanical prophylaxis

What are the common drug interactions with warfarin?

*common medications that can ↑ INR:* -Cimetidine -Phenytoin -Statins -Fenofibrate -*Amiodarone* -*SMX/TMP (Bactrim)* -*Levaquin/Cipro* -Azithromycin -*Metronidazole* -*Fluconazole* -Prednisone *common medications that can ↓ INR:* -Carbamazepine -Cholestyramine -Phenobarbital -*Rifampin* -Sucralfate -Vitamin K containing medications -multivitamins *bolded meds:* have a major effect on INR

What is the perioperative management of coagulation therapy in low bleed risk patients?

*discontinue:* -unfractionated heparin: *4-6 hrs* (normal & impaired renal fxn) -enoxaparin: *24 hrs* (normal); *24-36+ hrs* (impaired) -fondaparinux: *36-48 hrs* (normal); *4 days* (impaired) -warfarin: *5 days* (normal & impaired) -dabigatran: *2 days* (normal); *3 days* (impaired) -apixaban: *2 days* (normal); *3 days* (impaired) -edoxaban: *2 days* (normal); *3-4 days* (impaired) -rivaroxaban: *2 days* (normal); *2-3 days* (impaired)

What is the perioperative management of coagulation therapy in high bleed risk patients?

*discontinue:* -unfractionated heparin: *4-6 hrs* (normal & impaired renal fxn) -enoxaparin: *24 hrs* (normal); *24-36+ hrs* (impaired) -fondaparinux: *36-48 hrs* (normal); *4 days* (impaired) -warfarin: *5 days* (normal & impaired) -dabigatran: *3-5 days* (normal); *4-6 days* (impaired) -apixaban: *3 days* (normal); *4-6 days* (impaired) -edoxaban: *3 days* (normal); *5-6 days* (impaired) -rivaroxaban: *3 days* (normal); *3-4 days* (impaired)

What is the direct thrombin inhibitor reversal drug for dabigatran?

*idarucizumab (Praxbind)* -monoclonal antibody that binds to dabigatran and its metabolites with an affinity ~350 times that of thrombin -neutralizes anticoagulant effect within minutes -duration ~24 hours -dosing: IV: 5 gm (administered as two separate 2.5 gm doses, no more than 15 minutes apart) -hemodialysis will also remove dabigatran

What is low molecular weight heparin (LMWH)?

*products commercially available in the US:* -enoxaparin (Lovenox) -dalteparin (Fragmin) -tinzaparin (Innohep) -Clinical use: 1. VTE prophylaxis 2. VTE treatment *tx dosing 3. ACS *tx dosing 4. Afib (bridging or initial inpatient anticoagulation) *tx dosing 4. most common anticoagulant used in pregnancy 5. most data for VTE treatment in malignancy -*enoxaparin (Lovenox)* = most commonly used product & dosed based as follows: 1. CrCl >30 (a) prophylaxis: 30 mg subQ q12h or 40 mg subQ daily (b) treatment: 1 mg/kg subQ q12h or 1.5 mg/kg subQ daily 2. CrCl <30 (a) prophylaxis: 30 mg subQ daily (b) treatment: 1 mg/kg subQ daily

What is the medication used for heparin reversal?

*protamine* -provides 100% neutralization of heparin and ~60% neutralization of LMWH products

What are the clinical uses for unfractionated heparin?

*safe for use in pregnancy* 1. *IV heparin* is used for *therapeutic anticoagulation* -VTE Treatment -ACS -inpatient bridging (i.e. Afib patients) 2. dosing: (a) VTE Treatment: 80 units/kg IV bolus followed by 18 units/kg/hr infusion (b) ACS: 60 units/kg IV bolus followed by 12 units/kg/hr infusion (c) adjust infusion rates based upon aPTT goals -aPTTs typically monitored at baseline, 6 hours after dose change, and daily once stable 3. *subcutaneous heparin* is used for VTE *prophylaxis* --> 5000 units subQ every 8-12 hours may also be used intraoperatively and to maintain patency of lines

What is dabigatran (Pradaxa)?

