A. The blood clotting mechanism. The development of a theory of blood coagulation.

Abstract

The clotting mechanism is first on the list because it has been worked on for longest and the mass of data and speculation accumulated illustrates better than any other the pitfalls which beset any intensive investigation of a biological phenomenon. The reason for this almost obsessive interest is the dramatic end point, the spontaneous change from fluid blood to solid clot, and the ease with which endless experiments can be set up in vitro . Many schools of workers have made a life study of this subject, producing as many different theories, and, worse, as many different terminologies. Probably the most important advance in this field in recent years has been the introduction of a standard nomenclature recommended by an international committee which assigns a roman numeral to any clotting factor with a good claim to reality. This has cleared away a jungle of synonyms, hypothetical factors and semantic conflict to reveal a solid basis of factual agreement. Tracing the development of current theory one starts with the observation that clotting is due to the appearance of fibrin. Fibrin is a good, solid fact and about the only entity in clotting the existence of which has not been hotly denied. The appearance of fibrin in shed blood but not in the normal circulation naturally prompted a search for the cause, and, after some wild speculation, two trigger stimuli were found. One is contact of the blood with a surface other than vascular endothelium, as demonstrated by Lister during his Croonian Lecture to the Royal Society in 1863. He showed that blood which had remained fluid in the excised jugular vein of an ox clotted when it was transferred to a glass vessel. The other trigger was the coagulant effect of tissue extracts which are capable of clotting blood in a few seconds if added to it in sufficient quantity. This reaction seemed the more important, since it was supposed that physiological clotting at an injury site was due to tissue products mixing with the issuing blood, and the intensive investigation of this effect excluded interest in contact activation until quite recently.