Baker Thrombosis Part 2 PDF

Identify individuals at moderate or high risk of developing VTE. For VTE Prevention, which drugs are used following orthopedic & non-orthopedic surgery For medically ill patients, name drug (brand/generic), route, dose, and frequency For VTE Treatment, name drugs (brand/generic), route, dose, and...

Identify individuals at moderate or high risk of developing VTE. For VTE Prevention, which drugs are used following orthopedic & non-orthopedic surgery For medically ill patients, name drug (brand/generic), route, dose, and frequency For VTE Treatment, name drugs (brand/generic), route, dose, and frequency for overlapping, switching, and oral monotherapy as well as appropriate duration of therapy For massive PE, know who are candidates for initial thrombolytic therapy Unfractionated Heparins What is the biggest challenge Narrow therapeutic index with unfractionated heparin? MUST monitor anticoagulant effect What two factors can you use Antifactor Xa, aPPT to monitor anticoagulant effects of continuous infusion unfractionated heparin? How often do you monitor Measure prior to initiation to determine baseline UFH? IV UNH at BASELINE and then 6 hours after Either use aPTT OR anti10a. Not both, one or the other What are some adverse effects BLEEDING!! of UFH? LOW PLATELETS ( Thrombocytopenia ***Platelet monitoring is key to safety What factors can increase Antiplatelet drugs, NSAIDs, other antithrombotic therapy bleeding? What are the 4 T’s in diagnosis? Thrombocytopenia Timing of platelet count fall Thrombosis OTher explanation for falling platelets What lab measures whether Hemoglobin and hematocrit dropping -> losing blood somewhere in body someone is bleeding or not? What important things do you APTT or anti10a efficacy have to monitor in someone Platelets for safety taking UFH? Hemoglobin and hematocrit NOT monitoring for bleeding Low Molecule Weight Heparins Difference between LMWH and Smaller side chain UFh? Can bind to IIa but cant hold on as it could Inhibit more 10a than 2a because smaller side chain What 3 LMWH are available? Enoxaparin (Lovenox) Dalteparin (Fragmin) Tinzaparin (Innohep) What are some pros of LMWH Predictable anticoag dose response over UFH? Improved SC bioavail Dose-independent clearance Long half life Better absorption Difference between dosing in Enoxaparin dose = milligrams enoxaparin vs dalteparin and Dalteparin & tinzaparin doses = units of antifactor Xa activity tinzaparin? LMWHL Monitoring Not necessary due to predictable anticoag response w SQ administration Obtain baseline labs-> CBC w platelets, serum creatinine Monitor: Anti-10 activity, serum creatinine What are LMWH Patient history of HIT contraindicated in? What is the monitoring AntiXA parameter for LMWH? APTT does not inhibit factor IIa as much as UFH What is the difference in timing LMWH = baseline then 4 hours between LMWH and UFH? UFH = baseline then 6 hours T/F: aPTT tells you nothing True about LMW. You must look at anti-Xa Name some side effects of Bleeding (less than UFH) LMWH Epidural and spinal hematomas in pts with epidural catheters Thrombocytopenia -> AVOID WITH HIT HISTORY -> Safe in pregnancy!!! Fondaparinux T/F: Fondaparinux has 2 tails False. and is a pentasaccharide. NO TAIL -> does nothing to thrombin Thrombin says hi and leaves T/F: Fondaparinux holds onto False. thrombin tightly. It CANNOT hold onto it What does Fondaparinux Xa inhibit? Unlike UFH and LMWH, Does NOT impact platelet function Fondaparinux... What is the main indication for Patients with HIT the use of Fondaparinux? Brand name of Fondaparinux Arixtra What do you monitor in Hemoglobin, hematocrit, kidney function (SCr) Fondaparinux? NOT PLATELETS BC NO IMPACT Which classes are given SQ? LMWH and Fondaparinux Fondaparinux is dosed... Once daily Reminder: UFH -> Looking at aPTT or anti-Xa  LMWH -> Looking at anti-Xa, SCr Fondaparinux -> Nothing just kidney function it has stable PK Is Fondaparinux safe in elderly? Yes, but bleeding risk increases with age Pregnancy? Yes in pregnancy Most common ADE? Bleeding When should you discontinue When CrCl < 30 mL/min Fondaparinux? Warfarin