S2L1 - Coagulation and Anticoagulants

Question 1

What initiates the clotting sequence of events?

Answer 1

Tissue injury and platelets

Question 2

What is the final event in the coagulation cascade?

Answer 2

Fibrin deposition

Question 3

What retracts clots?

Answer 3

Plasminogen –> Plasmin degrades fibrin and releases fibrin degradation products (FDPs)

Question 4

What substances promote coagulation?

Answer 4

ADP and Thromboxane (TXA2)

Question 5

What substances inhibit coagulation?

Answer 5

Prostacyclin

Question 6

How does TXA2 transport?

Answer 6

Via platelets with membrane-bound fatty acids

Question 7

What generates TXA2?

Answer 7

COX

Question 8

What is TXA2 involved in?

Answer 8

Platelet aggregation, release response, arterial constriction

Question 9

What generates prostacyclin and where is it located?

Answer 9

COX, endothelial cell walls

Question 10

What does prostacyclin do?

Answer 10

It acts as a negative feedback mechanism to inhibit platelet aggregation and relax blood vessels

Question 11

What is the order of the intrinsic coagulation cascade?

Answer 11

12 - 11 - 9 - 10 - prothrombin - thrombin - fibrinogen

Question 12

What is the order of the extrinsic coagulation cascade?

Answer 12

7 - 10 - prothrombin - thrombin - fibrinogen

Question 13

What is fibrinolysis and what causes it?

Answer 13

The breaking of a clot - plasminogen becoming plasmin degrades the fibrin that creates the clot

Question 14

How is coagulation maintained in hemostasis?

Answer 14

Platelets circulate ready to be activated and are stabilized by the presence of prostacyclin

Question 15

What triggers the coagulation cascade?

Answer 15

Exposure to collagen from injury causes platelet aggregation and then release of tissue factor that signals for the cascade

Question 16

What is heparin and what are the types? Where do they work?

Answer 16

It is a rapid anticoagulant - unfractionated (nonspecific for Xa and thrombin IIa) and a low molecular weight version (specific for Xa)

Question 17

What reverses UFH action and how?

Answer 17

An infusion of protamine - it is a weak base that neutralizes the weak acid of UFH

Question 18

How do you monitor heparin dosing and what is a common side effect?

Answer 18

aPTT - side effect is thrombocytopenia or HIT

Question 19

Where do immune complexes bind to platelets?

Answer 19

Fc Receptor

Question 20

What are the ways to monitor HIT in a patient?

Answer 20

4T score from clinical manifestation and antibody immunoassay

Question 21

How is type II HIT managed?

Answer 21

Patient taken off heparin and put on other anticoagulant such as Fondaparinux, Argatroban, Bivalirudin

Question 22

What are the LMWH drugs?

Answer 22

Tinzaparin, Enoxaparin, Dalteparin - “TED”

Question 23

What are the LMWH drugs used for and why?

Answer 23

DVT, PE, AMI, TIA - long acting so don’t need monitoring and easier dosing, more predictable activity

Question 24

When should you not use heparin/contraindications?

Answer 24

Bleeding, recent surgery, hypersensitivity, aortic aneurysm, but can be given during pregnancy

Question 25

What are the direct thrombin inhibitors (DTI)?

Answer 25

Argatroban and bivalirudin

Question 26

What are DTIs used for and why?

Answer 26

HIT or narrowing arteries - they are expensive and less studied which is why heparin is used first - can cause bleeding as an ADE

Question 27

When is there paradoxical bleeding related to heparin use?

Answer 27

When large doses of protamine are given for reversal of heparin induced toxicity

Question 28

What is the difference in type I and II HIT?

Answer 28

Type I is only thrombocytopenia and will resolve on it's own Type II can lead to thrombocytopenia and thrombosis giving a hyper-coagulated state and takes longer to come up and requires therapy - more severe and immune mediated

Question 29

Why are heparins used over DTIs?

Answer 29

DTIs are expensive and less studied

Question 30

What does warfarin do and how?

Answer 30

It works by inhibiting the hepatic synthesis of vitamin K dependent clotting factors - II, VII, IX and X - inhibits reduced form of vitamin K via carboxylation

Question 31

How do you reverse the action of warfarin?

Answer 31

Giving vitamin K

Question 32

What drug interactions does warfarin have?

Answer 32

CYP 450 2C9 and 3A4 which can effect the blood level of warfarin

Question 33

What can be a result of use of warfarin?

Answer 33

Protein c deficiency which is a natural anticoagulant

Question 34

What are contraindications of warfarin?

Answer 34

pregnancy, bleeding, aneurysm, surgery and hypersensitivity

Question 35

What are the new oral anticoagulants?

Answer 35

Dabigatran, apixaban, rivaroxaban "RAD"

Question 36

What is used to treat bleeding secondary to newer anticoagulant drugs?

Answer 36

Prothrombin protein concentrates (PCCs)

Question 37

What do fibrinolytic/thrombolytic drugs do?

Answer 37

Break clots by activating the conversion of plasminogen to plasmin which breaks down fibrin to potentiate clot breakdown

Question 38

What are fibrinolytic drugs used for?

Answer 38

short-term emergency management of DVT, thromboembolism, thromboses in MI and stroke

Question 39

How are fibrinolytic drugs eliminated?

Answer 39

Hepatic clearance and reversed by cryoprecipitate a blood product

Question 40

What are the fibrinolytic drugs?

Answer 40

Streptokinase, tPA/alteplase, reteplase, tenecteplase, urokinase, anistreplase

Question 41

What are reteplase and tenecteplase mostly used for?

Answer 41

heart attacks

Question 42

How is tPA different from streptokinase?

Answer 42

It selectively lyses clots giving less hemorrhage and allergic response and has a shorter half-life so can be reversed easier

Question 43

How do platelets aggregate together?

Answer 43

Fibrinogen adheres two platelets together via the GPIIb/IIIa receptor and platelets release TXA2 in response to elevated calcium levels to stimulate clotting

Question 44

What are the antiplatelet drugs?

Answer 44

Aspirin, ADP antagonist, Dipyridamole, Glycoprotein IIb/IIIa receptor inhibitors

Question 45

How does aspiring work?

Answer 45

Irreversibly inhibits COX1 and TXA2 synthesis to prevent platelet aggregation

Question 46

What is aspirin used for and what are it's side effects?

Answer 46

Aspirin is used to prevent thrombosis in IHD, strok patients and to treat and prevent MI and TIA -- can cause GI bleeding and ulcers and salicylism at toxic doses

Question 47

How do ADP antagonists work?

Answer 47

Interfere with binding of ADP to platelet receptor which inhibits GPIIb/IIIa receptor activation for fibrinogen binding for aggregation

Question 48

What are the ADP antagonist drugs and when are they used?

Answer 48

Ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor - used as alternative to aspirin or after stent placement

Question 49

What do ADP antagonists cause as side effects?

Answer 49

GI bleeding and neutropenia but this is rare - ticlopidine can lead to thrombocytopenia and bruising

Question 50

How does dipyridamole work?

Answer 50

Acts as coronary vasodilator to inhibit cellular uptake of adenosine - Inhibits phosphodiesterase enzyme which results in decreased TXA2 synthesis

Question 51

When is dipyridamole used?

Answer 51

It is the weakest anti-platelet so it is used in combination with aspirin or warfarin as a prophylactic treatment

Question 52

What are the glycoprotein IIb/IIIa receptor inhibitors?

Answer 52

Abciximab,eptifibatide, tirofiban