PMID- 1562731 OWN - NLM STAT- MEDLINE DCOM- 19920515 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 79 IP - 8 DP - 1992 Apr 15 TI - Factor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo. PG - 2039-47 AB - We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tissue factor pathway is largely responsible for the activation of factor IX as well as factor X in the basal state (ie, the absence of thrombosis or provocative stimuli). We have administered a monoclonal antibody purified factor IX concentrate to individuals with hemophilia B. These studies show an increase in the plasma levels of FIXP that were initially greatly decreased, but no change in FXP or F1+2. We have also infused highly purified factor VIII concentrate into patients with hemophilia A. The data demonstrate no significant changes in the plasma concentrations of FXP and F1+2. The above observations indicate that factor IXa generated by the factor VII-tissue factor pathway is unable to activate factor X under basal conditions. Based upon the above findings, we outline a model of blood coagulation system function under basal conditions, and suggest a process by which the generation of factor Xa and thrombin might be accelerated during normal hemostasis and in the setting of thrombotic disorders. FAU - Bauer, K A AU - Bauer KA AD - Department of Medicine, Beth Israel Hospital, Boston, MA 02215. FAU - Mannucci, P M AU - Mannucci PM FAU - Gringeri, A AU - Gringeri A FAU - Tradati, F AU - Tradati F FAU - Barzegar, S AU - Barzegar S FAU - Kass, B L AU - Kass BL FAU - ten Cate, H AU - ten Cate H FAU - Kestin, A S AU - Kestin AS FAU - Brettler, D B AU - Brettler DB FAU - Rosenberg, R D AU - Rosenberg RD LA - eng GR - HL 33014/HL/NHLBI NIH HHS/United States GR - HL 41136/HL/NHLBI NIH HHS/United States GR - RR 01032/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies, Monoclonal) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Proteins) RN - 0 (prothrombin fragment 1.2) RN - 72175-66-7 (Factor VIIIa) RN - 9001-25-6 (Factor VII) RN - 9001-26-7 (Prothrombin) RN - 9001-29-0 (Factor X) RN - EC 3.4.21.21 (Factor VIIa) RN - EC 3.4.21.22 (Factor IXa) SB - IM MH - Adolescent MH - Adult MH - Antibodies, Monoclonal MH - *Blood Coagulation MH - Factor IXa/*metabolism MH - Factor VII/*metabolism MH - Factor VII Deficiency/*blood/therapy MH - Factor VIIIa/*metabolism MH - Factor VIIa/*therapeutic use MH - Factor X/*metabolism/*therapeutic use MH - Female MH - Hemophilia A/*blood/therapy MH - Humans MH - Male MH - Peptide Fragments/metabolism MH - Prothrombin/*metabolism MH - Recombinant Proteins/therapeutic use MH - Reference Values EDAT- 1992/04/15 00:00 MHDA- 1992/04/15 00:01 CRDT- 1992/04/15 00:00 PHST- 1992/04/15 00:00 [pubmed] PHST- 1992/04/15 00:01 [medline] PHST- 1992/04/15 00:00 [entrez] AID - S0006-4971(20)73037-5 [pii] PST - ppublish SO - Blood. 1992 Apr 15;79(8):2039-47.