Effect of Iron Ions on Functional Activity of Thrombin

Abstract

The kinetics of thrombin inhibition by irons ions was studied in the thrombin time test with normal plasma. The kinetic and concentration characteristics for recovery of thrombin activity by desferal were evaluated at various periods of thrombin incubation with iron ions. The thrombin time test showed that incubation of thrombin with iron sulfate in a final concentration of 200 microM for 25-35 min is followed by the loss of thrombin activity. Pretreatment of iron-containing incubation system with desferal was shown to decelerate the process of thrombin inactivation. The kinetic characteristics for recovery of thrombin activity by 2 mM desferal were estimated at various periods after addition of iron sulfate in the inhibitory dose. The effect of reversibility was shown to depend on the time of thrombin preincubation with iron. Incomplete recovery of thrombin activity after increasing the time of incubation with iron (more than 30 min) was probably related to oxidative modification of thrombin.

Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents

“…Figure 7E shows PRP and thrombin from an HH individual (SF = 1166 µg/L −1 ), where the typical fibrin fibers coagulate to form a tighter meshed network. It is known that iron ions may inhibit thrombin activity ([86]). Here this changed fibrin morphology may in part be the result of this inhibition.…”

Iron levels found in hemochromatosis patients inhibitγ-thrombin-induced platelet aggregation

“…Iron toxicity is poorly understood but appears to be due, in part, to free radical reactions and oxidative reactions that damage intracellular organelles [21,22]. Aside from one report about a direct effect of iron on thrombin [17], there have been no studies on the effects of iron on -thrombin vs. -thrombin and their ability to induce human platelet aggregation. Our studies indicate, like the original findings [17], that -thrombin-induced platelet aggregation may be partially inhibited by iron; however, the molar ratio of iron to enzyme is extremely high and may not have any physiological significance.…”

“…Aside from one report about a direct effect of iron on thrombin [17], there have been no studies on the effects of iron on -thrombin vs. -thrombin and their ability to induce human platelet aggregation. Our studies indicate, like the original findings [17], that -thrombin-induced platelet aggregation may be partially inhibited by iron; however, the molar ratio of iron to enzyme is extremely high and may not have any physiological significance. Unlike the observations with -thrombin, the inhibition of -thrombin-induced platelet aggregation by iron is very significant and may have an important physiological effect in the hemochromatotic patient.…”

“…Preincubation of -thrombin with iron (II), in the form of iron sulfate, has been shown to decrease the activity of thrombin and clot formation, in a manner that is dependent on time of incubation and iron concentration [17]. This effect is incompletely reversed in the presence of Desferal, an ironchelating agent that prevents/reverses the binding of iron to thrombin [17].…”

“…This effect is incompletely reversed in the presence of Desferal, an ironchelating agent that prevents/reverses the binding of iron to thrombin [17]. We serendipitously observed that platelet-rich plasma (PRP) derived from hemochromatosis patients showed virtually no response to the PAR-4 agonist, -thrombin.…”