thrombic disorders

Question 1

What are the three major risk factors for thrombosis?

Answer 1

1) endothelial damage (HTN, cholesterol, smoking)
2) stasis (bed rest, varicose veins, heart problems)
3) hypercoagulability ( trauma/surg, delivery, disorder)

Question 2

Which labs should you order if you suspect a thrombotic disorder?

Answer 2

1) INR
2) PTT
3) TT

Question 3

What is the effect of the genetic mutation common in Caucasians leading to factor five leiden disorder?

Answer 3

factor V is abnormal and cannot be cleaved by protein C and thus cannot be “turned off”

Question 4

How would you treat a patient with factor V leiden disorder?

Answer 4

no clots- no tx
1 clot- temporary anticoag
2+ clots- long term anticoag

Question 5

What is the natural role of AT III and how do we take advantage of it pharmacologically?

Answer 5

binds and inhibits activated factors 2, 7, 9, 10, and 11,

heparin potentiates it to prevent coagulation

Question 6

What are the clot risk probabilities for a heterozygote and homozygote with AT III def?

Answer 6

homo= no survival 
hetero= half of ppl with mutation will develop clots

Question 7

How do you treat ATIII def?

Answer 7

give antithrombin concentrates (heparin won’t work!)

Question 8

What are the three roles of protein C?

Answer 8

1) anticoagulant - inactivate Va and VIIIa
2) fibrinolytic (promote tPA)
3) anti-inflammatory (decrease cytokines)

Question 9

What are the major complications of a mutation producing decreased levels or a mutated form of protein C?

Answer 9

Warfarin induced skin necrosis (coumadin inhibits proteins C and S before II, VII, IX, and X)
purpura fulminans - thrombus + vascular injury

Question 10

What is protein S?

Answer 10

endothelial cell receptor for protein C

Question 11

What is the effect of the factor II (prothrombin) gene mutation?

Answer 11

too much (functionally normal) prothrombin

Question 12

What is the natural role of homocysteine?

Answer 12

converts precursors into THF (tetrahydrofolate)

Question 13

What is homocysteinuria?

Answer 13

rare metabolic deficiency in tran-sulfuration enzyme

Question 14

Why do increased levels of homocysteine in the blood and/or urine cause increased thrombi and premature atherosclerosis?

Answer 14

toxic to the endothelium (production of ROS) and interferes with NO, a natural vasodilator and antithrombotic

Question 15

What vitamin deficiency is homocysteinemia associated with?

Answer 15

B12/folate

Question 16

What is the only acquired thrombotic disorder we have discussed thus far?

Answer 16

antiphospholipid antibody syndrome

Question 17

How would you look for antiphospholipid antibody production?

Answer 17

1) PTT -prolonged
2) PTT mixing study- not corrected= inhibitor present in blood
3) “fancy tests”
* note normal PTT tests do not rule out Ab production

Question 18

What symptoms would you see in an adult with autoimmune problems whom you suspected of having antiphospholipid antibody syndrome?

Answer 18

recurrent thromboses
recurrent spontaneous abortions
increased risk of stroke
pulmonary HTN
renal failure

Question 19

Why would an INR be unhelpful in diagnosing antiphospholipid antibody syndrome?

Answer 19

in vivo antiphospholipid Ab promote coag

in vitro antiphospholipid Ab inhibit coag