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Block 2.3

Day 1: Dr. Riccio Hemostasis & Antithrombitics

QuestionAnswer
What is the process of hemostasis? 1.) Vasoconstriction 2.) Platelet adhesion, activation, & aggregation = plug 3.) Clotting cascade activation = fibrin clot 4.) Dissolution of clot, fibrinolysis
T/F In a healthy vessel wall, goal is to promote vasodilation. T
What is composed inside the endothelial lining of a healthy vessel wall? Nitric oxide (NO), Prostacyclin, and Adenosine diphosphatase (ADPase)
T/F In an injured vessel wall, goal is to promote vasoconstriction. T
What is composed inside the subendothelial matrix of an injured vessel wall? Endothelin, exposed collagen, vWF, fibrinogen, and tissue factor
What happens during platelet plug formation? 1. Adhesion (GP1a to collagen, GP1b to vWF to collagen) 2. Activation (Conformational change to express GP2b/3a, degranulation of vesicles, release of thromboxane-A2 (TXA2)) 3. Aggregation (GP2b/3a to fibrinogen to GP 2b/3a, GP 2b/3a to vWF to GP 2b/3a)
What happens during the activation phase during platelet plug formation? Recruitment of platelets, conformational change, degranulation of vesicles, and release of TXA2
What happens during the aggregation phase during platelet plug formation? Platelets binding together to form plug
What antiplatelet medications block ACTIVATION? Anti-thromboxane (Aspirin) ADP Receptor Antag (thienopyridines: ticlopidine(Ticlid), clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta)) PDE inhibitor (dipyridamole (Persantine), cilostazol (pletal)) Combo (dipyridamole ER/ASA (Aggrenox))
What antiplatelet medications block AGGREGATION? GP2b/3a antagonist (abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat))
What is ASA? MOA? Administration? Who should avoid? ADRs? Aspirin, irreversible COX inhibitor, DO NOT CRUSH EC tabs, with food or full glass of water to minimize GI distress, for AMI, pt chew tab. AVOID pts under 16, pts who are preg or breastfeeding. ADRs: GI discomfort, bronchospasm, tinnitus, rash, bleeding
What are Thienopyridines? MOA? ticlopidine(Ticlid), clopidogrel (Plavix), prasugrel (Effient), ticagrelor (Brilinta). IRREVERSIBLE bind to P2Y12 receptor.
What are the BBWs for each Thienopyridine med? Ticlid: neutropenia/agranulocytosis, TTP, and aplastic anemia (CBC q2 wks) Plavix: alt treatment for CYP2C19 poor metabolizers. Effient: C/I in pts >75 YO, less than 60 kg (consider 5mg daily), history of CVA, active or patho bleeding, thromoboctyopenia
What is Brilinta? MOA? BBW? ticagrelor, cyclopentyltriazolopyramidine, REVERSIBLY binds to P2Y12 receptor. BBW: caution bleeding risk and concomitant use of ASA > 100mg will decrease efficacy
What are GP2b/3a receptor antagonists? MOA? abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat)), blocks GP2b/3a receptors which decreases adhesion and aggregation
What are PDE inhibitors? MOA? dipyridamole (Persantine), dipyridamole ER/ASA (Aggrenox), cilostazol (pletal), inhibits PDE activity within the platelet, increasing cAMP & GMP, therefore decreasing platelet activation
What promotes the clotting cascade? Thrombin (LOW concentrations) and Xa (feedback activates VII)
What inhibitors the clotting cascade? 1.Thrombin (HIGH concentrations), complexes with thrombomodulin to active Protein C, Protein C & S with APC complex deactivates Va and VIIIa. 2. Antithrombin III: irreversibly binds 2a,9a,10a,11a, and 12a
What factors does VKA block the formation of? 2,7,9,10 and Protein C & S
What factors do DTI block the formation of? 2a (thrombin) directly
What factors do Anti-FXa block the formation of? 10a directly
What factors do UFH-ATIII block the formation of? 10a, 2a and Intrinsic factor pathway
What factors do LMWH-ATIII block the formation of? 10a and 2a, more selective for 10a
What factors do Synth. Pentasac-ATIII block the formation of? Selective for 10a only.
