The Involvement of Factors XII & XI in the Platelet Coagulant Activity

Abstract

Platelets provide coagulant activities, other than the Phospholipid Platelet factor 3, which can be released from the platelet. In Platelet Poor Plasma, the initiation of the intrinsic pathway is proposed to proceed via factors Xll & XI as well as 2 other factors, Prekallekrein and Kininogen. The role of these factors in the initiation of coagulation in Platelet Rich Plasma is under investigation. Walsh, (Br.J. Haemat. 22. 393, 1972) and Muntz (Haemostasis in press 1977), have shown that platelets devoid of factor Xll will still produce a coagulant activity when Platelet Rich Plasma is incubated with collagen. However, we have recently shown that this reaction requires the presence of factor XI. Factor XII has been purified by the method of Saito (Circ.Res.34,641,1974) , and factor XI has been purified by the method of Connellan, Castaldi and Muntz. (Haemostasis, in press 1977).Specific antibodies were developed in rabbits and the IgG from the antiserum was coupled to Sepharose. These factors could be extracted from plasma by the immobilized antibodies and could then be eluted by the use of alkali or guanidine HCL, thus resulting in a rapid purification of these factors.Platelets were washed free of loosely bound clotting factors and provided significant amounts of coagulant activity when ruptured by either freezing and thawing or by glycerol treatment. Platelets from a factor XI deficient patient also provided this activity. The platelet activity was extracted by passage through both Sepharose-heparin column and Sepharose-anti-factor XI column;the activity appeared to be identical to plasma factor XI.