Journal article
Iron levels found in hemochromatosis patients inhibit -thrombin-induced platelet aggregation
Platelets (Edinburgh), v 23(8), pp 611-616
Dec 2012
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hemochromatosis is a common genetic disorder of iron metabolism. The increase in systemic iron associated with hemochromatosis can negatively affect every system in the body, with potentially fatal implications. Little is known about the effects of iron overload on hemostasis and platelet activation.
While performing platelet aggregation studies on hemochromatotic blood samples, it was discovered that the increased serum iron levels associated with this disease almost completely inhibited -thrombin-induced platelet aggregation. Further studies were conducted with samples derived from control and hemochromatotic individuals to determine the effects of iron on both - and -thrombin-induced platelet aggregations.
It was found that -thrombin-induced platelet aggregations were strongly inhibited by the direct binding of iron to these enzymes. -Thrombin activates platelets at multiple receptor sites including the protease-activated receptor-1 (PAR-1), and at high concentrations, at protease-activated receptor-4 (PAR-4), while -thrombin selectively activates platelets at PAR-4. -Thrombin activity was significantly more sensitive to toxic levels of iron than -thrombin in the activation of the PAR receptors. Also, the hydrolysis of a synthetic peptide by -thrombin was unaffected by iron while -thrombin was strongly inhibited. These results indicate that the iron-thrombin complex strongly regulates the activity of -thrombin while has little or no effect on -thrombin-induced platelet aggregation or hydrolytic activity.
It is unknown, at this time, what specific clinical implications iron inhibition of -thrombin may have, but it is very possible that other conditions caused by hemochromatosis could be exacerbated by the inability of platelets to aggregate normally.
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Details
- Title
- Iron levels found in hemochromatosis patients inhibit -thrombin-induced platelet aggregation
- Creators
- Stephen Lynch - Drexel UniversityGerald Soslau - Drexel University
- Publication Details
- Platelets (Edinburgh), v 23(8), pp 611-616
- Publisher
- Informa UK, Ltd
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000310810300007
- Scopus ID
- 2-s2.0-84868613539
- Other Identifier
- 991019168890704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell Biology
- Hematology