What does it require? Continuous monitoring and patient education Narrow therapeutic index Many food and drug intx What is the MOA of Warfarin? Racemic mixture of R and S What is S isomer metabolized CYP2C9 by? What is R isomer metabolized Everything else -> CYP1A2 and 3A4 by? SNOT Factors Vitamin K Dependent Clotting Factors Seven, Nine, Ten, Two VII, IV, X, II Shortest half life -> longest Seven has half life of few hours -> couple days What to monitor in warfarin? Prothrombin time (PT), NOT aPTT INR What is the target INR in most Target: 2.5 (2-3.0) indications? What does a high INR mean More anticoagulation/higher bleed risk What does a low INR mean Not enough anticoagulation/ higher clot risk What is the body’s normal INR 1 How frequent is INR monitoring Hospitalized pts -> On 2nd day, then QD until INR is in therapeutic range (2-3.0) for Warfarin? Outpatient -> Check twice in first week  DONT GIVE INR DAILY – hyperreaction What to do when INR dose is Check INR every 1-2 weeks until INR stabilized established? Then check every 4-6 weeks Recheck in 1 week from dosage change, then every 1-2 weeks until INR stabilized, then every 4-6 weeks What is normal warfarin dose? Starting dose = 5 mg/day Lower dose in pts more prone to bleeding Elderly Poor nutrition Liver disease Genetic polymorphisms Concurrent interacting medicine Elevated baseline INR Why does it NOT make sense to Warfarin not anticoagulated quick even though labs may be better give loading dose of warfarin? FDA approved warfarin dose Can do it but makes no difference in most people range What do guidelines Against the routine use recommend in terms of pharmacogenetic testing for guiding doses of VKA? Warfarin: Drug-drug Alterations in hepatic metabolism interactions Drugs inhibiting/inducing CYP 2C9, 1A2, 3A4 isoenzyme shave greatest potential to impact What do they resutl from? INR/bleeding Drugs altering hemostasis or platelet function can increase bleeding risk without affecting INR Why pay attnetion to leafy High in vitamin K greens? Vitamin K counteracts warfarin -> decreases INR (more plone to clot) Which CYPs increase IN CYP inhibitors -> 1A2, 2C9, 3A4 More bleeding  More warfarin -> more anticoagulation -> INR increases -> more bleeding Which CYPs decrease INR? CYP inducers (seizure meds) - more prone to clot Ie phenytoin If you have someone on warfarin and phenytoin, phenytoin increases CYPs -> less anticoagulation -> INR decreases -> more prone to clot If a patient is eating lots of Decrease green leafy veggies (lots of Vit This means patient is more prone to.... K), does INR increase or Clot risk decrease? Warfarin Adverse Effects Bleeding/hemorrhage complications Warfarin DOES NOT CAUSE bleeding o It exacerbates bleeding from previous/exisitng lesions o You are not going to spontaneously start bleeding Purple-toe syndrome Warfarin-induced skin necrosis Watch bleeding- SHOULD NOT OCCUR IN nose, gums, skin, urine, stool, teeth when brushing, vagina, GI o Stool – pink, red, black ,tarry o Seek medical attention Direct Oral Anticoagulants MOA? - Dabigatran = direct thrombin inhibitor - Rivaroxaban, apixaban, edoxaban = Xa inhibitors - Direct = do not require cofactoring with thrombin - Free and clot bound Drug-Drug Interactions Dabigatran is the most eliminated in the urine and most susceptible to kidney function changes o IMPORTANT TO LOOK AT KIDNEY FUNCTION Apixaban is the least renally eliminated, used in people with bad kidneys  Rivaroxaban most CYP3A4 interactions, a little less with apixaban PgP drug-drug interactions - pretty much all of them What do you monitor? Just bleeding, no labs Can monitor kidney function and hematocrit/hemoglobin If someone has bad kidneys, Lean towards apixaban what do you use? Which DOACs are CYP3A4 and A and D P-gp substrates? a) Rivaroxaban b) Edoxaban c) Dabigatran d) Apixaban Which DOACs do NOT undergo F and G signiifcant CYP 3A4 metabolism but are both P-gp substrates? e) Rivaroxaban f) Edoxaban g) Dabigatran h) Apixaban Note - P-glycoprotein inhibitors = amiodarone, propafenone, quinidine, verapamil - P-glycoprotein inducers = carbamazepine, rifampin