Chapter 34 - Anticoagulation Flashcards

Question

What could be some causes of emesis?

Answer 1

■ Coffee-ground emesis (vomit)- from bleeding in upper GI tract ■ Esophageal chronic reflux (esophagitis, Barrett's) ■ Stomach From ulcer (NSADI-induced) ■ Duodenal From ulcer (H. pylori-induced)

Answer 2

- From UTls - Kidney stones (calculi) - Prostatitis - Kidney disease

Answer 3

- Light red: from hemorrhoids, rectal tear - Black and "tarry" (sticky), smelly stool: from esophagus, stomach (NSAID-induced) or duodenum (H.pylori-induced) - Other causes of rectal bleeding: . Diverticulosis . Colon cancer . IBD (Crohn's, ulcerative colitis) . Colon polyps (benign or cancerous) --> Rectal bleeding from polyps can be occult (not visible, requires tests (FOBT) to identify) - Bloody diarrhea (dysentery}- from infection (C.difficile, Shigella, Entamoeba histolytica)

Answer 4

- Anticoagulants - Antiplatelets - NSAIDs - Natural products (ginkgo/SSRls, SNRls increase bleeding risk.

Answer 5

- UFH binds to antithrombin (AT) - Which then inactivates thrombin (factor Ila) and factor Xa (as well as factors IXa, Xla, Xlla and plasmin) - And prevents the conversion of fibrinogen to fibrin

Answer 6

1) Prophylaxis of VTE: 5,000 units SC Q8-12H 2) Treatment of VTE: 80 units/kg IV bolus; 18 units/kg/hr infusion 3) Treatment of ACS/ STEMI: 60 units/kg IV bolus (max 4,000 units); 12 units/kg/hr infusion (max 1,000 units/hr)

Answer 7

Total body weight

Answer 8

Onset: - IV: immediate - SC: 20-30 min -- t1⁄2 =1.5 hrs

Answer 9

HIT antibodies have cross-sensitivity with LMWHs

Answer 10

- Uncontrolled active bleed (intracranial hemorrhage) - Severe thrombocytopenia - History of HIT - Hypersensitivity to pork products Some products contain benzyl alcohol as a preservative (do not use in neonates, infants, pregnancy and breastfeeding)

Answer 11

Fatal medication errors: - Verify the correct concentration is chosen

Answer 12

- Bleeding (Epistaxis, bruising, gingival, GI) - Thrombocytopenia - HIT - Hyperkalemia - Osteoporosis (with long-term use) - Alopecia

Answer 13

- aPTT or anti-Xa level: . Check 6 hours after initiation and . Every 6 hrs until therapeutic . Then every 24 hrs . With every dosage change - aPTT therapeutic range: 1.5-2.5 x control - Anti-Xa therapeutic range: 0.3-0.7 units/ml - aPTT and anti-Xa monitoring are not required for SC (prophylactic) dosing - Platelets, Hgb, Hct at baseline and daily (dec in platelets > 50% from baseline suggests possible HIT)

Answer 14

- Unpredictable anticoagulant response (has variable and extensive binding to plasma proteins and cells) - Continuous IV infusions are common for treating VTE and ACS because heparin has a very short half-life

Answer 15

Do not give IM due to hematoma risk

Answer 16

Heparin lock-flushes (HepFlush) are only used to keep IV lines open.

Answer 17

- Fatal errors, especially in neonates, occurred when the incorrect heparin strength (higher dose) was chosen. - Heparin injection 10,000 units/ml and flushes 10 or 100 units/ml look and sound alike.

Answer 18

- Enoxaparin (Lovenox) - Dalteparin (Fragmin)

Answer 19

1 mg= 100 units anti-Xa activity

Answer 20

1) Prophylaxis of VTE: 30 mg SC Q12H or 40 mg SC daily -- CrCI < 30 ml/min: 30 mg SC daily 2) Treatment of VTE & UA/ NSTEMI - 1 mg/kg SC Q12H or - 1.5 mg/kg SC daily (only for inpatient VTE treatment) -- CrCI < 30 ml/min: 1 mg/kg SQ daily -- Use total body weight for dosing 3) Treatment of STEMI - Patients < 75 years: 30 mg IV bolus plus 1 mg/kg SC dose followed by 1 mg/kg SC Q12H -- CrCI < 30 ml/min: 30 mg IV bolus plus 1 mg/kg SC dose followed by 1 mg/kg SC daily - Patients >= 75 years: 0.75 mg/kg SC Q12H (no bolus) -- CrCI < 30 ml/min: 1 mg/kg SC daily (no bolus)

Answer 21

- Fragmin - Prophylaxis of VTE: 2,500 - 5,000 units SC daily - Treatment of UA/NSTEMI: 120 units/kg (max 10,000 units) SC Q12H

Answer 22

- Patients receiving neuraxial anesthesia (epidural, spinal) or - Undergoing spinal puncture --> Are at risk of hematomas and subsequent paralysis

