Effect of height and weight on the in vivo recovery of transfused factor VIII C.

Abstract

SUMMARY The in vivo recovery of factor VIII has been estimated on 84 occasions in 53 severely affected adolescent haemophiliacs. There was wide individual variation in recovery, which was not affected by differences in the administered dose. Recovery increased steadily with increasing surface area, and it was only over a surface area of 1-7 m2 that a recovery of 2% of factor VIII per unit per kg became the norm. It is suggested that the only safe assumption to make below that surface area is an in vivo recovery of 1[5 %.The treatment of haemophilic haemarthroses with inadequate doses of factor VIII will predispose the joints to chronic synovitis, progressive arthropathy, and ultimately to crippling deformity.' There are, however, potentially harmful side effects associated with adequate and excessive exposure to factor VIIIcontaining materials,2 which also strain human and financial resources.3 Clearly, the use of the correct dose of factor VIII in varying situations is of great importance.Recent studies have identified minimum dosage schedules for bleeds of varying severity in specific sites,4 and in joints with or without previous and/or present damage. Patients and methodsThe subjects studied were 53 severely affected adolescent haemophiliacs (factor VIIIC < 1 %) resident at the Lord Mayor Treloar College. Blood samples were taken immediately before and between 20 and 30 minutes after infusions of factor VIII-containing material. Samples were immediately dispensed into plastic tubes containing 3 8 % sodium citrate (9 vols blood to 1 vol anticoagulant). The plasma was separated within two hours by centrifuging at 2000 g at 4°C and tested immediately.Factor VIIIC was tested by a two stage method modified from that of Denson." During the year in which the study took place, approximately 700 factor VIII assays were undertaken in our laboratory, 10 % of which were done in duplicate. Average variation between operators was never more than 10%.All weights and heights used were obtained within two months of the relevant estimation.

Factor VIII Procoagulant Antigen Recovery Is a Dose-Related Response to Factor VIII Concentrate Infusions

“…This is consistent with the observa tions of Aronstam et al [13] that variations in the dosage of factor VIII administered did not affect the in vivo recovery of VIIIC.…”

Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight

“…Therefore, several studies have aimed to clarify relationships between such characteristics and measured PK parameter values. [3][4][5][6][7][8][9][10][11][12][13] We have previously published a PK study on recombinant FVIII, comparing the results from patients 1 to 6 years of age and 10 to 65 years of age. 13 In brief, in vivo recovery was lower, BW-adjusted clearance (CL) was higher and elimination half-life (t 1 ⁄2) was on average shorter in children than in adults.…”

Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years

“…Relationships of FVIII PK with patient characteristics have been investigated in several studies [2,[6][7][8][9][10][11][12][13][14] on limited numbers of patients. Weight-adjusted clearance (CL) of FVIII (i.e.…”