-direct thrombin inhibitor (a) indicated for stroke prevention in non-valvular A-fib and treatment of DVT/PE --> VTE prophylaxis following hip surgery -dosing considerations: 1. dosage form: capsule 2. strengths: 75 mg and 150 mg 3. must dose adjust in renal impairment 4. requires *5-10 days* of parenteral lead-in therapy if used for VTE treatment 5. capsules not to be opened d/t increased exposure to medication 6. requires acidic environment for absorption 7. may be taken with or without meals 8. capsules must be stored in original bottle or blister pack to protect against moisture 9. bottle must be discarded 4 months after being opened -*ADRs:* 1. bleeding (a) lower incidence of intracranial bleeding compared to warfarin (b) higher incidence of GI bleeding compared to warfarin 2. dyspepsia 3. increase serum ALT -drug interactions: P-glycoprotein interactions (a) avoid use with P-gp inducers (i.e. rifampin) (b) caution with inhibitors (dronedarone, amiodarone, verapamil) -reversal: (a) ~60% dialyzable (b) idarucizumab (Praxbind) recently approved

What is edoxaban (Savaysa)?

-factor Xa inhibitor (a) indicated for stroke prevention in non-valvular Afib and treatment of DVT/PE -dosing considerations: 1. dosage form: tablet 2. strengths: 15 mg, 30 mg and 60 mg 3. must be dose adjusted for renal impairment --contraindicated if *CrCl > 95 mL/min* 4. requires *5-10 days of parenteral lead-in therapy* if used for VTE treatment 5. no recommendations provided regarding splitting or crushing tablets 6. may be taken with or without meals -*ADRs and contraindications:* 1. bleeding 2. elevations in AST/ALT 3. moderate to severe impairment (Child-Pugh class B and C): use is not recommended -reversal: (a) could consider *Andexanet Alfa* (Andexxa)? - however not studied (b) not dialyzable (c) for major bleeding, may consider *PCC*, *activated PCC* (ie, FEIBA), or *recombinant factor VIIa*

What is Apixaban (Eliquis)?

-factor Xa inhibitor (a) indicated for stroke prevention in non-valvular Afib and treatment of DVT/PE --VTE prophylaxis following hip and knee surgery -dosing considerations: 1. dosage form: tablet 2. strengths: 2.5 mg and 5 mg 3. dose adjustments based upon age, weight, and SCr 4. only DOAC with approved dosing in hemodialysis 5. may be crushed and suspended in 60 mL D5W and immediately delivered through feeding tube 6. may be taken with or without meals -*ADRs and contraindications:* 1. bleeding 2. nausea 3. elevations in AST/ALT 4. caution in moderate hepatic impairment (Child-Pugh class B); Use in severe hepatic impairment (Child-Pugh class C) is not recommended -drug interactions: (a) CYP 3A4 and P-gp drug interactions --inhibitors increase rivaroxaban concentration -*reversal:* 1. antidote: *Andexanet Alfa* (Andexxa) 2. not dialyzable 3. for major bleeding, may consider *PCC*, *activated PCC* (ie, FEIBA), or *recombinant factor VIIa*

What is Rivaroxaban (Xarelto)?

-factor Xa inhibitor (a) indicated for stroke prevention in non-valvular Afib and treatment of DVT/PE --VTE prophylaxis following hip and knee surgery (b) new indication (COMPASS Trial): --*risk reduction* of major CV events in patients with chronic CAD or PAD -dosing considerations: 1. dosage form: tablet 2. strengths: 2.5mg, 10mg, 15 mg and 20 mg 3. must dose adjust in renal impairment 4. may crush tablet and mix with water or applesauce immediately before use 5. don't administer via feeding tubes placed distal to the stomach 6. doses >10 mg need to be taken with meals -*ADRs and contraindications:* 1. bleeding 2. elevations in AST/ALT, hyperbilirubinemia 3. uscle pains/spasms 4. avoid use in patients with moderate to severe hepatic impairment (Child-Pugh classes B and C) -drug Interactions: (a) CYP 3A4 and P-gp drug interactions (b) inhibitors increase rivaroxaban concentration -reversal: (a) antidote: *Andexanet Alfa* (Andexxa) (b) not dialyzable (c) for major bleeding, may also consider *prothrombin complex concentrate* (PCC), *activated PCC* (ie, FEIBA), or *recombinant factor VIIa*

What is betrixaban (Bevyxxa)?