Answer 23

- History of HIT - Active major bleed - Hypersensitivity to pork

Answer 24

- Bleeding - Anemia - Injection site reactions (pain, bruising, hematomas) - Dec platelets (thrombocytopenia, including HIT)

Answer 25

- Platelets, Hgb, Hct, SCr - Anti-Xa monitoring: -- No need (More predictable anticoagulant response than UFH -- Monitor in pregnancy -- Obtain peak anti-Xa levels 4 hours post SC dose - Monitoring may be done in obesity, low body weight, pediatrics, elderly or renal insufficiency - aPTT is not used -- It measures how long it takes for your blood to form a clot

Answer 26

- Antidote: protamine - Do not expel air bubble from syringe prior to injection (can cause loss of drug) - Do not administer IM - Store at room temperature

Answer 27

- Other anticoagulants - Anti platelet drugs - Some herbal supplements - NSAIDs, SSRIs, SNRls - Thrombolytics

Answer 28

- An immune-mediated IgG drug reaction - Has a high risk of venous and arterial thrombosis. - The immune system forms antibodies against heparin bound to platelet factor 4 (PF4), the antibodies then join with heparin and PF4 to create a complex, and this complex binds to the Fc receptors on platelets. - This causes platelet activation and a release of pro-coagulant microparticles. - If left untreated, HIT can lead to a prothrombotic state causing many complications including heparin-induced thrombocytopenia (most common sign of HIT) and thrombosis (HITT). - HITT leads to amputations, post-thrombotic syndrome and/or death. - The estimated incidence of HIT is -3% of patients exposed to heparin for more than four days. It is lower with a shorter duration of treatment. - The typical onset of HIT occurs 5 - 14 days after the start of heparin or within hours if a patient has been exposed to heparin within the past 3 months. - A diagnosis is made by: -- A compatible clinical picture -- An unexplained drop in platelet count (defined as > 50% drop from baseline) and -- Laboratory confirmation of antibodies (ELISA test and confirmatory serotonin release assay) or -- Platelet activation by heparin

Answer 29

1) Stop all forms of heparin and LMWH including heparin flushes and heparin-coated catheters. 2) Stop warfarin & Give vitamin K -- Although the patient is at a high risk of thrombosis, warfarin use with a low platelet count has a high correlation with warfarin-induced limb gangrene and necrosis. 3) Non-heparin anticoagulants (in particular, Argatroban) over heparin, LMWH or vitamin K antagonists. 4) Do not start warfarin therapy until the platelets have recovered to > 150,000/mm3 5) Warfarin should be initiated at lower doses (5 mg maximum). 6) Overlap warfarin with a non-heparin anticoagulant for a minimum of five days and until the INR is within target range for 24 hours. 7) Argatroban can increase the INR; the value must be interpreted cautiously. 8) If urgent cardiac surgery or PCI is required, bivalirudin is the preferred anticoagulant.

Answer 30

Direct - PO: - Apixaban (Eliquis) - Edoxaban (Savaysa) - Rivaroxaban (Xarelto) Indirect inhibitor of factor Xa (Inj): - Fondaparinux (Arixtra) -- Injectable synthetic pentasaccharide -- Selectively inhibits factor Xa via antithrombin (AT) -- Used off-label for HIT

Answer 31

Eliquis DVT/PE Starter Pack: 30-day blister pack Usual dose: 10 mg PO BID x 7 days, then 5mg PO BID Missed Dose: - Take immediately on the same day - Then twice daily administration should be resumed - The dose should not be doubled to make up for a missed dose

Answer 32

1) Nonvalvular AFib (stroke prophylaxis): 5 mg PO BID 2.5 mg BID IF 2 of the following are present: - Age >= 80 years - Weight <= 60 kg - SCr >= 1.5 mg/dl 2) Treatment of DVT/PE: 10 mg PO BID x 7days then 5 mg PO BID 3) Prophylaxis for DVT: 2.5 mg PO BlD -- For 12 days after knee replacement surgery -- For 35 days after hip replacement surgery - Give first dose 12-24 hours after surgery 4) Reduction in the Risk of Recurrence of DVT/PE: 2.5 mg PO BID after at least 6 months of treatment for DVT/PE

Answer 33

- 30-day blister pack containing 15 mg and 20 mg tablets (for ease of prescribing for DVT/PE treatment) Missed Dose: Take as soon as possible on the same day as follows: - If taking 15 mg twice daily: -- Take immediately to ensure intake of 30 mg/day (in this particular instance, two 15 mg tablets may be taken at once); -- Then resume regular schedule on the following day - If taking 10, 15 or 20 mg once daily: -- Take immediately on the same day; otherwise skip

