428 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1945 



components necessary to form a clot instantly at a bleeding surface, 

 but also this enzyme capable of dissolving the clot. 



FIBRINOGEN, THROMBIN, AND THE CLOTTING OF THE BLOOD 



The clotting mechanism of the body is indeed complex. The struc- 

 tural element of the clot is the long rod-shaped fibrinogen molecule 

 which is dissolved in the plasma. Its aggregation and separation as 

 the fibrin clot are carried out by the globulin, thrombin. When throm- 

 bin and fibrinogen are mixed in vitro, a clot immediately occurs. 

 Thrombin, however, does not exist free in the blood stream but as 

 a precursor substance, prothrombin, readily transformed into throm- 

 bin in the presence of calcium by tissue extracts known as thrombo- 

 plastins. 



The various parts of this complex mechanism may be separated and 

 concentrated and made available in various forms. By controlling the 

 conditions of the reaction between fibrinogen and thrombin, structures 

 of a wide variety of properties can be obtained. Clots of one type are 

 clear, gelatinlike, elastic, and friable, do not readily synerize with 

 loss of fluid, and adhere to surfaces on which they are formed. 

 Clots of another type are opaque, doughy, and scuff-resistant, syner- 

 ize readily, become dense with loss of fluid, and do not adhere to under- 

 lying surfaces. Clots of intermediate properties can also be made. 



For surgical use in human patients, clots may be prepared from 

 fibrinogen and thrombin to meet the particular specifications chosen 

 for each type of application, and may be formed in situ in or over 

 wounds. Clots whose properties have been controlled in this way 

 have been used in pyelolithotomy and in a technique for skin grafting. 



Just as the asymmetry of certain synthetic polymers is responsible 

 for the remarkable mechanical properties of industrial plastics, the 

 fibrinogen molecule endows products of this human protein with re- 

 markable mechanical properties. Among these products is fibrin film. 

 Fibrin film may be prepared from fibrinogen and thrombin as a 

 strong, rubbery sheet which can be stretched reversibly from two to 

 three times its original length. This material can be made in various 

 shapes and thicknesses, and in the form of seamless tubing. Its 

 mechanical properties can also be varied from a soft, rubberlike elas- 

 ticity to a parchmentlike consistency. 



The mechanical properties of the soft, rubbery films (as shown by 

 their stress-strain curves) bear a marked similarity to those of the 

 elastic ligament of the neck, the ligamentum nuchae. The tough films 

 with delayed elasticity resemble rather wool or hair in their mechanical 

 properties. It may be possible to imitate, with different types of fibrin 

 products, still other natural structures of the body. 



