Studies of multimerin in patients with von Willebrand disease and platelet von Willebrand factor deficiency.
In normal platelet alpha-granules von Willebrand factor (VWF) is stored with multimerin and factor V in an eccentric electron-lucent zone. Because the platelet stores of VWF are deficient in 'platelet low' type 1 and type 3 von Willebrand disease (VWD), we investigated their electron-lucent zone proteins. The patients with VWD had partial to complete deficiencies of plasma and platelet VWF but normal alpha-granular multimerin and factor V, and normal alpha-granular fibrinogen, thrombospondin-1, fibronectin, osteonectin and P-selectin. In type 3 VWD platelets, alpha-granular electron-lucent zones lacking VWF-associated tubules were identified and multimerin was found in its normal alpha-granular location. These findings indicate that the formation of the electron-lucent zone and the sorting of multimerin to this region occur independent of VWE The isolated abnormalities in VWF suggests a VWF gene mutation is the cause of 'platelet low' type 1 VWD.
Chen
C I
CI
Department of Pathology, McMaster University and the Hamilton Health Sciences Corporation, Ontario, Canada.
Federici
A B
AB
Cramer
E M
EM
Canciani
M T
MT
Harrison
P
P
Zheng
S
S
Massé
J M
JM
Mannucci
P M
PM
Hayward
C P
CP
D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D005165:Factor V / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008854:Microscopy, Electron; D015676:Osteonectin / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D014842:von Willebrand Diseases / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D001798:Blood Proteins; D015676:Osteonectin; D019007:P-Selectin; D019700:Thrombospondin 1; C069282:multimerin; D014841:von Willebrand Factor; D005165:Factor V; D005340:Fibrinogen