Elevated Cell-Derived Microparticles (C-MP) in Myeloproliferative Disorders (MPD): High Red Cell Microparticles (RMP) as Risk Factor for Thrombosis.

BACKGROUND: In myeloproliferative diseases (MPD), including essential thrombocythemia (ET), myelofibrosis (MF), chronic myeloid leukemia (CML), polycythemia vera (PV), mutations of stem cells result in shape changes as well as functional aberration of each blood cell line. Both thrombosis and bleeding are major causes of morbidity and mortality. Cell-derived microparticles (C-MP), released during activation or apoptosis, are believed to play important roles in thrombotic and inflammatory disorders, and are emerging as promising biomarkers in these conditions. However little is known about C-MP in MPD. We investigated C-MP derived from platelets (PMP), leukocytes (LMP), endothelial cells (EMP) and red cells (RMP) in patients with MPD.

MATERIAL AND METHODS: We studied 49 pts with MPD including 30 with ET, 13 with MF, 2 with PV, and 4 with atypical MPD. There were 21M and 28F, mean age 59.7 yr. All pts were followed at clinics and history and natural courses of diseases were assessed along with incidences of thrombosis. Thrombosis was documented with ultrasound and radiologic imaging. They were divided into two groups: 16 pts with thrombosis (TB) (7M/9F; mean age 61.6 yr) and 33 with non-thrombosis (NTB) (14M/19F; mean age 59.8 yr). Laboratory studies included CBC, platelets count and RDW. For C-MP assay by flow cytometry, PMP were defined by CD41+; LMP by CD45+, EMP by CD31+/CD41− and RMP by glycophorin+.

RESULTS: Table 1 summarizes clinical data and C-MP profiles in TB and NTB groups and controls. The mean values of C-MP were higher in both TB and NTB than controls. The TB and NTB were comparable in sex, age and Hgb but TB had longer duration of MPD (p=0.007), higher RDW (p=0.001) and lower platelet counts (p=0.007), since they were treated more aggressively.

No significant difference was found between TB and NTB for LMP and EMP. However, RMP were significantly higher in TB (p<0.0001), whereas PMP were lower (p=0.003). The high PMP in NTB was likely due to the higher platelet counts in that gorup since PMP levels correlated closely with platelet counts.

RMP correlated with RDW (p=0.009) and RDW correlated with the duration of MPD (p= 0.004).

DISCUSSION/CONCLUSIONS:

• All species of C-MP were more elevated in pts with MPD, compared to controls, suggesting that aberrant blood cells in MPD generate more C-MP.

• Of all C-MP, only RMP were significantly elevated in TB vs NTB, indicating that high RMP is a risk factor for thrombosis in MPD.

• RMP correlated with RDW as reflected by anisocytosis and poichilocytosis.

The mechanism underlying RMP generation in MPD is largely unknown but we have shown that RBC and RMP provide anionic phospholipids in coagulation and generate thrombin (data not shown). Since the duration of MPD was longer in TB and correlated with RDW, we suggest that RBC in late stages of MPD may generate more RMP.