The Viscous Metamorphosis of the Blood Platelets

Abstract

The phenomenon of agglutination and fusion of the blood plate. lets into glassy masses and strands, as observed in films of wet blood between a slide and cover-glass, was first described by Hayem (1) in 1878. Some years later, it was more exactly described by Bizzozero (2) and named "viscous metamorphosis" by Eberth and Schim. melbusch (3). It occurs during the process of coagulation and is weU marked at the time of the first appearance of the fibrin threads. It does not take place if sodium oxalate or certain other salts have been added to the blood during the bleeding in sufficient amount to prevent coagulation and if other conditions are favorable. Mosen (4) in 1893 was the first to show that platelets from such a noncoagulating blood, freed from blood elements by centrifuging, do not fuse with one another, but retain their separate identity. They appear when in suspension in isotonic salt solution and observed with medium powers between a cover-glass and slide, as refringent, glistening granules or round bodies of a diameter varying approximately from one-fourth to one-half that of a red blood corpuscle (Fig. 1); they are not clumped but uniformly distributed and remain so until they disintegrate. We have found, however, that such platelets normally have not lost the ability of metamorphosis, but that they undergo the characteristic changes within a few minutes if serum or certain more or less closely related substances are added to the suspension. As observed under the conditions just mentioned, the platelets begin their metamorphosis by aggregating and agglutinating in masses and strands which increase in size up to a certain point within a few minutes. Then within a few more minutes, the plate-395 on

Effects of Thrombin and Platelet Concentrations and of Clot Retraction on Fibrin Strand Widths 12

“…The relation of the migration of platelets to strands of fibrin already formed can only be hypothesized (13 The lack of the increase in thickness of the fibrin strands upon retraction of the clot is consistent with the observations of other workers in this field (7,13). They believe that after coagulation, the platelets which either acted as foci for laying the fibrin network or migrated to the fibrin strands, become attached (14,61) to the fibrin and then begin to fuse together (viscous metamorphosis [50,62,63] ).9 As this fusion of the platelets continues, the fibrin network is drawn together to give the phenomena of clot retraction. Since the fibrin strands are not involved in this process, their sizes remain unchanged.…”

“…If imidazole buffer (69) was used and an extra amount of calcium ion added, urea insoluble clots were obtained from the unpurified bovine Fraction I. Since urea soluble clots, which are formed in the absence of calcium ions and in the presence of platelets and serum factor, will retract, it seems reasonable to assume that the serum factor in this situation merely increased the viscous metamorphosis of the platelets as described by Wright and Minot 36 years ago (62). It is also reasonable to assume that the fibrin stucture was the same as though the serum factor and platelets had been absent.…”

Qualitative description of factors involved in the retraction and lysis of dilute whole blood clots and in the aggregation and retraction of platelets

“…These serum preparations undoubtedly contain residual amounts of prothrombin and thrombin, a fact which is to be taken into account in the experimental procedures and discussion. A siliconized cover slip was placed over the serum-platelet preparation and was examined for platelet aggregation and retraction with the Zeiss phas microscope as described by Wright and Minot (22). The time required for aggregation and retraction to start in each of four quadrants was used as the end point.…”

Mechanism of Action of Thrombin on Platelets*

“…When coagulation occurs, platelets undergo a series of morphologic changes known as "viscous metamorphosis" (18,19), a phenomenon which is associated with aggregation and apparent fusion of the platelets and with retraction of the clot (11,20). These changes do not occur in the absence of available calcium or magnesium even though the platelets are embedded in fibrin clots formed by thrombin (11,21).…”

“…Some of these agents include serum (19), serum rich in prothrombin (7,37), "factor R" of Hellem (38) released from red blood cells, "product I" of Bergsagel (39), a "thrombocyte agglutinating factor" of Brinkhous and co-workers (40), EDTA plasma to which divalent cation was added (41), and an "interaction of Hageman or tissue factor with PTA or plasma platelet factor" (17). Some of the agents mentioned have been shown to contain thrombin or to produce it during their interaction with platelets (7); and in the present studies, serum containing a high concentration of prothrombin produced aggregation of nontrypsinized but not of trypsinized platelets.…”