Viscous metamorphosis

Thrombin, the two-chain derivative of the prothrombin molecule, has a molecular weight of approximately 37,000 daltons. Its proteolytic properties induce the conversion of fibrinogen to fibrin to produce the initial visible manifestation of coagulation, the soluble fibrin clot. In addition, thrombin influences the activity of Factors V, VIII, and XIII and plasmin. Thrombin affects platelet function by inducing viscous metamorphosis and the release reaction with subsequent aggregation. 

Fig. 2. Early phase of viscous metamorphosis. Addition of thrombin has induced aggregation and degranulation of platelets. Remaining dark bodies (arrows) are mitochondria (Parmeggiani, unpublished, 1962).

The third phase of extrinsic thromboplastin formation seems to be somewhat less complex than the first two steps. This phase involves the interaction of product I and platelet phospholipids. How the phospholipids are released from platelets during the formation of intrinsic thromboplastin is still debated, but two facts are significant normal platelets have no phospholipid activity, and the development of phospholipid activity is associated with viscous metamorphosis and granular release from platelets. Either product I or PTA has been thought to produce viscous metamorphosis (see below). In the formation of product II, product I is thought to act as an enzyme on the platelet phospholipid to yield product II. 

The sequence of events in homeostasis of larger vessels develops as follows platelets accumulate at the site of injury (forming a temporary clot), the vascular musculature (in arteries and large veins) constricts, and the platelet undergoes viscous metamorphosis. The mechanisms of aggregation and viscous metamorphosis of platelets will now be briefly reviewed. 

One unique property of platelets is their stickiness [30]. Platelets adhere to each other and to the endothelium when discontinuity in the endothelium occurs. Stickiness must be distinguished from viscous metamorphosis and clot formation. Stickiness is a more discrete property of platelets, and it is not unlikely to be important in priming the homeostatic process and the formation of thrombi. 

During viscous metamorphosis, the platelets lose their individuality and fuse into a large amorphous mass that is structureless on examination with the light microscope. Viscous metamorphosis is accompanied by metabolic alterations in the platelets. Before metamorphosis, the rate of glycolysis and ATP formation are increased. After metamorphosis, ATP is hydrolyzed, possibly by an ATPase released by the platelet, and AMP and ADP appear in the medium. 

The vascular theory of hemostasis postulates a vascular and a hematological step. In the vascular step, the vessel reacts by vasoconstriction, and a stickiness develops at the surface of the endothelial walls. This stickiness of the endothelial walls may cause the two opposing walls to adhere to each other and close the vessel. In small capillaries, the occlusion is sufficient to prevent hemorrhage in larger vessels, occlusion is followed by agglutination of platelets first, and formation of a fibrin clot later. After viscous metamorphosis, a second wave of vasoconstriction occurs, which probably results from serotonin release from platelets. In this second wave, the vasoconstriction is not restricted to the injured vessel but affects the neighboring vessels as well. 

Stickiness of platelets Agglutination of platelets Viscous metamorphosis Release of ADP Vasoconstriction... 

Platelets treated with l-p-chlorostyryl-3Hnethyl-3-carbomethoxy-6,7-dimethoxy-3,4 dihydroisoquinoline (SSDHI) lose their ability to spread, adhere, aggregate and retract. They cannot undergo the morphological and biochemical cluuiges of viscous metamorphosis produced by thrombin ... 

The term "viscous metamorphosis" is meant to designate the total of the changes accompanying irreversible aggregation under the influence of thrombin, i.e. release reaction, activation of the contractile system, and availability of phospholipid procoabu-lant (PF 3). 

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