Download Protein C and Protein S Deficiency

Protein C and Protein S
Deficiency
Paolo Aquino
18 February 2003
Hemostasis
The hematologic system is in a balanced
flux between pro-coagulant and anticoagulant factors
 Imbalance in either direction produces dire
consequences:

– Pro-coagulation: obstruction, stasis
ischemia
– Anti-coagulation: bleeding, blood loss
Protein C
62-kD vitamin K-dependent glycoprotein
 Synthesized in the liver as a singlechain zymogen
 Clipped into a serine-protease-like
enzyme on phospholipid cell surfaces by
thrombin

Protein C

Activated protein C (APC) then binds
protein S for further activity

Protein C also has pro-fibrinolytic, antiinflammatory and anti-ischemic properties
Protein S

Single chain, vitamin K-dependent
glycoprotein

Bound state with C4BbP (60%)

Only free state is capable of binding APC
(40%)
Protein S

2 identified genes on chromosome 3

PROS-a is the active gene

PROS-b is an evolutionarily duplicated
non-functional gene
Protein C/Protein S complex

Require negatively charged phospholipids
and Ca2+ for normal anti-coagulant activity

Complex acts by proteolyzing Factor VIII
and Factor V, which in turn prevents
activation of factor X and prothrombin
Deficiency of Protein C and S

Genetic
– Autosomal dominant disorders
– Homozygous and heterozygous forms
– Homozygous form presents in infancy as
neonatal purpura fulminans
– Heterozygotes generally are not symptomatic
until the 3rd and 4th decades
Deficiency of Protein C and S

Acquired
– Liver disease
– DIC
– Vitamin K deficiency
– Antagonism with anti-coagulant treatment
– Septic shock
– Chemotherapy
Symptoms
Deep vein thrombosis is the most common
symptomatic manifestation
 Pulmonary embolism
 Post-phlebitic syndrome
 Fetal loss

Lab studies
INR, PT, aPTT
 Protein activity level
 Protein antigen- total and free
 Classification

– Type I: decrease in total protein antigen
– Type II: decrease in protein activity
– Type III: decrease in free protein level
Confounders
Active clotting causes consumption of procoagulant and anti-coagulant proteins
 Coumadin therapy causes decreased
protein activity
 Check vitamin K levels
 Repeat test on separate specimen

Differential
Anti-thrombin deficiency
 DVT
 Dysfibrogenemia
 Subclavian vein thrombosis
 Superficial thrombophlebitis
 Anti-phosopholipid syndrome

Treatment





Heparin therapy for a minimum of 5 days with
standard protocol
Start Coumadin administration on day 1 or 2 of
heparin therapy
Once therapeutic on Coumadin based on INR,
can halt heparin therapy
6-9 months of initial treatment recommended
Controversy regarding lifelong Coumadin therapy