Viscous Metamorphosis of Blood Platelets: A Study of the Relationship to Coagulation Factors and Fibrin Formation

Platelet Clumping in vitro

“…The platelet aggregates produced by ADP are similar to those found in the early stages of the 'viscous metamorphosis' seen in a platelet-rich native plasma system during clotting, except that the ADP-induced aggregates do not appear to fuse, nor do they undergo the process ofpotocytosis (Sharp, 1958) as violently.…”

“…Clumping induced by the compounds we have tested is thus of in-vivo as well as in-vitro significance. Further, the phenomenon of platelet aggregation induced in both human and rabbit blood by the addition of ADP and related substances has many similarities to the 'viscous metamorphosis' observed in native and recalcified citrated platelet-rich plasma systems (the time sequence and the intensity of the reaction, the dependence on movement, and relationship to calcium concentration; Sharp, 1958). The dispersal phenomenon has also been seen in plasma systems from patients with congenital or acquired coagulation defects in whom fibrin formation was markedly delayed (Sharp, 1961).…”

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The Radclt@e Inzjirmary, Oxford OSLER (I 874), Hayem (I 878) and Eberth and Schimmelbusch (I 886) showed that the process of blood clotting initiated platelet clumping in shed blood, and later workers (Roskam, 1922; Zucker and BorreK, 1955;Bergsagel, 1956;Bounameaux, 1957) have shown that various coagulation factors released during the clotting process can produce this platelet clumping. There has, however, been a growing body of evidence to suggest that other mechanisms, not directly related to clotting, could also initiate platelet clumping (Sharp, 1958(Sharp, , 1961, and the existence of one such mechanism was confirmed by the observation that a proteinfree, heat-stable, dialysable extract of human red cells could increase platelet adhesiveness (Hellem, 1960). Hellem called the active principle of h s extract 'Factor R'; fractionation of the extract showed that the active agent was adenosine diphosphate (ADP) and it was found that when this substance was added to platelet-rich citrated plasma in concentrations as low as 0.02 ug./ml., platelet clumping was produced (Gaarder, Jonsen, Laland, Hellem and Owren,

1961).We have studied ths clumping phenomenon in vitro, tested other substances for clumping activity and searched for materials which would modify the process.

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Dicumarol Therapy

“…These findings agree with those of some investiga-tors, 4 ' ° but conflict with those of others. 8 ' 9 In Sharp's 8 observations made on 4 patients, the anticoagulant therapy was regulated by the prothrombin time. It is, therefore, possible that the subjects had not received anticoagulant adequate to affect platelet clumping.…”

“…Although this has been observed in animal experiments, 1 ' 2 a study of human subjects receiving "Dindevan" therapy, showed no such delay. 8 Fur-thermore, Fulton, Akers and Lutz 9 observed that the administration of Dicumarol to hamsters actually enhanced platelet adhesiveness and clumping. Factors which might account for the divergent results are differences in anticoagulant dosage and methods of controlling the dose.…”