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Thromb Haemost 1997; 77(04): 760-766
DOI: 10.1055/s-0038-1656047
von Willebrand Factor
Schattauer GmbH Stuttgart

Autoantibody Selectively Inhibits Binding of von Willebrand Factor to Glycoprotein Ib. Recognition Site Is Located in the A1 Loop of von Willebrand Factor

Hiroshi Mohri
1   The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama
,
Etsuko Yamazaki
1   The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama
,
Zekou Suzuki
3   The Department of Clinical Laboratory, Iwate Medical School, Morioka
,
Toshikuni Takano
4   The Department of Pediatrics, Iwate Medical School, Morioka, Japan
,
Shumpei Yokota
2   The Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Japan
,
Takao Okubo
1   The First Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama
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Publikationsverlauf

Received 25. Juli 1996

Accepted after resubmission 12. Dezember 1996

Publikationsdatum:
11. Juli 2018 (online)

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Summary

A 20-year-old man with severe von Willebrand disease recently presented a progressive bleeding tendency, characterized recurrent subcutaneous hemorrhages and cerebral hemorrhage. Mixing and infusion studies suggested the presence of an inhibitor directed against vWF:RCo activity of von Willebrand factor (vWF) without significant inhibition of the FVIII:C. The inhibitor was identified as an antibody of IgG class. The inhibitor inhibited the interaction of vWF in the presence of ristocetin and that of asialo-vWF with GPIb while it partially blocked botrocetin-mediated interaction of vWF to GPIb. The inhibitor reacted with native vWF, the 39/34kDa fragment (amino acids [aa] 480/ 481-718) and the recombinant vWF fragment (MalE-rvWF508-704), but not with Fragment III-T2 (heavy chains, aa 273-511; light chains, aa 674-728). A synthetic peptide (aa 514-542) did not inhibit vWF-inhibitor complex formation. We conclude that this is the first autoantibody of class IgG from human origin that recognizes the sequence in the A1 loop of vWF, resulting in a virtual absence of functional vWF and a concomitant severe bleeding tendency although recognition site is different from the residues 514-542 which is crucial for vWF-GPIb interaction.

 

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