Heghine Khachatryan: An Elegant Example of Precision Thrombolysis – Targeting the Scaffold of Microvascular Thrombosis
Heghine Khachatryan, Editor-in-Chief of Hemostasis Today, Head of Hemophilia and Thrombosis Center at Yeolyan Hematology and Oncology Center, shared a post on LinkedIn about a recent article by Steven de Maat et al, published in Blood, adding:
“An elegant example of precision thrombolysis: targeting the scaffold of microvascular thrombosis.
In thrombotic thrombocytopenic purpura (TTP), severe ADAMTS13 deficiency permits the accumulation of ultra-large von Willebrand factor (VWF) multimers, promoting platelet-rich microthrombi and ischemic organ injury.
The study by de Maat and colleagues describes Microlyse – a fusion protein that combines a high-affinity VWF-targeting antibody fragment with the protease domain of urokinase-type plasminogen activator.
By directing plasminogen activation specifically toward platelet–VWF complexes, Microlyse is designed not merely to prevent further thrombus formation, but to actively dismantle established microvascular thrombi.
In experimental models, Microlyse degraded microthrombi seven times faster than caplacizumab at equimolar concentrations.
In an ADAMTS13-deficient mouse model of TTP, it also improved thrombocytopenia and markers of tissue injury without impairing hemostasis in a tail-bleeding model.
This work represents an important conceptual shift – from systemic fibrinolysis toward targeted, lesion-directed thrombolysis.
Although these remain preclinical findings and require validation in human studies, the approach may have broader relevance to VWF-driven thrombotic microangiopathies.
My sincere thanks to Coen Maas, one of the authors, for bringing this fascinating article to my attention.”
Title: Microlyse: a thrombolytic agent that targets VWF for clearance of microvascular thrombosis
Authors: Steven de Maat, Chantal C. Clark, Arjan D. Barendrecht, Simone Smits, Nadine D. van Kleef, Hinde El Otmani, Manon Waning, Marc van Moorsel, Michael Szardenings, Nicolas Delaroque, Kristof Vercruysse, Rolf T. Urbanus, Silvie Sebastian, Peter J. Lenting, Christoph Hagemeyer, Thomas Renné, Karen Vanhoorelbeke, Claudia Tersteeg, Coen Maas
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