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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 anti-coagulant factors Imbalance in either direction produces dire consequences: Pro-coagulation: obstruction, stasis  ischemia

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Protein C and Protein S Deficiency

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  1. Protein C and Protein S Deficiency Paolo Aquino 18 February 2003

  2. Hemostasis • The hematologic system is in a balanced flux between pro-coagulant and anti-coagulant factors • Imbalance in either direction produces dire consequences: • Pro-coagulation: obstruction, stasis ischemia • Anti-coagulation: bleeding, blood loss

  3. Protein C • 62-kD vitamin K-dependent glycoprotein • Synthesized in the liver as a single-chain zymogen • Clipped into a serine-protease-like enzyme on phospholipid cell surfaces by thrombin

  4. Protein C • Activated protein C (APC) then binds protein S for further activity • Protein C also has pro-fibrinolytic, anti-inflammatory and anti-ischemic properties

  5. Protein S • Single chain, vitamin K-dependent glycoprotein • Bound state with C4BbP (60%) • Only free state is capable of binding APC (40%)

  6. Protein S • 2 identified genes on chromosome 3 • PROS-a is the active gene • PROS-b is an evolutionarily duplicated non-functional gene

  7. 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

  8. 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

  9. Deficiency of Protein C and S • Acquired • Liver disease • DIC • Vitamin K deficiency • Antagonism with anti-coagulant treatment • Septic shock • Chemotherapy

  10. Symptoms • Deep vein thrombosis is the most common symptomatic manifestation • Pulmonary embolism • Post-phlebitic syndrome • Fetal loss

  11. 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

  12. Confounders • Active clotting causes consumption of pro-coagulant and anti-coagulant proteins • Coumadin therapy causes decreased protein activity • Check vitamin K levels • Repeat test on separate specimen

  13. Differential • Anti-thrombin deficiency • DVT • Dysfibrogenemia • Subclavian vein thrombosis • Superficial thrombophlebitis • Anti-phosopholipid syndrome

  14. 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

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