Unit: 5 - Monitoring Antithrombotic Therapies Flashcards
Drugs that break down clots are also called?
Thrombolytic drugs
What os VTE?
Venous thromboembolic disease; includes DVT & PE
What is DVT?
Deep vein thrombosis
What is PE?
Pulmonary embolism
What is AMI?
Acute myocardial infarction (heart attack)
What is TIA?
Transient ischemic attack
What is PAO/PAD?
Peripheral artery occlusion or disease
What is NVAF?
Non-valvular atrial fibrillation
What are the 4 types of anticoagulant drugs we are studying?
Heparin, Coumadin/warfarin, anti-Xa, and DTI (direct thrombin inhibitors)
Coumadin is a vitamin K antagonist (VKA). T or F?
True
What enzyme does warfarin/Coumadin act on?
It suppresses vit K epoxide reductase
How is Coumadin metabolized?
It is metabolized by the CYP450 pathway, which is an enzyme found in the liver
How does knocking out the epoxide reductase enzyme suppress VK dependent coagulation factors?
It inhibits the carboxylation/decarboxylation cycle of VK, which makes VK dependent factors remain non-active due to their inability to bind Ca2+
What are the prophylactic uses for coumadin?
To prevent VTE and stroke and to help with other chronic medical conditions that may cause clotting
What are the therapuetic uses for Coumadin?
After DVT, PE, or AMI
What does an INR in the correct therapeutic range indicate about the patient?
The pt is metabolizing the drug properly, the dosage is correct, and the pt is not at risk for either clotting or bleeding.
What is the critical value for INR at DH?
Greater than 5
What is an alternative test to INR? Why might it be used instead?
Chromogenic FXa Assay (CFX); It is best to use when pt has LA, factor inhibitors, or factor deficiency
What is the therapeutic range for Coumadin at DH?
2-3
What does VK do to the effects of coumadin?
Reverses them
What is the first step to reverse a Coumadin OD?
Discontinue the Coumadin and administer oral or IV VK
What can also be administered for reversal of a Coumadin OD (2 options)? What coag factors does it contain?
Prothrombin complex concentrate (PCC) - FII, VII, IX, and X
Activated FVII
With severe bleeding, what should be administered to reverse a Coumadin OD?
FFP
What are the three types of heparin used?
UFH, LMWH, and Fondaparinux
Where is the antithrombin (AT) binding site on the UFH molecule?
The pentasaccharide sequence
Which factors does AT/UFH binding inhibit?
FIIa, IXa, Xa, XIa, and XIIa
What are the main uses of UFH?
To treat VTE, AMI, after stent placement, and during cardiac bypass surgery
When is LMWH used instead of UFW?
To prevent HIT (not to treat a pt who already has HIT)
What tests (4) are used to monitor UFH? How often is it monitored?
PTT; 4-6 hours after bolus, and then every 24 hours for up to 2 weeks or until properly adjusted
Plt count to monitor for HIT (<30% change)
Chromogenic anti-Xa heparin assay
ACT - POCT
What is the method used to determine a therapeutic range for each of these medications?
Brill Edwards Method (linear regression plot of 2 test methods)
What are two limitations of PTT?
Heparin resistance and prolonged baseline PTT
What drug is used to reverse OD with UFH? What is the mechanism? How is it monitored?
Protamine sulfate; Binds and neutralizes UFH so that it can’t bind with AT; PTT or ACT and plt count
What is the patented name for LMWH?
Lovenox
What is the size difference between LMWH and UFH? What is the benefit of this?
LMWH is 1/3 the size of UFH (depolymerized); Shorter TAT
What is the difference in action of LMWH compared to UFH?
It only inactivates Xa (not FIIa, IXa, XIa, and XIIa)
Why does LMWH only bind and inactivate Xa?
Because of the smaller size of the molecule and reduced binding sites available
What are the prophylactic uses of LMWH?
During or after surgery, After DVT, PE and unstable angina, During pregnancy for women at risk of VTE
What is the therapeutic use of LMWH?
During surgery after discontinuing Coumadin
Which of the two non-synthetic forms of heparin is likely to cause DIC?
UFH (not LMWH)
How is LMWH therapy monitored?
There is usually no need to monitor. For exceptions, perform chromogenic anti-Xa heparin assay to monitor
What does the chromogenic Anti-Xa heparin assay measure? How is this different than the PTT test?
It measures the concentration of heparin, rather than its anticoagulant effects
What are the reagents for the chromogenic Anti-Xa heparin assay?
Antithrombin and excess Xa
What is the method of the chromogenic Anti-Xa heparin assay?
AT binds to heparin, which in turn binds to Xa, excess free Xa digests its substrate to produce a color change which is measured spectrophotometrically.
How is the color change interpreted for the chromogenic Anti-Xa heparin assay?
Less color means more heparin (less free Xa is available to act on substrate and cause color change)
What is used to reverse OD with LMWH? How is it monitored?
