Shirley A. Johnson

Differentiation of Certain Platelet Factors Related to Blood Coagulation

Study of the platelets from the viewpoint of the blood coagulation mechanisms seems likely to be helpful for increasing our knowledge of thrombosis, and bleeding tendencies in thrombasthenias and thrombopathias. A logical approach to their study is the differentiation of their properties and where possible to ascribe those properties to individual components. Platelet factors 1, 3 and 4 are considered from that viewpoint. The first accelerates the formation of thrombin in a manner analogous to serum Ac-globulin. Factor 3 is required for the development of threone activity, and factor 4 has antiheparin properties.

Differentiation of Plasma Antithrombin Activities.

Summary The antithrombin capacity of plasma can be differentiated into 4 main effects. Antithrombin I is the adsorption of thrombin on fibrin. Antithrombin II is the co-factor of heparin. Antithrombin III neutralizes thrombin activity even in the absence of heparin, while antithrombin IV destroys thrombin only while it is being formed from prothrombin. Some of the properties of anti-thrombins II, III and IV have been investigated, together with those of the factor which acts with heparin to inhibit the activation of prothrombin, and which is referred to as the‘39 factor. The 4 activities have the common property of resistance to heating at 60° for three minutes, but are destroyed by heating at 70°. They are not adsorbed on BaCO3. They are water soluble. None of these activities is found in a commercial crystalized bovine plasma albumin. Antithrombin III activity is the only one removed by ether treatment of plasma. In ammonium sulfate fractionation antithrombin II is found predominantly in the 50-70% fraction, while antithrombin III is found only in the 0-50% fraction. It is believed that these 2 factors are two distinct entities. The relation of antithrombin IV to these 2 is not yet clear. It is possible that the‘39 factor and antithrombin II are identical.

The Reduction of Autoprothrombin II Activity with Dicumarol

It is generally considered that the administration of dicumarol is followed by a decrease in prothrombin concentration, and it has been suggested that another plasma factor may also decrease. We have found that there are two derivatives of prothrombin called autoprothrombin and autoprothrombin II. In this paper we present data which show that the concentration of autoprothrombin II can be reduced practically to zero with the use of Dicumarol without observing a bleeding tendency. The decrease in concentration coincides with a decrease in prothrombin concentration but is relatively more rapid.

Relationship of the oral anticoagulants to the blood coagulation mechanisms.

Dicumarol has become a major anticoagulant in the treatment of coronary thrombosis. Owen and Bollman5 found in 1948 that another component, later called Factor VII, in addition to prothrombin was reduced by the administration of Dicumarol. Koller and associates,6 in 1952, reported that Factor VII in blood, reduced in concentration by administration of Dicumarol, returned to normal levels following the administration of vitamin Ki. That same year Biggs and coworkers’ described the Christmas factor, tentatively suggesting that the levels in blood were reduced by coumarin drugs. Simultaneously Aggeler and co-workers8 reported on the same

Interrelationship of Prothrombin and Autoprothrombin I in Thrombocytopenia Following Aminopterin Administration

The poor prothrombin consumption test supported by thrombocytopenic serum has been shown in a previous publication to be due to some activity other than prothrombin—a thrombocytopenic activity. This thrombocytopenic factor or activity can be readily adsorbed on inorganic agents and eluted. The autoprothrombin I values were found to be lower in thrombocytopenic serum than in normal serum. When the patient with thrombocytopenia was treated with aminopterin, the prothrombin consumption test remained short while the autoprothrombin I values increased to that of normal serum and then fell again as the treatment was withdrawn. The prothrombin in the serum remained uniformly low throughout the treatment. The relationship of the thrombocytopenic activity and autoprothrombin I as possible derivatives of prothrombin is considered. Submitted on June 12, 1957

Note on calcium ion requirements for threone activity.

Summary When threone is involved in the conversion of purified prothrombin to thrombin, the optimum calcium concentration ranges from 0.009 M to 0.04 M. This is a much broader range than found when throm-boplastin is used for the activation of prothrombin.