Protein S deficiency may be expected in ≈1 of every 500 people 3.
The spectrum of severity varies in those with mild (heterozygous) protein S deficiency. About 50% of patients present with symptoms by 55 years old. Common presentations include DVT/PE, DIC (disseminated intravascular coagulation) and thrombi of the viscera 4.
Severe (homozygous) protein S deficiency usually presents in the puerperium with distinctive purpura fulminans (PF). Most individuals succumb during childhood unless treatment is instituted early 4.
Protein S, a vitamin K-dependent physiological anticoagulant, acts as a non-enzymatic cofactor to activate protein C in the degradation of factor Va and factor VIIIa. Decreased (antigen) levels or impaired function of protein S leads to decreased degradation of factor Va and factor VIIIa and therefore an increased propensity to venous thrombosis.
Most cases are caused by mutations in the PROS1 gene.
- 1. D Cros, P C Comp, G Beltran, G Gum. Superior sagittal sinus thrombosis in a patient with protein S deficiency. Stroke. 21 (4): 633. doi:10.1161/01.STR.21.4.633 - Pubmed
- 2. Earls JP, McAdams HP, Colon E, Jelinek JS. Protein S deficiency: imaging findings. AJR. American journal of roentgenology. 161 (6): 1283-7. doi:10.2214/ajr.161.6.8249743 - Pubmed
- 3. Brea Lipe, Deborah L. Ornstein. Deficiencies of Natural Anticoagulants, Protein C, Protein S, and Antithrombin. Circulation. 124 (14): e365. doi:10.1161/CIRCULATIONAHA.111.044412 - Pubmed
- 4. Ashish Gupta, Aung M. Tun, Faiz Tuma. Protein S Deficiency. (2019) Pubmed