Wendt - AntiCoag Flashcards by Kappa Epsilon Pi Chapter

role of plasmin?

degrades fibrin – and dissolves clot

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all thromboembolytics work to increase the conversion of ______ to ______?

plasminogen; plasmin

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What activates plasminogen to plasmin

t-PA

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t-PA cleaves a ______ bond to activate plasmin

arg-val bond

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Thrombolytics:

______ cleaves a arg-val bond to activate plasmin

t-PA

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t-PA is inhibited by what things?

PAI-1 and PAI-2

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plasmin is a ________ that digests fibrin and fibrinogen

proteolytic enzyme

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Plasminogen is an anticoagulant protein that circulates in _______ form and is deposited on to a growing clot.

inactive

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t-PA is known as a _______ protease

serine

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plasmin is inactivated by _________

a2-antiplasmin

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indications for thrombolytic therapy:

acute or chronic?

acute!

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indications for thrombolytic therapy:

3 things

acute MI
acute ischemic thrombotic stroke
PE

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what are the 5 options of thrombolytic drugs

Alteplase
Reteplase
Tenecteplase
Streptokinase
Urokinase

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which thrombolytic drugs are known to be recombinant t-PA drugs

Alteplase
Reteplase
Tenecteplase

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Thrombolytic drug:

Streptokinase makes a complex with _______

plasminogen

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Thrombolytic drug:

Streptokinase promotes ________ by the _________ molecule

promotes plasminogen activation; by adjacent plasminogen molecule

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T or F: Streptokinase has intrinsic enzyme activity

FALSE! it does not directly degrade clots — it makes a complex that catalyzes conversion of inactive plasminogen to active plasmin

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Anti-Fibrolytic Agents are?

Lysine
Tranexamic acid
Aminocaproic acid (EACA)

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plasmin binds to fibrin through a ______ binding site to activate fibrinolysis

lysine

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anti-fibrinolytic agents are used to stop _____ caused by _______ drugs

stop bleeding; caused by thrombolytic drugs

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how does plasminogen get converted to plasmin?

t-PA

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how does Alteplase work?

its a thrombolytic drug that is a recombiant human t-PA

binds to fibrin

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how does Reteplase work?

recombinant human t-PA

LESS FIBRIN specific/lacks fibrin binding domain

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is Reteplase more or less fibrin specific than Alteplase?

less fibrin specific

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is Tenecteplase more or less fibrin specific than Alteplase?

more specific!

Tenecteplase: | short or long 1/2 life?

long

-plase thrombolytic drug lacks fibrin binding domain

Reteplase

t-PA binds to _____ and activates bound ________ 100x more rapidly than in circulation

fibrin; plasminogen

Mutations in Tenecteplase lead to: ______ half life reduce __________ enhance activity at ______

LONGER half life; reduce INHIBITION by PAI enhance activity at THROMBI

______ drug is a recombinant t-PA with the 527 aa residue

Altelplase

_______ drug is a recombinant t-PA with the 527 aa residue deletion

Reteplase

Anti-fibrinolytic agents act as a ________ to bind to the receptor on plasminogen and plasmin - leads to a ______ of plasmin binding to target fibrin

lysine analog; blockade

is Tranexamic Acid or Aminocaproic Acid (EACA) more potent as being a anti-fibrinolytic agent

Tranexamic Agent

do platelets have a nucleus?

are platelets made of granules?

yes

do platelets have organelles?

yes (but no nucleus)

Thrombus Formation is also known as what?

platelet plug or white thrombus

3 main steps for Thrombus formation are...

1 - platelet adhesion/Shape change 2 - platelet secretion 3 - Platelet aggregation

Thrombus Formation: STEP 1 | Adhesion is mediated by what 2 things binding

GP1a; GP1b

GP 1a binds to ________ | GP1b binds to _______

1a - collagen | 1b - von willebrand factor (bridged to collagen)

Platelet adhesion mediated by: _____ binding to collagen _____ binding to VonWillebrand Factor (bridged to collagen) ________ facilitates receptor binding

GP1a GP1b Shape change

platelet adhesion: | intact ______ cells secret _____ to inhibit thrombogenesis

intact ENDOTHELIAL; secret PGI2 (prostacyclin)

Platelet secretion: | Platelet granules release what 3 things?

- ADP - TXA2 (thromboxane A2) - 5-HT (serotonin)

ADP, 5-HT, TXA2 activate and recruit what

other platelets

Platelet Aggregation: | ADP/5-HT/TXA2 activate/induce conformation of ______ receptors to bind _____

GP11b/111a receptors bind fibrinogen

Platelets get cross linked by ______

fibrinogen

_____ is used to stabilize and anchor aggregated platelets

Fibrin

Platelet Activation: 1) _______ injury 2) exposed ______ 3) Platelet ______ 4) platelet _______ 5) ______ activation 6) Platelet ______ 7) Platelet ______

``` vascular injury exposed collagen adhesion activation integrin activation aggregation plug ```

what are the 5 options for Antiplatelet drugs

