02/23d Thrombosis I

Question 1

What happens during primary hemostasis?

Answer 1

Platelets adhere to and activate at sites of injury

Question 2

What happens during secondary hemostasis?

Answer 2

Coagulation proteins act on platelet surfaces to form fibrin, which stabilizes the platelet plug

Question 3

What are the two steps of the initially proposed 1904 model of coagulation?

Answer 3

1) Prothrombin is converted to thrombin by thrombokinase + calcium
2) Thrombin converts fibrinogen to fibrin

Question 4

What are the two pathways of the clotting cascade?

Answer 4

Intrinsic pathway

Extrinsic pathway

Question 5

What pathway is assessed by the prothrombin time test? What is involved in the test?

Answer 5

Extrinsic pathway

Tissue factor, phospholipid, and calcium are added to a blood sample, and clot time is measured

Question 6

How do you assess the intrinsic pathway?

Answer 6

Activated partial thromboplastin time
A charged surface is added to a blood sample - this activates factor XII
Calcium and phospholipid are then added and clot time is measured

Question 7

What are the vitamin K-dependent coagulation factors? What are their relevant characteristics?

Answer 7

Serine proteases that circulate as inactive zymogens, and are activated by proteolysis
Work best in complex with a protein cofactor on a phospholipid surface
Activity is calcium-dependent

Question 8

What processes and factors are necessary for coagulation protease activity?

Answer 8

Post-translational modification to produce negatively charged amino acid residues (vitamin K dependent)
Calcium cofactor
Phospholipid surface

Question 9

How does warfarin work?

Answer 9

Vitamin K is a required cofactor for the activity of coagulation proteases
When coagulation proteases are activated, Vitamin K is oxidized
In order to maintain activity, Vitamin K must be re-reduced
Warfarin blocks the enzyme that reduces Vitamin K to the usable state

Question 10

Which coagulation factors are affected by warfarin? Why?

Answer 10

Factors II, VII, IX, and X

They are vitamin K dependent

Question 11

On what cell surfaces does hemostasis occur in the body?

Answer 11

Tissue factor-bearing cells

Platelets

Question 12

Which factor is the precursor of thrombin?

Answer 12

Factor II

Question 13

Which factor is the precursor of fibrin?

Answer 13

Factor I

Question 14

What will occur during the PT and aPTT tests if a patient is deficient in a coagulation factor?

Answer 14

Time to clot will be prolonged

Question 15

What is a major drawback of the PT and aPTT tests?

Answer 15

They cannot predict bleeding tendency in the patient

Question 16

What are the three steps of hemostasis in the body?

Answer 16

1) Initiation
2) Amplification
3) Propagation

Question 17

What is involved in initiation of hemostasis?

Answer 17

Tissue factor-bearing cell activates factors X and IX, which generates a small amount of thrombin

Question 18

What is involved in amplification during hemostasis?

Answer 18

Initial small amount of thrombin, plus other coagulation factors, activate platelets

Question 19

What is involved in propagation during hemostasis?

Answer 19

Activated platelets generate lots of thrombin through the intrinsic pathway
Thrombin converts fibrinogen to fibrin

Question 20

What is the structure of the fibrin clot?

Answer 20

Fibrin form polymers that are cross-linked and stabilized by factor XIII

Question 21

What are the major steps and components of fibrinolysis?

Answer 21

Plasminogen is activated to plasmin

Plasmin dissolves the fibrin clot into many fibrin fragments

Question 22

What sorts of things can activate plasminogen, and where are they found?

Answer 22

Tissue plasminogen activator (tPA) - found on endothelial cells
Streptokinase - comes from bacteria
Urokinase - found in urine, produced by WBCs
Factors XIIa and kallikrein

Question 23

What are Amicar and Aprotinin? How do they work?

Answer 23

Anti-fibrinolysis treatments
Amicar blocks activation of plasminogen by tPA
Aprotinin inhibits breakdown of fibrin clots by plasmin

Question 24

How is clot formation controlled in the body? List three ways

Answer 24

Separation of initiation and propagation steps by blood vessel walls
Presence of plasma coagulation inhibitors such as antithrombin (AT) and tissue factor pathway inhibitor (TFPI)
Anti-thrombotic mechanisms on healthy vascular endothelial cells

Question 25

What are the symptoms of a platelet-related bleeding problem?

Answer 25

Petechiae and purpura

Mucocutaneous bleeding

Question 26

What are the symptoms of a coagulation factor-related bleeding problem?

Answer 26

Bruises (ecchymoses)

Soft tissue hemorrhage

Question 27

How does thrombocytopenia (lack of platelets) cause petechiae and purpura?

Answer 27

Causes endothelial changes that causes RBCs to extravasate

Question 28

What does von Willebrand’s factor do?

Answer 28

Mediates platelet adhesion under high shear and acts as a carrier for factor VIII

Question 29

What are the symptoms of von Willebrand’s disease?

Answer 29

Most commonly inherited bleeding disorder
Bleeding, petechiae, excessive menstrual bleeding in women
Reduced level of factor VIII
Prolonged aPTT

Question 30

What is hemophilia, at the cellular/molecular level? What does this mean for the clotting cascade?

Answer 30

A failure of platelet surface thrombin generation

A platelet plug may form initially, but the rest of clotting cascade is deficient, and thus the wound will rebleed

Question 31

What factors are deficient in Hemophilia A and B?

Answer 31

Factors VIII or IX

Question 32

What are the general symptoms of hemophilia A and B?

Answer 32

Prolonged aPTT

Spontaneous soft tissue and joint hemorrhage in the severely affected

Question 33

What are the signs and characteristics of Factor XI deficiency?

Answer 33

Autosomal disorder, common in populations with lots of consanguinity
Bleeding is usually mild except with trauma or surgery