Clotting Disorders

Question 1

What is thrombophilia?

Answer 1

hypercoagulopathy - risk factor for pathologic formation of intravascular blood clot (thrombosis) caused by a lack or defect in anticoagulant proteins - usually multifactorial

Question 2

What is Virchow’s Triad?

Answer 2

(1) endothelial dysfunction/damage
(2) hypercoagulability (hereditary or acquired)
(3) stasis (immobility or polycythemia)

Question 3

What are the inherited causes of thrombophilia (hypercoagulopathy)?

Answer 3

mutations that disable Protein C or Protein S (natural anticoagulants produced by a blood clot that limit the size of the clot - inhibit Factors V and VIII and lead to excessive clotting)

Factor V Leiden mutation - most common - results in resistance in degradation of Factor V

Question 4

What are the acquired causes of thrombophilia (hypercoagulopathy)?

Answer 4

cancer (pancreatic, ovarian, and lung); pregnancy (up to 2 months postpartum); oral contraception or estrogen replacement

Question 5

What are the clinical features of inherited thrombophilia?

Answer 5

thrombosis before age 50, recurrent venous thrombosis (DVT and PE), family Hx, presence of other risk factors (pregnancy, oral contraceptive use, immobility)

Question 6

When is testing for thrombophilia recommended?

Answer 6

in the presence of risk factors - routine testing is NOT recommended (especially in cancer patients) as result will not change disease management

Question 7

What are the tests available for thrombophilia?

Answer 7

• Protein C activity assay - abnormal in PTs with Protein C deficiency
• Protein S activity assay - abnormal in PTs with Protein S deficiency
• molecular genetic testing for Factor V Leiden - level is normal => problem is a mutation
• PT/INR will be normal
• platelets will be normal

Question 8

What is the treatment for thrombophilia?

Answer 8

(1) atherosclerotic (arterial) clots (problem is due to plaques and platelets) - give drugs that prevent platelet aggregation (aspirin and Plavix)
(2) DVT/PE (venous) clots (problem is due to clotting factors) - give anticoagulants at least 3 months (Coumadin and Heparin)

Question 9

What is the drug management for DVTs/PEs?

Answer 9

Heparin first, followed by Warfarin (giving Warfarin alone - without Heparin - can cause transient coagulopathy)

Question 10

What is the distinction in mechanism of action between Warfarin and Heparin?

Answer 10

• Warfarin reduces production of clotting factors and Proteins C and S, but does not reduce clotting factors already in the system
• Heparin reduces production of clotting factors in the liver, but does not affect Proteins C and S and works faster than Warfarin