Answer 34

1) Nonvalvular AFib (stroke prophylaxis) (Ens) - CrCI > 50 ml/min: 20 mg PO daily WITH EVENING MEAL - CrCI 15-50 ml/min: 15 mg PO daily WITH EVENING MEAL - CrCI < 15 ml/min: avoid use 2) Treatment of DVT/PE (To know) - 15 mg PO BID x 21 days then 20 mg PO daily with food -- CrCI < 30 ml/min: avoid use 3) Prophylaxis for DVT (after knee/hip replacement) (Ens) - 10 mg PO daily (for 12 days after knee or 35 days after hip replacement surgery); - Give first dose 6-10 hours after surgery - CrCI < 30 ml/min: avoid use 4) Reduction in the Risk of Recurrence of DVT and PE (Ens) - 10 mg PO daily after at least 6 months of standard treatment - CrCI < 30 ml/min: avoid use 5) Reduction in the Risk of Major CVD Events in CAD/PAD (Ens): 2.5 mg PO BID in combination with low-dose aspirin -- CrCI < 15 ml/min: avoid use 6) Prophylaxis of VTE in Acutely ill Medical Patients (Ens): 10 mg PO daily for a duration of 31 to 39 days -- CrCI < 30 ml/min: avoid use Doses >=15 mg must be taken with food; 10 mg dose can be taken without regard to meals

Answer 35

- >= 15 mg must be taken with food; - 10 mg dose can be taken without regard to meals

Answer 36

Take immediately on the same day; the dose should not be doubled to make up for a missed dose

Answer 37

Nonvalvular AFib (stroke prophylaxis): CrCI > 95 ml/min: do not use (to know) (Ens) - CrCI 51-95 ml/min: 60 mg daily - CrCI 15-50 ml/min: 30 mg daily - CrCI < 15 ml/min: not recommended 2) Treatment of DVT/PE - 60 mg daily - Start after 5-10 days of parenteral anticoagulation (To know) (Ens) - CrCI 15-50 ml/min, body weight <= 60 kg or on certain P-gp inhibitors: 30 mg daily - CrCI < 15 ml/min: not recommended

Answer 38

- All: -- Patients receiving neuraxial anesthesia (epidural, spinal) or -- Undergoing spinal puncture are at risk of hematomas and subsequent paralysis - Apixaban, edoxaban and rivaroxaban: premature discontinuation inc risk of thrombotic events - Edoxaban only: reduced efficacy in non valvular AFib patients with CrCI > 95 ml/min; do not use

Answer 39

Active pathological bleeding

Answer 40

Not recommended with: - Prosthetic heart valves or - Antiphospholipid syndrome Avoid in patients with: - Moderate to severe hepatic impairment

Answer 41

Generally well-tolerated, unless bleeding occurs Edoxaban: rash, inc LFTs

Answer 42

- Hgb, Hct, SCr, LFTs - No monitoring of efficacy required

Answer 43

1) Andexanet alfa (Andexxa) 2) Can be crushed and put on applesauce; crushed and mixed in water, D5W or apple juice or suspended in water to administer by NG tube 3) Betrixaban is no longer available in the U.S.

Answer 44

- Discontinue 24 hours prior to elective surgery (rivaroxaban, edoxaban) - Discontinue 48 hours prior to elective surgery with moderate-high bleeding risk or 24 hours prior with a low bleeding risk (apixaban)

Answer 45

Arixtra Injectable Indirect Factor Xa Inhibitor (SC)

Answer 46

1) Prophylaxis of VTE >=50 kg: 2.5 mg SC daily < 50 kg: contraindicated 2) Treatmentof VTE < 50 kg: 5 mg SC daily 50-100 kg: 7.5 mg SC daily > 100 kg: 10 mg SC daily Both Indications CrCI 30-50 ml/min: use caution

Answer 47

Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis

Answer 48

- Severe renal impairment (CrCI< 30 ml/min) - Active major bleed - Bacterial endocarditis - Thrombocytopenia with positive test for anti-platelet antibodies in presence of fondaparinux

Answer 49

- Bleeding (Epistaxis, bruising, gingival, GI) - Anemia - Local injection site reactions (rash, pruritus, bruising) - Thrombocytopenia - Hypokalemia - Hypotension

Answer 50

- Anti-Xa levels (3 hrs post-dose) - Platelets - Hgb - Hct - SCr

Answer 51

- Do not expel air bubble from syringe prior to injection - No antidote - Do not administer IM

Answer 52

1) Other anticoagulants (Avoid) -- Monitor for antiplatelet drugs, some herbals, NSAIDs, SSRis, SNRis, thrombolytics 2) Apixaban is a substrate of CYP450 3A4 (major) and P-gp. -- Avoid use with inducers of CYP3A4 and P-gp (carbamazepine, phenytoin, rifampin, St. John's wort). 3) Rivaroxaban is a substrate of CYP3A4 (major) and P-gp. - Avoid use with drugs that are combined P-gp and strong CYP3A4 inducers or combined P-gp and strong CYP3A4 inhibitors (ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, conivaptan). 4) Edoxaban is a substrate of P-gp; avoid use with rifampin. - When treating DVT/PE, reduce dose to 30 mg daily with verapamil, macrolides (azithromycin, clarithromycin, erythromycin) and oral itraconazole or ketoconazole. 5) Cobicistat (Tybost), Stribild and Genvoya (each containing cobicistat) can increase exposure to the factor Xa inhibitors. - Rivaroxaban should not be used with any of these medications.

