protein S deficiency

Classification

• type 1:
  • low serum protein S antigen
  • low protein S activity
• type 2: (rare)
  • normal serum protein S antigen
  • free protein S antigen normal
  • low protein S activity
• type 3, in which
  • normal serum protein S antigen
  • free protein S antigen low
  • low protein S activity

Etiology

• hereditary defect
• autoantibodies to protein S may occur in association with lupus anticoagulant, especially in children after infection (varicella)
• pregnancy is associated with type 3
  • protein S activity as low as 30% 2-3 weeks before delivery
• HIV/AIDS patients may be susceptible

Epidemiology

• accounts for 2-10% of thrombotic events
• inherited loss of PROS1 is rare

Pathology

• thrombophilia
  • impaired regulation of blood coagulation
  • tendency to recurrent venous thrombosis

Genetics

• autosomal dominant inheritance
  • strong risk factor for venous thromboembolism
• associated with defects in protein S (PROS1)
• acquired, environmental, or trans-acting genetic factors are more likely to cause protein S deficiency than a mutation in PROS1

Clinical manifestations

• homozygous individuals
  • high intrauterine mortality
  • may develop fulminant purpura fulminans during infancy
• heterozygotes
  • present with 1st thrombotic event in mid to late teens
  • many adults are asymptomatic

Laboratory

• serum protein S activity (functional assay)
• serum protein S antigen
• free protein S antigen

Management

• heparin
• low molecular weight heparin
• warfarin (initial therapy with heparin) with INR of 2-3

More general terms

• blood protein disorder
• hypercoagulability
• genetic disease of the blood/bone marrow

Additional terms

• protein S activity in plasma (protein S assay)
• protein S; vitamin K-dependent protein S (PROS1, PROS)

Database

• OMIM: https://mirror.omim.org/entry/612336