title: Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count.
abstract: 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.
  
  
  OBJECTIVE
  We studied different VWF- and platelet-associated parameters in ET patients treated according to current recommendations.
  
  
  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)B2 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 TXB2 . 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 VWFm 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.
authors: Center for Haemorrhagic and Thrombotic Diseases, Department of Medical Sciences, Catholic University School of Medicine, 'A. Gemelli' Hospital, Rome, Italy.
authors: S
authors: S
authors: Lancellotti
authors: Center for Haemorrhagic, Thrombotic and Rare Hematologic Diseases, Spirito Santo Hospital, Pescara, Italy.
authors: A
authors: A
authors: Dragani
authors: Center for Haemorrhagic, Thrombotic and Rare Hematologic Diseases, Spirito Santo Hospital, Pescara, Italy.
authors: P
authors: P
authors: Ranalli
authors: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors: G
authors: G
authors: Petrucci
authors: Center for Haemorrhagic and Thrombotic Diseases, Department of Medical Sciences, Catholic University School of Medicine, 'A. Gemelli' Hospital, Rome, Italy.
authors: M
authors: M
authors: Basso
authors: Institute of Haematology, Complesso Integrato Columbus, Catholic University School of Medicine, Rome, Italy.
authors: R
authors: R
authors: Tartaglione
authors: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.
authors: B
authors: B
authors: Rocca
authors: Center for Haemorrhagic and Thrombotic Diseases, Department of Medical Sciences, Catholic University School of Medicine, 'A. Gemelli' Hospital, Rome, Italy.
authors: R
authors: R
authors: De Cristofaro
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006868:Hydrolysis; D006918:Hydroxyurea / Q000627:therapeutic use; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010976:Platelet Count; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; D001241:Aspirin; D006918:Hydroxyurea
keywords: ADAMTS13 protein, human; essential thrombocythemia; glycocalicin; platelet membrane glycoprotein V; von Willebrand factor