Thrombosis Flashcards
What is the indication of use of an anticoagulant, and what are the general classes?
- use for VENOUS thromboembolism (prophylaxis or treatment - clot preventer)
- indirect thrombin inhibitors (heparins), vitamin K antagonists, direct thrombin inhibitors, and direct Xa inhibitors
What is the indication of use of a fibrinolytic drug?
- ACUTE arterial and venous thrombosis (lysing already formed clots - clot buster)
What is the indication of use of a antiplatelet drug?
- ARTERIAL thrombosis
What is the mechanism of action of heparins?
- bind to antithrombin and potentiate formation of anti-thrombin coagulation factor complex (IIa, Xa, IXa, XIa, XIIa)
What does standard unfractionated heparin inhibit?
- Factor Xa and thrombin
On your surgery rotation, an elderly patient is put on prophylactic heparin pre-op. The surgery goes well but the patient wakes up confused and falls out of bed, hard. What do you administer to counteract the action of heparin?
protamine sulfate (highly basic peptide that binds heparin)
How do you monitor effectiveness of heparin, and what are two major side effects to watch out for?
- monitored with PTT
- heparin induced thrombocytopenia and thrombosis
What does low molecular weight heparin inhibit? What are the names of the three LMWHs?
- Factor Xa (inhibits thrombin less effectively due to smaller size and lack of binding)
- dalteparin, enoxaparin, tinzaparin
What does fondaparinux inhibit and what special condition can it be administered in?
- activates anti-thrombin to inhibit Xa
- can be given in HIT, but cannot be reversed if serious bleeding occurs
What factors do Vitamin K antagonists affect?
Factors II, VII, IX, X, protein C, protein S
Alternative compounds (i.e. other drugs) binding to what protein displaces warfarin and can increase endogenous activity?
albumin
How do you monitor warfarin effectiveness and how is that value expressed clinically?
monitor PT, which is expressed as INR
INR = [PT patient/PT control] x international sensitivity index
You start a patient on warfarin and two days later, she ends up in the ER with a pulmonary embolism. What did you forget about warfarin?
Warfarin inhibits carboxylation of protein S and C, which temporarily shifts the balance toward coagulation at the onset of therapy
How are direct thrombin inhibitors’ effectiveness monitored and how are they reversed?
monitored by PTT and cannot be reversed
What procedure are lepirudin and bivalirudin approved for?
Percutaneous cardiac interventions
- directly inhibits thrombin
What condition is argatroban used for?
HIT
- inhibits the catalytic site of thrombin
How is dabigatran administered and how does it work?
orally, works as competitive inhibitor of thrombin but there is still no reversibility or antidote
What two drugs are direct Xa inhibitors, and what are some drawbacks to use?
- Rivaroxaban and apixaban
- no specific antidotes and no method to assess levels in serum
How do fibrinolytics (such as tPA, streptokinase, or urokinase) work?
induce activation of plasminogen which converts to plasmin and degrades fibrinogen, coagulation factors, and plasminogen
How does aspirin’s antiplatelet action work?
- irreversibly inhibits COX in platelets, which prevents TXA2 formation and prevents platelet aggregation
Which antiplatelet drug works by causing an increase in platelet cAMP, which decreases platelet aggregation?
dipyridamole (a phosphodiesterase inhibitor)
Which antiplatelet drug works by inhibiting platelet ADP receptors?
clopidogrel
What drug antagonizes GPIIb-IIIa? What is the effect of this drug that limits its use?
Abciximab, a monoclonal antibody
- elicits an immune response, so this drug is once in a lifetime
What drugs compete with fibrinogen and vWF binding to GPIIb-IIIa?
eptifibatide and tirofiban (fibrinogen analogs)
