A Normal Inhibitor of the Blood Coagulation Contact Reaction Product

A method is described for studying and measuring the activity of a normallyoccurring inhibitor of the blood coagulation contact reaction product (activated PTA). The inhibitor, stable on storage at -20 C. was inactivated byheating plasma to 56 C. for 30 minutes. The inhibitor was stable betweenpH 5 and 9. Inhibitory activity was increased by aluminum hydroxide adsorption and not apparently affected by celite exhaustion of plasma. The inhibitorwas present in the fraction of plasma precipitated between 55 and 65 per centammonium sulphate saturation and migrated with the alpha globulins electrophoretically. The action of the inhibitor was prevented by soy bean trypsininhibitor. Inhibitory activity was present in serum and in all normal plasmasamples examined as well as in plasma from patients deficient in Hagemanfactor, PTA factor or factors VIII or IX. The physiologic and pathologicsignificance of this inhibitor remains to be determined.

Submitted on April 30, 1964 Accepted on July 14, 1964     

Differential Consumption of Coagulation Factors Resulting from Activation of the Extrinsic (Tissue Thromboplastin) or the Intrinsic (Foreign Surface Contact) Pathways

1. The consumption of coagulation Factors IX, X, and XI was studied innormal whole blood clotted with celite (intrinsic activation) or tissue thromboplastin (extrinsic activation).

2. During these studies an assay method for Factor XI was developed whichwas not influenced by the presence of tissue thromboplastin. The assay methodis based on the thromboplastin generation principle.

3. When blood clotted in silicone treated tubes, the serum and plasma concentrations of Factors IX, X, and XI were almost identical, indicating that littleconsumption or activation of these factors had occurred.

4. In the presence of celite, coagulation Factors IX and XI are consumed,whereas Factor X is consumed only slightly.

5. In the presence of tissue thromboplastin, Factor X is consumed, whereasFactors IX and XI are not consumed.

6. In the presence of both celite and thromboplastin, the thromboplastindecreased the consumption of Factors IX and XI produced by celite.

7. The study of serum coagulation factor levels may provide evidence as towhether the coagulation process had been initiated by the intrinsic (foreignsurface contact) or extrinsic (thromboplastin) pathways.

Submitted on May 9, 1966 Accepted on July 21, 1966