Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs.

Abstract

The procoagulant protein F.VIII:C is noncovalently bound to von Willebrand factor (vWF) to give the factor VIII macromolecular complex. New highly purified preparations of isolated human F.VIII:C, devoid of vWF and about 500,000-fold purified, were administered to hemophilia A and von Willebrand disease (vWD) dogs to determine their hemostatic effectiveness and survival in the circulation. Two preparations of F.VIII:C were used: peak 1, with active components of Mr 185,000-280,000, and peak 2, with a single component of Mr 170,000. In hemophilic dogs, with no plasma F.VIII:C but normal vWF, both preparations immediately elevated plasma F.VIII:C to expected levels, promptly stopped induced and spontaneous hemorrhages, and gave sustained plasma levels of F.VIII:C. The isolated F.VIII:C immediately complexed with endogenous vWF in hemophilic plasma and was eliminated exponentially, with a half-life (t1/2) of about 9 hr. Survival of peak 2 F.VIII:C was longer than that of peak 1 material. In contrast, F.VIII:C complexed to vWF in a therapeutic concentrate administered to hemophilic dogs was eliminated biexponentially with first-phase t1/2 of 3.2 hr and second-phase t1/2 of 9 hr. In vWD dogs with no vWF and reduced F.VIII:C levels, the isolated F.VIII:C produced supernormal levels of F.VIII:C without effect on induced bleeding. It was rapidly eliminated from plasma with a t1/2 of about 1 hr, as was the complexed F.VIII:C in the concentrate. These data indicate that isolated F.VIII:C promptly complexes with vWF and in this form is highly effective in controlling hemophilic hemorrhages with good survival in plasma. Without endogenous vWF with which to complex, the F.VIII:C is promptly eliminated.

• Authors: K M Brinkhous, H Sandberg, J B Garris, C Mattsson, M Palm, T Griggs, M S Read
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 82 Issue 24 Pg. 8752-6 (Dec 1985) ISSN: 0027-8424 [Print] United States
• PMID: 3936044 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Macromolecular Substances
• von Willebrand Factor
• Factor VIII

Topics

• Animals
• Blood Coagulation
• Dogs
• Factor VIII (isolation & purification, physiology, therapeutic use)
• Female
• Hemophilia A (therapy)
• Humans
• Macromolecular Substances
• Male
• Metabolic Clearance Rate
• Molecular Weight
• von Willebrand Diseases (therapy)
• von Willebrand Factor (metabolism)