MT2: Hemostasis

Question 1

What activates protein C?

Answer 1

Complex of thrombomidulin, calcium and thrombin

Question 2

Where is tissue factor not present under normal conditions?

Answer 2

in blood

Question 3

What is the mechanism of action of heparin?

Answer 3

Heparin is mainly released from basophils and mast cells (or admninistered). It binds to AT-II (serine protease inhibitor) and increases its activity greatly. It then forms a irreversible complex with thrombin (mainly) and VIIa, IX, X, XI and XII.

It can also inactivate trypsin, kallikrein and plasmin

Question 4

How is fibronolysis terminated?

Answer 4

fibrinolysis is terminated by circulating inhibitors of plasminogen (PAI-1/2), plasmin (alpha2-antiplasmin), and by clearance of the fibrinolytic factors through the liver.

Question 5

What is the background of the APC (activated protein C) resistance?

Answer 5

The main cause of protein C resistance in Caucasians is mutation in the active site of V. Due to this mutation, protein C will not be able to inactivate V, thus it will increase the active time of the prothrombinase complex (higher risk of clotting). It can also occur through a mutation of VIII

Question 6

1. Describe the composition of the prothrombinase complex.

2. What are the structurally important elements for complex formation?

Answer 6

1. The complex is composed by Xa and Va.

2. These factors are bound by calcium ions to the negative PL membrane on the platelets

Question 7

What are the substrates for thrombin in blood coagulation system?

Answer 7

fibrinogen, XIIIa, thrombocytes, XIIa, XIa, VIIIa, Va, thrombomodulin

Question 8

How is plasmin formed?

Answer 8

Plasminogen is converted to plasmin by tissue plasminogen activater (tPA) or by uPA (urokinase)

Question 9

Give the names of at least one drug that can inhibit platelet activation.

Answer 9

Aspirin - which inhibits the COX enzyme

Question 10

Is it possible that thrombin excert any antithrimbotic effects?

Answer 10

thrombin is involved in the activation of APC.

Question 11

1. Which diagnostic assay is based on the intrinsic pathway?

2. List examples of application.

Answer 11

1. APTT (activated partial thromboplastin time) - used for detection of coagulation abnormalities in the intrinsic pathway. Done by adding citrate to the sample, then for activation calcium, phospholipids and an activator (Kaolin) is added. time is measured until a thrombus is formed.
2. Can be used to detect Vit K deficiency, vWf disease, hemophilia, fXII deficiency, APC resistance antiohisoholipif syndrom

Question 12

What is the significance of phospholipid bound complexes in blood coagulation?

Answer 12

the extreme increase of reaction rate

Question 13

how can tPA activity increase?

Answer 13

in the presence of fibrin

Question 14

which one is the primary thrombin inhibitor in the blood? How is its effect pharmacologically increased?

Answer 14

AT-II, heparin

Question 15

list 3 triggers for platelets activation?

Answer 15

collagen, PAF, thromboxane, ADP

Question 16

what initiate blood coagulation at site of vessel injury?

Answer 16

TF

Question 17

How does Hirudin act? When may its actions be exploited therapeutically?

Answer 17

it inhibits the active site of thrombin and inactivates it, preventing clotting. Used with people that have AT-II deficiency so heparin doesnt work.

Question 18

What kind of plasminogen activators are used in thrombolytic therapy?

Answer 18

tPA, uPA, streptokinase

Question 19

How is the formation of blood coagulation complexes inhibited in the clinic?

Answer 19

By the use of heparin. Cumarins (Vit K epoxide inhibitor) can be used