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Question 1

Clot Formation

Answer 1

1. Damaged endothelium reveals underlying collagen & other proteins
2. Platelets aggregate and adhere to surface to form a temporary seal
3. Blood clotting factors form strong, durable thrombin‐fibrin clot

Question 2

Why interfere with blood clotting?

Answer 2

• Venous thrombosis
• Myocardial infarction (heart attack)
• Cerebral artery occlusion (stroke)
• Peripheral artery thrombosis,

Question 3

Venous thrombosis

Answer 3

blood clot forms in a vein

Question 4

Myocardial infarction

Answer 4

(heart attack)

Question 5

Cerebral artery occlusion

Answer 5

(stroke)

Question 6

Peripheral artery thrombosis

Answer 6

blood clot forms in peripheral arteries
Can prevent clood from travelling through to lung to the heart.

Question 7

Explain how clotting factors work

Answer 7

• Clotting factor = serine protease - enzyme that speeds up the breakdown of another protein.
• The clotting factors are initially inactive and called zymogens.
• When placed with its glycoprotein co-factor, the clotting factor is activated and is then able to catalyze the next reaction

Question 8

Explain the cascade and CF for an intrinsic damage

Abnormal blood vessel

Answer 8

1. XII
2. XI
3. IX
4. X
5. prothrombin –(Xa)–> thrombin + fibrinogen
6. Thrombin fibrin clot

Question 9

Explain the cascade and CF for an extrinsic damage

Damage tissue

Answer 9

1. VII
2. x –(VIIa)–> Xa
   3.5. prothrombin –(Xa)–> thrombin + fibrinogen
3. Thrombin fibrin clot

Question 10

What inhibits thrombin

Answer 10

Antithrombin III

Question 11

Agents that deplete functional clotting factors

Answer 11

– Warfarin
– Heparin
– Direct enzyme inhibitors: dabigatrin and rivaroxaban

Question 12

• Agents that accelerate clot lysis

Answer 12

– Tissue plasminogen activator

Question 13

• Antiplatelet drugs

Answer 13

– Aspirin
– Clopidogrel

Question 14

Preventing clotting factor synthesis with

Answer 14

Warfarin

Question 15

Vitamin K

Answer 15

cofactor for post‐ translational carboxylation of glutamic acid groups on Factors II, VII, IX & X

Question 16

What does warfarin do to vitamin k

Answer 16

Warfarin inhibits Vitamin K recycling from KO (inactive) to KH2 (active

Question 17

VKORC1

Answer 17

Vitamin K Epoxide Reductase Complex 1

Question 18

Heparin will inhibit:

Answer 18

Inactivation of Xa and Thrombin

Question 19

Heparin is

Answer 19

• Mixture of glycosaminoglycans
• Molecular weight ranges 3000 to 58000
• Strong acid, so strong electronegative charge

Question 20

Heparin: mechanism of action

Answer 20

• Binds to Lysine on Antithrombin III (ATIII)
• Conformational change to ATIII.
• increase affinity for activated factors of intrinsic arm, esp. Xa & thrombin
• Accelerated inactivation of these
• Prevents conversion of fibrinogen to fibrin
• Stops clot propagation.

Question 21

Direct enzyme inhibitors

Dabigatran inhibits what

Answer 21

IIa (2a) or thrombin

Question 22

Direct enzyme inhibitors

Rivaroxaban inhibits what

Answer 22

Xa/10a

Question 23

(tissue plasminogen activator) t‐PA

Answer 23

• Recombinant human protein
• IV Administration Immediate onset of action
• Relieves blockage of critical
• vessels, e.g. coronary artery occlusion (heart attack)

Question 24

Clot lysis with t-PA

Answer 24

1. Plasminogen is cleaved by t-PA
2. Releases plasmin
3. Plasmin facilitates lysis as it digests fibrin, fibrinogen and factor 2, 5, 7

Main point is that plasmin facilitates lysis for 3

Question 25

Antiplatelet Drugs: Aspirin & Clopidogrel

Answer 25

* irreversible acetylation and inhibition of cyclooxygenase (COX) enzyme so no TxA2 * Clopidogrel’s active metabolite blocks platelet ADP receptors irreversibly

Question 26

Aspirin (acetyl salicylic acid) in cox

Answer 26

1. Acetylation of NH2‐terminal serine of cyclooxygenase (irreversible) 2. Permanent loss of TxA2 production 3. Defective platelet clot formation 4. Protection from thrombotic disorders

Question 27

Synthesis of ThromboxaneA2 (TxA2) in Platelets

Answer 27

1. Arachidonic acid cyclooxygenase 2. Prostaglandin G2 3. Prostaglandin H2 4. TxA2

Question 28

TxA2 and ADP do what?

Answer 28

enhance platelet aggregation & adhesion

Question 29

How is warfarin taken

Answer 29

– Oral; Vit K has to deplete before it works; – Needs regular monitoring of coagulation

Question 30

How is heparin taken

Answer 30

IV

Question 31

How is Factor IIa and Factor Xa inhibitors taken

Answer 31

– Oral,monitoring not needed in most patients | Dabigatrin and rivaroxaban

Question 32

Why is aspirin and clopidogrel taken

Answer 32

Mostly for arterial disease ;Lower bleeding risk than anticoagulant drugs

Question 33

How is Thrombolytic drugs taken | tissue plasminogen activator

Answer 33

– Treatment of established, life threatening thrombosis | IV

Question 34

Warfarin is a teratogen t/f

Answer 34

true

Question 35

Tissue plasminogen activator (tPA) is particularly effective against platelet clots t/f

Answer 35

false

Question 36

Tissue plasminogen activator (tPA) can lyse thrombi in the coronary circulation, preventing myocardial damage from developing t/f

Answer 36

true