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Tissue factor is a particle-bound lipoprotein which initiates coagulation uia the extrinsic system. The present study presents a modification and extension of previous techniques by which 40 mg of soluble tissue factor can be prepared from 100 g of lung acetone powders with 800-to 1500-fold purification. Although the purified protein contains 7z residual phospholipid, recombination with 7.5 mg of phospholipid per mg of protein is required for maximal coagulant activity; this lipid to protein ratio stimulates activity 950-fold. The protein has been characterized by gel filtration, sucrose density gradient ultracentrifugation, and disc gel T he predominant mechanism of blood coagulation involves the sequential conversion of proenzymes into active, proteolytic enzymes. Tissue factor is a particle-bound lipoprotein that can initiate blood coagulation by combining stoichiometrically with factor VII, a plasma protein (Nemerson, 1966; Williams and Norris, 1966). The complex formed by these factors enzymatically converts factor X into its activated form which generates thrombin from prothrombin. The mechanisms of complex formation and factor X activation are not yet understood in detail.

Peroxidase-conjugated antibodies were used to determine the histologic and cytologic localization of bovine and human tissue factor (thromboplastin). Tissue factor antigen was found in highest concentration in the intima of blood vessels, particularly in the plasma membranes of endothelial cells and in human atheromatous plaques. Tissue factor was also found limited to the plasma membranes of many cell types. The presence of tissue factor in the plasma membranes of endothelial cells and atheromata suggests that it may play a significant role in hemostasis and thrombosis.

Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.