Protein C Deficiency – Response to Danazol and DDAVP

Abstract

SummaryWe studied a Spanish family in which one of the female members presented recurrent thrombophlebitis in both legs after three different deliveries. Biological and antigenic activity of protein C was decreased (35% and 42% respectively). Reduced protein C levels were also observed in 6 other family members. Administration of danazol (600 mg/day) in two patients with protein C deficiency elevated this protein and discontinuation of the drug resulted in a reduction of protein C to pretreatment values. The proposita showed a normal fibrinolytic activity and infusion of DDAVP produced a similar response of FVIII/VWF and plasminogen activator to those observed in healthy subjects.

Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene.

“…Protein C deficiency represents a major cause of thrombotic disease (3,(20)(21)(22)(23)(24) through the malfunction of an antithrombotic regulatory system including protein C, protein S, and an endothelial cell cofactor, thrombomodulin (24). However, the molecular basis of protein C deficiency is still almost completely unknown.…”

Pharmacologic Intervention to Prevent Hemodialysis Vascular Access Thrombosis

“…Androgens have been shown to directly stimulate erythro cyte colony-forming units (CFU-e) [143] in bone marrow and have been employed for decades in the treatment of the anemia of chronic renal failure [144]. Recently, there has been some suggestion that desmopressin acetate and dana zol may stimulate the production of protein C [145]. Protein C is a zymogen serine protease that regulates blood coagu lation by inactivating thrombin-activated blood coagula tion factors V, VII [146].…”

Protein S Deficiency Associated to Anti-Protein S Antibodies in a Patient with Mixed Connective-Tissue Disease and Its Reversal by Danazol

“…The patient reported herein fulfills criteria for the di agnosis of MCTD [18,19], a condition not previously iden tified as a cause of acquired deficiencies of natural anti coagulants, although antiphospholipid antibodies can also be found in it [20], Danazol, an impeded androgenic ste roid [21], has been shown to be useful in the treatment of inherited deficiencies of various coagulation-related pro teins such as coagulation factors VIII and IX [22], fibrino gen [23], prothrombin [24], Cl sterase inhibitor [25], anti thrombin III [26], PC [13,14,27,28] and PS [29]; danazol has also antithrombotic effects by increasing fibrinolysis, raising the levels of plasminogen and PC and raising the levels of antithrombin III. The mechanism of action of the drug is not fully understood; it seems to raise the levels of certain proteins that are synthesized in the liver [21,22,30].…”