anticoagulants

Question 1

acute MI treatment

Answer 1

fibrinolytics if < 3 hr
acceptable treatment window < 12 hours
fibrinolytic + 2 x anticoagulant + platelet aggregation inhibitor
(TNK + ASA+ heparin + aspirin + clopidogrel)

Question 2

DVT, PE treatment

Answer 2

IV heparin immediately -> add oral warfarin -> stop heparin when therapeutic warfarin effect attained -> outpatient warfarin therapy

Question 3

heparin / LMWH / fondaparinux MOA

Answer 3

heparin - speed up the inactivation of clotting factors by antithrombin III and bind thrombin for anti-thrombin effects
LMWH - speed up atIII; more effect on Xa reactions than IIa reactions
fondaparinus - indirect factor Xa inhibitor, no anti-thrombin effects

Question 4

heparin / LMWH / fondaparinux reversal

Answer 4

heparin - protamine

LMWH - 60-75% protamine, factor VIIa fondaparinux - factor VIIa

Question 5

heparin / LMWH / fondaparinux ADME (4)

Answer 5

synthesized in body by mast cells and basophils
rapid onset; t1/2 = 1.5 hr
ROA: subQ injection, IV bolus, or IV infusion
non-renal elimination (poss. by reticuloendothelial system)

Question 6

heparin / LMWH / fondaparinux reversal (2)

Answer 6

protamine - proteins from salmon sperm that are an anti-coagulant unless in the presence of acidic heparin when they form a salt
rapid onset - within 5 minutes
tincture of time

Question 7

heparin / LMWH / fondaparinux AE’s

Answer 7

HIT - heparin binds platelet factor 4 which binds IgG

• > activates platelets and thrombosis
• > causes platelet removal by splenic macrophages and thrombocytopenia

Question 8

heparin / LMWH / fondaparinux monitoring

Answer 8

PTT (activated partial thromboplastin time)

Question 9

warfarin MOA

Answer 9

inhibit VKOR -> no active factors 2, 7, 9, 10 or protein C, S

Question 10

warfarin ADME (4)

Answer 10

effects not seen until 3-4 days after initiation
S warfarin more potent but racemic mix
t1/2 = 1.5 days; steady state = 6 days
highly bound to serum albumin; only 1% active adn free

Question 11

Warfarin metabolism

Answer 11

CYP2C9

Question 12

warfarin reversal (5)

Answer 12

FFP
tincture of time
recombinant F VIIa (novoseven)
prothrombin complex concentrate
vitamin K (phytonadion)

Question 13

warfarin AE’s

Answer 13

early pro-coagulant effects due to Pro C drop
pregnancy category D+
also used as mouse / rat poison

Question 14

warfarin monitoring

Answer 14

INR results (based on PT)
may take 1-2 weeks to reach desired INR
INR increased by intestinal flora, fever, hyperthyroid, stress
INR decreased by hypothyroid, smoking

Question 15

extrinsic pathway of coagulation

Answer 15

thrombin, VIIa, Xa activate VIIa =>

VIIa binds TF and Ca++ to activate Xa

Question 16

intrinsic pathway of coagulation

Answer 16

kallikrien activates XIIa =>
XIIa activates XIa =>
XIa activates IXa =>
IXa binds activated VIIIa to form tenase =>
tenase activates Xa

Question 17

common pathway

Answer 17

Xa binds Va, Ca++, and phospholipid to form prothrombinase =>
activates IIa =>
forms fibrin clot =>
crosslinked by XIIIa

Question 18

thrombin’s 7 actions

Answer 18

activate VIIIa, XIa, Va, XIIIa
activate platelets
activate fibrinogen
combine with thrombomodulin to activate protein C

Question 19

6 controls of clotting

Answer 19

only local activation
ATIII (inhibits thrombin, IXa, Xa, XIa, XIIa)
thrombomodulin inactivates thrombin
thrombomodulin-thrombin activates Protein C (inhibits Va, VIIIa)
endothelia secretion of TFPI inhibits thrombin and VIIa-TF
TPA activates fibrinolysis