Severe congenital protein C deficiency: description of a new mutation and prophylactic protein C therapy and in vivo pharmacokinetics.
Severe congenital protein C deficiency is a rare life-threatening disorder that presents with purpura fulminans, disseminated intravascular coagulation, and thrombotic complications during the neonatal period. Affected children require acute replacement therapy with fresh frozen plasma or protein C concentrate, for example, Ceprotin (Baxter AG, Vienna). Long-term management and outcome is dependent on effective anticoagulation with warfarin, low-molecular weight heparin, or protein C concentrate. We describe the successful use of intravenous protein C concentrate for thrombotic prophylaxis in 2 sisters with severe type I protein C deficiency. Individualized long-term prophylactic regimens were developed based on clinical response. In vivo pharmacokinetic analyses of protein C concentrate were performed in each patient. Analysis of the protein C gene coding sequences identified 2 mutations in both patients, the previously described Arg169 to Trp mutation, and a novel mutation that changes Cys17 into a stop codon.
Tcheng
Wendy Y
WY
Division of Hematology-Oncology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
Dovat
Sinisa
S
Gurel
Zafer
Z
Donkin
Jennifer
J
Wong
Wing-Yen
WY
D001483:Base Sequence; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D011486:Protein C / Q000235:genetics* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020151:Protein C Deficiency / Q000235:genetics*
D011486:Protein C