Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients.
Polycythemia vera (PV) is associated with high morbidity and mortality for thrombosis. We hypothesized that in PV altered sensitivity to aspirin might be related to dysfunction of the endothelial repair and/or of the nitric oxide (NO) system. Urinary thromboxane (TX) A(2) metabolite (TXM), endothelial colony-forming cells (ECFCs), plasma asymmetric dimethylarginine (ADMA) and von Willebrand factor (VWF) were measured in 37 PV patients on low-dose aspirin and 12 healthy controls. Patients showed an approximately 2-fold increase in median TXM and plasma ADMA levels (P < .001), while ECFC numbers were reduced by approximately 7-fold (P < .001) as compared with non-aspirinated control. These differences were more pronounced in patients with previous thrombosis. An 8-week course of aspirin did not affect ECFCs in 6 controls. VWF and TXM correlated directly with ADMA, and inversely with ECFCs. By multiple regression analysis, lower ECFC quartiles (beta = -0.39; SE = 0.17; P = .028) and higher VWF levels (beta = 0.338, SE = 0.002, P = .034) were independent predictors of higher TXM quartiles (R(2) = 0.39). Serum TXB(2), measured in 22 patients, was approximately 10-fold higher than aspirin-treated controls. PV patients appear to have an unbalanced ECFC/NO axis, and an apparent altered sensitivity of platelet TXA(2) production, all potentially contributing to aspirin-insensitive TXM formation. Thus, additional antithrombotic strategies may be beneficial in PV.
Center of Excellence on Aging, G d'Annunzio University Foundation, Chieti, Italy.
Francesca
F
Santilli
Mario
M
Romano
Antonio
A
Recchiuti
Alfredo
A
Dragani
Angela
A
Falco
Gianfranco
G
Lessiani
Francesca
F
Fioritoni
Stefano
S
Lattanzio
Domenico
D
Mattoscio
Raimondo
R
De Cristofaro
Bianca
B
Rocca
Giovanni
G
Davì
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001769:Blood; D016022:Case-Control Studies; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000097:blood* / Q000188:drug therapy*; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; C487735:dimethylarginine; D013929:Thromboxane B2; D013928:Thromboxane A2; D001120:Arginine; D001241:Aspirin