T/F UFH is safe for pregnancy and lactation patients T
What is the dosing for VTE prophylaxis of UFH? 5000 units SC q8-12hrs
What is the dosing for VTE treatment of UFH? 80 units/kg IV bolus, then 18 units/kg/hr CIVI
What is the dosing for Afib treatment of UFH? 333 units/kg SC bolus, then 250 units/kg SC q8 hr
What do we use to monitor UFH? What is the therapeutic range? aPPT or PTT , Therapeutic range: 1.5-2.5 x normal aPTT Anti-factor Xa level therapeutic range: 0.3 - 0.7 IU/mL ACT: bedside
What are the ADRs and Drug interactions of UFH? Bleeding, HIT/HAT, and osteoporosis with chronic use. D/I: antiplatelet, anticoagulant, fibrinolytic, NSAIDS
T/F LMWH is safe in pregnancy (NOT during labor/delivery) T
What is the dosing for VTE prophylaxis of Lovenox? 40 mg SC daily 30 mg SC q12 hr (Orthopedic surgery ONLY) Renal: CrCl <30 ml/min: 30 mg SC daily
What is the dosing for VTE/ACS treatment of Lovenox? 1 mg/kg SC q12 hr 1.5 mg/kg SC daily Renal: Crcl <30 ml/min: 1 mg/kg SC daily
How do we monitor LMWH? Renal function (SCr), platelet count, and Anti-factor Xa( not routinely recommended, may be useful in pregnancy, renal impairment, obese patients.
What is the therapeutic level for LMWH using Anti-Factor Xa? >1 unit
What are the ADRs, D/I and BBW with LMWH? Bleeding, lower rates of HIT than UFH. D/I: antiplatelet, anticoagulant, fibrinolytic, NSAIDS. BBW: hematoma risk with epidural/spinal puncture
What is the reversal agent for heparin products? Protamine
How do we dose Protamine on patients who overdose on UFH? 100 units UFH = within 30 mins, 1 mg protamine. within 30-120 min, 0.5 mg protamine. >120 min, 0.25 mg protamine.
How do we dose Protamine on patients who overdose on LMWH? 1 mg enoxaparin, 100 units dalteparin, 100 units tinzaparin= within 8 hrs, 1mg protamine. 8-12hr, 0.5mg protamine. >12 hr, do no use.
What is the dosing for VTE prophylaxis of Arixtra? 2.5mg SC daily
What is the dosing for VTE treatment of Arixtra? <50kg: 5mg SC daily. 50-100kg: 7.5 mg SC daily, >100kg: 10mg SC daily. Renal: CrCl 30-50ml/min: decrease dose 50%, if <30: do NOT use
How do we monitor Arixtra? ADRs? D/I? Half-life? SCr and sign/symptoms of bleeding. Bleeding but no reports of HIT. D/I: antiplatelet, anticoagulant, fibrinolytic, NSAIDs. Half life: 17-21hrs
What is the MOA of rivaroxaban & edoxaban? binds directly to FREE F10a
What is the MOA of apixaban? Binds directly to free and clot bound F10a
T/F Xarelto should be taken with food at higher dosing (>15mg). T
T/F Xarelto has CYP and P-gp substrate interactions. T
What is the dosing for VTE prophylaxis of Xarelto? 10 mg PO daily, if CrCl is 15-30 ml/min: caution, if <15 ml/min: AVOID use.
What is the dosing for VTE treatment of Xarelto? 15mg PO BID with food for 21 days, then 20 mg PO daily with food thereafter. 10mg daily may be considered beyond 6 months
What are counseling points for Xarelto? may chew/crush, doses >15mg require large meal intake, missed dose can be taken same day for max dose of 30 mg PO for VTE ONLY, hold dosing 24 hours prior to surgery or invasive procedures
T/F Eliquis has CYP and P-gp substrate interactions T
What is the dosing for VTE prophylaxis of Eliquis? 2.5mg PO BID
What is the dosing for VTE treatment of Eliquis? 10 mg PO BID for 7 days, then 5 mg PO BID, extended duration: 2.5mg BID
T/F Eliquis should be AVOIDED in pts taking strong CYP3A4 & P-gp inhibitors T
What are counseling points for Eliquis? NG tube: may crush or chew & mixed with 60 mL D5W, with or without food, no double dosing if missed dose, hold dosing 48 hours prior to moderate or high risk of bleeding surgery or invasive procedures; hold 24 hours with mild/low bleed risk
T/F Savaysa has only P-gp substrate interactions T
What is the dosing for VTE treatment of Savaysa? 60 mg PO daily after 5 days-10 days of parental anticoagulant. < 60kg or CrCl 15-50ml/min = 30 mg daily.
How do we monitor Savaysa? SCr
What are some counseling points of Savaysa? take with or without food, missed doses may be taken if >6 hours before next dose, hold dosing 24 hours prior to surgery or invasive.
Continued on Day 2 slide deck
Created by: SPangKee
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