Platelet function in myeloproliferative disorders: Characterization and sequential studies show multiple platelet abnormalities, and change with time

Abstract

Bleeding and thrombosis are well known major causes of morbidity and mortality in patients with myeloproliferative disorders (MPD) but the relationship between these clinical events and the commonly found platelet function abnormalities have not been established. In this study we performed simultaneous laboratory evaluations in 54 patients with MPD to investigate abnormalities in platelet aggregation and cyclooxygenase activity, the latter by using an in vitro aspirin inhibition test; the studies were repeated in 22 patients 1–27 months later. We have found platelet hyper‐ and hypofunction co‐existing in some patients (9/54), and change of platelet function during the course of the disease (7/22) with platelet hypofunction being the only constant abnormality over time. These results may explain the lack of correlation between the clinical events and the limited assessment of platelet function in the hitherto published studies, and also suggest the need for repeated evaluations to properly assess the relative risk for bleeding and thrombosis.

Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation

“…46,47 Most functional studies on MPN platelets have been performed by measuring in vitro platelet aggregation in response to various stimuli. 48 In spite of the intrinsic limitation of the technique, aggregation measurements have provided some interesting findings such as the phenomenon of spontaneous aggregation 49 and the reduced platelet response to some aggregating agents such as adenosine diphosphate collagen and epinephrine. 46 In PV and ET platelets, multiple abnormalities of membrane glycoproteins (Gps) and receptors have been reported.…”

Stimulus‐specific defect in platelet aggregation in polycythemia vera

“…With regard to ADP-induced aggregation, previous studies have shown conflicting results with either a minority (18,19) or a majority (16, 17) of PV patients showing an abnormal response. In this study, there was no significant difference between patients and controls in ADP-induced aggregation even though the results were seen to vary more than those with PMA as the stimulus.…”

The management of thrombocytosis

“…It has been claimed that the absence of aggregation response was related to past history of thrombotic or hemorrhagic complications (60), whereas others did not find such a relationship (61); following therapy, abnormalities in platelet aggregation response frequently improved (61,63). One study demonstrated that the two paradoxical abnormalities of platelet hyperfunction and hypofunction may co-exist in a significant proportion of patients, and that platelet function can and does change with time in some, with platelet hypofunction being the only constant abnormality (65). The pathophysiologic and molecular defects that account for acquired platelet function defects as seen in MPD are still poorly understood.…”