Cardio Exam 2: Anti-Coags

KNOW

Pathways of Clot Formation

• Tissue Factor _____ forms activated complex (_____)

• Activates Factor _____ → Factor _____

• Xla proceeds the cascade

• Activates Factor _____ → _____

• _____ activates/converts prothrombin (Factor _____) → Thrombin (Factor _____)

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

• Forms a blood clot

VII, VIIa-TF, XI, XIa, XIa, X, Xa, Xa, II, IIa, Thrombin, IIA, Fibrinogen, I, Fibrin, IA

Pathways of Clot Formation

• Additional Info:

  • _____, acting in the blood, activates anti-clotting factors, specifically _____, which _____ the factors enclosed in _____ (makes it _____)

  • _____, acting in the liver, _____ the _____ of the factors enclosed in _____ (_____)

  • __________ = decreased clotting factors

Heparin, anti-thrombin, inactivates, rectangles, work better, Warfarin, inhibits, synthesis, circles, prevention, non-functional liver

KNOW

Indirect Inhibitors of Common Pathway: Anti-thrombin

• Made by the _____, circulates _____

• _____ clotting factors _____ by binding in a stable _____ complex

liver, blood, Inhibits, IIa and Xa, 1:1

__________

• MOA: binds to ATIII → enhance ATIII’s ability to inactivate IIa (thrombin) + Xa

  • Allosteric activation of ATIII

  • Forms complex with ATIII + thrombin and ATIII + Xa

• ATIII: endogenous inhibitor of thrombin (IIa) + changes conformation

• 5-saccharide sequence → allosteric activation

  • Binds to ATIII

• >18-saccharide length → thrombin inhibition

  • Binds + inhibits Xa/Thrombin (IIa)

Unfractionated Heparin (UFH)

Unfractionated Heparin (UFH)

• MOA: binds to _____ → enhance its ability to _____ (_____) + _____

• __-saccharide sequence → _____

  • Binds to _____

• > __-saccharide length → _____

  • Binds to _____ (_____)

ATIII, inactivate IIa, Thrombin, Xa, 5, allosteric activation, ATIII, 18, thrombin inhibition, and inhibits Xa/IIa, thrombin

__________

• Ends with “parin”

  • Enoxaparin (Lovenox, doesn’t bind thrombin as effectively as heparin)

    • SubQ

    • Weight-based + needs renal dose adjustment

    • Preferred anticoag in oncology + pregnant pts

  • Dalteparin

  • Tinzaparin

Low Molecular Weight Heparin (LMWH)

Low Molecular Weight Heparin (LMWH)

• _____ (Lovenox, doesn’t bind thrombin as effectively as heparin)

  • _____

  • Weight-based + needs renal dose adjustment

  • Preferred anticoag in _____

• _____

• _____

Enoxaparin, SubQ, oncology and pregnant, Dalteparin, Tinzaparin

Low Molecular Weight Heparin (LMWH)

• Low MW Heparin bc it’s a _____ chain

• Less _____ (<18 saccharides), but still _____

• ATIII (Anti-Thrombin) → Inhibits Factor _____

• _____ (Heparin-Induced Thrombocytopenia/HIT) + _____: LMHW < UFH 

  • HIT: platelet _____, _____, and _____

  • TYPE-2 HIT: 

    • _____-mediated

    • Onset: _____

    • Discontinue all heparin agents → Start _____

shorter, thrombin inhibition, inhibits Xa, X and II, Bleeding, Hyperkalemia, activation, consumption, thrombosis, Ab, 5-10 days, non-heparin anticoagulants

_____

• MOA: synthetic pentasaccharide analog that inhibits Factor Xa (no inhibition of thrombin)

  • Pentasaccharide binds to antithrombin → causes allosteric activation → allows to inhibit Factor Xa

• Can use in pts with HIT

• Weight-based dosing

Fondaparinux

Fondaparinux

• MOA: _____ analog that inhibits Factor _____ (no inhibition of _____)

  • _____ binds to antithrombin → causes _____ → allows to inhibit Factor _____

• Can use in pts with _____

• Weight-based dosing

synthetic pentasaccharide, Xa, thrombin, Pentasaccharide, allosteric activation, Xa, HIT,

Heparin

• Target: _____

• Antidote Effect (Reversal): _____

Xa and II2, Complete

LMWH

• Target: _____

• Antidote Effect (Reversal): _____

Xa and IIa, partial

Fondaparinux

• Target: _____

• Antidote Effect (Reversal): _____

Xa, None

__________

• MOA: inhibits both circulating + clot-bound thrombin (Factor IIa)

• Can be used in patients with heparin-induced thrombocytopenia (HIT)

Direct Thrombin Inhibitors

Oral Direct Thrombin Inhibitor = __________

• DVT/PE treatment (blood stays in atria → coag cascade starts → increases blood clots)

• A. fib.

