Wk 3 Drugs Affecting Hemostasis

Question 1

What is INR?

Answer 1

International Normalized Ratio
-calculated from PT to standardize results to be compared across labs

Question 2

How is warfarin monitored?

Answer 2

PT testing

Question 3

MOA warfarin

Answer 3

Anticoagulates by acting as a vitamin K antagonist, reducing [] of F II, VII, IX, and X

Question 4

Therapeutic range of warfarin

Answer 4

INR of 2-3

Question 5

What does it mean to be vitamin K dependent?

Answer 5

IMP to create Ca2+ binding sites so the factors can participate in Ca-dependent rxns in the coagulation cascade

Question 6

What factors in the thrombolysis pathway does warfarin affect?

Answer 6

Protein C and S

Question 6

What factors in the thrombolysis pathway does warfarin affect?

Answer 6

Protein C and S

Question 7

What is heparin for?

Answer 7

Anticoagulant (naturally occurring)
-Indirect thrombin inhibitor

Question 8

Heparin MOA

Answer 8

potentiates antithrombin (makes antithrombin better at doing its job of inactivating certain coagulation factors)
anti FII and FXa activity paired w/ antithrombin

Question 8

Heparin MOA

Answer 8

potentiates antithrombin (makes antithrombin better at doing its job of inactivating certain coagulation factors)
-either IV or subcutaneous injection (parenteral administration)

Question 9

Heparin key things to know

Answer 9

tx for blood clots, maintain vascular access
-large (heparin hunter)
-monitored w/ aPTT or anti-Xa activity (measures heparin paired w/ antithrombin)
-LMWH does not require monitoring
-either IV or subcutaneous injection (parenteral administration)
-indirect mechanism b/c requires antithrombin for action

Question 10

What is the difference b/w unfractionated heparin (UFH) and low molecular weight heparin (LMWH)

Answer 10

UFH = lots of big sticky molecules w/ long polysaccharide tails. Good activity against IIa and Xa
LMWH = more purified w/ fewer big sticky molecules. Mostly active against Xa, less so IIa

Question 11

Fondaparinux

Answer 11

synthetic
-binds to antithrombin to change its confirmation
-only has anti-Xa activity
-fragment of heparin

Question 12

What are the direct oral anticoagulants (DOACs)?

Answer 12

1. dabigatran - direct thrombin inhibitor
2. rivaroxaban - direct Xa inhibitor
3. apixaban -“
4. edoxaban - “

• do not require lab monitoring
• avail in pill form
• newer (approved 2010-2015)

Question 13

What is the class of drugs that affect platelet fxn?

Answer 13

Antiplatelet agents:
COX-1 inhibitor - aspirin

Question 14

What are the LMWHs?

Answer 14

1. dalteparin
2. enoxaparin
3. tinzaparin

Question 15

What is HITS?

Answer 15

=heparin-induced thrombocytopenia syndrome
-life-threatening

Question 16

What happens to cause HITS?

Answer 16

formation of antibodies that recognize complexes of heparin and PF4 on the surface of platelets, and complexes of heparin-like molecules and PF4-like proteins on endothelial cells

Question 17

What are 3 direct thrombin inhibitors?

Answer 17

1. bivalirudin
2. argatroban
3. dabigatran

Question 18

3 direct F Xa inhibitors

Answer 18

1. rivaroxaban
2. apixaban
3. edoxaban

Question 19

What are 2 antiplatelet agents that work as thienopyridine P2Y12 inhibitors?

Answer 19

1. clopidogrel
2. prasugrel

Question 20

What are reversal agents to anticoagulants?

Answer 20

Vitamin K
Desmopressin
Plasma fractions
protamine
idarucizaumab (dabigatran reversal)
andexanet alfa (rivaroxaban and apixaban reversal)

Question 21

2 Antiplatelet agents, non-thienopyridine P2Y12 inhibitors

Answer 21

ticagrelor
cangrelor

Question 22

Antiplatelet agents - glycoprotein IIb/IIIa inhibitors

Answer 22

abciximab
eptifibatide
tirofiban

Question 23

Antiplatelet Agent - glycoprotein IIb/IIIa inhibitor

Answer 23

abciximab

Question 24

Sketchy F II

Answer 24

Thrombin = throm-beaver w/ 2 front teeth

Question 25

How is F II activated?

