Lecture 19

Question 1

thrombus

Answer 1

in vivo (inside)

Question 2

clot

Answer 2

in vitro (outside)

Question 3

Arterial thrombus

Answer 3

platelets plus WBC in fibrin mesh (white)

Question 4

Venous thrombus

Answer 4

Fibrin, platelets, RBC (red)

Question 5

Mechanism of hemostasis (2)

Answer 5

collagen exposed-platelets stick and activate

ADP and 5-HT(powerful vasoconstrictor) released

Question 6

Platelet activation and adhesion

platelet activation arrows (6)

Answer 6

Platelets aggregate and adhere via fibrinogen binding between GP2b/3a receptors->soft plug formed
PLA2->arachadonic acid-COX->TXA2->Ca->adhesion and aggregation

Question 7

Stimuli for platelet activation (4)

Answer 7

collagen
thrombin
thomboxane (TXA2)
ADP

Question 8

What does thrombin cleave

Answer 8

fibrinogen->fibrin

Question 9

Activation of prothrombin(cascade rxn)(2)

Answer 9

extrinsic-in vivo-damages tissues release thromboplastin

Intrinsic-in vitro-exposed collagen or other material, negative charges

Question 10

Coagulation cascade(3)

Answer 10

amplification
factors are proteases
Extrinsic pathway faster

Question 11

Control of blood coagulation by (2)

(2) including steps

Answer 11

enzyme inhibitors (eg. Antithrombin 3->cascade inhibition)
fibrinolysis by plasmin: thrombin+thrombomodulin->activates protein C->inactivation of 5,8, inhibitor of tissue plasminogen->plasminogen->plasmin->fibrinolysis

Question 12

Situations of blood stasis leading to thrombus formation

Answer 12

Atrial fibrillation: cerebral, renal, saddle thrombosis

Deep Vein Thrombosis (DVT);pulmonary embolism

Question 13

Situations of blood vessel damage leading to thrombus formation
2 locations and what they cause

Answer 13

Atherosclerosis (plaque build up)

• coronary-myocardial infarction
• carotid artery-stroke

Question 14

Drugs affecting fibrin formation(3 and ex)

Answer 14

procoag drugs- Vit K
injectable anticoagulants eg Heparin
oral anticoagulants- warfarin

Question 15

Injectable coagulants: Heparin
action
why is it injectable

Answer 15

enhances activity of antithrombin 3->inactivates factor 10 and thrombin
it is largely negatively charged so not orally available

Question 16

What does Activated partial thromboplastin time (aPTT) measure

Answer 16

intrinsic pathway

used to monitor effect of heparin

Question 17

Warfarin and its derivatives
what is its action?
where is it active
how long does it take to work

Answer 17

Inhibit reduction of vit K (2,7,9,10)->inhibiting gamma glutamyl carboxylase
only active in vivo(inside)-orally available
delayed onset of action because it does not affect already active factors (could take days to see effects)

Question 18

Adverse effects of warfarin

and reversal

Answer 18

hemorrhage

reversal with vit K (oral) and fresh frozen plasma

Question 19

Monitoring the effect of coumarin and rodenticide poisoning

Answer 19

prothrombin time (PT)
extrinsic pathway

Question 20

What other drugs will affect warfarin activity

Answer 20

aspirin- impaired platelet activity
NSAIDs- competition form plasma protein binding
Alcohol- Competition from cytochrome p450 pathway so dec warfarin clearance->inc availability

Question 21

TXA2 synthesis

and what is thromboxane

Answer 21

thromboxane is a potent platelet activator
synthesized in platelets from arachadonic acid
Rxn catalysed by COX

Question 22

Aspirin is
leads to(3)

Answer 22

irreversible COX inhibitor
dec TXA2 synthesis
dec platelet aggregation

Question 23

Low dose aspirin therapy-why does it work(3)

Answer 23

platelets exposed to aspirin in portal vein->bind COX->dec platelet aggregation
90% aspirin cleared in first pass metabolism
beneficial vasodilation is preserved (kidneys)