Protamine sulfate; With anti-Xa assay
What is Fondaparinux?
A synthetic pentasaccharide sequence of UFH/LMWH
What is the action of Fondaparinux?
The same as LMWH - inactivates Xa
What is the use of Fondaparinux? How is it monitored?
To prevent VTE after surgery and to treat VTE; With chromogenic Anti-Xa assay (after establishing therapeutic range)
What is used to reverse OD with Fondaparinux?
rFVIIa
What are the three Anti-Xa drugs?
Rivaroxaban, Apixaban, Edoxaban
What makes Anti-Xa drugs an attractive alternative to warfarin and LMWH?
There is no need for monitoring therapy with these drugs
What is Rivaroxaban used for?
VTE, prevent stroke with NVAF
What is Apixaban used for?
NVAF
What is Edoxaban used for?
NVAF, DVT and PE
If Anti-Xa drug therapy needs to be monitored, what tests will be used?
PT and chromogenic Anti-Xa assay (calibrated with specific medicine, not heparin)
How is OD with Anti-Xa reversed?
There is no approved treatment for reversal other than discontinuing the drug
What is the alternative anticoagulant for a pt experiencing HIT?
Aragatroban
What are the three DTIs? Which ones are administered intravenously?
Aragatroban, Bivalirudin, and Dabigatran; Aragatroban and Bivalirudin
What is the mode of action of DTIs?
They bind to clot-bound thrombin and free thrombin
What is used to monitor therapy with DTIs?
PTT and ACT (for surgery and cath lab) - other options are ECT and Hemoclot
What is ECT? What is the mode of action?
Ecarin clotting time; Cleaves prothrombin to thrombin (insensitive to heparin, Coumadin and inhibitors such as LA)
What are the oral antiplatelet drugs?
Aspirin, Clopidogrel, Prasugrel, and Ticagrelor
How is aspirin therapy monitored?
VerifyNow, Aspirin Works, and Plt aggregation studies
What is the mode of action of aspirin?
It irreversibly acetylates the COX 1 enzyme in the eicosanoid pathway and inhibits the synthesis of TXA2
What is thromboxane B2 used for?
It is a stable measurable plasma product that is reduced in aspirin therapy; it can be measured to assess effectiveness of therapy; if there are high levels of TXB2, the aspirin is NOT working efficiently
What are oral antiplatelet drugs (besides aspirin) used for? What is their mode of action?
They are used following MI or stroke; They bind to P2Y12 plt receptors (which inhibit the binding of ADP and activation of plts)
What is PFA-100 used for?
It is a rapid method to determine aspirin and clopidogrel responses and VWD
What is the principle of the PFA-100 assay?
It is a high-shear force dynamic flow system; Collagen is used with either epinephrine of ADP and the time to closure is measured
What does it mean if the Col/Epi and Col/ADP PFA-100 tests are both prolonged?
The following should be considered: Anemia, thrombocytopenia or significant plt disorder, VWD, BS, GT, storage pool disease, etc.
What will be the result of the Col/Epi and Col/ADP PFA-100 tests if the pt is on aspirin or NSAIDs?
Col/Epi prolonged & Col/ADP normal
What are the IV antiplatelet drugs?
Eptifibatide, Abciximab and Tirofiban
What is the mode of action of IV antiplatelet drugs?
They are anti GPIIa/IIIb
What are IV antiplatelet drugs used for ?
Cardiac catheterization and stent placement
What tests are performed before a pt is started on IV antiplatelet drugs?
PT, PTT, and CBC
What tests are performed while a pt is on IV antiplatelet drugs?
PTT, ACT, and plt count
What tests are performed after a pt is on IV antiplatelet drugs?
Plt count
What is the VerifyNow P2Y12 assay used for?
It is a POC light transmittance aggregometry test used to measure P2Y12 receptor blockade for pts who have been on P2Y12 inhibitors
How are the light transmittance results for the P2Y12 test interpreted?
Increased light transmittance > plts are aggregating (normal)
Less light transmittance > plt aggregation is inhibited
What are the three thrombolytic drugs?
TPA, Streptokinase and urokinase
What is the mode of action of streptokinase?
It dissolves fibrin clots
What is the mode of action of Urokinase and TPA?
They cleave plasminogen to plasmin to initiate fibrinolysis
What are the three thrombolytic drugs?
TPA, Streptokinase and urokinase
What is done in the case of a venous clot?
Anticoag or thrombolytic drugs are given, and/or an inferior vena cava filter is placed to help prevent blood clots from traveling to the heart or lungs
What is the mode of action of Urokinase and TPA?
They cleave plasminogen to plasmin to initiate fibrinolysis
What is done in the case of a arterial clot?
Catheter-directed thrombolysis and/or surgery to remove the clot
Why is it especially important to know the differences in the thromboplastin reagents?
If you are trying to detect LA, only certain reagents can be used
