Cardio Exam 2: Elsaid Anti-Coags (DRUGS + PATHWAY)

Which pathway is initiated by Tissue Factor (TF)?

_____ pathway.

• Tissue Factor + Factor _____ → _____ complex

• _____ activates Factor _____ → _____

• Also activates Factor _____ → _____

Extrinsic, VII, VIIa-TF, VIIa-TF, X, Xa, XI, XIa

What is the key enzyme that converts prothrombin into thrombin?

_____.

• It converts Factor _____ (_____) → Factor _____ (_____)

Factor Xa, II, Prothrombin, IIa, Thrombin

What is the role of thrombin (Factor IIa)?

Converts fibrinogen (Factor I) to fibrin (Factor Ia) to form a clot.

What is the clotting sequence most often tested?

_____ → _____ → _____ → _____ (_____) → _____

TF + VII, VIIa-TF, Xa, IIa (Thrombin), Fibrin

Why do patients with liver failure bleed easily?

The liver produces clotting factors:

• _____

• _____
  ↓ Liver function = ↓ clotting factor production

II, VII, IX, and X, Protein S and C

What endogenous anticoagulant is required for heparin to work?

Antithrombin III (ATIII)

Which clotting factors does antithrombin inhibit?

Factor IIa (Thrombin) and Factor Xa

What is heparin's true target?

Antithrombin III

What is UFH's MOA?

Binds ATIII and causes allosteric activation, resulting in increased inhibition of Xa and IIa

Why can UFH inhibit thrombin (IIa)?

Long chain (>18 saccharides) allows binding of both ATIII and thrombin

What ratio of Xa:IIa inhibition does UFH have?

1:1

What adverse effect is classically associated with UFH?

Heparin-Induced Thrombocytopenia (HIT)

What antidote reverses UFH?

Protamine sulfate

A patient develops thrombocytopenia 7 days after starting heparin. What is occurring?

_____

• _____-mediated

• _____ activation

• _____ risk

• STOP all _____ products

Type II HIT, Ab, platelet, thrombosis, heparin

Which LMWH is most commonly tested?

Enoxaparin (Lovenox)

Why does LMWH inhibit Xa more than IIa?

Shorter chain (<18 saccharides), Cannot effectively bridge ATIII and thrombin

What is the Xa:IIa inhibition ratio of LMWH?

3:1

Preferred anticoagulant in pregnancy?

LMWH (Enoxaparin)

Preferred anticoagulant in oncology patients?

LMWH (Enoxaparin)

What dosing adjustment is required for LMWH?

Renal dose adjustment

What antidote partially reverses LMWH?

Protamine sulfate

Which causes more HIT?

UFH > LMWH

What is Fondaparinux?

Synthetic pentasaccharide

What receptor/protein does Fondaparinux bind?

Antithrombin III

What clotting factor does Fondaparinux inhibit?

Factor Xa ONLY

Why can't Fondaparinux inhibit thrombin?

Too short to bridge ATIII and thrombin

Which anticoagulant is often used in patients with HIT?

Fondaparinux

Which oral direct thrombin inhibitor exists?

Dabigatran (Pradaxa)

What factor does Dabigatran directly inhibit?

Thrombin (Factor IIa)

What advantage do DTIs have over heparin?

Inhibit BOTH:

• _____

• _____

Circulating thrombin, clot-bound thrombin

Main indications for Dabigatran?

Non-valvular A-fib and DVT/PE treatment

What monoclonal antibody reverses Dabigatran?

Idarucizumab (Praxbind)

What does Idarucizumab bind?

Dabigatran itself

Which DTI is preferred for HIT with renal impairment?

Argatroban

Which DTI is hepatically cleared?

Argatroban

Which DTI is renally cleared?

Bivalirudin

Which drugs are direct oral Factor Xa inhibitors?

Edoxaban, Apixaban, and Rivaroxaban

What factor do Apixaban, Rivaroxaban, and Edoxaban directly inhibit?