-factor Xa inhibitor (a) indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE (b) to continue for *35-42 days* (started in the hospital and then continued at home) -dosing considerations: 160mg on day one, followed by 80mg once daily for 35-42 days -*ADRs and contraindications:* 1. bleeding 2. hypokalemia 3. GI effects (constipation, diarrhea, nausea) -reversal: (a) could consider *Andexanet Alfa* (Andexxa)? - however not studied (b) not dialyzable (c) for major bleeding, may consider *PCC*, *activated PCC* (ie, FEIBA), or *recombinant factor VIIa*

What are the dietary considerations with warfarin?

-foods with high vit K interact with warfarin --> cause INR decrease (a) kale, spinach, broccoli, brussel sprouts (b) nutrition supplements (i.e. Boost Shakes) -consistency = key to keeping INRs from fluctuating related to diet -assure patient understands they do not need to avoid these foods but to have a diet consistent in vit K-containing foods

What are the main types of parenteral anticoagulants?

-heparin -LMWH: enoxaparin (Lovenox), dalteparin (Fragmin) & tinzaparin (Innohep) -fondaparinux (Arixtra) -direct thrombin inhibitors: argatroban & bivalirudin (Angiomax)

How should you educate your patients who are taking warfarin?

-importance of: (a) compliance with taking meds daily (b) taking meds at the same time each day (c) getting INR checked -discuss foods ↑ in vit K and advise patients on importance of consistency with these foods -discuss drug interactions (a) OTC + INR effects (b) herbal supplements + INR effects -make sure patient informs the provider managing their warfarin of any medications that are added/changed/discontinued -discuss S/Sx of bleeding (a) difference between major and minor bleeding (b) what to do if they experience this -assure patient informs all medical providers of warfarin use

What are some important considerations regarding bleeding in coagulation therapy?

-increased risk 1. age >65 2. hx of GI bleed or peptic ulcer disease 3. alcohol use 4. chronic NSAID use 5. chronic aspirin or antiplatelet use --> copidogrel, prasugrel, ticagrelor, dipyridamole, cilostazol 6. renal insufficiency 7. malignancy 8. sx or major trauma *bleeding risk assessment tools:* HAS-BLED score

What is heparin-induced thrombocytopenia?

-severe, immune-mediated, drug-induced complication -differs from heparin-associated thrombocytopenia (HAT) (a) typically occurs 48-72 hours after initiation of heparin (b) mild and transient decrease in platelets -HIT most often occurs between 7-14 days of therapy -platelets drop *>50% from baseline* or fall to *< 100,000/mm^3* -may be associated with *venous thromboembolic complications*

How do you manage HIT?

-stop all forms of heparin -order heparin antibody lab (a) send out lab at many hospitals (b) while waiting, assess need for pharmacological anticoagulation vs mechanical vs no need at all (c) if positive --> patient should never receive heparin products again --> includes LMWH (enoxaparin) -if a parenteral anticoagulant is needed, may use: (a) argatroban (b) fondaparinux

Why do we anticoagulate?

-treatment & prevention (VTE): (a) DVT (b) PE -A-fib --> prevent stroke -mechanical heart valves -ACS (a) STEMI (b)UA (c) NSTEMI -hip/knee replacement sx (prophylaxis) -CABG -LV thrombus -hypercoagulable states

What is the bridging regimen for warfarin?