Answer 25

Thrombin activated by F X (fox) -> F Xa (a= activated) Converts F II -> IIa

Question 26

What does thrombin do?

Answer 26

Builds damn w/ fibrin (sticks) monomers cross-linked w/ F XIII (aided by platelet phospholipids and Ca2+)

Question 27

What does antithrombin target?

Answer 27

-endogenous, floating around -inactivates F II (thrombin), F IXa, Xa, XIa, and XIIa by forming stable complexes with them (usually slow, but heparin accelerates them) -think of anti-thrombin as heparin hunter's trap to capture the throm-beaver -specifically binds anti-thrombin III (think trap bars)

Question 28

What happens when heparin binds anti-thrombin III?

Answer 28

A complex is formed that irreversibly inactivates thrombin and factor Xa

Question 29

How is heparin monitored?

Answer 29

aPTT b/c the heparin-anti-thrombin complex inhibits most of the instrinsic pathway factors -eliminated by liver -does not cross placenta

Question 30

Is heparin a clot-buster?

Answer 30

No, it prevents clots from forming. Used in acute setting to prevent further clotting, often for venous thrombosis - DVT and then PE, or acute MI -can also be used prophylactically for conditions that may predispose to thrombosis- major surgery, pregnant, lying in hospital, malignancy, hx of oral contraceptives -> subcutaneous heparin

Question 31

What causes acute MI?

Answer 31

Usually due to piece of thrombotic plaque that breaks off -immediately start pt on anti-platelet therapy

Question 32

What are adverse effects of heparin?

Answer 32

1. bleeding 2. heparin-induced thrombocytopenia (HIT)

Question 33

What is HIT?

Answer 33

-hypercoaguable state -occurs in up to 5% of pts tx w/ heparin (usually over 7 days) -body makes antibodies against heparin bound to platelet F IV -heparin is most common cause of thrombocytopenia (think of broken clay plates) in hospital that paradoxically happens w/ thrombosis

Question 34

What are 2 rare effects w/ heparin?

Answer 34

1. Hyperkalemia -due to toxic effect on adrenal cells that produce aldosterone (mineralcorticoid that -> increased Na+ retention at expense of increased K+ excretion) -> hypoaldosteronism -heparin-induced hypoaldosteronism causes hyperkalemia 2. osteoporosis: heparin can decrease bone formation

Question 35

What is protamine?

Answer 35

Heparin reversal agent -reverses anticoagulant effect (less effective for LMWH and fondaparinux) -sketchy protective fence that blocks heppy hunter from hunting in an area -a (+) charged molecule that binds to negatively charged unfractionated heparin

Question 36

How do LMWH work?

Answer 36

LMWH-antithrombin complex inhibits F Xa w/ less effect on thrombin (think smaller cage can only fit foX, no space for throm-beaver) -IV or commonly subcutaneous -acute setting an prophylactically -small, so can sneak through protamine protective fence and is not effectively reversed by protamine -longer half-life, less frequent dosing -no routine monitoring -eliminated renally (if renal insufficiency, half-life cound be extended) -does not cross placenta

Question 37

What is fondaparinux?

Answer 37

-synthetic heparin derivative -fido w/ foxes (F Xa) in pair of tiny cages that snuck by the protective protamine -binds anti-thrombin III -lowest risk of HIT (fido cannot shoot at clay platelets)

Question 38

Direct Thrombin inhibitors

Answer 38

Sketchy: no "intrudin" (bivalirudin) to gator area - arGATROban and dabiGATRAN where gator is about to bite into throm-beaver

Question 39

Direct F Xa Inhibitors

Answer 39

FoXes are banned from chicken coup - rivaroXaBAN and apiXaBAN and edoXaBAN -fixed oral dosing, no monitoring -a-fib