PB1318 - Platelet functional activity in untreated patients with Ph-negative myeloproliferative neoplasms

Background: Thrombotic complications represent one of the main causes of morbidity and mortality in Ph-negative myeloproliferative neoplasms (MPN) including essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Thrombosis pathogenesis in MPN is multifaceted anyway resulting in coagulation activation, platelets playing a great role in it.

Aims: To characterize platelet functional activity in MPN patients without treatment.

Methods: Study included 22 MPN patients (5 ET, 6 PV and 11 PMF) without treatment with any medications at least 10 days before enrollment. Control group included 30 practically healthy volunteers. Platelet functional activity was evaluated in platelet-rich plasma using light-transmission aggregometry induced by ADP (end concentrations 1 or 5 µM), collagen (2 µg/mL) or ristocetin (1.2 mg/mL). Aggregation initial velocity and maximal amplitude (MA) were assessed. Mann-Whitney U-test and Kruskal-Wallis H-test (STATISTICA 6.0) were applied, differences considered statistically significant at p< 0.05.

Results: Compared with controls all patient groups had significant decrease in platelet aggregation induced by low-dose АDP (1 µМ) (Image 1). Effects of other inducers including high ADP differed. Parameters of ADP(5µМ)-, collagen- and ristocetin-induced aggregation in ET significantly exceeded controls. PV patients parameters tended to increase compared with healthy persons. In contrast to ET and PV, group of PMF was characterized by significant deceleration or a tendency to decrease of collagen- and ADP(5µМ)-induced aggregation compared with controls. Along with indicated changes, suggesting platelet functional activity decrease in PMF patients, they had higher ristocetin-induced aggregation MA than healthy persons (p=0,055).

Conclusion(s): Significantly decreased parameters of aggregation induced by low-concentration ADP in all MPN groups without treatment can indicate platelet receptor apparatus deficiency. Pronounced increase of platelet aggregation activity induced by high-concentration ADP and other applied agonists in ET and a tendency to likely changes in PV as well as enhanced ristocetin-induced aggregation in PMF can play role in high thrombotic risk in MPN.