Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency.
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.
Dreyfus
M
M
Hospital Bicêtre, Paris, France.
Masterson
M
M
David
M
M
Rivard
G E
GE
Müller
F M
FM
Kreuz
W
W
Beeg
T
T
Minford
A
A
Allgrove
J
J
Cohen
J D
JD
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001766:Blindness / Q000209:etiology; D003241:Consanguinity; D004211:Disseminated Intravascular Coagulation / Q000151:congenital / Q000209:etiology / Q000628:therapy; D005260:Female; D006207:Half-Life; D006470:Hemorrhage / Q000151:congenital / Q000209:etiology / Q000628:therapy; D006701:Home Nursing; D006801:Humans; D007231:Infant, Newborn; D002542:Intracranial Embolism and Thrombosis / Q000151:congenital / Q000209:etiology / Q000628:therapy; D008297:Male; D010949:Plasma; D017354:Point Mutation; D011486:Protein C / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020151:Protein C Deficiency; D011693:Purpura / Q000151:congenital / Q000209:etiology / Q000628:therapy; D012008:Recurrence; D012166:Retinal Hemorrhage / Q000151:congenital / Q000209:etiology / Q000628:therapy
D000911:Antibodies, Monoclonal; D011486:Protein C