Week 11 Flashcards

Question

why do we need to reverse the coumadin

Answer 1

if INR is too high - bleeding risk especially if going into surgery takes time for carboxylation factors to be produced and then activate the Vit K dependent factors

Answer 2

Just to reduce INR -not alot of bleeding INR 3-5= stop taking coumadin and monitor INR >5 stop taking coumadin and get Vit K orally or through injections - monitoring

Answer 3

Urgent – Significant bleeding or emergency surgery required -- Stop taking coumadin and give IV Vit K + PCC -- Prothrombin Complex Concentrate is blood containing Vit K dependent factors (FII, FVII, FIX, FX) and control proteins (Protein C and Protein S) -- Note: If PCC not available, use fresh frozen plasma (also contains missing factors)

Answer 4

binds -activates antithrombin to neutralize serine proteases activated by thrombin - changes the structure of antithrombin -given intravenously - half life is 1-2H -Dr/LAB determines therapeutic levels antithrombin inactivates F IIa, IXa, Xa, XIa & XIIa

Answer 5

1. Traditional or Unfractionated Long molecule with variable number of chains 2. Low Molecular Weight (LMWH) Shorter molecule with predetermined molecular weight

Answer 6

UFH acts as an anticoagulant by forming a complex with antithrombin (AT) -catalyzes the inhibition of thrombin (factor IIa), factor IXa, Xa, XIa and XIIa -UFH + AT complex prevents fibrin formation and inhibits activation of PLTs and FV, FVIII, and FXI

Answer 7

- derived from UFH -reduced inhibitory activity against FII but the same inhibitory activity on FX relative to UFH -more predictable pharmacokinetic properties vs UFH so they can be given in fixed doses without the need for constant monitoring

Answer 8

by APTT but before the therapy you need a APTT baseline to make sure its not already prolonged (indication of factor deficiency, LAC) -overdose of Hep can prolong APTT -APTT monitored every 6 hours until dose is adjusted then every 24 hours -PLT needs to be monitored - risk of HIT -therapy wont work if pt has AT deficiency (heparin needs AT to work)

Answer 9

1)AT binds UFH, causing a conformational change in AT to activate it 2). Because UFH is long, Thrombin (FII) can also bind to UFH 3). Bridging between AT and Thrombin enhances the reaction. 4). AT-Thrombin complex will be released. This is inactive and UFH is recycled

Answer 10

protamine sulfate is catatonic and a heparin antidote removed by the reticuloendothelial sytem

Answer 11

-prevention of thrombosis in high risk patients pregnancy -limit progression thrombosis DIC -keep IV lines open / renal dialysis -cardiac bypass surgery / unstable angina -Used to treat thromboembolic disease

Answer 12

Bleeding mild platelet dysfunction (thrombin usually activates PLTs) Thrombocytopenia -HIT Osteoporosis common with long-term use Heterogeneous mixture (varies in length) therefore dosing problematic

Answer 13

-Produced by enzymatic fractionation of UFH -minimal effect on thrombin activity because its too short to bind FII so it binds to FX for inactivation -given SUBCUTANEOUSLY with half life of 3-5 h

Answer 14

LMWH - has short chains UFH - has long chains any chain size can bind to AT and inhibit FX but inorder to inhibit FII, the heparin molecule needs to be long enough to bind BOTH AT and Thrombin

Answer 15

- just as effective as UFH -easy to adminster subcutaneous dose 1/2 a day , pts can do themselves -easy to monitor with heparin assay (FX assay) -safer then standard heparin because there is less risk of HIT, bleeding and inhibition of PLTs. So thrombin is still available to activate PLTs

Answer 16

-decreased heparin resistance. UFH tends to bind to non specific heparin binding proteins which leaves less heparin to activate AT but LWMH has decreased binding to those proteins

Answer 17

not necessary in most pts- cleared by kidneys can be useful in renal insufficiency (creatinine >2.0 mg/dl) obese patients with altered drug pK major bleeding risk factors aPTT monitoring is not useful because we would just see a prolonged APTT - no bridging so its not sensitive enough -anti-factor Xa chromogenic assay is more appropriate but not really used

Answer 18

chromogenic assay to detect LMWH Reagent is AT & excess Xa If LMWH is present, Hep-AT-Xa complex forms Free Xa (that didn’t complex) + substrate = colour end products ∴ > free Xa = > the colour = < Heparin Colour intensity of the product is INVERSELY proportional to the LMWH plasma levels

Answer 19

synthetic drug - made of the antithrombin region of heparin -indirect antithrombin anticoagulant - inactivates Xa by combining with AT -subcutaneous administration -doesnt need to be lab monitored just do a Fx assay if you do need to -No antidote - protamine will not work

