Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency

• Published in: Seminars in thrombosis and hemostasis Vol. 21; no. 4; p. 371
• Main Authors: Dreyfus, M, Masterson, M, David, M, Rivard, G E, Müller, F M, Kreuz, W, Beeg, T, Minford, A, Allgrove, J, Cohen, J D
• Format: Journal Article
• Language: English
• Published: United States 01-01-1995
• Subjects: Antibodies, Monoclonal - immunology; Blindness - etiology; Consanguinity; Disseminated Intravascular Coagulation - congenital; Disseminated Intravascular Coagulation - etiology; Disseminated Intravascular Coagulation - therapy; Female; Half-Life; Hemorrhage - congenital; Hemorrhage - etiology; Hemorrhage - therapy; Home Nursing; Humans; Infant, Newborn; Intracranial Embolism and Thrombosis - congenital; Intracranial Embolism and Thrombosis - etiology; Intracranial Embolism and Thrombosis - therapy; Male; Plasma; Point Mutation; Protein C - genetics; Protein C - immunology; Protein C - isolation & purification; Protein C - pharmacokinetics; Protein C - therapeutic use; Protein C Deficiency; Purpura - congenital; Purpura - etiology; Purpura - therapy; Recurrence; Retinal Hemorrhage - congenital; Retinal Hemorrhage - etiology; Retinal Hemorrhage - therapy
• ISSN: 0094-6176
• DOI: 10.1055/s-2007-1000658

Protein C replacement therapy with a monoclonal antibody purified, virus inactivated protein C concentrate was carried out in nine infants (three male, six female) with severe congenital protein C deficiency and life-threatening purpura fulminans and/or thrombosis associated with disseminated intravascular coagulation (DIC). Eight infants were homozygous for protein C deficiency; one was a compound heterozygote. The treatment period varied from 22 days to three years. The half-life of protein C was found to be as short as two to three hours during activation of the coagulation system, increasing to approximately ten hours after stabilization. During the acute phase, protein C levels of 0.10 to 0.25 IU/mL were associated with elevated markers of coagulation activation indicating DIC, while protein C levels greater than 0.25 were associated with normalization of coagulation markers. No product-related side effects were reported. Episodes of bleeding or purpura recurred in all patients who were switched to oral anticoagulant therapy, necessitating reinstatement of protein C replacement therapy, either as needed to control symptoms, or on a long-term prophylactic schedule, alone or in addition to oral anticoagulation. Home treatment with protein C concentrate allowed a near-normal life-style for patients who otherwise would be hospitalized for long periods of time.