Lecture 19-22 Thromboembolism Flashcards

Question

What are drugs which cause inducing DDIs with DOACs and are contraindicated/cautioned with concomitant use, and their MOAs of DDI?

Answer 1

Rifampin: P-gp and 3A4 induction Carbamazepine: strong 3A4 and P-gp inducer Phenytoin: strong 3A4 and P-gp inducer Phenobarbital: strong 3A4 and P-gp inducer

Answer 2

competitively inhibits Vitamin K epoxide reductase complex subunit 1 (VKORC1) an enzyme that plays a part in activating available vitamin K ⇒ therefore it leads to inhibition of clotting factors II (prothrombin), VII, IX, and X

Answer 3

prothrombin time (PT) INR standardizes the PT to allow universal interpretation = patient PT/mean normal PT INR crudely measures time it takes for blood clot to form INR without warfarin = 1.0 (0.8-1.2) ⇒ with warfarin = 2.0-3.0, 2.5-3.5 the INR range for VTE is 2-3

Answer 4

has a delayed effect ⇒ must cross-over using a rapid acting anticoagulant = a parenteral one (LMWH, fondaparinux, UFH) overlap at least 5 days until the INR is at least 2.0 for 24 hours (= 2 consecutive days) should be started on the day parenteral is used for those at high risk of clot in 1st month and whose INR falls below 2 should have cross-coverage using rapid acting anticoagulant (ex. LMWH, fondaparinux, UFH)

Answer 5

dose ranges from 0.5 mg QD - 38 mg QD, dose response is curvilinear Phases: 1. Initiation: establishing INR target, hospitalized vs ambulatory, stability of dosing achieved 2. Maintenance: ongoing achievement of INR

Answer 6

if pt is sufficiently healthy for outpatient tx ⇒ initial dose 10 mg x 1-2 days, with INR measure on day 2 or 3 if pt is elderly, debilitated, malnourished, CHF, liver disease, recent surgery, drug intx ⇒ initial dose

Answer 7

clotting factors are at Css, make small changes in response to INRs out of range unless changes that may impact warfarin are identified full effect of a given dose may not be evident until 3-5 days after should use weekly (even past 10 days) doses to guide future due to: delayed effect, response not linear With INR Target of 2.5 (3.0): <1.5 (1.9) ⇒ reload 0-2x, increase weekly dose by 5-15% 1.5-1.9 (2-2.4) ⇒ reload 0-1x, increase weekly by 0-10% 2-3 (2.5-3.5) ⇒ no change, 3.1-3.5 (3.6-4) ⇒ hold 0-1x, decrease weekly by 0-10% 3.6-4.9 (4.1-4.9) ⇒ hold 0-2x, decrease weekly by 5-15% 5-9 ⇒ hold warfarin, use vitamin K 1-2.5 mg PO x 0-1 >9 ⇒ hold warfarin, vitamin K 2-5 mg PO

Answer 8

A. Induction/inhibition of Cyt P450 ⇒ major 2C9, minor 3A4 and 1A2 B. Displacement of plasma binding proteins C. alterations in Vitamin K status D. contributing to bleeding/clotting risk

Answer 9

A. Changes to health ⇒ acute changes (fever, flu, diarrhea, etc), chronic changes - exacerbation of HF, alterations in thyroid fxn, etc B. Changes to Meds C. Changes to lifestyle ⇒ vitamin K intake, alcohol consumption, level of activity

Answer 10

if an INR > 5 check for S&S or bleeding, unusual bruising or something more concerning clot vs bleed risk, factors contributing to the critical INR Management/Recommendations: if INR 4.5-10 ⇒ omit 1-2 warfarin doses, consider vitamin K PO 1-2.5 mg and reassess IN if INR > 10 ⇒ hold warfarin, vitamin K PO 2.5-5 mg and reassess INR

Answer 11

Vitamin K ⇒ oral works within 16-24 hours, IV in 6-8 hours, SC and IM not recommended Prothrombin Complex Concentrate (Factors II, VII, IX, X) ⇒ temporary reversal of INR within minutes, used for urgent bleeding cases