Answer 20

heparin induced thrombocytopenia -people who are on heparin therapy can develop IgG AB to heparin platelet factor 4 -the ABs will bind to the complex on PLT surfaces which will cause a decrease in PLT count -this leads to thrombosis because the PLT have been inactivated by the immune complex -UFH best because it binds PLT factor 4 -thrombocytopenia is not a significant risk but complications can arise venous vs arterial thrombosis -medical emergency - stop heparin DUAL ACTION

Answer 21

40% PLT decrease in 5 days = thrombocytopenia -thrombin increases = thrombosis -discontinue treatment -dont use LMWH because there is cross reactivity to HIT ABs use Argatroban Bivalirudin Lepirudin Hirudin

Answer 22

-give orally direct thrombin inhibitor -doenst need routine monitoring -reduces coagulation AND fibrinolysis by binding free and clot bound thrombin -APTT/PT can be affected but it wont be because of the drug -Normal TT would exclude presence of Dabigatran -Acts quick 1-3 hours can be used instead of heparin to start therapy- good bridging drug -used for thrombosis in pts with Atrial fibrillation, Venous Thromboembolism -not affected be diet -can use fixed dosing -metabolism can be affected by renal or liver disease because Dabigatran needs to be activated by digestive enzymes made there -contradiction if PT have CrCl of <30mL/min -to reverse use Idarucizumab (Praxbind®) - likes this better then thrombin

Answer 23

Argatroban Bivalirudin Lepirudin All used to treat HIT Biva and Lepi are based on hirudin which are found in leeches. Hirudin is a Potent Direct Thrombin Inhibitor

Answer 24

PTT prolonged use Ecarin Clotting time -Ecarin is from viper venom -converts prothrombin to meizothrombin (converts fibrinogen to fibrin) -all direct thrombin inhibitors bind meizo and generate linear dose dependent prolongation of ECT

Answer 25

Apixaban (Eliquis) Riveroxaban (Xaralto) Edoxaban (Lixiana) oral administration dont need AT synthetic better than LWMH and Warfarin doesnt need monitoring or dose adjustments -2 pills daily half life of 5-11 hours Used for prevention of: Thrombosis in non-valvular atrial fibrillation Venous thromboembolism Treat HIT

Answer 26

-no antidote yet and dialysis doesnt work -contradiction if you have renal insuffiencies because its cleared by the kidneys -metabolism is also affected by renal/liver disease because it needs liver cytochromes for activation -PT/APTT/FXa assays are affected -a standardized assay is needed for each drug

Answer 27

Trial Antidote -Universal Factor Xa inhibitor antidote -Recombinant, human Factor Xa acts as a decoy and neturalizes Factor Xa inhibitors and LMWH -given as bolus after a 2 hour infusion

Answer 28

-can affect Lupus Anticoagulant by falsely prolonging tests like dRVVT and giving false positive LAC -are able to cause inhibitor like effect to factor assays which give them a false decrease in factor concentration

Answer 29

-Vasodilators -Platelet Inhibitors-ASA (acetylsalicylic acid) -Plasminogen activators -(Fibrinolytic Agents:) Tissue Plasminogen Activator (tPA), Streptokinase ,Urokinase Direct Thrombin Inhibitor (DTI)- Hirudin Defibrinogenating agent - Ancrod

Answer 30

Inhibition of Thromboxane A2 used for prevent of heart disease because it is a platelet inhibitor -stops plts from aggregating when are about to form plaques to cause arterial thrombosis -not monitored

Answer 31

- acetylates a platelet enzyme that produces thromboxane A2 (plt agnoist) -stops access to arachidonic acid (plt agonist) to prevent production of A2 -acetylation is irreversible so this A2 production is shut down for the life of the platelet

Answer 32

GOLD standard is platelet aggregation studies using arachidonic acid (AA) as the agonist -so if PT is on aspirin and AA is added the platelets should not be able to clump- NO LIGHT TRANSMITTANCE CHANGE PFA 100 system 2 cartridges - 1 with collagen and epinephrine while the 2nd has collagen and ADP both have apertures -whole blood will go through the aperture and the time it takes to close the aperture by platelet formation will be measured -if the pt is on aspirin then the time is prolonged

Answer 33

in MI and stroke because it lyses coronary thrombi and is able to reduce mortality -lyses hemostatic plugs increasing bleeding incidence, lowering plasma Fibrinogen which causes plasmin to break down plasminogen which causes a high rate of re occlusion -not done in outpatient

Answer 34

-made by endothelial cells - recomb -activates fibrin bound plasminogen to plasmin which breaks fibrin in clot -clot buster -limited to site of thrombus

Answer 35

Bacterial protein (endotoxin) Produced by of β -hemolytic streptococci Not used anymore bc: Often triggers DIC highly antigenic ** when used therapeutically can induce immune response can cause bleeding complications

Answer 36

Made in the kidney in small amounts Purified from urine initially Recombinant form now available can cause bleeding complications