Answer 53

- Rivaroxaban when INR is < 3 - Edoxaban when INR is <= 2.5 - Apixaban when INR is < 2 - Dabigatran when INR is < 2 (Remember: READ)

Answer 54

- Overlap Xa inhibitor with warfarin until INR therapeutic - Stop Xa inhibitor - Start parenteral anticoagulant and warfarin at next scheduled dose https://tam.nhsh.scot/healthcare-professional-information/therapeutic-guidelines/cardiovascular/anticoagulation/anticoagulant-switching/

Answer 55

- Start warfarin 1-3 days before stopping dabigatran (determined by renal function).

Answer 56

- Directly inhibit thrombin (factor Ila); - Bind to the active thrombin site of free and clot-associated thrombin.

Answer 57

- Pradaxa - Oral Direct Thrombin Inhibitor Missed Dose: - Take immediately unless it is within 6 hours of next scheduled dose; - The dose should not be doubled to make up for a missed dose

Answer 58

150 mg BID - CrCI 15-30 ml/min: 75 mg BID - CrCI<15ml/min: avoid use

Answer 59

- 150 mg BID - To know: start after 5-10 days of parenteral anticoagulation - CrCI <= 30 ml/min: avoid use

Answer 60

110 mg on day 1, then 220 mg daily CrCI <= 30 ml/min: avoid use

Answer 61

- Patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis - Premature discontinuation inc risk of thrombotic events

Answer 62

- Active pathological bleeding - Treatment of patients with mechanical prosthetic heart valves

Answer 63

Antiphospholipid syndrome

Answer 64

Dyspepsia, gastritis-like symptoms, bleeding (including more GI bleeding)

Answer 65

- Hgb, Hct, SCr - No monitoring of efficacy required

Answer 66

- Antidote: idarucizumab (Praxbind) - Protect from moisture; dispense in original container and discard 4 months after opening - Blister packs are good until the date on the pack - Swallow capsules whole (do not break, chew, crush or open); do not administer by NG tube - Can inc aPTT, PT/INR - Discontinue if undergoing invasive surgery -- 1-2 days before if CrCI >= 50 ml/min -- 3-5 days before if CrCI < 50 ml/min)

Answer 67

1) Argatroban Indicated for HIT and in patients undergoing PCI who are at risk for HIT 2) Bivalirudin (Angiomax) Indicated for patients with ACS undergoing PCI who are at risk for HIT

Answer 68

To know: - Used in patients at risk for HIT - Argatroban: dec dose in hepatic impairment - Bivalirudin: dec dose when CrCI <30 ml/min HIT - CrCI <= 30 ml/min: avoid use - Argatroban: start at 2 mcg/kg/ min, then titrate to target aPTT - Max: 10 mcg/kg/min PCI - IV bolus followed by an infusion; - All are weight-based

Answer 69

Argatroban & Bivalirudin CONTRAINDICATIONS Active major bleeding SIDE EFFECTS Bleeding (mild to severe), anemia MONITORING aPTT and/or activated clotting time (for bivalirudin), platelets, Hgb, Hct, renal function NOTES - Safe with history of HIT; no cross-reaction with HIT antibodies - No antidote - Argatroban can inc INR; if starting on warfarin concurrently, dose cautiously and do not use a loading dose of warfarin

Answer 70

■ Avoid using with other anticoagulants (unless benefit outweighs risk). - Monitor for additive effects with other drugs that can inc bleeding risk (antiplatelet drugs, some herbals, NSAIDs, SSRis, SNRis, thrombolytics). ■ Dabigatran is a substrate of P-gp; avoid use with rifampin. ■ Nonvalvular AFib: - If CrCl 30 - 50 mL/min and patient is taking P-gp inhibitors (dronedarone or systemic ketoconazole), reduce dose to 75 mg BID. - In severe renal impairment (CrCl 15 - 30 mL/min), avoid use with any P-gp inhibitors. ■ Other indications: avoid use with P-gp inhibitors in patients with CrCl< 50 mL/min. ■ Cobicistat (Tybost) and cobicistat-containing Stribild and Genvoya can increase exposure to dabigatran. - Recommendations depend on renal function and indication for dabigatran.

Answer 71

- Competitively inhibits the C1 subunit of the multi-unit vitamin K epoxide reductase (VKORCl) enzyme complex. - This reduces the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and proteins C and S.