``` COX1 inhibitors ADP receptor inhibitors blockers of GP11b/111a receptors PDE3 inhibitors Protease Activated Receptor inhibitors ```

what drug is a COX 1 inhibitor

Aspirin

Aspirin (ASA): | inhibits platelet COX1 by ______

acetylation

Aspirin (ASA): | Blocks the conversion of ___ to ___

AA to PGG2

Aspirin (ASA): | Interferes with platelet ______

aggregation

Aspirin (ASA): | Prolongs _____ time

bleeding

Aspirin (ASA): | Prevents ________ formation

aterial thrombi

Aspirin (ASA): | Inhibition of _______ in platelets is the key to anti-platelet activity of ASA

TXA2 synthesis

Aspirin (ASA): | (reversible or irreversible) inhibition by acetylation of COX1

IRREVERSIBLE;

Aspirin (ASA): | end up having permanent loss of platelet cox1 activity bc of decreased ______

TXA2

Aspirin (ASA): | Irreversible inhibition by acetylation of _____

COX1

Aspirin (ASA): | (reversible or irreversible) inhibition by ________ of COX1

acetylation

at higher doses of aspirin, _______ production in tissue is inhibited

prostacyclin

T or F: aspirin increases PT time

FALSE (aspirin prolongs bleeding time but no PT time...)

is it used in Platelet Adhesion or Platelet Aggregation? | GP1a

platelet adhesion (binds to collagen)

is it used in Platelet Adhesion or Platelet Aggregation? | GP2a

platelet adhesion

is it used in Platelet Adhesion or Platelet Aggregation? | GP11b

platelet aggregation (it is an integrin)

is it used in Platelet Adhesion or Platelet Aggregation? | GP111a

platelet aggregation (it is an integrin)

what are the 2 ADP receptors involved in activating platelets

P2Y1; P2Y12

which ADP receptor is coupled to Gq-PLC-IP3-Ca2+ pathway

P2Y1

which ADP receptor is coupled to Gi & Inhibition of adenylyl cyclase

P2Y12

ADP comes from _______ and will bind to ______

from GRANULES; | binds to P2Y1 and P2Y12

what are the ADP receptor inhibitors (both direct and prodrugs)

Direct: Ticagrelo; Cangrelor Prodrugs: Prassugrel; Clopidogrel; Ticlodipine

how do the "Thienopyridine" P2Y12 ADP receptors work?

irreversibly block ADP receptor on platelet & subsequent activation of GP11b/GP111a (action will last for a couple days)

Brand/Generic: | Prasugrel

Effient

Brand/Generic: | Effient

Prasugrel

Brand/Generic: | Brilinta

Ticagrelor

Brand/Generic: | Ticagrelo

Brilinta

How does Ticagrelor work?

binds to allosteric site; REVERSIBLE binding NOT a prodrug

which ADP receptors have REVERSIBLE binding AND do NOT require bioactivation

Ticagrelor (Brilinta) | Cangrelor (Kengreal)

what are the PDE3 inhibitors are used for decrease platelet activation

Dipyridamole; Cilostazol

how do PDE3 inhibitors act as an antiplatelet?

if cAMP levels are increased (which they are when PDE3 inhibitors are used) more cAMP leads to decreased intracellular calcium = decreases platelet aggregation and activation

do PDE3 inhibitors act as an antiplatelet or anticoagulant

antiplatelet

both Dipyridamole and Cilostazol: | work to inhibit ________ by prevent degradation of _____ to _____

PDE3; cAMP; AMP (equals more cAMP = equals less platelet aggregation)

which drugs are known as glycoproteins IIb/IIIA receptor inhibitors

- Tirofiban (Aggrastat) - Abciximab (ReoPro) - Eptifibitide

how does thrombin activate platelets

proteolytic cleavage of PAR-1 receptors on platelet surface

what drugs are known as Protease Activated Receptor Inhibitors

Vorapaxar | Atopaxar

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? COX1 Inhibitors

Anti-platelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Alteplase

Thrombolytic

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Aspirin

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Ticagrelor

Anti-Platelet | Brilinta/ADP Receptor Inhibitor

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Cangrelor

Antiplatelet | ADP Receptor inhibitor

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? ADP Receptor Inhibitors

Anti Platelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Cilostazol

Antiplatelet PDE3 inhibitor

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? PDE 3 Inhibitors

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Dipyridamole

Antiplatelet PDE 3 inhibitor

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Atopaxar

Antiplatelet Protease Activated Receptor Inhibitor

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Warfarin

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Direct Thrombin inhibitor

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? t-PA analogs

Thrombolytic

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Direct Factor Xa Inhibitors

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Fondaparinux

AntiCoag | Indirect Factor Xa Inhibitors

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Rivaroxaban

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Apixaban

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Edoxaban

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Xarelto

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Eliquis

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Savasya

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Clopidogrel

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Prassugrel

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Ticlodipine

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Abciximan

Antiplatelet | GPIIB/GPIIIa receptor inhibitors

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Eptifibitide

Antiplatelet | GPIIB/GPIIIa receptor inhibitors

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Tirofiban

Antiplatelet | GPIIB/GPIIIa receptor inhibitors

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Tenecteplase

Thrombolytic | t-PA Analog

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Reteplase

Thrombolytic | t-PA Analog

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Protease activated receptor inhibitor

