INHERITED PROTEIN-S DEFICIENCY - CLINICAL MANIFESTATIONS AND LABORATORY FINDINGS IN 63 PATIENTS

To further characterize inherited heterozygous protein S (PS) deficien cies, we studied 63 patients belonging to 33 families. Diagnosis of PS deficiency was based on protein S activity (PS Act) and/or free PS an tigen (FPS Ag) levels below the lower limit of the normal range in pat ients not on oral anticoagulation. Depending on the level of total PS antigen (TPS Ag), two subpopulations could be distinguished: in the fi rst one (25 patients belonging to 11 families) level of TPS Ag was red uced whereas in the second one (38 patients belonging to 22 families), TPS Ag was normal. In none of the families studied the two types of P S deficiency coexisted suggesting that they are different entities. In the 63 patients, thromboembolic events occurred in 57% of cases and w ere recurrent in 36,5% of patients. Age at the time of the first throm bosis ranged from 14 to 74 years, and was below 40 years in 69% of sym ptomatic cases. Thrombotic events were spontaneous in 64% of cases, an d were associated with other risk factors in 36%. There was no apparen t relationship between clinical status, symptomatic or asymptomatic, a nd the type or degree of the PS deficiency. Long-term anticoagulation prevented the recurrence of thrombosis in every case but one, and led to a decrease in circulating levels of C(4)b-binding protein suggestin g the existence of a regulation between C4b-BP and PS concentrations. Together with previous reports, these findings underline the clinical and biological heterogeneity of inherited protein S deficiency.