12-1: 1/9 - Anti-Coagulants, Anti-Thrombotics, And Anti-Fibrinolytics

Front 1

Anticoagulation:
Indication

Back 1

Arterial or venous thrombosis

Front 2

Heparin:
Drug Class
MOA

Back 2

Indirect thrombin inhibitor

Inhibits only free thrombin, not thrombin bound to fibrin

Works by causing ATIII to bind Factors II, VII, IX, and X.

Front 3

This drug class requires Anti-Thrombin III.

Back 3

Indirect thrombin inhibitors (heparin, LMWH--enoxaparin, heparinoids)

Front 4

This drug inhibits thrombin action and generation.

Back 4

LMWH (enoxaparin)

Because inhibits Factor Xa better than thrombin!

Front 5

ATIII inhibits these factors.

Back 5

II, VII, IX, and X

FACTOR II = THROMBIN

Front 6

Indirect thrombin inhibitors:
MOA

Back 6

Enhances anticoag activity of ATIII (binds and inhibits factors II, VII, IX, and X).

Front 7

Enoxaparin:
Drug Class

Back 7

Indirect Thrombin inhibitor

Front 8

Danaparoid:
Drug Class

Back 8

Indirect thrombin inhibitor

Front 9

Unfractionated Heparin:
Uses
Disadvantages

Back 9

Venous thrombosis
PE

Disadvantages:
Depends on ATIII
Reqires frequent monitoring to ensure therapeutic levels
Risk of HIT
Rapidly bound (only free heparin is active) in plasma

Front 10

Heparin:
AEs

Back 10

Bleeding (5%, but can be higher with concomitant use of ASA; age >60, liver dz)
Osteoporosis with >2 mos tx
***HIT***

Front 11

Heparin-Induced Thrombocytopenia:
Pathophys
Complications
Treatment

Back 11

Anti-heparin ab's (IgG mediated) lead to platelet release, activtn, and thrombocytopenia. Occurs in ~3% of pts treated for more than 4 days.

Complications: thromboembolism (DVT), MI, ischemic stroke

Tx:
d/c heparin, tx w/lepirudin/argatroban (direct thrombin inhibitors)

Front 12

LMWH vs Heparin:
Advantages
Clearance (physiologic)

Back 12

LMWH:
Greater bioavailability
Longer half-life
90% less risk of HIT
No need to monitor
Less bleeding
SAFE IN PREGNANCY

LMWH = renal clearance
Heparin = hepatic clearance

Front 13

Dalteparin:
Suffix
Drug Class

Back 13

-parin; enoxaparin, ardeparin, deleparin

LMWH

Front 14

Disadvantage of LMWH vs Heparin.

Back 14

LMWH is irreverible; there's no antidode.

Front 15

Hirudin:
-suffix
Drug Class
Use
Clearance (Physiologic)

Back 15

-rudin: Hirudin, peirudin, bivalirudin

Direct thrombin inhibitor (directly inhibits thrombin); no co-factor req'd


Inhibits FREE and BOUND thrombin

Use in treating HIT

Cleared by kidneys

Front 16

Argatroban:
Drug Class
Use
Clearance (Physiologic)

Back 16

Direct thrombin inhibitor; no co-factor req'd

Inhibits FREE and BOUND thrombin

Use in treating HIT

Excreted by liver

Front 17

This class of drugs inhibits free and bound thrombin.

Back 17

Direct thrombin inhibitors (-irudins, argatroban)

Front 18

Which direct thrombin inhibitors require monitoring? What test would you monitor with?

Back 18

Hirudin, argatroban require monitoring with PTT

Front 19

Dabigatran:
Drug Class

Back 19

Direct thrombin inhibitor

Front 20

This drug is only approved for prevention of venous thromboembolism in atrial fibrillation.

Back 20

Dabigatran

AND NO NEED FOR MONITORING

Front 21

Warfarin:
MOA
Uses
Clearance (Physiology)

Back 21

Gen: Inhibit thrombin generation
Specifics: Inhibits reduction of vitamin K expoxide-->vitamin K req'd for carboxylation of II, VII, IX, X, Prots C and S (can no longer bind Ca2+ and thus reduces their activity)

Indications:
Prophylaxis/tx of VTE, PE, cardiac embolism
Thromboembolic complications due to a fib and valve replacement
Post MI, recurrent MI, Stroke

Hepatic clearance (cyp450)

Front 22

Why does warfarin exhibit a 2 day lag before treatment takes effect?

Back 22

Warfarin only affects synthesis of II (THROMBIN), VII, IX, and X, so has a 2 day lag.

Front 23

What is the recommended INR for prophylaxis and treatment of VTE with warfarin?

