Thrombotic Microangiopathies and the Linkage between von Willebrand Factor and the Alternative Complement Pathway

Nancy Turner; Leticia Nolasco; Jennifer Nolasco; Sarah Sartain; Joel Moake

doi:10.1055/s-0034-1383547

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2014; 40(05): 544-550
DOI: 10.1055/s-0034-1383547

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thrombotic Microangiopathies and the Linkage between von Willebrand Factor and the Alternative Complement Pathway^[*]

Nancy Turner

¹Department of Bioengineering, Rice University, Houston, Texas

,

Leticia Nolasco

¹Department of Bioengineering, Rice University, Houston, Texas

,

Jennifer Nolasco

¹Department of Bioengineering, Rice University, Houston, Texas

,

Sarah Sartain

¹Department of Bioengineering, Rice University, Houston, Texas

²Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas

,

Joel Moake

¹Department of Bioengineering, Rice University, Houston, Texas

› Author Affiliations

Abstract

Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and promotes the assembly of C3bBb (C3 convertase) and C3bBbC3b (C5 convertase). These linkages may help to explain enigmatic clinical problems related to thrombotic microangiopathies, including some cases of refractory thrombotic thrombocytopenic purpura (TTP), TTP associated with only mild–modest deficiencies of ADAMTS-13, the provocation (or exacerbation) of acute episodes in patients with the atypical hemolytic uremic syndrome, and thrombosis in paroxysmal nocturnal hemoglobinuria. Recent experiments have also demonstrated that complement factor H performs a dual role: participating in regulation of the AP by binding to EC-anchored ULVWF strings; and functioning as a reductase to decrease the size of soluble VWF multimers.

Keywords

VWF - alternative complement pathway - factor H - thrombotic microangiopathies

Full Text

References

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Thrombotic Microangiopathies and the Linkage between von Willebrand Factor and the Alternative Complement Pathway[*]

Thrombotic Microangiopathies and the Linkage between von Willebrand Factor and the Alternative Complement Pathway^[*]