BLOOD COAGULATION AS STUDIED BY INTRAVENOUS INJECTION OF TISSUE EXTRACT

1. WOOLDRIDGE'S “tissue‐fibrinogen” (thrombokinase) is not obtainable in true solution, its active component being bound up with material in suspension. By filtration through a Pasteur‐Chamberland filter a “solution” of tissue extract (or thrombokinase) is rendered inactive. 2. Any injection of active tissue extract causes a prompt fall in the number of circulating platelets. The number soon rises again, to fall once more on repetition of the injection. The immediate fall in number of platelets on each successive injection of the active extract is due to the presence of particulate matter (cell‐debris) in the extract. 3. Negative‐phase blood produced by repeated slow injection of tissue extract may behave anomalously when one attempts to defibrinate it by whipping with a stick. If the platelets are still relatively abundant fibrin collects in small amount, and after a considerable delay, on the stick, the rest of the blood staying fluid. If the platelets are considerably reduced in number no fibrin collects, but the blood eventually and after long delay clots in lumps. 4. When a starved animal is killed by injection of a minimal lethal amount of active tissue extract, death is due to the formation of a platelet thrombus in the right ventricle and pulmonary artery. The remaining blood, which is fluid, is found to have been all but denuded of its platelets. 5. Blood which has been virtually deplateletised in this way still contains fibrinogen and will clot firmly on addition of tissue extract. Apart from a slight local coagulation due to contact of the few remaining platelets with the foreign surface, this blood does not spontaneously clot on glass. If the blood could be wholly deplateletised it would be found to have lost the property of spontaneous coagulation. 6. To describe the exact condition of a negative‐phase blood it is not sufficient to specify simply the amount of fibrinogen it contains. For full description one must also specify the relative number of contained platelets, which number does not run parallel to the amount of fibrinogen. 7. A blood in which the platelets have been sensibly reduced in number by injection of old and inactive tissue extract exhibits delay in spontaneous coagulation. 8. The fatal platelet thrombus in the right ventricle and pulmonary artery after injection of a minimal lethal dose of active tissue extract is similar to that described by Welsh as occurring sometimes in pneumonia. The expenses of this research were defrayed in part by a grant from the James Cooper Fund of M'Gill University for Research in Experimental Medicine.