Answer 72

- Coumadin, Jantoven - Tablet - Racemic mixture of R- and S- enantiomers with the S-enantiomer being 2.7-3.8 times more potent Missed Dose: - Take immediately on the same day - Do not double the dose the next day to make up for a missed dose

Answer 73

Healthy outpatients: - 10 mg daily for first 2 days - Then adjust dose per INR values Lower doses (< 5 mg) for: - Elderly - Malnourished - Taking drugs which can inc warfarin levels, - Liver disease - Heart failure - Have a high risk of bleeding Notes: - Take at the same time each day - Highly protein bound (99%)

Answer 74

BOXED WARNINGS Major or fatal bleeding CONTRAINDICATIONS - Pregnancy (except with mechanical heart valves at high risk for thromboembolism) - Preeclampsia/eclampsia - Possible miscarriage - Noncompliance - Hemorrhagic tendencies - Blood dyscrasias - Uncontrolled hypertension - Pericarditis or pericardial effusion - Bacterial endocarditis - Recent or potential surgery of the eye or CNS - Major regional lumbar block anesthesia or traumatic surgery resulting in large open surfaces

Answer 75

- Tissue necrosis/gangrene - HIT (contraindicated as monotherapy in the initial treatment of active HIT) - Systemic atheroemboli and cholesterol microemboli - Presence of CYP2C9*2 or *3 alleles and/or polymorphism of VKORC1 gene may increase bleeding risk (routine genetic testing is not currently recommended)

Answer 76

Bleeding/bruising (mild to severe), skin necrosis, purple toe syndrome

Answer 77

- Goal INR 2-3 (target 2.5): most indications -- VTE -- AFib -- Bioprosthetic mitral valve -- Mechanical aortic valve -- Antiphospholipid syndrome - Goal INR 2.5-3.5: high-risk indications such as -- A mechanical mitral valve -- 2 mechanical heart valves - Begin INR monitoring after the initial 2 or 3 doses, or if on a chronic, stable dose of warfarin, monitor every 4-12 weeks Hct, Hgb, signs of bleeding

Answer 78

Dental cleanings and single tooth extraction do not generally require a change in warfarin dosing, if INR is in therapeutic range

Answer 79

Pink (1 mg) Lavender (2 mg) Green (2.5 mg) Brown/Tan (3 mg) Blue (4 mg) Peach (5 mg) Teal (6 mg) Yellow (7.5 mg) White (10 mg) Please Let Greg Brown Bring Peaches To Your Wedding

Answer 80

■ Warfarin: - CYP2C9 (major) substrate - CYP2C19 (minor) substrate - CYP3A4 (minor) substrate - Inhibitor of CYP2C9 (weak) and 2Cl9 (weak). -- Avoid use with tamoxifen. ■ CYP2C9 inducers can dec INR; these include: - Aprepitant, bosentan, carbamazepine, phenobarbital, phenytoin, primidone, RIFAMPIN (large dec in INR), licorice and St. John's wort. ■ CYP2C9 inhibitors can inc INR; these include: - Amiodarone, azole antifungals (fluconazole, ketoconazole, voriconazole), capecitabine, fluvastatin, fluvoxamine, metronidazole, tigecycline, TMP/SMX and zafirlukast. -- When starting amiodarone, dec the dose of warfarin by 30-50%. ■ Other antibiotics: penicillins, including amoxicillin, some cephalosporins, quinolones and tetracyclines inc the anticoagulant effect of warfarin - monitor INR. ■ Check for CYP1A2, 2Cl9 and 3A4 interactions; these occur, but usually have less of an effect on INR.

Answer 81

■ NSAIDs, antiplatelet agents, other anticoagulants, SSRis and SNRis. These interactions inc bleeding risk, but the INR may not be increased. ■ Drugs that inc clotting risk (estrogen and SERMs) should be discontinued if possible.

Answer 82

■ Warfarin + Natural products: Monitor the INR closely - But some natural products contain plant salicylates (willow bark) which increase the risk of bleeding without increasing the INR. -- INC bleeding risk with warfarin: . "the 5 G's" (garlic, ginger, ginkgo, ginseng, glucosamine) . Dong quai . Vitamin E . High doses of fish oils . Grapefruit . Willow bark . Wintergreen oil -- DEC effectiveness of warfarin: . Green tea . Coenzyme Ql0 . St. John's wort. American ginseng may decrease the effects of warfarin, but there is evidence that both American and Panax ginseng inhibit platelet aggregation (listed above), which potentially has the opposite effect. ■ Any additions of vitamin K will dec the INR. - Stay consistent with the amount of vitamin K in the diet - Tube feeds should be held one hour before and after warfarin.

Answer 83

- Spinach - Broccoli - Brussel sprouts - Cabbage - Beef liver - Kale - Mustard greens - Swiss chard - Collard greens - Parsley Others: canola oil, cauliflower, chickpeas, cole slaw, coriander, endive, lettuce (red leaf or butterhead), soybean oil, some teas

Answer 84

- In healthy outpatients, the initial starting dose of warfarin should be 10 mg daily for the first two days, then adjust per INR values. - In patients with acute DVT/PE, start warfarin on the same day as the parenteral anticoagulant (enoxaparin or UFH) and continue both anticoagulants for a minimum of 5 days and until the INR is > 2 for at least 24 hours. Both criteria must be met. - Routine pharmacogenomic testing is not recommended. - Routine use of vitamin K supplementation is not recommended in patients taking warfarin. - For patients with stable therapeutic INRs presenting with a single subtherapeutic (low) INR value, routinely bridging with UFH or LMWH is not recommended. - For patients with previously stable therapeutic INRs who present with a single out-of-range INR of <= 0.5 below or above the therapeutic range, continue current dose and obtain another INR within 1- 2weeks. - For patients with consistently stable INRs on warfarin therapy, INR testing can be done up to every 12 weeks rather than every 4 weeks. - Warfarin is highly protein bound. Caution is advised with other highly protein bound drugs that may displace warfarin such as phenytoin, valproic acid and others

