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Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
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Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease

Pier Mannuccio Mannucci1, Cristina Capoferri, Maria Teresa Canciani

  • 1Department of Internal Medicine, Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital, University of Milan, Milan, Italy. pmmannucci@libero.it

British Journal of Haematology
|July 9, 2004
PubMed

Insights

Plasma ADAMTS-13 levels inversely correlate with von Willebrand factor (VWF) levels. This relationship holds across various physiological and clinical conditions, indicating a dynamic balance between VWF and its cleaving protease, ADAMTS-13.

Area of Science:

  • Hematology
  • Biochemistry
  • Molecular Biology

Background:

  • ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, 13) is a protease responsible for cleaving von Willebrand factor (VWF).
  • VWF is crucial for hemostasis, but its large multimers can be highly thrombogenic.
  • A physiological inverse relationship between plasma VWF and ADAMTS-13 levels has been suggested.

Purpose of the Study:

  • To investigate the relationship between ADAMTS-13 activity and VWF levels.
  • To evaluate this relationship across a wide spectrum of VWF concentrations, including normal, low, and supranormal levels.
  • To assess the dynamic behavior of ADAMTS-13 in response to changes in VWF levels in various settings.

Main Methods:

  • Comparative analysis of ADAMTS-13 and VWF levels in healthy individuals based on blood groups.
  • Measurement of ADAMTS-13 and VWF in patients with type 3 von Willebrand disease (VWD).
  • Assessment of ADAMTS-13 and VWF changes following desmopressin (DDAVP) administration in healthy volunteers and VWD patients.
  • Monitoring of ADAMTS-13 and VWF levels after VWF-containing plasma concentrate infusions in VWD patients.

Main Results:

  • Healthy individuals with blood group O had higher ADAMTS-13 and lower VWF compared to other blood groups.
  • Patients with type 3 VWD (undetectable VWF) exhibited significantly higher ADAMTS-13 levels than healthy controls.
  • VWF elevation via DDAVP in healthy volunteers led to a decrease in ADAMTS-13, while protease levels remained unchanged in VWD patients lacking a VWF response.
  • Infusion of VWF concentrates in VWD patients resulted in a parallel decrease in ADAMTS-13 levels as VWF rose.

Conclusions:

  • A consistent inverse association exists between plasma VWF levels and ADAMTS-13 activity across a broad physiological range.
  • This inverse relationship is maintained in both physiological and pathological conditions affecting VWF levels.
  • The findings underscore a regulatory mechanism where ADAMTS-13 levels adjust in response to VWF concentration, potentially to prevent excessive VWF-mediated thrombosis.

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