Hereditary thrombophilias

Question 0

List the 2 categories and 5 examples given in this lecture of hereditary thrombophilias.

Answer 0

• Procoagulant: Factor V Leiden, Prothombin mutation

- Decreased anticoagulant: Protein C deficiency, Protein S deficiency, Antithrombin deficiency

Question 1

What does thrombophilia refer to?

Answer 1

• any condition that results in an imbalance that favors clotting and formation of pathological thrombosis
• can be inherited or acquired

Question 2

What are the clinical manifestations of hereditary thrombophilias?

Answer 2

• increased risk of VTE, but NO or negligible increased risk of arterial thrombosis
• VTE= DVT and PE; venous thromboembolism

Question 3

Discuss the activities of antithrombin and Protein C and S.

Answer 3

• Antithrombin inactivates thrombin and Xa

- PC and PS: work together to inhibit Va and VIIIa

Question 4

Inheritance pattern and “types” of antithombin deficiency

Answer 4

• autosomal dominant
• Type I: reduced levels of functionally normal AT
• Type II: functionally abnormal AT in normal amounts; 3 groups of type II include those with thrombin binding site defects, heparin binding site defects, or defects affecting both

Question 5

How to diagnose antithombin deficiency in the lab and what the results look like when differentiating Type I vs. Type II.

Answer 5

• antigen assay: measure levels of AT in plasma, irrespective of functional activity
• functional assay: measure ability of plasma to neutralize thrombin or Xa in the presence of heparin
• Type I has decreased results for antigen assay and functional assay
• Type II has normal antigen assay but decreased functional assay

Question 6

Protein C is a zymogen that is converted to its active form (APC) by ____________.

Answer 6

-thrombomodulin-bound thrombin

Question 7

Describe what determines active protein S.

Answer 7

• PS circulates unbound (40-50%) or bound to C4b-binding protein
• only unbound fraction is active