全血凝固過程中のヒト第Ⅷ因子/von Willebrand因子複合体の動態

Abstract

Changes of factor Ⅷ(F Ⅷ), von Willebrand Factor (vWF) and FV Ⅷ/vWF complex during whole blood clotting were investigated. 1. Although F Ⅷ activity in normal sera was low (13.9±12.0 u/dl), F Ⅷ antigen (F Ⅷ : Ag) was nearly normal (73.7±32.7 u/dl). Levels of vWF antigen (vWF : Ag) in the plasmas or sera assayed by immunoradiometric assay (IRMA) were 103.7±35.0 u/dl and 51.7±26.2 u/dl, respectively. Each value of F Ⅷ/vWF complex in the plasmas or sera was 101.7±29.1 u/dl or 24.1±18.1 u/dl. 2. When platelet-rich plasma from normal individual was clotted with an equal volume of 1/40 M CaCl_2, F Ⅷ showed a moderate decrease. Incubation of normal plasma with various concentrations of phospholipid (PL) resulted in a dose-dependent loss of F Ⅷ : Ag. 3. In normal subjects, F Ⅷ : C increased 2-folds within 10 min after clot formation, then gradually decreased remaining the level around 10-20 u/dl. F Ⅷ : Ag also increased once, then decreased keeping the level around 50-60 u/dl. VWF : Ag assayed by IRMA increased once, then gradually decreased and stayed around 60-70 u/dl. F Ⅷ/vWF complex decreased rapidly after initiation of clotting, then it stayed at constant level of 10 u/dl at 20 min. 4. Time-course of F Ⅷ proteolysis during whole blood clotting was monitored by an enzyme-linked immunosorbent assay (ELISA). Interval between 30 and 60 min after coagulation, levels of the aminoterminal "acidic" region of F Ⅷ light chain and of the middle "acidic" region of F Ⅷ heavy chain decreased to the same level of F Ⅷ : C. However, the 72 kDa-fragment of F Ⅷ light chain decreased more slowly. These results indicate that F Ⅷ is immediately dissociated from F Ⅷ/vWF complex after initiation of whole blood clotting, and the F Ⅷ undergoes rapid proteolytic modification in serum.