Clotting Drugs Flashcards
5 stages of coagulation
Vasospasm
Primary haemostasis- platelet plug and anteplatelets
Secondary haemostasis- clotting cascade and anticoagulants
Clot retraction
Fibrinolysis
What stages of coagulation do anti platelets and anticoagulants act in
Antiplatelets - primary haemostasis
Anticoagulants - secondary haemostasis
What substances are released by damaged cells in response to injury
Endothelin
Thromboxane A2
Serotonin
Noradrenaline
Direct monocyte contraction also occurs
3 stages of platelet plug formation
Adhesion
Activation
Aggregation
What happens in the adhesion phase of platelet plug formation
Smooth endothelium disrupted -> turbulence and adherence
VWF sticks to exposed collagen, platelets attach to GP1A receptors on vWF
What substances are released in the activation phase of platelet plug formation
ADP (P2Y12)
Thromboxane a2
Collagen thrombin
What receptor becomes available when platelets are activated
GIIb/IIIa receptor
What happens in aggregation phase of platelet plug formation
Fibrinogen links between GIIb/IIIa receptors on activated platelets
What mediation targets thromboxane A2
Aspirin
What medications target ADP ( act as P2Y12 receptor antagonists)
Clopidogrel
Prasugrel
Ticagrelor
What medications antagonise GPIIB/IIIa receptors
Abciximab
Aspirin MOA
Irreversible COX 1+2 inhibitor
Prevents formation of thromboxane A2 by blocking conversion of Arachidonic acid to PGH2 -> decr circ TXA2
Also anti platelet effect
Irreversible antiplatelets
Aspirin (COX1)
Ticlopinide (ADP)
Clopidogrel (ADP)
Prasugrel (ADP)
Abxicimab (GP IIB/iiia)
Reversible antiplatelets
Cangrelor (ADP)
Ticagrelor (ADP)
Tirocinanti (GO IIB/IIIa)
Eprifibatide (GO IIA/IIIB)
Why is clopidogrel used more than prasugrel, cangrelor, ticlopidine and ticagrelor
P - more Haemorrhagic complications and cost
C - less effective
To - more side effects
Tg - more Haemorrhagic complications and side effects
Clopidogrel limitations
Inter patient variability
Slow onset and offset of action
Which antiplatelets are given IV
Cangrelor
Abciximab
Tirofiban
Eptifibatide
Indications for antiplatelets
Athersclerosis
Stents
CVA
Which receptor on ADP do some antiplatelets target
P2Y12
What does reduction in thromboxane A2 by aspirin prevent
Vasospasm and platelet activation
Which phase of primary haemostasis is targeted by aspirin clopidogrel and Abciximab
Aspirin - activation TXA2
Clopidogrel - activation ADP
Abciximab - aggregation GPIIB/IIIA
Which clotting factors are in the extrinsic pathway
3
7
Which clotting factors are in the intrinsic pathway
12
11
9
8
Which clotting factors are in the common pathway
1
2
4
5
10
13
What does prothrombin time measure
External and common pathways
Formation of fibrin by thromboplastin
Clotting blood tests
Prothrombin time
International normalised ratio
Activated partial thromboplastin time
Fibrinogen
What does INR measure
External and common pathways
Which drug is INR used to monitor
Warfarin
What does aPTT measure
Fibrin formation when partial thromboplastin added to plasma
Internal and common pathways
What does Fibrogen blood test measure
Quantative test of amount of fibrinogen
What conditions may have a low fibrinogen test result
Liver failure
DIC
Which blood clotting test measures the internal pathway
aPTT
Which blood clotting tests measure the external pathway
PT
INR
What factors are effected in haemophilia
A - VIII
B - IX
Both disrupt intrinsic pathway
What clotting factors does Antithrombin III act on
Thrombin (II)
9
10
11
12
What clotting factors do protein c and s act on
5
8
Antithrombin III MOI
Binds thrombin and factors 9 10 11 12
What clotting factors does unfractionated heparin work on
9
10a
11
