The Phenotypic Profile of Circulating Microparticles Is Different in Polycythemia Vera and Secondary Erythrocytosis

In Ph1 myeloproliferative neoplasms (MPN), the blood stream carries a variety of microparticles and exosomes released by cells from myeloid lineages and endothelium; we had already demonstrated an excess of platelet microparticles (PMP) in ET and PV patients (ASH Annual Meeting 2009, Abstr. 1906). A further step has been to characterize five categories of MP depending on their origin. Then we used this method to compare the sub-populations found in Polycythemia vera (PV) and secondary erythrocytosis (SE).

We analyzed plasma samples from 20 PV diagnosed in accordance to WHO classification and 20 SE patients. SE was defined by elevated hematocrit, normal or increased serum EPO, Jak2^V617F negative and a presumable cause, mainly respiratory. The 2 groups were comparable for age and sex-ratio. Mean Hb level was 18.0g/dl in the PV group and 18.1g/dl in the SE group. The concentration of MP was measured by flow cytometry using a FC500 cytometer (BeckmanCoulter™). All the MP subtypes express Annexin V thus defining the total MP. Additional co-expression of either CD41, CD144, CD14, CD11b or GPA identify MP populations originating respectively from platelets (PMP), endothelial cells (EMP), monocytes (MoMP), granulocytes (GrMP) and red cells (EryMP). Pre-analytical and testing procedures complied with the recommendations of the ISTH Standardization Sub-committee.

MP from endothelial cells (EMP) and leukocytes (GrMP and MoMP) are minor populations whose proportions are similar in both groups of patients (7%, 4% and 2% respectively). Conversely, EryMP and PMP are significantly different (p<0.001 Kursall-Wallis test) in PV and SE as shown in the following table.

So, in PV most of the MP are PMP while EryMP widely predominate in SE; in an attempt to explain such unexpected results we postulate that the cells generating MP are more or less mature depending on the physiopathology: clonal hematopoietic progenitors in MPN and well-differentiated cells in reactive conditions. However, even in SE, the EryMP concentration does not correlate with RBC count, haemoglobin or hematocrit.

This study demonstrates a different phenotypic profile of circulating MP in PV and SE, possibly helpful to precise the origin of an elevated hematocrit, especially when molecular markers are negative. The significance of the MP subtype pattern observed in PV and SE remains unclear, calling for further studies.

No relevant conflicts of interest to declare.