Platelet Function in Essential Thrombocythemia

Abstract

Platelets from two patients with essential thrombocythemia failed to aggregate or release serotonin in response to concentrations of epinephrine that aggregated platelets from normal controls. Therefore, we studied their alpha-adrenergic receptors, using 3H-dihydroergocryptine (3H-DHE), an alpha-adrenergic antagonist. These platelets contained an average (mean +/- S.E.) of 210 +/- 18 and 227 +/- 27 3H-DHE binding sites per platelet--less than half that found on control platelets, 464 +/- 37 (P less than 0.01). In contrast, platelets from two other patients with essential thrombocythemia responded to epinephrine and contained a normal number of 3H-DHE sites. Platelets in essential thrombocythemia demonstrated normal kinetics of 3H-DHE binding and normal affinities for 3H-DHE and for epinephrine. When control platelets were preincubated with a half-saturating concentration of 3H-DHE, there was a diminution of epinephrine-induced platelet function comparable to that seen in essential thrombocythemia. Thus, a deficiency of alpha-adrenergic receptors may account for diminished functional responsiveness of platelets to epinephrine in some patients with essential thrombocythemia.

Incidence of Nonresponsiveness to Epinephrine in Platelets from Healthy Humans

“…Absent or decreased platelet aggregability to epinephrine has been known to be a feature of myeloproliferative disorders, and this abnormality provides information that helps to differentiate platelet neoplastic proliferation from reactive production [1, 2]. A depressed responsiveness to epinephrine in platelets from healthy subjects has been sporadically reported [3, 4]; however, epidemiological studies on this abnormality in the broader population are limited.…”

Clinical and Laboratory Significance of Defective P2Y₁₂ Pathway Function in Patients with Myeloproliferative Neoplasms: A Pilot Study

“…For example, the copy number of platelet surface P2Y 12 receptors may be decreased in MPN patient platelets just like the α-2b adrenergic receptors [6]. Alternatively, storage pool deficiency, which is well characterized in some MPN patients [9,23] and which is associated with reduced or absent ADP-induced second wave aggregation in platelet aggregation tests with the light transmission method, may affect ADP-induced VASP phosphorylation.…”

“…The risk of thrombosis is further increased in MPN patients bearing the JAK2 V617F mutation [1]. Abnormal platelet function is found in a significant proportion of MPN patients [3,4,5,6,7]. Studies done with platelet aggregation tests revealed that MPN platelets have an impaired response to various stimulants, mainly epinephrine and adenosine diphosphate (ADP).…”

Acquired von Willebrand syndrome: An update

“…aVWS is also associated with multiple myeloma [24][25][26][27][28][29], Waldenstrom macroglobulinaemia [30,31], chronic lymphocytic leukemia [32], hairy cell leukemia [33], and non-Hodgkin lymphoma [34][35][36]. Most cases of myeloproliferative disorders associated with aVWS are essential thrombocythemia [37][38][39][40][41][42][43][44][45][46][47], while polycythemia vera [48] and chronic myeloid leukemia [49][50][51] are less frequent. The second most common groups of disorders associated with aVWS is neoplasia, including Wilms tumors [52][53][54][55][56][57] and carcinomas [58,59], followed by immunological diseases, most notably SLE [14,60,61] and hypothyroidism [62][63][64][65][66][67][68]…”