Answer 85

- Major adverse effect of anticoagulants: Bleeding - Life-threatening bleeding or requires surgery --> Give antidote - Protamine combines with strongly acidic heparin to form a stable salt complex, neutralizing the anticoagulant activity of UFH and LMWH. Other drug-specific antidotes include: - Phytonadione (vitamin K) - Praxbind - Andexxa - Kcentra is indicated for the urgent reversal of warfarin. - Prothrombin complex concentrates (PCCs) are sometimes used (off-label) for reversal of factor Xa inhibitors. - If PCCs are used in this manner, monitoring clotting tests (PT, PTT, INR, anti-Xa) to assess reversal is not useful and is not recommended.

Answer 86

Protamine sulfate 1) For IV UFH Reversal - 1 mg protamine will reverse ~100 units of heparin - Since UFH has a very short half-life, reverse the amount of heparin given in the last 2-2.5 hours; max dose: 50 mg 2) For LMWH Reversal - Enoxaparin given within the last 8 hours: 1 mg protamine per 1 mg of enoxaparin (can neutralize ~60% of the anti-Xa activity of LMWH) - Enoxaparin given > 8 hours ago: 0.5 mg protamine per 1 mg of enoxaparin - Dalteparin: 1 mg protamine for each 100 anti-Xa units of dalteparin

Answer 87

- Hypersensitivity - Hypotension - Cardiovascular collapse - Non- cardiogenic pulmonary edema - Pulmonary vasoconstriction

Answer 88

SIDE EFFECTS - Hypotension - Bradycardia - Flushing - Anaphylaxis MONITORING - aPTT - anti-Xa levels - cardiac monitoring {ECG, BP, HR) NOTES - Rapid IV infusion causes hypotension - Administer slow IV push {50mg over 10 minutes) - Inject without further dilution over 1-3 minutes

Answer 89

- ldarucizumab (Praxbind) Dose: 5 grams IV {given as 2 separate 2.5 gram doses no more than 15 minutes apart) WARNINGS Thromboembolic risk, risk of serious adverse reactions due to sorbitol excipient SIDE EFFECTS HA, dec K,delirium, constipation, fever NOTES Do not confuse with IDArubicin

Answer 90

- Andexanet alfa (Andexxa) Bolus, followed by infusion Dosing is specific to the Xa inhibitor, the dose and when the last Xa inhibitor dose was taken BBW: Thromboembolic risks, ischemic events, cardiac arrest, sudden death SIDE EFFECTS Injection site reaction, DVT,ischemic stroke, UTI, pneumonia NOTES Not indicated for reversal of factor Xa inhibitors other than apixaban and rivaroxaban

Answer 91

- Vitamin K or phytonadione (Mephyton) - IV/PO (SC route not recommended due to variable absorption; IM route not recommended due to risk of hematoma) BBW: Hypersensitivity reactions (anaphylaxis) SIDE EFFECTS: Anaphylaxis NOTES: Requires light protection during administration

Answer 92

- Antidote for warfarin reversal: - Factors: II, VII, IX, X, ProteinC, Protein S - BBW: Arterial and venous thromboembolic complications have been reported - CI: Disseminated intravascular coagulation (DIC) and known HIT (Contains heparin) - WARNINGS: Made from human blood and may carry risk of transmitting infectious agents - SIDE EFFECTS: HA, N/V/D, arthralgia, hypotension, dec K, thrombotic events NOTES: -- Administer with vitamin K -- Do not let drug back-up into line; will clot -- Refrigerate; allow to reach room temp prior to administration -- Each vial can have a different potency of multiple coagulation factors; actual potency is stated on the vial

Answer 93

- Antidote for warfarin reversal: (No 7) - WARNINGS Contains factors II, IX and X but low or non therapeutic levels of factor VII and should not be confused with Kcentra, which contains therapeutic levels of factor VII - Made from human blood and may carry risk of transmitting infectious agents (e.g.,viruses) NOTES Slow infusion and give antihistamine to minimize side effects Administer with vitamin K

Answer 94

- Antidote for warfarin reversal - BOXED WARNINGS Serious thrombotic events are associated with the use of factor VIia

Answer 95

- Elevated INRs--> increased risk of bleeding. - Vitamin K is used to reverse warfarin; it can be used by itself or with other medications for life-threatening bleeding. - Bleeding (regardless of the INR) will warrant more serious intervention. - Oral formulations of vitamin K (generally at doses of 2.5 - 5 mg) are preferred for reversal in patients without significant or major bleeding. - Vitamin K given subcutaneously (SC) has a slow onset and a variable response; avoid SC injections. - Avoid the intramuscular (IM) route due to the risk of hematoma formation. - Intravenous vitamin K should be used only when the patient is experiencing serious bleeding. - IV injection is reported to cause anaphylaxis in 3 out of 100,000 patients, so infuse slowly.

