Gallium nitrate induces fibrinogen flocculation: an explanation for its hemostatic effect?

Abstract

A novel hemostatic effect of gallium nitrate has recently been discovered. Our aim was to perform a preliminary investigation into its mode of action. Thromboelastography® showed no effect on coagulation but pointed instead to changes in fibrinogen concentration. We measured functional fibrinogen in whole blood after addition of gallium nitrate and nitric acid. We found that gallium nitrate induces fibrinogen precipitation in whole blood to a significantly higher degree than solutions of nitric acid alone. This precipitate is not primarily pH driven, and appears to occur via flocculation. This behavior is in line with the generally observed ability of metals to induce fibrinogen precipitation. Further investigation is required into this novel phenomenon.

The Gilded Clot: Review of Metal-Modulated Platelet Activation, Coagulation, and Fibrinolysis

“…As our search strategy, we combined the metal of interest with “platelet activity or aggregation,” “coagulation” or “fibrinolysis” to obtain the literature to be presented [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , ...…”

“…Of interest, Ga(NO 3 ) 3 was initially found to exert local hemostatic effects and was subsequently investigated to determine the mechanisms responsible for these effects [ 37 ]. With regard to plasmatic coagulation, 7.5–15 mM Ga(NO 3 ) 3 diminishes whole blood clot strength by over 50% as determined by thrombelastography; further 39–50 mM Ga(NO 3 ) 3 removed clottable fibrinogen in human plasma [ 37 ]. No other significant effects on coagulation kinetics (e.g., onset time of coagulation) were observed [ 37 ].…”

“…While the roles played by cellular components and circulating proteins in coagulation and fibrinolysis are widely acknowledged, the impact of metals on these processes is at best underappreciated. Specifically, there are twenty-five metals that can modulate the activity of platelets, plasmatic coagulation, and fibrinolysis [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ,…”

Gallium containing bioactive materials: A review of anticancer, antibacterial, and osteogenic properties

“…Moreover, besides reducing the inflammation in the latter stage of wound healing, gallium also shows improvement during the very early stage of hemostasis - either coagulation, platelet activation, or clot formation [ 17 , 40 , 41 , [66] , [67] , [68] ]. This effect of gallium has been proven by comparing gallium containing composites with two different commercial products [ 69 ].…”

“…Gallium is also being tested in clinical trials to fight against infections [ 36 , 37 ]: gallium incorporation into coatings or scaffolds enhances the antibacterial properties of biomaterials [ 38 ]. Recently, gallium's hemostatic effects have been also examined [ 17 , [39] , [40] , [41] ]. The addition of gallium increased the capability of MBGs regarding platelet aggregation, thrombus formation, and blood coagulation activation [ 41 ].…”