Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
, 62 (2), 763-6

Familial Dysfunction of Protein S

  • PMID: 2530648
Case Reports

Familial Dysfunction of Protein S

P M Mannucci et al. Thromb Haemost.


We describe a previously unreported defect of protein S characterized by low levels of cofactor activity for activated protein C contrasting with low normal levels of total and free protein S antigen. The distribution of protein S between the free form and the form complexed with the complement component C4b-binding protein was normal on two-dimensional immunoelectrophoresis. The proband developed juvenile deep-vein thrombosis while taking oral contraceptives. Her defect was transmitted in an autosomal dominant fashion from her asymptomatic mother. Other relatives carrying the same laboratory abnormality (mother, maternal uncle, two sisters and one brother) were also asymptomatic. We postulate that the defect is due to a dysfunctional protein S present in plasma in normal amounts and with normal proportions of the free and complexed forms of the protein.

PIP: A case of deep-vein thrombosis in a 23-year old woman 1 month after starting oral contraceptives is described, the 1st known incident of defective Protein S activity with normal levels of Protein S but defective APC cofactor. The woman had no known personal risk factors or family history of thromboembolism. She noticed pain and swelling of her right leg, and on admission to the Institute of Internal Medicine of the University of Milan, bilateral leg venography demonstrated occlusion of the right popliteal, femoral and iliac veins. She was treated with intravenous heparin for 10 days, and then warfarin. Protein S is a vitamin K-dependent plasma protein which binds to platelets and endothelial cells and functions as a cofactor for Protein C in the proteolytic cleavage of the activated forms of coagulation factors V and VIII. Persons with Protein S deficiency are at a high risk for thromboembolism. All coagulation laboratory screens were normal on repeated testing of the proband's plasma before initiating therapy, as well as her family members. In this patient total protein S antigen was low normal by EIA and ELISA. APC-cofactor was the only assay clearly abnormal, in the proband, her mother, siblings and maternal uncle; APC- cofactor activity was restored to normal by adding back pure Protein S.

Similar articles

See all similar articles

Cited by 2 PubMed Central articles

Publication types

LinkOut - more resources