Back 23

INR 2-3

Front 24

What drugs potentiate the effect of warfarin? How?

Back 24

Cimetidine
Clofibrate
Cotrimoxazole
Metronidazole

GRAPEFRUIT JUICE

These drugs inhibit metabolic clearance of warfarin.

Front 25

What drugs potentiate warfarin's anticoagulant effect without changing ts plasma levels?

Back 25

Heparin
ASA
NSAID
COX-2 Inhibitors

Front 26

What drugs increase the metabolic clearance of warfarin?

Back 26

Barbiturates
Rifampin
Carbamazepine
Chronic EtOH

Front 27

What variant polymorphisms lead to decreased clearance of warfarin?

How should this effect dosing?

AE?

Back 27

cytochrome p2C9

Reduce dose

AE: 3x inc'd risk of bleeding with warfarin

Front 28

Warfarin:
Risk of bleeding
Association with INR

Back 28

Hemorhage; there's a narrow therapeutic window and risk of intracranial hemorrhage increases when you are outside of this window (INR above 3.5)

HOWEVER, 20 strokes are prevented for every major bleed

Hemorrhage assocd with INR above 4.

Front 29

Treatment options to reverse warfarin.

Back 29

1) Vitamin K, IV usually effective in 12 hours.
PO Vitamin K for moderate INR elevation.

AVOID SQ vitamin K (erratic absorption)

2) FFP for high risk bleeding; immediate effect, but short-lived. repeat q6h.

Front 30

Treatment of DVT/PE

Back 30

1) LMWH, UFH x 5 days until INR <2
2) Warfarin on day 1 of tx

Front 31

How long should a patient be anticoagulated?

Back 31

If reversible risk factor present (OCP, indwelling catheter); anticoag x 3 mos

For first unprovoked DVT, x3 mos

For second unprovoked DVT, long-term anticoag

Front 32

Role of plasmin.

Back 32

Limits clot formation by cleaving fibrin.

Front 33

Describe the process of fibrinolysis beginning with plasminogen.

Back 33

Plasminogen binds fibrin as it forms

Fibrin stimulates endothelial cell release of tPA

tPA cleaves plasminogen to plasmin (on fibrin surface)

plasmin breaks down fibrin, releases d-dimer

[alpha-2 antiplasmin inhibitor inactives unbound plasmin

plasminogen activator inhibitor (PAI) inactivates tPA]

Front 34

When is fibrinolytic therapy indicated?

Back 34

When there is a pre-existing clot

Front 35

When are clot blusters indicated?

Back 35

Acute MI
Thrombotic stroke within THREE hours
Acute peripheral artery occlusion
Massive PE w/hemodynamic instability

Front 36

Streptokinase:
MOA
AE's

Back 36

Binds plasminogen and causes auto-catalytic reaction to form plasmin (which limits clot formation by cleaving fibrin)

AEs:
Bleeding
Many pts have Abs against streptokinase (+/-allergic rxn) requiring loading dose

Front 37

Anistreplase:
Drug Class

Back 37

Streptokinase (binds plasminogen and causes auto-catalytic rxn to form plasmin)

Front 38

Tissue Plasminogen Activators:
MOA
How is its action localized in the body?

Back 38

Cleaves plasminogen to plasmin

2 mechs for specificity for clots:
-fibrin = co-factor, strongly stimulates t-PA activation of plasminogen
-blood contains plasminogen activator inhibitor to prevent widespread activation of plasminogen

Front 39

Alteplase:
Suffix
Drug Class

Back 39

-plase; reteplase, tenecteplase
t-PA

Front 40

Which tPA exhibits single-bolus dosing and a greater specificity for fibrin?

Why can it be given as a single bolus?

Back 40

Tenecteplase; has prolonged t1/2 that enables single-bolus dosing.

Front 41

Urokinase:
MOA

Back 41

Renal enzyme that directly converts plasminogen to plasmin

On-off availability bc products manufactured from human sources always have potential to contain infectious agents.

Front 42

rFactor VIIa:
Use
MOA (general)

Back 42

Pro-hemostatic agent

Increases TF occupancy on injured cells
Binds activated platelets (to activate Factor II)
Provides Factor X activation independent of TF

Front 43

Aminocaproic Acid:
Use

Back 43

Adjunctive tx in hemophilia, OD of fibrinolytic tx, prophylaxis for rebleeding from intracranial aneurysms

Front 44

Tranexamic Acid:
Drug Class

Back 44

Anti-fibrinolytic (pro-hemostasis)

Front 45

Aprotinin:
Drug Class

Back 45

Anti-fibrinolytic (pro-hemostasis)

Front 46

Epsilon Aminocaproic Acid:
Drug Class

Back 46

Anti-fibrinolytic (pro-hemostasis)