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Thrombopoietin increases platelet adhesion under flow and decreases rolling
Author(s) -
Van Os Erim,
Wu YaPing,
Pouwels Jos G.,
Ijsseldijk Martin J. W.,
Sixma Jan J.,
Akkerman Jan Willem N.,
De Groot Philip G.,
Van Willigen Gijsbert
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04292.x
Subject(s) - platelet , chemistry , thrombopoietin , thromboxane a2 , von willebrand factor , endocrinology , medicine , thromboxane , adhesion , biology , microbiology and biotechnology , haematopoiesis , stem cell , organic chemistry
Summary. Thrombopoietin (TPO) is known to sensitize platelets to other agonists at 20 ng/ml, and above 100 ng/ml it is an independent activator of aggregation and secretion. In studies with a perfusion chamber, TPO, between 0·01 ng/ml and 1 ng/ml, increased platelet adhesion to surface‐coated fibrinogen, fibronectin and von Willebrand Factor (VWF) but not to a collagen‐coated surface. Increased adhesion was observed at shear rates of 300/s and 800/s in perfusions with whole blood as well as in suspensions of platelets and red blood cells reconstituted in plasma. The by the cyclooxygenase inhibitor, indomethacin, and the thromboxane A 2 ‐receptor blocker, SQ30741, abolished the stimulation by TPO. The effect of TPO was mimicked by a very low concentration (10 nmol/l) of the thromboxane TxA 2 analogue, U46619. Real‐time studies of platelet adhesion to a VWF‐coated surface at a shear of 1000/s showed that about 20% of the platelets were in a rolling phase before they became firmly attached. TPO (1 ng/ml) pretreatment reduced this number to < 5%, an effect again abolished by indomethacin. Thus, TPO potentiates the direct and firm attachment of platelets to surface‐coated ligands for α IIb β 3 , possibly by increasing the ligand affinity of the integrin.