Coagulation
Hereditary thrombophilia / hypercoagulopathies
Protein S deficiency
Author: Jeremy C. Parsons, M.D.
Last author update: 1 June 2012
Last staff update: 22 April 2022
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Protein S deficiency [title]
Cite this page: Parsons J. Protein S deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationproteinSdef.html. Accessed June 3rd, 2023.
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
Additional references
