20- Anticoags and Thrombolytics

Question 1

dalteparin (Fragmin)

Answer 1

low molecular weight heparin

• enhances antithrombin action on Factor X
• MW between 4K-6K daltons and used for prophylaxis and treatment
• do not require laboratory monitoring d/t their specificity
• not fully reversed by protamine but do not induce HIT
• metabolized in the kidney

Question 2

enoxaparin (Lovenox)

Answer 2

low molecular weight heparin

• enhances antithrombin action on Factor X
• MW between 4K-6K daltons and used for prophylaxis and treatment
• do not require laboratory monitoring d/t their specificity
• not fully reversed by protamine but do not induce HIT
• metabolized in the kidney

Question 3

fondaparinux (Arixtra)

Answer 3

low molecular weight heparin

• enhances antithrombin action on Factor X
• MW between 4K-6K daltons and used for prophylaxis and treatment
• do not require laboratory monitoring d/t their specificity
• no good reversal agent
• metabolized in the kidney
• pentasaccharide with added methyl groups

Question 4

argatroban

Answer 4

direct thrombin inhibitor

• directly inhibit function of thrombin in clotting cascade
• small molecule only given IV d/t short half-life
• hepatic clearance (contraindicated in liver failure)

Question 5

bivalirudin (Angiomax)

Answer 5

direct thrombin inhibitor

• directly inhibits function of thrombin in clotting cascade
• mostly hepatic and some renal clearance (avoid use in liver failure)

Question 6

lepirudin (Refludan)

Answer 6

direct thrombin inhibitor

• directly inhibits function of thrombin in clotting cascade
• renal clearance (avoid use in renal failure)

Question 7

dabigatran (Pradaxa)

Answer 7

direct thrombin inhibitor

• directly inhibits function of thrombin in clotting cascade
• orally active, short half-life
• effects in 2-3 hrs, 80% renal clearance
• no monitoring needed, no reversal agent
• S/FX: GI bleeding

Question 8

heparin sulfate

Answer 8

anticoagulant
catalyzes ANTITHROMBIN activity
-inhibits IIA, IXa, Xa
-must be delivered parenterally
-side effects: bleeding, allergy, thrombosis and osteporosis
-HIT (heparin induced thrombocytopenia) systemic hypercoagulabe state that occurs in patients treated with UFH for at least 7 days
-requires PTT monitoring
-saturable mechanism for clearance= reticuloendothelial system (marchphage)
-non-saturable mechanism for clearance = renal excretion

Question 9

protamine sulfate

Answer 9

heparin antagonist
-highly cationic peptide that binds heparin to form a stable ion pair, which inhibits anticoagulant activity
dissociates heparin from anti-thrombin

Question 10

rivaroxaban

Answer 10

anticoagulant

• orally administered
• factor Xa inhibitor
• no monitoring needed
• short half-life
• no good reversal agent
• maximum inhibition of factor Xa occurs 4 hours after a dose
• once daily dose
• liver, renal and fecal-biliary clearance

Question 11

warfarin

Answer 11

anticoagulant
-inhibits vitamin K metabolism which disrupts gamma-carboxylation of several glutamate residues in factors II, VII, IX, X, C & S
partially inhibits synthesis, not degradation, thus effects on coagulation is dependent on factor half-life
-patients need to be on heparin for first 3 days of warfarin treatment because protein C and S levels drop faster than pro-coagulation proteins
-side effects: bleeding, skin necrosis, teratogenesis, thrombosis
-NUMEROUS DRUG INTERACTIONS
-cleared by liver and kidney
-PT/INR monitoring
affects factor VII- extrinsic pathway

Question 12

menadione

Answer 12

vitamin K

warfarin antidote

Question 13

antithrombin III

Answer 13

• directly inhibits factors IXa, Xa and IIa

- activated by heparin

Question 14

extrinsic pathway

Answer 14

• initiated by factor VIIa

- activated by contact with substances from outside blood vessels

Question 15

factor II

Answer 15

• prothrombin that turns into thrombin (IIa)

- activated by factor X

Question 16

factor VII

Answer 16

-initiates extrinsic pathway by activating factors IX and X

Question 17

factor IX

Answer 17

• beginning of intrinsic pathway

- activated by contact system or factor XIa

Question 18

factor X

Answer 18

-activated by factor IX and VII

Question 19

fibrin

Answer 19

• active form of fibrinogen

- forms clot at end of coag. cascade

Question 20

fibrinogen

Answer 20

• precursor to fibrin

- activated by factor IIa (thrombin)

Question 21

intrinsic pathway

Answer 21

-initiated when factor IX activated by contact with intravascular event, factor XIa, or XIIa

Question 22

partial thromboplastin time (PTT)

Answer 22

-used to monitor intrinsic pathway and heparin therapy

Question 23

prothrombin time (PT)

Answer 23

-used to monitor extrinsic pathway and warfarin therapy

Question 24

plasmin

Answer 24

• active form of plasminogen

- breaks down fibrin clot formation after it is no longer needed

Question 25

plasminogen

Answer 25

• precursor to plasmin

- activated by SK, UK, t-PA

Question 26

protein C and S

Answer 26

• inhibit the coagulation cascade by inhibitin conversion of factor X to Xa and factor II to IIa (prothrombin to thrombin)
• preventing hypercoagulation
• inhibited by warfarin

Question 27

INR

Answer 27

• standardizes measurement of PT from hospital to hospital
• normal: 0.9-1.3
• High: 4-5
• Low: 0.5
• warfarin therapy: 2-3