Thrombophilic Disorders

Question 1

it is more common for thrombosis to form in:
a. venous system
b. arterial system

explain your answer

Answer 1

a. venous system

arterial system has high blood flow rate - but when thrombosis does occur, it is associated with severe endothelial injury (atherosclerosis, ischemia, infarction)

Question 2

what about the venous system makes it more susceptible to thrombosis than the arterial system?

Answer 2

slow flow rate + lower pressure contributes to stasis —> blood clot formation

commonly involves endothelial inflammation

almost always in lower extremities

Question 3

what is a patient with DVT at risk for?

Answer 3

DVT = deep venous thrombosis

at risk for embolus breaking off and causing pulmonary embolism

DVT + pulmonary embolism = venous thromboembolic disease (VTE)

Question 4

what does Virchow’s Triad describe?

Answer 4

risk factors for thrombosis: endothelial injury, stasis (slow blood flow), hypercoagulable state

Question 5

what are some important considerations in diagnosing an inherited cause of thrombosis? (hypercoagulability)

Answer 5

• family history
• lost pregnancies
• PMH of thrombus
• thrombus at multiple sites or unusual sites (portal vein)

Question 6

autosomal dominant deficiencies in Protein C or Antithrombin lead to…

Answer 6

inherited hypercoagulation

[remember that these are anticoagulant factors]

Question 7

AD mutations in Factor V Leiden or prothrombin gene lead to…

Answer 7

inherited hypercoagulation

[remember that these are procoagulants]

Question 8

Factor Va [coagulant] is degraded by _____ [anticoagulant]

Answer 8

Protein C: degrades Factor V and VIII

Question 9

what occurs from a Factor V Leiden mutation?

Answer 9

prevents Factor V from being degraded by Protein C (APC)

AD mutation, leads to inherited hypercoagulation (most common inherited form)

4-5x more likely to have venous thrombosis

Question 10

a mutation in prothrombin can lead to inherited hypercoagulation - what mutation causes this?

Answer 10

second most common inherited hypercoagulation

mutation in 3’UTR prothrombin gene —> increased mRNA stability

3-4x increased risk of venous thrombosis

Question 11

contrast Type I and Type II Protein C Deficiency and the consequence of this

Answer 11

Type I: less Protein C
Type II: nonfunctional Protein C

AD mutation —> inherited hypercoagulation

—> 7x risk of venous thrombosis
—> Warfarin-induced skin necrosis (Protein C has short half-life)

—> if homozygous, neonatal purpura fulminant (bleeding under skin)

*note that acquired Protein C deficiency via liver disease, kidney failure, cancer, Vitamin K antagonists (produces transient procoagulant state)

Question 12

T/F: a patient with less than 80% of normal antithrombin activity will develop hypercoagulation

Answer 12

TRUE: antithrombin deficiency is potent

AD disorder, will only see heterozygous (homozygous is incompatible with life)

lowest prevalence of inherited hypercoagulation and highest relative risk (16x risk of venous thrombosis) —> will not respond to heparin, which relies on interaction with antithrombin

Question 13

describe anti-phospholipid antibody syndrome

Answer 13

acquired autoimmune thrombophilic disorder mediated by autoantibodies against neg charged phospholipids (beta2 glycoprotein I)

recurrent arterial or venous thrombosis, primarily affects females, occurs alone or with another autoimmune disease (Lupus)

placental infarction - see recurrent unexplained miscarriages