title: Homozygous protein C deficiency: observations on the nature of the molecular abnormality and the effectiveness of warfarin therapy.
abstract: An infant with severe homozygous protein C deficiency was brought to medical attention because of purpura fulminans and severe bilateral vitreous hemorrhages in the neonatal period. Infusions of fresh frozen plasma were given for 8 months. On two occasions, attempts to decrease the frequency of fresh frozen plasma infusions to less than twice a day led to episodes of microangiopathic hemolysis, fibrinolysis, and acute renal failure. Infarction of skin and subcutaneous tissues did not recur. Both episodes were controlled after reinstitution of fresh frozen plasma. Complications of therapy with fresh frozen plasma included hyperproteinemia and hypertension. Warfarin therapy was instituted when the baby was 8 months of age, followed by a gradual withdrawal of fresh frozen plasma therapy. The dose of warfarin required to maintain the prothrombin time in a range of 1.8 to 2.2 times normal varied considerably during short periods, a phenomenon that may have been due to several factors: hypercatabolism of the drug with prolonged administration, abnormality of liver function, variation in levels of serum albumin, fluctuations in drug dosage secondary to oral administration, and variations in dietary vitamin K. Protein C determinations by immunologic and functional assays consistently showed detectable but reduced protein C antigen levels with undetectable activity levels, suggesting that a dysproteinemia rather than a deficiency of synthesis is responsible for the child's coagulopathy.
authors.affiliation: Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: J F
authors.initials: JF
authors.lastname: Casella
authors.forename: R A
authors.initials: RA
authors.lastname: Marlar
authors.forename: R R
authors.initials: RR
authors.lastname: Montgomery
authors.forename: W H
authors.initials: WH
authors.lastname: Zinkham
mesh_terms: D001778:Blood Coagulation Disorders / Q000235:genetics*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007519:Isoantigens / Q000302:isolation & purification; D008297:Male; D010949:Plasma; D011486:Protein C / Q000276:immunology; D020151:Protein C Deficiency; D011693:Purpura / Q000209:etiology; D014823:Vitreous Hemorrhage / Q000209:etiology; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D007519:Isoantigens; D011486:Protein C; D014859:Warfarin