Factor Xa

Main indication for Factor Xa inhibitors?

Non-valvular A-fib and DVT/PE

Which enzyme/transporter interactions are important for Xa inhibitors?

CYP3A4 and P-gp

Which patients should NOT receive Xa inhibitors?

Patients with prosthetic heart valves

Which reversal agent acts as a decoy Factor Xa protein?

Andexanet alfa (Andexxa)

What enzyme does warfarin inhibit?

Vitamin K Epoxide Reductase (VKOR)

What is warfarin's MOA?

_____ → depletes _____ → prevents _____

Inhibits VKOR, active Vitamin K, activation of clotting factors

Which clotting factors are Vitamin K dependent?

2, 7, 9, and 10

Which anticoagulant proteins are Vitamin K dependent?

Protein S and C

Why does warfarin take 5–7 days to work?

Existing clotting factors must first be degraded

What lab monitors warfarin?

INR

What is the typical INR goal?

2-3

Which genetic polymorphism increases warfarin sensitivity?

CYP2C9 mutation

What food interaction is classically tested with warfarin?
_____

• _____

• _____

• _____

Vitamin K-rich foods, Spinach, Kale, Broccoli

A patient started warfarin and asks why they need bridging with heparin.

Warfarin takes several days to reduce clotting factor levels; heparin provides immediate anticoagulation

What is the reversal strategy for life-threatening warfarin bleeding?

Kcentra + Vitamin K.

ENTER AFTER EACH BULLET POINT

• UFH → ATIII → _____

• LMWH → ATIII → _____

• Fondaparinux → ATIII → _____

• Dabigatran → _____ inhibitor

• Argatroban → _____ inhibitor

• Bivalirudin → _____ inhibitor

• Apixaban → _____ inhibitor

• Rivaroxaban → _____ inhibitor

• Edoxaban → _____ inhibitor

• Warfarin → _____ inhibitor

• Protamine → _____

• Idarucizumab → _____

• Andexanet → _____

• Kcentra → replaces clotting factors _____

Xa + IIa
mostly Xa
Xa only
Direct IIa

Direct IIa

Direct IIa

Direct Xa

Direct Xa

VKOR

binds heparin

binds Dabigatran

decoy Xa

II, VII, IX, and X

Name the three LMWHs commonly tested.

Enoxaparin (Lovenox), Dalteparin, and Tinzaparin

Which IV direct thrombin inhibitor is preferred in a patient with HIT and renal dysfunction?

Argatroban (hepatically cleared)

Which IV direct thrombin inhibitor is preferred in a patient with HIT and hepatic dysfunction?

Bivalirudin (renally cleared)

What are the three direct thrombin inhibitors you need to know?

Dabigatran (oral), Argatroban (IV), and Bivalirudin (IV)

What are the other Factor Xa drugs? (3)

Apixaban (Eliquis), Rivaroxaban (Xarelto), and Edoxaban (Savaysa)

Match the reversal agent to the anticoagulant.

• Protamine → _____

• Idarucizumab (Praxbind) → _____

• Andexanet alfa (Andexxa) → _____

• Kcentra (4-factor PCC) → _____

UFH (full) and LMWH (partial), Dabigatran, Apixaban and Rivaroxaban, Warfarin

How much protamine is needed to reverse heparin?

1 mg protamine per 100 units of heparin administered in the previous 30 mins

A patient develops Type II HIT while receiving UFH. What should you do?

• Stop _____ products immediately.

• Start a _____:

  • _____

  • _____

  • _____

all heparin, non-heparin anticoagulant, Argatroban, Bivalirudin, Fondaparinux

Which anticoagulants require Antithrombin III to work?

UFH, LMWH, and Fondaparinux

Which drugs directly inhibit clotting factors versus indirectly inhibit them?

UFH (Xa + IIa), LMWH (mostly Xa), and Fondaparinux (Xa only)