Dabigatran (Pradadex)

Direct Thrombin Inhibitors

• MOA: inhibits both circulating + clot-bound _____ (Factor _____)

• Can be used in patients with __________

thrombin, IIa, Heparin-Induced Thrombocytopenia (HIT)

IV Direct Thrombin Inhibitors: IV bolus + IV cont. infusion

• _____ → HIT + ACS → renal

• _____ → HIT + Acute Coronary Syndrome (ACS) → hepatic

Bivalirudin, Argatroban

__________

• Edoxaban, Apixaban, Rivaroxaban

• Indications: Non-Valvular A. fib. + treatment of DVT/PE

• DDIs (CYP3A4, p-gp)

• C/I with prosthetic heart valves

Direct Factor Xa Inhibitors

Direct Factor Xa Inhibitors

• _____, _____, _____

• Indications: Non-Valvular A. fib. + treatment of DVT/PE

• DDIs (_____, _____)

• C/I with __________

Edoxaban, Apixaban, and Rivaroxaban, CYP3A4, p-gp, prosthetic heart valves

Vitamin K-Dependent Clotting Factors

• In the _____

• Diet → Vitamin K (_____) → Inactive Factors → Active Factors → Vitamin K _____ (oxidized) → Vitamin K _____ (VKOR) → Vitamin K

  • Pro-Coagulating Factors: _____

  • Anti-Coagulating Factors: _____

Liver, co-factor, Epoxide, epoxide reductase, II, VII, IX, X, S, C

__________

• Vitamin K Antagonist

• In the liver

• Prevents new coag factors from being produced

• Starts when existing coag factors are turned over (5-7 days)

• MOA: Inhibits VKOR → depletes Vitamin K → Prevents activation of clotting factors: II, VII, IX, X, S, C

Warfarin

Warfarin

• _____

• In the _____

• Prevents _____ coag factors from being produced

• Starts when _____ coag factors are turned over (5-7 days)

• MOA: _____ → depletes _____ → _____ of clotting factors: II, VII, IX, X, S, C

Vitamin K Antagonist, liver, new, existing, inhibits VKOR, Vitamin K, prevents activation

Warfarin

• Indication: Prophylaxis of DVT/PE, Thromboembolic, and A. fib.

• Warfarin specifically affects Protein _____

• Warfarin Sensitivity due to __________ (_____)

• Warfarin Monitoring: _____ therapeutic window medication

• Increased INR intensity = _____ Haemorrhagic SEs + _____ thromboembotic SEs (Goal INR = 2-3)

S and C, Enzyme Gene Polymorphisms, CYP2C9, Narrow, Increased, decreased

Warfarin

• MOA: _____

• Route: _____

• Reversal Agent: _____ 

• Titration Labs: _____

VKOR inhibitor, oral, Vitamin K, Ecentra, INR

Dabigatran

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Titration Labs: _____

IIa inhibitor, Oral, Praxbind, n/a

Rivaroxaban

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Titration Labs: _____

Xa inhibitor, Oral, Andexxa, n/a

Apixaban

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Titration Labs: _____

Xa inhibitor, oral, andexxa, n/a

Edoxaban

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Titration Labs: _____

Xa inhibitor, oral, n/a, n/a

Argatroban

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Causes HIT? → _____

IIa inhibitor, IV, n/a, n/a

Bivalirudin

• MOA: _____

• Route: _____

• Reversal Agent: _____

• Causes HIT? → _____

IIa inhibitor, IV, n/a, n/a

UFH

• MOA: _____, _____ = _____

• Route: _____

• Reversal Agent: _____

• Causes HIT? → _____

ATIII activator, Xa:IIa, 1:1, IV or SQ, Protamine, Sometimes

LMWH

• MOA: _____, _____ = _____

• Route: _____

• Reversal Agent: _____

• Causes HIT? → _____

ATIII activator, Xa:IIa, 3:1, SQ, Protamine (partial), Rarely

Fondaparinux

• MOA: _____, _____

• Route: _____

• Reversal Agent: _____

• Causes HIT? → _____

ATIII activator, Xa only, SQ, n/a, n/a

__________

• Reversal Agent for UFH (full) + LMWH (partial)

• MOA: _____ by binding to it so it does not bind to _____

  • Heparin = acid (negatively-charged)

  • _____ = base (positively-charged)

• 1 mg _____ for every 100 units of heparin given in the last 30 mins

Protamine, chemically neutralized heparin, ATIII, Protamine, Protamine

Idarucizumab (__________)

• Reversal Agent for Dabigatran

• MOA: _____

• Dabigatran is _____ (2nd best option (other than Ab) = _____ than Ab)

Praxbind, humanized mouse Mab, dialyzable, longer

__________

• Reversal Agent for Warfarin

• Prothrombin Complex Concentrates → has heparin (stabilizes coag factors)

• Ready to use (already _____) + _____ coag factors (for _____)

• Administer with _____ → waiting is not an option (quick administration)

Kcentra, activated, infusible, active bleeding, Vitamin K

__________

• Reversal for Rivaroxaban + Apixaban

• Removed from market due to increased risk of _____

Andexxa, clot formation

Parenteral Agents (4):

UFH, LMWH, Factor Xa inhibitors, DTIs

Oral Agents (3):

Vitamin K Antagonist, Factor Xa Inhibitors, DTIs

_____ + _____ = DOACs or NOACs

• DOAC → _____ Oral Anticoag

• NOAC → _____ Oral Anticoag

Factor Xa Inhibitors, DTIs, Direct, New