Anti-thrombotics: anticoagulants, antiplatelets, thrombolytics

Question 1

Thrombosis definition

Answer 1

When a clot blocks veins or arteries and can lead to many medical conditions
example:
1) TIA - clot brain
2) PE- clot lungs
3) DVT - clot in appendages
4) HA - clot in coronary arteries leading to myocardial death

Question 2

Hemostasis definition

Answer 2

physiologic process by which bleeding stops by two steps:

1) formation of a platelet plug
2) reinforcement of platelet plug with fibrin

Question 3

3 types of drugs used to treat or prevent clots

Answer 3

1) antiplatelets- various mechanisms to decreases platelet aggregation
2) anticoagulants - affect the coagulation cascade in various mechanisms and steps to decrease clot formation
3) thrombolytics- “clot busters” - dissolve the clot that has formed to reverse severe/life threatening clots
* * all inherit risk to cause bleeding**

Question 4

Hemostasis stage 1- platelet plug formation

Answer 4

1) . initiated when platelets come into contact with collagen on the exposed surface of a damaged blood vessel
2) in response to contact with collagen, platelets adhere to the site of vessel injury
3) adherence to the site of injury results in activation which results to further aggregation
4) the complex process ends in massive platelet aggregation with formation of fibrinogen bridges between glycoprotein iib and iiia receptors on adjacent platelets
5) for bridges to form, the iib/iiia receptors must undergo activation -this can be stimulated for multiple factors including thromboxanes a2, thrombin, collagen, PAF and ADP

Question 5

Of the 3 types of antithrombotics which has the greatest bleeding risk?

Answer 5

thrombolytics

Question 6

Stage 2 of hemostasis

Answer 6

1) coagulation is the production of fibrin

Question 7

fibrin is produced via which two pathways

Answer 7

1) contact activation pathway (intrinsic)
2) tissue factor pathway (extrinsic)
- intersect at factor 10a, after which they results in the same series of final reactions
- in both pathways, each reaction in the sequence amplifies the next reaction and once the sequence is initiated, it becomes self-sustaining and self-interacting

Question 8

Intrinsic pathway ( contact activation pathway)

Answer 8

• aka contact activation pathway
• intrinsic pathway is turned on when blood makes contact with collagen after trauma to a blood vessel wall
• cascade starts witha ctivation for favtor 12 to factor 12a and proceeds until factor 10 is activated to 10a

Question 9

what is fibrin

Answer 9

threadlike protein that reinforces the platelet plug

- stable and long term clot

Question 10

extrinsic pathway

Answer 10

• extrinsic pathway is truned on by trauma to the vascualr wall which triggers release of tissue factor
• cascade starts with activation form factor VII to factor viia and proceeds until factor 10 goes to 10a

Question 11

coagulation pathway convergence

Answer 11

-activated factor Xa then converges to activate prothrombin (factor ii) into thrombin (factor iia)

Question 12

three factors of thrombin

Answer 12

1) catalyzes fibrinogen to fibrin
2) catalyzed factor V to Va which results in increased Xa activity
3) catalyzes factor VIII into VIIIa which results in increased IXa activity and thus more Xa

Question 13

Controlling hemostasis and physiologic removal of clots

Answer 13

• to protect against widespread coagulation, the body must inactive the clotting factors- this is done with antithrombin

Question 14

How to remove clots in hemostasis

Answer 14

• to remove the clots plasminogen is activated to plasmin, and plasmin is associated with clot dissolving

Question 15

What helps with clot removal and plasminogen

Answer 15

• tissue plasminogen activator (tPA) activates conversion from plasminogen to plasmin
• tPA is found in endothelial cells- continuously released but increased. when stimulation of certain endothelial cell receptors occur