Coagulation
Hereditary thrombophilia / hypercoagulopathies
Protein S deficiency

Author: Jeremy Parsons, M.D. (see Authors page)

Revised: 2 May 2016, last major update June 2012

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Protein S deficiency [title]

Cite this page: Protein S deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/coagulationproteinSdef.html. Accessed December 8th, 2016.
Definition / General
  • Hereditary deficiencies occur in 0.7% of general population
  • Many mutations exist (qualitative or quantitative)
  • Much lower prevalence of thrombophilia with clustering in families
  • Variable penetrance may be due to coexisting risk factors, such as factor V Leiden
  • Causes 1 - 9% of cases of venous thrombosis
  • These patients also at risk for warfarin - induced skin necrosis if started on warfarin without the addition of heparin until warfarin levels are therapeutic
  • Heterozygotes have levels 35 - 65% of normal
  • First thrombotic event occurs between ages 10 - 50 years
  • 50% risk by age 45
  • Homozygotes with severely decreased levels present as newborns with DIC and purpura fulminans, leading to death unless anticoagulation and replacement therapy with fresh frozen plasma is started

  • Type I (2 / 3):
    • Low free and total protein S antigen, with decreased APC cofactor activity

  • Type II (rare):
    • Normal free and total protein S antigen, and decreased APC cofactor activity

  • Type III (1 / 3):
    • Normal to low total protein S, low free protein S antigen, and an elevated fraction of protein S bound to C4B protein

  • Testing recommended:
    • Individual with family history who requests testing, to confirm abnormal protein S result
    • Must interpret with caution

  • Testing not recommended:
    • During pregnancy or postpartum, during inflammatory, thrombotic or surgical event
    • Within 30 days of taking warfarin
    • Must delay longer periods for vitamin K antagonists (Phenprocoumon)

  • Clinical note:
    • Acquired protein S deficiency is often seen during pregnancy due to increased C4b, which may reduce levels to 40% or less