Answer 96

1) INR above therapeutic range but < 4.5 without bleeding: - Reduce or skip warfarin dose - Monitor INR - Resume warfarin when INR therapeutic - Dose reduction may not be needed if only slightly above therapeutic range 2) Supratherapeutic INR of 4.5-10 without bleeding - Routine use of vitamin K is not recommended if no evidence of bleeding - Hold 1-2 doses of warfarin - Monitor INR - Resume warfarin at lower dose when INR therapeutic - Vitamin K can be used if urgent surgery needed (<= 5 mg, with additional 1-2 mg in 24 hours if needed) or bleeding risk is high (1- 2.5 mg) 3) INR > 10 without bleeding - Hold warfarin - Give oral vitamin K 2.5-5 mg even if not bleeding - Monitor INR - Resume warfarin at a lower dose when INR is therapeutic 4) Major bleeding - Hold warfarin - Give vitamin K 5-10 mg by slow IV injection and four-factor prothrombin complex concentrate (PCC) - PCC suggested over fresh frozen plasma (FFP) due to risks of allergic reactions, infection transmission, longer preparation time, slower onset and higher volume.

Answer 97

■ Stop warfarin therapy approximately 5 days before major surgery. - In patients with a mechanical heart valve, AFib or VTE at high risk for thromboembolism, bridging therapy with LMWH or UFH is recommended (bridging means stopping the warfarin and using anticoagulant doses of the LMWH or UFH for a short period to prevent clotting). - Discontinue therapeutic-dose SC LMWH 24 hours before surgery (stop the UFH IV therapy 4 - 6 hours before surgery). - Patients at low risk for thromboembolism do not require bridging; stop the warfarin and restart after surgery when hemostasis is achieved. ■ If INR is still elevated 1- 2 days before surgery, give low- dose vitamin K (1- 2 mg). ■ If reversal of warfarin is needed in a patient requiring an urgent surgical procedure, give low-dose (2.5- 5mg) IV or oral vitamin K. ■ Resume warfarin therapy 12- 24 hours after the surgery, when there is adequate hemostasis.

Answer 98

- Symptoms of a DVT include pain in the affected limb and unilateral lower extremity swelling. - DVTs can be diagnosed with an ultrasound (or MRI or venography, in some cases). - A D-dimer (a lab test) can aid in the diagnosis. - If a PE is suspected, it is diagnosed with a pulmonary CT angiogram.

Answer 99

- The CHEST guidelines provide specific recommendations for the prevention of VTE depending on the patient's level of risk. - UFH, LMWHs, fondaparinux, rivaroxaban, apixaban and dabigatran are all approved for VTE prophylaxis. - If patients have a contraindication to anticoagulants (such as an active bleed) or have a high risk for bleeding, they will need non- drug alternatives to prevent VTE. - These options include intermittent pneumatic compression (IPC) devices or graduated compression stockings. - For long-distance travelers at risk for VTE (previous VTE, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity or known thrombophilic disorder), the following recommendations will dec VTE risk: -- frequent ambulation, calf muscle exercises, sitting in an aisle seat and using graduated compression stockings with 15- 30 mmHg of pressure at the ankle during travel. -- Aspirin or anticoagulants should not be used.

Answer 100

- Surgery - Major trauma or lower extremity injury - Immobility - Cancer or chemotherapy - Previous VTE - Pregnancy and postpartum period - Estrogen-containing medications or SERMs - Erythropoiesis-stimulating agents - Increasing age - Obesity - Inherited or acquired thrombophilia (antithrombin deficiency, factor V Leiden, antiphospholipid syndrome, protein C or protein S deficiency) - Acute medical illness - Venous compression (tumor, hematoma, arterial abnormality) - Inflammatory bowel disease - Nephrotic syndrome - Myeloproliferative disorders - Paroxysmal nocturnal hemoglobinuria - Central venous catheterization

Answer 101

- Any VTE that is caused by surgery or a reversible risk factor should be treated for 3 months. - If the VTE is unprovoked (unknown cause), extending therapy longer than three months is recommended, as long as the patient's bleeding risk is low-to-moderate. - If the risk of bleeding is high, limit the treatment to three months. - If a patient has two unprovoked VTE episodes, long-term treatment can be considered. - Estrogen-containing medications and selective estrogen receptor modulators (SERMs) are contraindicated in patients with history of, or current, VTE and should be discontinued. - For patients without cancer, dabigatran and the oral factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are preferred over warfarin for the first three months of treatment for a DVT in the leg or a PE. - For patients with cancer, LMWH is preferred over all oral anticoagulants (including warfarin). - In patients with an unprovoked DVT or PE who are stopping anticoagulation, aspirin is recommended to prevent recurrence (if there are no CI).