Answer 12

bleeding - major and minor teratogenic - 6-12 weeks gestation, lower body weight, slower growth, intellectual disability, hypoplastic nose, stippled epiphyses, skeletal and ocular abnormalities,, Rare: skin necrosis, purple toe syndrome

Answer 13

Drugs: LMWH (SC) - enoxaparin, dalteparin, tinzaparin,,, Fondaparinux (SC) UFH (SC or IV) they act quickly, indirectly act as cofactor to impact clotting factors in circulation MOA: LMWH - anti Xa >> anti IIa, is smaller molecule so mainly inhibits Xa, pentasaccharide that binds to antithrombin = accelerated interaction with Xa Fondaparinux - anti Xa, synthetic pentasaccharide sequence that binds to antithrombin UFH - anti IIa >> anti Xa, larger molecule than LMWH so it can wrap around IIa, pentasaccharide that binds to antithrombin they ALL require antithrombin = they aren't direct acting unlike DOACs which don't require cofactor

Answer 14

UFH onset is immediate with t1/2 of 1-2 hours, LMWH peaks at 2-4 hours and t1/2 of 4-6 hours, while fondaparinux peaks at 3 hours with t1/2 of 17-21 hours they are all dosed based on weight, but if CrCl < 30 then LMWH and fondaparinux are not recommended the antidote for UFH is protamine, as well as for LMWH but it's not as effective, fondaparinux doesn't have one

Answer 15

situations wherein reversal of anticoagulant effect may be anticipated (extensive clot, circulatory compromise = massive PE) ⇒ IV drip typically used renal dysfunction (CrCl <20) is monitored using PTT

Answer 16

since it's primarily renally eliminated (enoxaparin >> dalteparin > tinzaparin): CrCl <20 = use UFH, if 20-30 = tinzaparin, >30 = any three for obese patients its recommended to dose based on total body weight (TBW), with no dose capping and admin Q12H pretty much exclusively uses pre-filled syringes Monitoring: recommends against routine anti Xa level monitoring, may be used to assess if potentially unsure of dosing (ex. weight extremes, renal dysfunction, failure of tx)

Answer 17

bleeding - less with LMWH vs UFH, hematoma at injection site osteoporosis - increases with tx duration, lower risk with LMWH,, alopecia Heparin-induced thrombocytopenia (HIT) - Type I: non-immune mediated, transient, mild, early onset <4 days and reversible Type II: immunologic rxn, severe, more common with UFH vs LMWH, delayed 5-14 days, can be with 1 day if exposure in last 100 days = thrombotic disorder in 20-50%, limb amputation in 10%, fatal in 8-20%

Answer 18

Monitoring: Low risk (<0.1%) - pt with medical and obstetrical getting LMWH, or LMWH after minor surgery or trauma = no monitoring intermediate (0.1-1%) - medical and obstetrical with UFH, LMWH after major surgery or trauma = platelet count Q2-3D for 4-14 days until heparin stopped High (>1%) - surgical and trauma pt getting UFH = platelet counts at least Q2D for 4-14 days or until heparin stopped Indication: platelet count typically falls below 150 x 10^9/L, however decrease from baseline of 40-50% is hallmark, S&S - clot, skin necrosis/lesions at injection site, systemic rxn after bolus Tx: stop UFH/LMWH immediately, reverse warfarin with Vitamin K if bridging, initiate tx doses of an alternative non-heparin anticoagulant ⇒ Direct thrombin inhibitor: lepirudin, argatroban, bivalirudin (all short acting IV), danaparoid (heparanoid), fondaparinux, DOACs

Answer 19

recommended for a 3-month treatment phase, and on completion of the 3 months all patients should be assessed for extended phase therapy,, in practice we often see a 6 month treatment phase,,,, if VTE provoked by major transient risk factor - surgery with general anesthesia > 30 min, hospital bed confinement, >/= 3 days with acute illness, caesarean section ⇒ recommended AGAINST EXTENSION if VTE provoked by minor transient risk factor - surgery with general anesthesia < 30 min, hospitalized < 3 days with acute illness, estrogen tx, pregnancy or puerperium, confinement to bed out of hospital for at least 3 days with acute illness, leg injury associated with reduced mobility for at least 3 days ⇒ favours SUGGESTION AGAINST EXTENSION if absence of transient provocation - unprovoked VTE or persistent risk fx ⇒ recommended FOR EXTENSION