12
What factor does LMWH work on
Xa
What is the reversal agent for unfrac heparin and LMWH
Protamine
Warfarin MOI and which clotting factors effected
Vitamin K antagonist
2 7 9 10 (1972)
Also impacts protein c and s
Warfarin reversal
Vitamin K
Prothrombin complex
Factors 10 9 7 2
Apixaban rivaroxaban edoxaban MOA
Direct Xa inhibitors
Apixaban rivaroxaban edoxaban MOA
Direct Xa inhibitors
Direct Xa inhibitors reversal
Adexanet alpha
What endogenous substances control the clotting cascade
Anti thrombin iii
Protein c
Protein s
Dabigatran MOA
direct thrombin inhibitor
Dabigatran reversal
Idarucizumab
Indications for anticoagulants
DVT
PE
AF
Prophylaxis
What triggers the intrinsic extrinsic and common clotting pathways
Intrinsic - exposed subendothelial collagen
Extrinsic - tissue factor
Common - factor X
Infrac heparin MOA
Potentiates Antithrombin
DOACS
Direct Xa inhibitors (ixabans)
Direct thrombin (IIa) inhibitors - Dabigatran
Stages of clot breakdown
Clot retraction
Fibrinolysis
What enzyme causes fibrinolysis
Plasmin
How is plasmin formed
Plasminogen activated to plasmin by tPA produced by injured endothelium
What are the products of fibronolysis
Fibrinogen breakdown - fibrinogen degradation products
Fibrin breakdown - fibrin degradation products
Stabilised fibrin breakdown - d dimer
Additional breakdown - plasma proteins, V, VIII, complements, VWF
What substance is broken down into D dimer
Stabilised fibrin
TXA MOA
Antifibrinolytics
Competitive inhibitor of binding sites on plasminogen stopping tPA binding (prevents plasminogen binding to fibrin)
Thrombolytic drugs
Streptokinase
Urokinase
Anistreplase
Alteplase
Reteplase
Tenectaplase
Fibronolysis processes
Tissue plasminogen activator (tPA) released from damaged endothelial cell a few days after injury -> plasminogen to plasmin -> plasmin breaks down fibrinogen, fibrin, and stabilised fibrin
Fibronolysis processes
Tissue plasminogen activator (tPA) released from damaged endothelial cell a few days after injury -> plasminogen to plasmin -> plasmin breaks down fibrinogen, fibrin, and stabilised fibrin
Thrombolytic drug MOA
Analogues of tissue plasminogen activator tPA leading to rapid fibrinolysis
What prevents blood from clotting normally
Endothelial cells very smooth preventing adhesion
NO dilates blood vessels maintaining laminar flow
Heparin sulphate secretes heparin and heparin like subapstances into blood
Protein C and S control clotting when it occurs
What causes Vasospasm in response to injury
Damage to muscle -> calcium release -> direct muscle contraction
What causes Vasospasm in response to injury
Damage to muscle -> calcium release -> direct muscle contraction
Antithrombin III route, half life, monitoring
Given as infusion
Very short half life
Needs monitoring
Heparin route
Infusion
Complications of heparin
Heparin induced coagulopathy
Development of antibodies
LMWH MOA
Converts Xa back to X
Is protamine more effective at reversing unfrac heparin or LMWH
Unfrac
How does warfarin effect coagulation in the first couple of days
Coagulation increased for a few days, then overall effect becomes anticoagulant
What anticoagulant is broken down by P450
Warfarin
How does Adexanet alpha work
Directly competes with direct Xa inhibitors
DOAC monitoring
No monitoring needed
Why are thrombolytics high risk drugs
Degrade all clots in body so can cause bleeding from other minor injuries, cannula sites, etc
Only used in haemodynamically unstable pts due to risks
What is ROTEM
POC test to assess blood coagulation
How are antiplatelets drugs reversed
Usually don’t need reversal - just wait for half life to pass usually 24-48hrs
In emergency/high risk procedure - give more platelets