Answer 102

- AFib/ Aflutter --> Heart clots Risk --> Can go to brain and cause a stroke (cardioembolic stroke) or transient ischemic attack (TIA). -- !! Stroke prevention !! - AFib and Aflutter are common in patients with heart valve problems. -- Some require valve replacement surgery. - Mechanical (prosthetic) Valve - Animal (sometimes called a bioprosthetic) valve - Patients with mechanical heart valves have the highest risk for clotting/strokes and are treated with warfarin only. -- Factor Xa inhibitors and DTI are not approved for this population. - The majority of patients with AFib/AFlutter do not have heart valve involvement (called nonvalvular AFib), but they still require evaluation of their stroke risk. - The CHEST guidelines use the CHADS-VASc scoring system to estimate risk of stroke in AFib/AFlutter and guide therapy.

Answer 103

- AFib > 48 hours or unknown duration: -- Anticoagulation (if warfarin, target INR 2-3) for at least 3 weeks prior to and -- 4 weeks after cardioversion (regardless of method - electrical or pharmacologic) when normal sinus rhythm is restored. - AFib <= 48 hours duration undergoing elective cardioversion: -- Start full therapeutic anticoagulation at presentation -- Perform cardioversion, and -- Continue full anticoagulation for at least 4 weeks while patient is in normal sinus rhythm. - For patients staying in AFib, -- Chronic anticoagulation therapy may be needed for stroke prevention. -- Treatment depends on the number of risk factors present.

Answer 104

- Count the number of risk factors the patient has, then select the recommended therapy. - The higher the score, the greater the stroke risk and the more intensive the anticoagulant recommendations. -- CHF: 1 -- HTN: 1 -- Age >= 75 Years: 2 -- Diabetes: 1 -- Stroke/TIA Hx: 2 -- Vascular Disease: 1 (prior Ml, PAD, aortic plaque) -- Age 65-74 Years: 1 -- Sex: Female: 1 Recommendations: - No anticoagulation recommended: -- Score = 0 (males) -- Score = 1 (females) - Oral anticoagulation may be considered. -- Score >= 1(males) -- Score >= 2 (females) - Oral anticoagulation is recommended. Non-vitamin K oral anticoagulant (DOAC) is recommended over warfarin. -- Score >= 2 {males) -- Score >= 3 (females) DOAC:apixaban,rivaroxaban,edoxaban,dabigatran

Answer 105

- For prevention and treatment of VTE in pregnant women, LMWH is preferred over UFH. - Pneumatic compression devices can be used alone or with LMWH in select patients. - Since warfarin is teratogenic, women who require chronic warfarin therapy for mechanical heart valves or inherited thrombophilias are generally converted to LMWH during pregnancy. -- They may be switched back to warfarin after the 13th week of pregnancy, then back to LMWH close to delivery. - When LMWH is used in pregnancy, anti-Xa levels are recommended to monitor therapy. - The oral factor Xa inhibitors and direct thrombin inhibitors have not been adequately studied in pregnancy and are not recommended .

Answer 106

■ Can cause serious and life-threatening bleeding/bruising. ■ Tell physicians and dentists that you are using this medication before any surgery is performed. ■ Call your healthcare provider right away if you fall or injure yourself, especially if you hit your head. ■ Avoid alcohol. ■ Many drug interactions. ■ Missed dose: take as soon as possible on the same day. Do not take a double dose the next day to make up for a missed dose.

Answer 107

■ Take with a full glass of water; swallow capsules whole. ■ Can cause dyspepsia. ■ Only open one bottle of dabigatran at a time. After opening a bottle of dabigatran, use within 4 months. ■ Keep dabigatran in the original bottle or blister package. Do not put dabigatran in pill boxes or pill organizers. ■ Missed dose: if your next dose is less than six hours away, skip the missed dose.

Answer 108

■ Atrial fibrillation: take once daily with the evening meal. ■ Blood clots in the veins of your legs or in the lungs: take once or twice daily as prescribed with food at the same time each day. ■ Missed dose: if taken twice daily, can take two doses at the same time to make up for the missed dose.

Answer 109

■ SQ: choose an area on the right or left side of your abdomen, at least two inches from the belly button. Wash your hands and clean the site. ■ Remove the needle cap by pulling it straight off the syringe. Do not twist the cap off as this can bend the needle. ■ Do not expel the air bubble in the syringe prior to injection unless your healthcare provider has advised you to do so. ■ Hold the syringe like a pencil. Pinch an inch of skin to make a fold. Insert the full length of the needle straight down at a 90 degree angle into the fold of the skin. ■ Press the plunger with your thumb until the syringe is empty. ■ Pull the needle straight out at the same angle that it was inserted, and release the skin fold. ■ Point the needle down and away from yourself and others, and push down on the plunger to activate the safety shield. ■ Do not rub the site of injection as this can lead to bruising. Place the used syringe in the sharps collector.

Answer 110

■ Take at the same time every day. ■ Ask your pharmacist if your tablet looks different. ■ Can rarely cause: o Purple toe syndrome (painful toes and purple discoloration). o Death of skin tissue (with pain). ■ Frequent blood monitoring required (INR). ■ Consistent intake of vitamin K required (mainly found in green, leafy vegetables).

Chapter 34 - Anticoagulation Flashcards

(136 cards)