title: Keeping von Willebrand Factor under Control: Alternatives for ADAMTS13.
abstract: Von Willebrand factor (VWF) is one of the most important proteins of the hemostatic system. Its multimeric state is essential for its natural function to guide platelets to sites of injury. ADAMTS13 is the key protease that regulates the multimeric state of VWF. Without ADAMTS13, VWF multimers can grow to pathologically large sizes. This is a risk factor for the life-threatening condition thrombotic thrombocytopenic purpura (TTP). In this condition, VWF-rich thrombi occlude the microvasculature of various tissues. Intriguingly, a complete ADAMTS13 deficiency does not cause continuous TTP, either in patients or genetically targeted mice. Instead, TTP occurs in episodes of disease, separated by extended periods of remission. This indicates that regulating factors beyond ADAMTS13 are likely involved in this pathologic cascade of events. This raises the question of what really happens when ADAMTS13 is (temporarily) unavailable. In this review, we explore the possible role of complementary mechanisms that are capable of modifying the thrombogenic potential of VWF.
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tersteeg
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: de Maat
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: Coen
authors.initials: C
authors.lastname: Maas
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000818:Animals; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011697:Purpura, Thrombotic Thrombocytopenic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human