Anti-Coagulant, fibrinolytic, and anti-platelet agents Flashcards
(26 cards)
Give the 4 groups of anticoagulants presented in lecture.
- Unfractionated heparin
- Low molecular weight heparin
- direct inhibitors of thrombin or Xa
- coumadin
Define: anticoagulants, fibrinolytic agents, anti-platelet agents.
- Anticoagulant: drugs that work by either 1. inhibiting thrombin of F. Xa or 2. decreasing the level of competent clotting factors
- Fibrinolytic agents: accelerate degradation of existing fibrin clots
- Anti-platelet agents: inhibit platelet plug formation by inhibiting platelet activation of prevent them from aggregating
Describe the mechanism and structure of heparin. What cells in the body naturally synthesize it?
- inactivates serine proteases (IIa, Xa, IXa, XIa, VIIa) by binding to antithrombin (AT-III)
- It is a proteoglycan with many (-) sulfates that bind (+) antithrombin
- Mast cells
How is heparin administered? What its half-life?
- IV or SQ, NOT orally
- short half life of about 1 hour so need many administrations
Indications of heparin use and toxicities.
- Indications: Rx of acute arterial and venous thromboembolism, prevention of thromboembolism in at-risk patients
- Toxicities: bleeding, osteoporosis when used for weeks-months, thrombocytopenia with potential thrombosis
Describe Heparin-Induce Thrombocytopenia with Thrombosis (HIT)
- platelets’ alpha granules release PF4 (many + residues) that bind heparin and reside on platelets’ surfaces
- antibodies are generated against this complex and bind to platelet Fc receptors, triggering platelet activation and clumping
- Antibodies may also activate macrophages, yielding TF-bearing microparticles that fuel the fire
- Result: thrombocytopenia and microvascular thrombosis (arterial !!and venous)
How should UFH be monitored?
- aPTT: 1.5- 2.0x baseline: helpful without being toxic
- PT is also prolonged, but less sensitive
Compare and contrast the inhibitory action of UFH and LMWH
-UFH can inhibit thrombin and Xa due to its large enough size, but LMWH can only inhibit Xa and is too small to inhibit thrombin
How is LMWH administered? What is its half-life?
- SQ
- longer than UFH, so required less injections a day
- dosed by patients weight
T/F: Patients on LMWH are monitored by aPTT.
-false; at clinical doses, it does not prolong the aPTT
T/F: LMWH is less immunogenic than UFH.
-True, it forms less complexes with PF4 and is less associated with thrombocytopenia
When is LMWH used?
- pretty much the same as UFH
- Rx of acute arterial or venous thromboembolism
- Prevention of thromboembolism in patients with increased risk
Name and compare and contrast the 3 examples of drugs that are direct thrombin inhibitors.
- Lepirudin: approved for HIT use, renal excretion, IV
- Argatroban: approved for HIT use, hepatic excretion, IV
- Dabigatran: PO, long half life, renal excretion, fixed dose, monitoring not required, poorly reversible
Give examples of Xa inhibitors and their properties.
- Fondaparinux: IV and SQ
2. Apixaban, Rivaroxaban, Edoxaban, etc: PO, fixed dose, no monitoring, not easily reversed, replacements for coumadin
How does coumadin (warfarin) work?
-inhibit recycling of vitamin K and therefore, depletes factors II, VII, IX, X, Protein C and protein S
3 ways we get Vitamin K
- eat it (green leafy vegetables)
- gut flora
- store it in liver for about 1 week
How is coumadin administered and what are some of its uses?
- PO
- venous and (sometimes) arterial thrombosis to prevent recurrence
- atrial fibrillation to prevent thrombus formation and embolism
- prosthetic heart valves
- DVT prophylaxis
- rat poison
How should patients on coumadin be monitored?
-PT test (increases) and INR
Why is there a conundrum of coumadin dosing? What are its toxicities?
- very narrow therapeutic window: higher INR target is higher risk of bleeding, but lower INR is risk of clotting recurrence
- Bleeding (tx with Vitamin K and FFP), embryopathy in 1st trimester, coumadin-induced skin necrosis
3 examples given of fibrinolytic factors.
- Streptokinase
- Urokinase
- Tissue-type Plasminogen Activator (t-PA)
Fibrinolytic agents are not commonly used, but are sometimes. Describe scenarios they are indicated for use.
- acute MI
- PE
- Peripheral arterial occlusion
- DVT (proximal)
- Catheter occlusion (sometimes)
2 contraindications of coumadin use and their risk
- Hemorrhagic CVA, intracranial neoplasm, recent cranial surgery/trauma, uncontrolled severe hypertension—Intracranial bleed risk
- Major surgery of thorax or abdomen (10 days), prolonged CPR, current severe bleeding— massive hemorrhage
Current treatment of venous thrombosis
- Start on UFH (IV) or LMWH (SQ)
- Start coumadin (PO) within 1-2 days after heparin
- maintain on coumadin for 3-6 months (or forever)
3 main categories of Anti-platelet agents and examples for each category.
- Receptor antagonist: ADP2Y12 receptor antagonist; Clopidogrel (Plavex), Prasugrel, Ticlopidine (Ticlid)
- Signal blockers: aspirin
- Integrin (aIIbB3) blockers: ReoPro (Abiciximab), Integrilin (Epifibatide), Tirofiban (Aggrastat)
