1. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.
- Author
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Smith MP, Ludlam CA, Collins PW, Hay CR, Wilde JT, Grigeri A, Melsen T, and Savidge GF
- Subjects
- Adult, Antigens analysis, Blood Loss, Surgical prevention & control, Blood Platelets metabolism, Comorbidity, Drug Administration Schedule, Elective Surgical Procedures, Embolization, Therapeutic, Factor VII analysis, Factor VIIa adverse effects, Factor VIIa pharmacokinetics, Factor VIIa therapeutic use, Female, Hematoma chemically induced, Hematoma surgery, Hemophilia A complications, Hemorrhage chemically induced, Hemorrhage therapy, Humans, Infusions, Intravenous, Isoantibodies immunology, Male, Middle Aged, Postoperative Hemorrhage prevention & control, Prospective Studies, Recombinant Proteins administration & dosage, Recombinant Proteins adverse effects, Recombinant Proteins pharmacokinetics, Recombinant Proteins therapeutic use, Reoperation, Treatment Outcome, Factor VIIa administration & dosage, Hemophilia A drug therapy, Hemostasis, Surgical
- Abstract
We examined recombinant activated factor VII (rVIIa) administered by continuous infusion to eight patients with inhibitors to factor VIII, undergoing elective surgery. rVIIa was infused at a fixed rate of 16.5 microg/kg/h for a median of 13.5 days (range 1-26). There was effective haemostasis at this infusion rate in only one of two minor procedures and two of six major operations. Three patients experienced excessive bleeding despite plasma factor VII activity around 10 IU/ml. Serious bleeding occurred in two other patients caused by procedural errors unrelated to rVIIa and required re-operation. The median rVIIa clearance on day 1 was 57 ml/h/kg (range 18-100) and on day 3 was 100 ml/h/kg (range 61-200). Clearance on the final infusion day was not significantly different from day 3. The infusion did not induce pathological activation of the coagulation mechanism. The only thrombotic adverse events were two episodes of superficial thrombophlebitis of the infused vein in one subject. In conclusion, the 16.5 microg/kg/h infusion rate reliably achieves plasma factor VII activity levels of 10 IU/ml, but this level does not provide reliable haemostasis.
- Published
- 2001