Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia
Sickle cell anemia (SCA) is a common hemolytic disorder caused by a gene mutation in the β-globin subunit of hemoglobin (Hb) and affects millions of people. The intravascular hemolysis releases excessive amount of extracellular hemoglobin (ECHb) into plasma that causes many cellular dysfunctions in...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Anemia |
| Online Access: | http://dx.doi.org/10.1155/2011/918916 |
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| author | Zhou Zhou Molly Behymer Prasenjit Guchhait |
| author_facet | Zhou Zhou Molly Behymer Prasenjit Guchhait |
| author_sort | Zhou Zhou |
| collection | DOAJ |
| description | Sickle cell anemia (SCA) is a common hemolytic disorder caused by a gene mutation in the β-globin subunit of hemoglobin (Hb) and affects millions of people. The intravascular hemolysis releases excessive amount of extracellular hemoglobin (ECHb) into plasma that causes many cellular dysfunctions in patients with SCA. ECHb scavenges NO which promotes crisis events such as vasoconstriction, thrombosis and hypercoagulation. ECHb and its degradation product, heme, are known to cause oxidative damage to the vessel wall and stimulate the expression of adhesive protein ligands on vascular endothelium. Our study shows that ECHb binds potently to VWF—largest multimeric glycoprotein in circulation—through the A2-domain, and significantly inhibits its cleavage by the metalloprotease ADAMTS13. Furthermore, a subpopulation of VWF multimers bound to ECHb exists in significant amount, accounting for about 14% of total plasma VWF, in SCD patients. The Hb-bound VWF multimers are resistant to ADAMTS13, and are hyperactive in aggregating platelets. Thus, the data suggest that Hb-bound VWF multimers are ultralarge and hyperactive because they are resistant to the protease. The Hb-bound VWF multimers are elevated parallely with the level of ECHb in patients' plasma, and is associated with the pathogenesis of thrombosis and vascular occlusion in SCA. |
| format | Article |
| id | doaj-art-55e2e2444e204446a1020fed9f1ab9d4 |
| institution | Kabale University |
| issn | 2090-1267 2090-1275 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Anemia |
| spelling | doaj-art-55e2e2444e204446a1020fed9f1ab9d42025-02-03T06:08:31ZengWileyAnemia2090-12672090-12752011-01-01201110.1155/2011/918916918916Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell AnemiaZhou Zhou0Molly Behymer1Prasenjit Guchhait2Thrombosis Research Division, Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, N1319, Houston, TX 77030, USAThrombosis Research Division, Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, N1319, Houston, TX 77030, USAThrombosis Research Division, Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, N1319, Houston, TX 77030, USASickle cell anemia (SCA) is a common hemolytic disorder caused by a gene mutation in the β-globin subunit of hemoglobin (Hb) and affects millions of people. The intravascular hemolysis releases excessive amount of extracellular hemoglobin (ECHb) into plasma that causes many cellular dysfunctions in patients with SCA. ECHb scavenges NO which promotes crisis events such as vasoconstriction, thrombosis and hypercoagulation. ECHb and its degradation product, heme, are known to cause oxidative damage to the vessel wall and stimulate the expression of adhesive protein ligands on vascular endothelium. Our study shows that ECHb binds potently to VWF—largest multimeric glycoprotein in circulation—through the A2-domain, and significantly inhibits its cleavage by the metalloprotease ADAMTS13. Furthermore, a subpopulation of VWF multimers bound to ECHb exists in significant amount, accounting for about 14% of total plasma VWF, in SCD patients. The Hb-bound VWF multimers are resistant to ADAMTS13, and are hyperactive in aggregating platelets. Thus, the data suggest that Hb-bound VWF multimers are ultralarge and hyperactive because they are resistant to the protease. The Hb-bound VWF multimers are elevated parallely with the level of ECHb in patients' plasma, and is associated with the pathogenesis of thrombosis and vascular occlusion in SCA.http://dx.doi.org/10.1155/2011/918916 |
| spellingShingle | Zhou Zhou Molly Behymer Prasenjit Guchhait Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia Anemia |
| title | Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia |
| title_full | Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia |
| title_fullStr | Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia |
| title_full_unstemmed | Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia |
| title_short | Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia |
| title_sort | role of extracellular hemoglobin in thrombosis and vascular occlusion in patients with sickle cell anemia |
| url | http://dx.doi.org/10.1155/2011/918916 |
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