Thrombotic Microangiopathies and Plasma Exchange Therapies

Thrombotic microangiopathies constitute a group of disorders characterised by small-vessel platelet-rich thrombi, microangiopathic haemolysis and ensuing organ dysfunction. They encompass immune-mediated thrombotic thrombocytopenic purpura and complement-mediated haemolytic uraemic syndrome, both of which carry significant morbidity and mortality if not rapidly treated. Central to many of these conditions is a severe deficiency of ADAMTS13, the metalloprotease responsible for cleaving ultra-large von Willebrand factor multimers; its absence permits accumulation of adhesive multimers that precipitate intravascular platelet aggregation under high shear stress. Plasma exchange remains the cornerstone of therapy, removing pathogenic autoantibodies and replenishing ADAMTS13 to restore microvascular patency. Adjunctive immunosuppression targets autoantibody production, while emerging agents aim to modulate von Willebrand factor activity or deliver recombinant ADAMTS13, promising further improvements in patient outcomes.

Research from Nature Portfolio

Recent work has used microengineered vessels to elucidate the biophysical requirements for microvascular thrombosis. Under conditions of high shear stress and complex vessel geometries, endothelial-secreted von Willebrand factor assembles into thick bundles and intricate meshes that bind platelets, leukocytes and erythrocytes, ultimately obstructing flow in microvessels. These findings define how vessel diameter, flow acceleration and turns influence thrombus initiation in thrombotic microangiopathies. In parallel, structural studies of ADAMTS13 have revealed a latent metalloprotease domain with an occluded active-site cleft. Binding of von Willebrand factor A2 domain exosites induces an allosteric transition, exposing the catalytic site and enabling precise proteolysis of unfolded substrate. This mechanistic insight underpins the rational design of next-generation recombinant enzymes and exosite-targeting therapeutics.

Thrombotic Microangiopathies and Plasma Exchange Therapies publication trend

The graph below shows the total number of articles in thrombotic microangiopathies and plasma exchange therapies across all publications each year (not limited to Nature Index journals).

Technical terms

Thrombotic microangiopathy (TMA): A clinical syndrome characterised by platelet-rich thrombi in small vessels, microangiopathic haemolytic anaemia and thrombocytopenia.

Plasma exchange: A blood purification procedure that removes and replaces a patient’s plasma to eliminate pathogenic factors and restore deficient proteins.

ADAMTS13: A zinc-dependent metalloprotease that cleaves ultra-large von Willebrand factor multimers to regulate platelet adhesion under shear stress.

von Willebrand factor (VWF): A multimeric glycoprotein central to platelet tethering and aggregation in high-shear microcirculation, regulated by ADAMTS13.

References

1. Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura. Critical Care (2023).
2. The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi‐center analysis of 719 disease episodes. American Journal of Hematology (2024).
3. Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. Journal of Clinical Medicine (2021).
4. Flow-driven assembly of VWF fibres and webs in in vitro microvessels. Nature Communications (2015).
5. Crystal structure and substrate-induced activation of ADAMTS13. Nature Communications (2019).