Answer 20

apixaban 5 mg BID ⇒ 2.5 mg BID (AMPLIFY EXTENSION) - similar efficacy to 5 mg rivaroxaban 20 mg QD ⇒ 10 mg QD (EINSTEIN CHOICE) - similar efficacy with less bleeding

Answer 21

in pt indicated - suggest use of reduced-dose apixaban 2.5 mg BID OR rivaroxaban 10 mg QD over full dose of either agent can also recommend reduced dose DOAC over aspirin or no tx, and suggest rivaroxaban over aspirin in pt with unprovoked proximal DVT or PE and stopping anticoagulants and no contra to ASA then can use ASA to prevent recurrent VTE

Answer 22

useful in pt with acute proximal DVT with contra to therapeutic anticoagulation due to high bleeding risk reduces risk of fatal PE in short-term and increases risk of DVT in long-term presence of permanent one may require long-term anticoagulation if it is a retrievable filter the removal rates are poor (20%)

Answer 23

occurs in nearly 1/3 of pt within 5 years after unprovoked DVT characterized by: pain - not as bad as DVT pain, usually worse after being on feet edema - usually will decrease after feet are elevated unlike DVT, and it gets worse as leg is used, whereas with DVT its bad all the time hyperpigmentation, eczema, varicose collateral veins, venous ulceration severe cases can lead to intractable painful venous leg ulcers requiring ongoing nursing and medical care

Answer 24

can be used to reduce acute sx of DVT or chronic sx in those with PTS worn during waking hours, may start wearing within 1 month, designed to fit tight on leg to assist in moving blood from leg veins to circulation Contra: arterial insufficiency, intermittent claudication, uncontrolled HF, infection in area covered by stocking

Answer 25

serious complication of PE,, up to 5% of pt with PE are reported to develop this thromboembolism may fail to resolve and organize into fibrotic deposits = permanent occluding of pulmonary arteries initial phase of disease often asymptomatic and followed by progressive dyspnea and hypoxemia right HF can frequently occur progressive condition associated with mortality rates of 4-20%

Answer 26

prophylactic anticoagulation with rivaroxaban 10 mg QD OR fondaparinux 2.5 mg QD if: this > 5 cm long that is 3 cm away from SFJ or SPJ, if severe sx or risk extension therapeutic anticoagulation (x 3 months) if: concomitant VTE, this within 3 cm SFJ or SPJ PRN use of topical NSAIDs, compresses (warm and cool), compression stockings

Answer 27

Stenosis - mechanical obstruction to blood flow, net result of reduced valve orifice area (mitral, aortic) Regurgitation - backward flow of blood, leaky valve, may be called 'insufficiency' (mitral, aortic) Prolapse - fall or slip down (mitral)

Answer 28

Bioprosthetic (Tissue): heterograph (porcine), less durable with up to 30% failure rate at 10-15 years, less thrombogenic Prosthetic (Mechanical): 3 gens - ball cage, single leaflet, double leaflet more durable, more thrombogenic

Answer 29

Mechanical Valves: uses anticoagulant +/- antiplatelet (usually warfarin + ASA 50-100 mg/day) for aortic goes from 12% chance to 0.5%, for mitral goes from 23% to 0.9% (MITRAL HAS HIGHER RISK THAN AORTIC) Bioprosthetic: highest risk of thrombosis < 3 months post-surgery, long term risk at 0.2-0.6% per year, up to 30% failure at 10-15 years anticoagulant for some and antiplatelet long-term (ex. antiplatelet alone, or warfarin for 3 months then antiplatelet (more likely with mitral to use warfarin)) DO NOT USE DOACs for PATIENT WITH MECHANICAL HEART VALVES

Answer 30

must hold warfarin for 5 days prior to procedure ⇒ then will take it >/= 4 days after procedure to achieve therapeutic anticoagulation, can take at 1.5 x maintenance dose for 3 days then assess INR,,, if clotting risk is high may need to bridge with LMWH

Lecture 19-22 Thromboembolism Flashcards

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