Overcoming factor VIII inhibitors: a possible new approach.

Treatment of haemophiliacs with antibodies to Factor viii is still a major clinical problem, neither high-dose Factor viii nor Factor ix concentrates being completely effective. An alternative approach was suggested by the finding that Factor viii, when complexed with phospholipid and Factor IXa, was protected from antibody attack, and that the major protective effect was provided by the phospholipid. The protective effects of various phospholipids were assessed by addition to Factor viii concentrates, incubation with human antibodies to VIII:C and measurement of residual clotting activity in three different assay systems. The most active material was a home-made extract of bovine brain, prepared by a modified Folch method. Of three commercial lipid preparations manufactured for intravenous injection, one was inactive and the other two were only active at high concentration. Studies with purified phospholipids showed that phosphatidyl serine (PS) was the most active fraction. Phospholipid analyses showed that the three intravenous lipid preparations all contained less than 10% PS, whereas the bovine brain extract contained 20–25%. These studies show that Factor viii can be protected from antibody attack by addition of phospholipid extracts which are rich in PS, and suggest that a Factor viii product containing a suitable phospholipid could be of benefit to haemophiliacs with inhibitors.