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Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count
Author(s) -
Lancellotti S.,
Dragani A.,
Ranalli P.,
Petrucci G.,
Basso M.,
Tartaglione R.,
Rocca B.,
De Cristofaro R.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12967
Subject(s) - von willebrand factor , platelet , thrombocytosis , medicine , thrombospondin , platelet activation , essential thrombocythemia , elastase , endocrinology , immunology , chemistry , biochemistry , enzyme , metalloproteinase , matrix metalloproteinase
Summary Background Essential thrombocythemia ( ET ) is characterized by increased platelets and prevalent thrombosis. An acquired von Willebrand factor ( VWF ) disease has been hypothesized and inconsistently associated with extreme thrombocytosis or rare bleeding in ET . Whether VWF is modified in ET patients with controlled platelet count remains unclear. Objectives We studied different VWF ‐ and platelet‐associated parameters in ET patients treated according to current recommendations. Patients/Methods Sixty‐nine ET patients ( M = 29; median age, 62 [48–70] years; platelets, 432 [337–620] × 10 3 μL −1 ), 69 matched controls and 10 subjects with reactive thrombocytosis ( RT ) were studied. VWF :antigen (Ag), activity (act), electrophoretic patterns, VWF :propeptide, plasma glycocalycin ( GC ), glycoproteinV (GpV), ADAMTS ‐13, elastase, C‐reactive protein and serum thromboxane ( TX )B 2 were measured. Results In ET patients, VWF :Ag was increased by 31 ± 13% vs. controls ( P < 0.01), without dependence of blood groups, while VWF :act was reduced by 21 ± 12% vs. controls and by 50 ± 24% vs. RT ( P < 0.01). The VWF :act/ VWF :Ag ratios in ET were reduced by 35 ± 17% vs. controls and RT patients ( P < 0.001) and significantly associated with: immature or total platelet counts, GC , GpV and TXB 2 . In multivariable analysis, only GC inversely predicted ET patients’ VWF :act/ VWF :Ag ratios (β = −0.42, P = 0.01). By electrophoresis analyses, high‐molecular‐weight VWF multimers were variably reduced with atypical cleavage bands in ET only. VWF :propeptide, ADAMTS ‐13 and elastase levels were normal in ET patients. Platelet‐associated ADAM ‐10 and ADAM ‐17 hydrolyzed VWF m in vitro , showing patterns similar to those in ET samples. Conclusions In ET patients with controlled platelet counts, the VWF :act/ VWF :Ag ratio is decreased and predicted by GC , a product of platelet activation. ADAM ‐10 and/or ADAM ‐17 might be involved. In vivo platelet activation, which characterizes ET , might contribute to disease‐specific VWF alterations.