Activated Coagulation Factors: In‐Vivo and in‐Vitro Studies

Abstract

Summary: In the course of serial coagulation studies on patients with acute leukaemia, defibrination was frequently encountered in the lymphoblastic, myeloblastic and promyelocytic varieties of the disease. Factor‐VIII levels were often high and varied very considerably, a particular phenomenon being the association at times of very high one‐stage levels with decreased two‐stage levels. In one patient heparin infusion was associated with a rise in the two‐stage Factor‐VIII level and cessation of the infusion with a prompt drop in level. Less frequently, gross elevation of one‐stage Factor‐XI activity occurred compared with two‐stage (eluate test) levels. In order to study possible mechanisms for the phenomena observed, the effect of adding various pro‐coagulants to normal plasma on the one‐ and two‐stage methods for measuring Factors VIII, IX and XI was studied. Thrombin caused a marked rise in one‐stage Factor‐VIII activity and a much smaller rise in one‐stage Factor IX and XI measurements. Two‐stage Factor‐VIII activity was reduced and Factors IX and XI little affected. These findings simulate some of the findings in vivo. The effect of activated Factors IX, X and XI on the one‐stage activity of Factors VIII, IX and XI may be explained by assuming that an activated product increases the one‐stage activity of any factor which participates in the clotting reaction sequence at a stage preceding the formation of the product. The actual findings were that an activated Factor‐X preparation increased one‐stage Factors VIII, IX and XI measurements; an activated Factor‐IX preparation considerably increased one‐stage Factor IX and XI measurements but affected Factor‐VIII activity only when used at very high concentrations; an activated Factor‐XI preparation did not affect Factor VIII, IX or XI one‐stage activity. None of these three activated products influenced the two‐stage measurements of Factors VIII, IX and XI. Tissue thromboplastin increased one‐stage Factor VIII, IX and XI activity to a similar extent, did not influence two‐stage Factor VIII and IX measurements and slightly increased two‐stage Factor‐XI activity.

Studies on the purification and characterization of human factor VIII

“…Thrombin in trace amounts has been shown to activate factor VIII (35,36). It was suggested by Biggs, MacFarlane, Denson, and Ash (32) that thrombin activates Purification and Characterization of Factor VIII factor VIII in part by release of factor VIII from fibrinogen during cleavage of the fibrinopeptides.…”

Leukocyte procoagulant activity: enhancement of production in vitro by IgG and antigen-antibody complexes.

“…Factor VII-deficient plasma with less than 1% of normal VII activity was obtained commercially (George King Bio-Medical, Inc., Salem, N. H.). A barium stulfate eluate of normal huiman serum containing factors VII, IX, X, and traces of thrombin and prothrombin was prepared as previously described by Niemetz and Nossel (19) for use in the two-stage test as a source of Factor V1II and X.…”

Coagulant Activity of Leukocytes. TISSUE FACTOR ACTIVITY

“…Assay methods. Factors VIII and IX were assayed by one-stage methods on the appropriate congenitally-deficient human plasma after activation for 1 min with Celite, as previously described (10). Factors II, V, VII, and X were assayed as described by Soulier and Larrieu (21).…”

“…White cells have been shown to contain both procoagulant and anticoagulant activity (1)(2)(3), the anticoagulant activity having been more thoroughly investigated (4). Also, patients with acute leukemia may present with defibrination and thrombosis (5)(6)(7)(8)(9)(10). Defibrination occurs with great frequency in acute promyelocytic leukemia and heparin may reverse the defibrination syndrome (10 Received for publication 3 June 1971 and in revised form 19 August 1971. Shwartzman phenomenon.…”

“…Also, patients with acute leukemia may present with defibrination and thrombosis (5)(6)(7)(8)(9)(10). Defibrination occurs with great frequency in acute promyelocytic leukemia and heparin may reverse the defibrination syndrome (10 Received for publication 3 June 1971 and in revised form 19 August 1971. Shwartzman phenomenon. White cells have been implicated in the Shwartzman phenomenon.…”