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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
1   Department of Bioengineering, Rice University, Houston, Texas
,
Leticia Nolasco
1   Department of Bioengineering, Rice University, Houston, Texas
,
Jennifer Nolasco
1   Department of Bioengineering, Rice University, Houston, Texas
,
Sarah Sartain
1   Department of Bioengineering, Rice University, Houston, Texas
2   Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas
,
Joel Moake
1   Department of Bioengineering, Rice University, Houston, Texas
› Author Affiliations
Further Information

Publication History

Publication Date:
26 June 2014 (online)

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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

* This article is dedicated to Prof. Duane Schultz of the University of Miami School of Medicine with gratitude for his continuing friendship and for his kind and careful instruction in complement biochemistry.


 

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