Anti-Coagulation Therapy

Question 1

Aspirin

Answer 1

• Acetylates COX irreversibly - inhibits platelet for lifespan (10 days)
• Best for L-sided prevention (where platelets more involved) - MI and stroke prevention
• Side effects - ulceration of GI, GI irritation, ototoxicity, inc bleeding

Question 2

P2Y12 Inhibitors

Answer 2

• ADP receptor
• Clopidogrel - oral; works for life of platelet; used for those w/ TIAs and stents
• Prasugrel / Ticagrelor- used for acute coronary syndromes; higher bleeding risk than clopidogrel

Question 3

Dipyridamole

Answer 3

• Decreases platelet adenosine uptake and dilates coronary arteries
• Used for cardiac valve disease along w/ aspirin and/or Warfarin

Question 4

Anti-GPIIbIIIa

Answer 4

• both used to prevent abrupt coronary vessel closure post-angioplasty; give in cath lab
• Abciximab - monoclonal antibody
• Eptifibatide - small molecule that reversibly binds receptor to reduce aggregation

Question 5

Unfractioned Heparin (MAO, monitoring, side effects, contraindications)

Answer 5

• MAO: binds anti-thrombin to inc its ability to inactivate thrombin
• Safe in pregnancy but not oral
• Prolongs APTT (used to monitor) b/c thrombin needed to activate FXI
• Stop 6 hrs b/f invasive surgery or b/f switching to oral agent (1/2 life of 1-3 hrs)
• Side Effects: bleeding, thrombocytopenia, osteoporosis, alopecia
• Contraindications: aspirin use, alcohol use, hepatic or renal disease, thrombocytopenia, GI bleed, tumors esp CNS
• HITT

Question 6

What reverses heparin?

Answer 6

protamine sulfate

Question 7

Low Molecular Wt Heparin

Answer 7

• MAO: mall fragments that work more on Xa then thrombin
• SubQ or IV
• HITT less common
• Can be used in pregnancy
• Renal excretion - may need to adjust

Question 8

Fondaparinux

Answer 8

• synthetic pentasaccharide made of small portion of heparin
• only needs to be monitored if renal problems
• long half-life (17-21 hrs)

Question 9

Direct Thrombin Inhibitors

Answer 9

(monitor w/ APTT)

• Desirudin - cannot use in pregnancy or renal failure; can use if Type 2 HITT
• Argatroban - IV; liver clearance; also good if Type 2 HITT; limited in very prolonger PT
• Bivalirudin - IV; metabolized in plasma so good for people w/ liver and renal disease
• Dabigatran - ORAL; less bleeding risk than Warfarin; not safe for pregnancy; does not require monitoring

Question 10

Direct Xa Inhibitors

Answer 10

ALL ORAL

• RivaroXAban - dec intracerebral bleeding compared to Warfarin; no antidote but give prothrombin complex concentrate if bleed
• ApiXAban - very similar
  -
  EdoXAban - excellent renal function may dec efficacy

Question 11

Warfarin

Answer 11

• MAO: inhibits formation of Vit needed for production of factors 2, 7, 9, 10 and protein S and C
• Monitor via INR (2.0-3.0 is goal)
• Adv - oral
• Disadv - cannot use in pregnancy, interactions, takes 5 days to reach full effect, genetic polymorphisms
• Side Effects - hemorrhage, localized skin necrosis, fetal abnormalities if taken while pregnant

Question 12

How to treat Warfarin overdose?

Answer 12

Treat overdose w/ vit K, fresh frozen plasma or KCentra (4 factor prothrombin complex concentrate) or recombinant FVIIa (Novoseven)

Question 13

Warfarin Potentiators

Answer 13

• Amiodarone
• Anabolic steroids
• Aspirin
• NSAIDs
• Cimetidine
• Omeprazole
• Quinidine
• Sulfas
• Tamoxifen

Question 14

Warfarin Antagonists

Answer 14

• Adrenocortical steroids
• Antacids
• Barbiturates
• Oral contraceptives
• PCNs
• Rifampin
• Vit C

Question 15

Thrombolytic Agents

Answer 15

• Activate plasminogen; monitor via TT or APTT
• Can reverse w/ fresh frozen plasma or cryoprecipitate
• t-PA - in MI, PE, occluded venous catheter, new-onset stroke, if extensive DVTs less than 5 days old