-warfarin must be stopped *4-5 days prior* to procedure -if bridging is required (high-risk patients): 1. start LMWH 24-36 hours after stopping warfarin 2. hold LMWH at least 12 hours prior to procedure 3. restart LMWH 12-24 hours after procedure* 4. restart warfarin 24 hours after procedure* 5. stop LMWH after 5 days AND therapeutic INR *if okay with surgeon and no minor bleeding complications

What are the ADRs for LMWH?

1. *bleeding:* -Hgb/HCT -signs/symptoms 2. *HIT* -occurs much more infrequently than compared with heparin, but still a risk -must avoid if history of HIT 3. *black box warning:* -use with *neural anesthesia or spinal puncture* can lead to increased risk of *spinal hematoma and paralysis* -reversal: (a) may be partially reversed by protamine (no as effectively as UFH reversal) (b) consider heparin over LMWH for: obesity, renal failure, surgical candidates

When is it appropriate to bridge?

1. *following DVT or PE* -must bridge with LMWH for at least 5 days AND therapeutic INR 2. *mechanical heart valve*: subtherapeutic INR 3. *A-fib*: subtherapeutic INRs -controversial if bridging needed - often used for high risk patients with CHA2DS2-VASc score ≥ 5 -should be used if hx of CVA/TIA or cardioversion in the last month 4. *peri-procedural* - warfarin must be held for 5 days prior to an invasive procedure -high risk patients may require bridging -goal INR < 1.5 for surgery (~1 for neurosurgery) -bridge with LMWH for 5 days prior to surgery and following surgery until INR is therapeutic

What are other methods for anticoagulant reversal?

1. *prothrombin complex concentrates (PCC):* -products derived from pooled human plasma containing coagulation factors II, VII, IX, and X -unlike plasma, PCC does not require blood group typing or thawing -products include: (a) profilnine SD and Bebulin VH: 3-factor PCCs (Inactivated factor II, IX, and X) (b) FEIBA NH (activated factor VII + inactivated factor II, IX, and X) (c) Kcentra (Inactivated factor II, VII, IX, and X) 2. *fresh frozen plasma:* -blood product containing all coagulation factors -kept frozen and must thaw 15-20 minutes prior to use -requires ABO blood testing

What disease states affect INR?

1. CHF exacerbation - increases INR 2. liver disease - increases INR 3. EtOH abuse - increases INR ("binge drinking") 4. thyroid disease: (a) hyperthyroid - increases INR (b) hypothyroid - decreases INR 5. malignancy 6. infections can be associated with INR instability (a) fever (b) diarrhea/dehydration (c) change in diet, metabolism, drug clearance

What is the warfarin dosing adjustment algorithm?

1. INR <2: increase dose by 5-15% 2. INR 3.1-3.5: decrease dose by 5-10% 3. INR 3.5-4: hold ~1 dose (decrease 10-15%) 4. INR >4: hold 1-2 doses (decrease 10-15%) *remember:* -don't just treat the number -just a guideline --> also must use clinical judgement & consider patient specific factors -dose adjustments made based upon weekly dose

What are the types of oral anticoagulants?

1. Vit K antagonist -Warfarin (Coumadin) 2. Factor Xa inhibitors - *Rivaroxaban (Xarelto)* -*Apixaban (Eliquis)* -Edoxaban(Savaysa) -Betrixaban (Bevyxxa) 3. Direct thrombin inhibitor -*Dabigatran (Pradaxa)* -new oral anticoagulants (NOAC)s = factor Xa & direct thrombin inhibitors -now referred to as direct oral anticoagulants (DOC)

What is the FDA approved dosing for DOACs?

1. apixaban: 2.5 mg BID 2. edoxaban: not approved 3. dabigatran (THA only): 110 mg within 1-4 hrs after sx, then 220 mg daily 4. rivaroxaban: 10 mg daily -patients with CrCl <30 mL/min --> not included in FDA trials -avoid use

What is the dosing regiment for warfarin (Coumadin)?

