Cell-Derived Microparticle (C-MP) Profiles in Lymphoproliferative Disorders: Association of Elevated Red Cell Microparticles (RMP) with Thrombosis.

Abstract INTRODUCTION: Lymphoproliferative diseases embrace a variety of disorders including chronic lymphocytic leukemia (CLL), lymphomas and multiple myeloma (MM). The incidence of thrombosis varies in these disorders. C-MP are microvesicles released upon activation or apoptosis from endothelial cells (EMP), platelets (PMP), leukocytes (LMP) and red cells (RMP), and are believed to play a role as mediators of inflammation, hemostasis and thrombosis. METHODS: Forty-two patients with lymphoproliferative diseases were enrolled (24M/ 18F; mean age 67.5yr). These included 18 CLL (11M/7F; mean 69.2yr), 11 lymphomas (7M/4F; mean 65.3yr) and 13 MM (6M/7F; mean 67.1yr). History of thrombosis during the course of the lymphoproliferative disease was obtained. C-MP were measured by flow cytometry. LMP were identified by anti-CD45, PMP by anti-CD41, RMP by anti-glycophorin and EMP by CD31+ / CD41−. C-MP were compared between the three groups, and between patients with thrombosis (TB) and without (NTB). RESULTS: (1) History of thrombosis was most prevalent in MM (29%), followed by lymphomas (18%) and none of the CLL. (2) When C-MP were compared among CLL vs. lymphomas, and CLL vs. MM groups, mean levels of EMP, PMP showed no significant differences. However, RMP were higher in lymphomas than CLL (1193 vs. 746, p=0.03), and were markedly higher in MM than CLL (1623 vs. 746, p=0.009). LMP were also higher in CLL vs. MM (1,495 vs. 1,086, p = 0.02). No significant difference was seen in MP when comparing CLL vs. MM. Table 1. Data on patients and C-MP CLL Lymphoma MM p value p value CLL vs. Lymph CLL vs. MM No pts 18 11 13 Age 69.2 65.3 67.1 Sex (M/F) 11/7 7/4 6/7 Thrombosis 0/0 0/2 (18%) 0/4 (29%) n. s. 0.04 C-MP:     EMP 349 340 442 n. s. n. s.     PMP 8,688 8,691 8,079 n. s. n. s.     LMP 1,495 1,270 1,086 n. s. 0.02     RMP 746 1,193 1,623 0.03 0.009 (3) When c omparing C-MP between TB vs. NTB groups, RMP were nearly 3-fold higher in TB (mean values 2423 vs. 900; p<0.0001). EMP were also significantly higher in TB but less markedly (568 vs. 344; p= 0.008). There was no significant difference of PMP or LMP, between these 2 groups (p>0.05). Table 2. Comparison of C-MP in TB vs. NTB TB NTB p value No pts 6 36 C-MP: EMP 568 344 0.008 PMP 11,253 8,042 n. s. LMP 1,151 1,315 n. s. RMP 2,423 900 <0.0001 CONCLUSIONS: History of thrombosis was most prevalent in MM, followed by lymphomas, least in CLL. Our data from this limited patient population is consistent with the literature. PMP and EMP were similar in CLL, lymphomas and MM. However, RMP were higher in lymphomas and MM. Conversely, LMP were higher in CLL than in MM probably due to higher white count. Levels of RMP and EMP were associated strongly with thrombosis, being higher in TB. RMP are enriched in procoagulant phospholipids. We reported elevated RMP as a risk factor for thrombosis in myeloproliferative disorders [Fontana et al, ASH Abst #1483, 2006] and prevent bleeding in thrombocytopenia [Fontana et al, ASH Abst #1087, 2006]. These findings suggest that RMP play a role in the pathogenesis of thrombosis in lympho- and myelo-prolifertive disorders. However, the mechanism of their generation and the exact nature of their likely role remains to be elucidated.