BIIC Pathology Lecture 5_Hypercoagulation

Question 1

What are the 4 steps of normal hemostasis?

Answer 1

1) Arteriolar vasoconstriction
2) Primary Hemostasis (formation of platelet plug)
3) Secondary hemostatsis )deposition of fibrin
4) Clot stabilization and resorption

Question 2

What are the three parts of the Virchow Triad?

Answer 2

1) Endothelial Injury (Toxins, phyisical injury, hypertension, inflamation, metabolic products)
2) Abnormal blood flow (turbulent or stasis)
3) Hypercoagulability (Factor 5 leiden, increased prothrombin synthesis, anti-thrombin III deficency

Question 3

Which part of the triad most likely plays a role in arterial thrombolitic events? How?

Answer 3

Endothelial injury. It causes prothrombitic changes in endotherial cells like down regulating the expression of anti-coagulants like thrombomodulin and protein C

Question 4

What two events cause stasis to lead to thrombis formation?

Answer 4

1) Stasis allows platlets to come into contact with endothelium
2) Stasis slows washout of activated clotting factors

Question 5

What is the Factor V Liden mutation G1691A mutaion?

Answer 5

It is a mutation that substitutes a glutamine for an arginine on the 506 residue of factor V. This leaves factor V resistant to inactivation by Protein C and thus leads to hypercoagulability

Question 6

How is prothrombin mutated to lead to hypercoagulability?

Answer 6

There is a G to A substitution in the promotor region of the prothrombin gene. This causes significantly increased prothrombin production and thus hyper coagulability

Question 7

What three anti coagulants can be modified and lead to hyper coagulability?

Answer 7

Antithrombin III, Protein C, and Protein S

Question 8

How does elevated levels of homocysteine effect coagulation?

Answer 8

It leads to hypercoagulability and both arterial and venous thrombosis as well as the development of atherosclerosis.

Question 9

What are the secondary causes of hypercoagulability?

Answer 9

Oral contraceptive, hyperestrogenic state associated with pregnancy, cancers that release pro coagulation factors, old age, smoking and obesity, bed rest

Question 10

What is Herparin induced thrombocytopenia (HIT)?

Answer 10

HIT is caused caused by auto antibodies that bind heparin and the platlet membrane protein factor 4. These antibodies then also bind endothelial cells which activates the platelets and causes a thrombis to form and thrombocytopenia. This occures in up to 5% of patients treated with heparin