title: Clinical efficacy and recovery levels of recombinant FVIIa (NovoSeven) in the treatment of intracranial haemorrhage in severe neonatal FVII deficiency.
abstract: The use of replacement FVII is critical to the successful treatment of life-threatening bleeds in newborns and infants with severe FVII deficiency (<1%). However, the clinical efficacy, optimum dosage and pharmacologic recovery of rFVIIa in such children has not been studied systematically. This report is a case of an infant with severe FVII deficiency (FVII:C at 0%) and massive intracranial haemorrhage in which successful use of rFVIIa (NovoSeven) was carefully monitored. The drug was administered by intravenous bolus through a central line every 4 h at each of three dose levels: 15 microg kg-1, 22 microg kg-1 and 30 microg kg-1. FVII:C was >100% between 30 and 180 min after each infusion with mean trough levels above 25% for all three dose levels. There was no evidence of hyper-coagulation as indicated by measurements of the platelet count, D-dimer, plasma protamine paracoagulant and fibrinogen levels in spite of high FVII:C concentration. In this infant, rFVIIa was well-tolerated, maintained effective haemostasis with good clinical outcome, and produced consistent therapeutic mean trough levels above 25% FVII:C even at 15 microg kg-1 every 4 h.
authors.affiliation: Division of Hematology-Oncology, Childrens Hospital of Los Angeles, Los Angeles, California 90027-6016, USA.
authors.forename: W Y
authors.initials: WY
authors.lastname: Wong
authors.forename: W C
authors.initials: WC
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Miller
authors.forename: K
authors.initials: K
authors.lastname: McGinty
authors.forename: J K
authors.initials: JK
authors.lastname: Whisnant
mesh_terms: D000941:Antigens / Q000097:blood / Q000378:metabolism; D001780:Blood Coagulation Tests; D005167:Factor VII / Q000378:metabolism; D005168:Factor VII Deficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006406:Hematoma / Q000209:etiology; D006487:Hemostasis; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000097:blood / Q000188:drug therapy*; D020300:Intracranial Hemorrhages / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010976:Platelet Count; D011479:Protamines / Q000097:blood; D011516:Prothrombin / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014812:Vitamin K / Q000008:administration & dosage
chemical_list: D000941:Antigens; D005338:Fibrin Fibrinogen Degradation Products; D011479:Protamines; D011994:Recombinant Proteins; C042580:factor VII clotting antigen; C036309:fibrin fragment D; D014812:Vitamin K; D005167:Factor VII; D011516:Prothrombin; D005340:Fibrinogen; D015942:Factor VIIa