Lecture 9 Hemostasis and Clotting

Question 1

What are the general steps of hemostasis?

Answer 1

1. vascular constriction
2. formation of a platelet plug
3. formation of a blood clot
4. vessel repair- clot dissolution and wound healing

Question 2

What is the major role of thromboxane A?

Answer 2

recruits platelets

Question 3

What are the 3 essential steps of blood clotting?

Answer 3

1. prothrombin activator complex must be formed via 2 pathways (extrinsic: tissue factor dependent, fast and intrinsic: collagen-dependent, slow)
2. Prothrombin is converted to thrombin
3. Thrombin converts fibrinogen to fibrin monomers which polymerize to fibers

Question 4

What are the five conditions that promote anticoagulation?

Answer 4

1. smooth endothelium- mucopolysaccharide coat
2. endothelial surface contains thrombomodulin which binds and inactivates thrombin
3. fibrin attaches thrombin to clot
4. antithrombin III inactivates thrombin
5. heparin- negatively charged anticoagulant

Question 5

What is the role of tPA? (tissue plasminogen activator)

Answer 5

It is released from endothelium after several days and activates a protease to cleave plasminogen to plasmin.

Question 6

For which clotting factor is Vitamin K a cofactor for carboxylation?

Answer 6

prothrombin, Factors 7, 9, 10 and protein C; vitamin K epoxide reducatse complex 1 required for oxidation

Question 7

What is the treatment for someone with deep vein thrombosis (DVT) who has a pulmonary embolism?

Answer 7

tPA (tissue plasminogen activator) is administered

Question 8

What is the mechanism of platelet plug formation?

Answer 8

platelet contact with collagen -> swelling (shape change) -> pseudopods extend -> granules extend (ADP/ATP and thromboxane A2 recruit more platelets; serotonin, histamine, fibrogen stabilizing factor) -> collagen adherence recruits von Willebrand factor to stabilize plug

Question 9

Describe the most severe an prevalent form of hemophilia.

Answer 9

Hemophilia A is a factor VIII deficiency, almost exclusively in males. Factor VIII gene is found on the X chromosome. It comprises 85% of hemophilia cases, and affects ~1/10k males. It affects the intrinsic pathway, and is treated with recombinant Factor VIII therapy.

Question 10

Describe the less common form of hemophilia

Answer 10

Hemophilia B is factor IX deficiency, 15% of cases, affects 1/60K males. The gene for factor IX is on the X chromosome.

Question 11

What are the steps of fibrinolysis, or dissolution of blood clots?

Answer 11

1. Tissue plasminogen activator (tPA) is released from the endothelium after several days. It activates a protease to cleave plasminogen to plasmin.
2. Plasmin digests fibrin fibers and Factors V, VIII, prothrombin, and XII. Fibrin digestion produces d-dimer.

Question 12

Why is hemophilia almost exclusively seen in males?

Answer 12

Factor VIII and IX are on X chromosome and since males only have one X chromosome it is more common.