1. individualized dosing -tablets available as: (a) 1mg, 2 mg, 2.5 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7.5 mg, 10 mg --typically starting dose *~5 mg once daily* or for *healthy individuals* (b) may consider 10 mg once daily for 2 days followed by 5 mg daily 2. lower dosing should be considered with: -CHF or liver disease -malnourishment -increased bleeding risk -interacting medications -age *≥ 75* 3. dosing adjusted based on *INR results* -INR = International Normalized Ratio -healthy patients not on warfarin --> *normal INR = 1*

What are the recommended safety monitoring guidelines for DOACs?

1. renal function -prior to initiation to determine appropriate dosing -for CrCl >60 mL/min: *monitor annually* -for CrCl 30-60 mL/min, age >75 years, or presence of drug interactions: monitor *every 6 mo* -for CrCl 15-30 mL/min or fluctuating CrCl: *monitor every 3 mo* 2. CBC -*annually* for most patients -patients with low baseline hemoglobin or hematocrit, presence of drug interactions, or age >75 years: *monitor every 6 mo* or more if clinically indicated 3. Hepatic function -*annually* for most patients

How long do we a patient's first blood clot?

3-6 mo

ML is a 72yom who is on warfarin 6mg daily as a home medication for A- fib. For each scenario listed, determine whether you would expect ML's INR to increase or decrease. A. It is now spring and ML starts eating more fresh vegetables and salads. B. ML develops and upper respiratory infection and is started on levofloxacin. C. It's near the holidays and ML consumes more alcoholic beverages than normal.

A. decrease B. increase C. increase

LD is a 66 y/o F with a PMH of HTN, osteoarthritis, and GI bleed 4 years ago. She presented to the hospital with a TIA and was also found to be in A-fib. Would you recommend starting an anticoagulant for LD? If so, recommend a medication and monitoring plan.

CHA2DS2-VASc = 5 Throboembolism Rate (% per year) = 6.7% *options:* -Warfarin -Apixaban -Dabigatran -Edoxaban -Rivaroxaban

RF is a 32yof with no significant past medical history who presented to the ED with chief complaint of pain and swelling in her RLE. A venous Doppler was preformed which revealed a thrombus in the R femoral vein. Home medications: Lo-Loestrin 1 tablet PO daily Social Hx: smokes ½ PPD Pertinent labs: SCr 0.6, Hgb 13.4, Plt 258, INR 1 Wt = 83kg Which of the following would be an appropriate anticoagulation option for RF at this time? Select all that apply: A. Warfarin 5mg daily B. Warfarin 5mg daily + enoxaparin 80mg BID C. Warfarin 5mg daily + enoxaparin 40mg daily D. Heparin 5000 units subcu q8h E. Dabigatran 150mg BID F. Apixaban 10mg BID G. Rivaroxaban 20mg daily

Warfarin 5mg daily + enoxaparin 80mg BID Apixaban 10mg BID

True or false: warfarin is contraindicated in pregnancy.

true -pregnancy category X and should be avoided in pregnancy -pregnancy category D for patients with mechanical heart valves

What is bridging therapy?

use of short-acting anticoagulants (such as heparin or LMWH) for a period of time during interruption of warfarin therapy when the INR is not within therapeutic range

What are the FDA indications for each oral anticoagulant? A. tx of acute DVT/PE B. secondary prevention of DVT/PE C. primary prevention of DVT/PE D. VTE prevention in total hip & knee replacement surgeries E. risk reduction of stroke & systemic embolism in *non-vavular* AF F. thromboembolic complication associated with *vavular* AF and/or mechanical prosthetic cardiac valves G. reduction of risk of death, recurrent MI, and thromboembolic events after MI H. risk reduction of major CV events in patients with chronic CAD or PAD - in combo with ASA

warfarin: A (combo unti INR 2), B, E, F, G dabigatran: A, B, D (total hip only), E rivaroxaban: A (↑ starting dose), B, D, E, H (2.5 mg BID dose) apixaban: A (↑ starting dose), B, D, E edoxabab: A & E betrixaban: C