Thrombophilia (Hereditary Thrombophilia)

Question 1

Serpin inhibitor
Decreased inhibition of Xa and thrombin
Unregulated coagulation
Heterozygous: reduced AT activity
Homozygous type 1: incompatible with life.
Homozygous type 2: life threatening thrombotic problems.
Lab tests:
Concentration of AT in plasma
**Progressive AT
Heparin Cofactor( can be treated with heparin)

Answer 1

Antithrombin Deficiency

Question 2

Vitamin K dependent inhibitor.
Type 1: most common, decrease in functional activity and antigen levels.
Type 2: decrease in functional activity but normal antigen levels
Inhibits Va and VIIIa, which leads to increased production of thrombin to fibrin.
Can cause venous thrombosis and purpura fulminans (skin becomes necrotic)
Lab:
PC levels in plasma
Antigen assay
Function assay
*APC degrades factors Va and VIIIa in the presence of cofactors protein S and calcium.

Answer 2

Protein C Deficiency

Question 3

Vitamin K dependent protein.
Inactivates Va and VIIIa.
Autosomal dominant.
Lab: 
Concentration in plasma
Total/Free assay
Functional assay.
Treated with Heparin

Answer 3

Protein S Deficiency

Question 4

Thrombin activates C to APC which inhibits Va and VIIIa.
Inability to prolong clotting tests.
Diminished ability to destroy Va.
Lab:
Screening-clot based tests.
Confirmatory is PCR
***With APCR see diminished ability of APC to destroy Va.

Answer 4

Activated Protein C Resistance

Question 5

G to A in untranslated region of prothrombin gene.
Mild elevations of plasma levels.
Increases thrombin generation.
Lab:
Confirmatory: PCR for mutation

Answer 5

Prothrombin Gene Mutation 20210