Protein C and Protein S Deficiency
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Transcript 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