Abstract
Abstract
BACKGROUND: Cell-derived microparticles (C-MP) are microvesicles released during activation and apoptosis from platelets (PMP), leukocytes (LMP), endothelial cells (EMP) and red cells (RMP). They commonly express phosphatidylserine (PS) judged by binding annexin V (AnV) and carry markers of parent cells. C-MP are involved in thrombosis, inflammation and angiogenesis. Little is known how C-MP are cleared from circulation. To test that the spleen might be involved, we investigated C-MP profiles in patients who underwent splenectomy for various causes (group A), those with hypersplenism (group B), and healthy controls with spleen (group C).
MATERIAL AND METHODS: Group A (Gr A) consisted of 44 patients (18 M and 26 F, mean age 57.2 yr) with splenectomy; group B (Gr B) consisted of 25 patients (12 M and 13 F, mean age 61.6 yr) with hypersplenism. Gr A had 25 ITP, 7 myeloproliferative disorders, 4 lymphoma, 3 hemolytic anemias, 4 trauma related splenectomy, 1 unknown reason. Group B had 19 chronic hepatitis C, 2 alcoholic, 2 idiopathic and 1 autoimmune hepatitis, 1 portal vein thrombosis. Group C (Gr C) were healthy controls with spleen (n=109). Flow cytometry was used to assay C-MP. PMP were identified by CD41+, LMP by CD45+, EMP by CD31+/CD41−, and RMP by glycophorin+. Profile of C-MP and blood counts were compared among the 3 groups.
RESULTS: Table 1 summarizes C-MP data among the 3 groups. Gr A and B were well matched for ages and sex. Mean values of WBC and Hgb were normal in all groups while the platelet count was low in Gr B. Mean values of LMP, EMP and RMP were significantly higher in Gr A compared to Gr B and C, but PMP were not. All species of C-MP (PMP, LMP, EMP, RMP) in Gr B were significantly lower than Gr C (healthy control) and were markedly depressed compared to Gr A (see Table 1). Correlation analysis revealed that PMP correlated with platelet count (p<0.0001) but no correlation between LMP and WBC was seen, or between RMP and Hgb. Accordingly, high LMP and RMP in Gr A cannot explain the relatively high Hgb and WBC levels in this group.
DISCUSSION/COMCLUSIONS: Our data suggest that spleen sequesters and/or clears C-MP of all types (PMP, LMP, EMP, RMP). C-MP express PS (bind AnV), which is known to promote clearance from circulation. Splenectomy is known to be associated with thrombosis but its mechanism in not well elucidated. Elevated C-MP in splenectomized patients may contribute to their increased risk of thrombosis.
Table 1 Gr A (Splntomy) Gr B (Hyperspln) Gr C (Control) p value (A-C) p value (B-C) Patient no. 44 25 109 PMP 13858 7073 15992 n. s. <0.0001 LMP 2043 1180 1385 <0.0001 <0.001 EMP 857 238 436 <0.001 <0.0001 RMP 2964 926 1138 <0.0001 <0.005
