Platelet Interaction with Polymerizing Fibrin

Abstract

A B S T R A C T Interaction of washed pig, rabbit, or human platelets with fibrinogen was studied during its transition to fibrin using photometric, isotopic, and electron microscopic techniques. Untreated fibrinogen and fully polymerized fibrin had no detectable effect on platelets. Fibrinogen, incubated with low concentrations of reptilase or thrombin, formed intermediate products which readily became associated with platelets and caused their aggregation. Neutralization of the thrombin did not prevent this interaction. In the absence of fibrinogen, reptilase did not affect platelets.The interaction of polymerizing fibrin with platelets was accompanied by small losses of platelet constituents (serotonin, adenine nucleotides, platelet factor 4, and lactic dehydrogenase). This loss did not appear to be the result of the platelet release reaction. Inhibitors of the release reaction or of adenosine diphosphate (ADP)-induced aggregation did not prevent the interaction of platelets with polymerizing fibrin. Apyrase or prostaglandin E1 (PGE1) reduced the extent of platelet aggregation by polymerizing fibrin, but the amount of protein associated with platelets was slightly increased.The interaction of polymerizing fibrin with platelets was completely inhibited by ethylenediaminetetraacetate (EDTA) or ethylene glycol bis (,-aminoethyl ether) N, N,N',N'-tetraacetic acid (EGTA).Fibers formed in solutions of polymerizing fibrin were larger in the presence than in the absence of washed platelets, suggesting that platelets affect fibrin polymerization. The adherence of platelets to polymerizing fibrin may be responsible for the establishment of links between platelets and fibrin in hemostatic plugs and thrombi.Dr. Stewart's present address is

Endothelin‐1 inhibits platelet aggregation in vivo: a study with 111indium‐labelled platelets

“…The weak inhibition of thrombinstimulated platelet aggregation by ET-1 was not unexpected, for thrombin-generated fibrin stabilizes the growing platelet mass resulting in deposition of irreversible platelet aggregates in the microcirculation (Niewiarowski et al, 1972). This is reflected by our finding that the thrombin-induced accumulation of "'In-labelled platelets in the pulmonary vasculature is not completely reversible and associated with a long-lasting thrombocytopenia.…”

Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation

“…Although integrin aIIbb3 is a recognized receptor for fibrinogen and fibrin, another as-yet-unidentified receptor is thought to play a role. [13][14][15][16]29 Here, we show that GPVI acts as a fibrin receptor with 2 main functions: its interaction with polymerized fibrin (1) represents a new amplification loop for thrombin generation and (2) allows platelet recruitment at the surface of the clot.…”

“…11 Fibrin interacts with the activated form of aIIbb3, as does fibrinogen, 11,12 but also binds to platelets which lack this integrin. [13][14][15][16] In the presence of thrombin, the interaction of polymerizing fibrin with GPIb has been reported as an alternative aggregation pathway. 17 Furthermore, several studies indicated the existence of an as-yet-unidentified platelet receptor for fibrin.…”

Assessing blood coagulation status with laser speckle rheology

“…It is important to mention here that the presence of aggregated platelets may also contribute to the increased viscoelastic modulus of the stabilized clot. During blood coagulation, platelets serve as cross-linking sites during formation of fibrin network and exert contractile forces on the fibrin scaffold via the protein thrombosthenin which further increases the stiffness of the blood clot [47]. As a result, platelet count and platelet function may also likely to affect τ Max which will be further evaluated in future studies.…”