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? ADP receptor inhibitor

Antiplatelet

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Vit. K Antagonist

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Warfarin

Anti Coag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Heparin Agents

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Enoxaparin

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Dalataparin

Anticoag

Is it an Antiplatelet, Antiocoagulant, or a Thrombolytic Agent? Vorapaxar

Antiplatelet | Protease activated receptor inhibitors

which GPIIb/GPIIIa receptor inhibitor is a chimeric mouse human monoclonal Ab

Abciximab

which GPIIb/GPIIIa receptor inhibitor is a | synthetic peptide

Eptifibitide

which GPIIb/GPIIIa receptor inhibitor is a nonpeptide tyrosine analogue

Tirofiban

GPIIb/IIIa Receptor is: - known to be a receptor for ________ - known to anchor _______ to foreign surfaces and to each other

fibrinogen; platelets;

GPIIb/IIIa Receptors are activated by what 3 things?

TXA2 (thromboxane); thrombin; Collagen

Are GPIIb/IIIa Receptors take by oral or IV route

IV!

All clotting factors are made in the _____ (Except ________)

made in lifer; Except Von Willebrand Factor

Protein C: is it pro-coagulant factor or anti-coagulant

(self made) ANTI-coagulant

what is Transglutaminiase's role in the clotting cascade

Cross link fibrin fibers

what are glycoproteins used for in the clotting cascade?

they are COFACTORs for activation of proteases

Factors XII, XI, X, IX, VII, II are known as _____coagulants that are work by cleaving down stream factors to activate them (aka a _________)

known as PRO-coagulant; they are SERINE PROTEASES

The extrinsic pathway needs ______ to get activated: The intrinsic pathway needs ______ to get activated

Extrinisic - needs Tissue Factor Intrinsic - collagen gets exposed in wall of the blood vessels

Notable things apart of the Extrinisc Pathway

Factors VII and X | Tissue Factor

what are the notable parts of the common pathway

X, Thrombin; Fibrin

Step by Step of Extrinsic Pathway: - TF found on _________ - Factor VII normally resides in ______ - ____ binds to _____ to activate it - Factor __ binds and cleaves factor ____

found on surface of cells outside; resides in blood; TF binds to Factor VII (activates VII to VIIa) VIIa binds/cleaves X

_______ changes fibrinogen to fibrin

Thrombin

Factor _____ changes prothrombin to thrombin

Factor Xa

______ activates factor XIII

Thrombin

Activated Factor XIII leads to _______

cross linking of fibrin = fibrin clot

What are some things that be produced by the body that prevent the coagulation cascade

- AT (antithrombin) - Protein C: - A tissue Factor Pathway Inhibitor

what is a POSITIVE Feedback mechanism for Regulating Coagulation

Thrombin!

what are the NEGATIVE feedback mechanisms for Regulating Coagulation

- Antithrombin - Protein C system - Factor Xa

How does Antithrombin act to DECREASE coagulation:

neutralizes procoagulant serine proteases (aka thrombin, Xa, IXa)

Antithrombin decrease coagulation is accelerated by ______

heparin

how does Protein C decrease coagulation how does the system get activated and what does it do?

Protein C system gets activated by thrombin binding to thrombomodulin Activated Protein C complex (APC) forms a complex with Protein S = inactivates factors Va and VIIIa

how does Factor Xa activate tissue factor pathway inhibitor

activates tissue factor pathway inhibitor (TFPI) to block initial activation of Factor VII

what drugs are direct factor Xa inhibitors

Rivaroxaban Apixaban Edoxaban

what drugs are direct thrombin inhibitors

Argatroban Dabigatran Bivalirudin

which drugs are vit. k antagonists

warfarin

Normal Prothrombin Time (PT)?

12 - 14 seconds

Normal aPTT?

26 - 33 seconds

Normal recalcification time?

2 - 4 minutes

aPTT or PT? | measures intrinsic pathway

aPTT

aPTT or PT? | measures extrinsic pathway

Possible Tests for hemostatic function

- platelet count - PT/INR - aPTT - D-Dimer - Fibrinogen

warfarin inhibits _____ of vit. K

REDUCTION

why is it relevant that warfarin inhibits vit. K?

vit. k is essential for post translation modification of clotting factors

Warfarin inhibits ___________ thus blocking it to get back to its active form

Vit. K epoxide reductase

warfarin acts by inhibiting synthesis of which factors?

II, VII, IX, X | 2,7,9,10

How is warfarin metabolized

in liver by CYP2C9

Idea behind Warfarin Necrosis:

Protein C decreases initially before the pro-coag levels decrease and puts pt at an increased risk for coagulation (esp of pt is protein C deficient before therapy)

use warfarin in pregnancy?

hellll no

what drugs decrease warfarins effect

- VIT K - Cholestyramine - Carbamazepine; Rifampin; Barbituates

what common drug can ENHANCE warfarins anticoag effects

Broad-Spectrum Abx

what drugs are low molecular weight heparins

Enoxaparin; Daltaparin

Heparin and heparin related drugs are known as ____________ inhibitors

indirect factor Xa