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Review
. 2012 Mar;32(2):208-14.
doi: 10.1016/j.semnephrol.2012.02.007.

Endothelial cells and thrombotic microangiopathy

David Motto  1
Affiliations
Review

Endothelial cells and thrombotic microangiopathy

David Motto. Semin Nephrol. 2012 Mar.

Abstract

Thrombotic microangiopathy represents the clinical picture of thrombocytopenia and hemolytic anemia in the setting of small blood vessel thrombosis, accompanied by varying degrees of organ dysfunction. Well known to both nephrologists and hematologists alike, among the most common and best-studied thrombotic microangiopathy are hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura. Despite sharing a strong clinical and historical relationship, these disorders represent distinct clinical and pathophysiological entities. This article reviews recent progress into the pathogenesis of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, focusing on events taking place at the endothelial surface.

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Figures

Figure 1
Figure 1
Schematic representation of VWF. Domains of VWF are indicated by lettering. Known functional elements are as labeled.
Figure 2
Figure 2
Multimerization of VWF. Individual VWF monomers form dimers via disulfide bonds near the C-termini of each molecule. Much larger multimers form via N-terminal disulfide bonds between dimers. Multimers of VWF can comprise greater than 100 individual monomers, and exceed 20,000 kDa in molecular weight.
Figure 3
Figure 3
The roles of ADAMTS13 and VWF in TTP pathogenesis. Panels A–C represent the normal state of ADAMTS13 sufficiency, while panels D–F represent the pathological state of ADAMTS13 deficiency. Black triangles represent ADAMTS13 in the circulation. VWF is stored in the Weibel-Palade bodies of resting/unactivated endothelial cells (A and D). Endothelial stimulation results in the rapid release of VWF, which remains adherent to the endothelial surface (B and E). When present, ADAMTS13 rapidly binds to and cleaves VWF (B), releasing it into the circulation (C). If ADAMTS13 is absent or non-functional, platelets bind to endothelial-associated VWF (E), leading to the formation of platelet/VWF thrombi throughout the circulation (F).
Figure 4
Figure 4
Mechanisms of pathogenesis in TTP and HUS. Question marks indicate either hypothetical links between events, or poorly-understood mechanisms of action. Please see text for detailed explanation.
See this image and copyright information in PMC

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