Increased Procoagulant Cell-Derived Microparticles (MP) in Splenectomized Patients with ITP: New Prediisposing Factors for Thrombosis.
Authors: Fontana Vincenzo , Jy Wenche , Dudkiewicz Pamela , Yaniz Miriam , Bidot Carlos J. , Jimenez Joaquin J. , Ahn Yeon S. 
Published: October 2019

INTRODUCTION: Splenectomy has been widely employed in the treatment of immune thrombocytopenic purpura (ITP) and various other disorders. Increased life threatening infection is well recognized but the long-term safety of splenectomy has not yet been delineated. Splenectomy has been associated with increased incidence of cardiovascular death [Lancet, 1977; 2 (8029):127–9] and ischemic small vessel disease leading to recurrent TIA and cognitive impairment [Thromb Res, 2000; 107: 337–44]. Recent studies have demonstrated that procoagulant MP play an important role in the pathogenesis of thrombosis and cardiovascular complications (JTH, 2005; 3: 884–7). In the present study, we investigated profiles of cell-derived microparticles (MP) and thrombotic events in ITP patients with / without splenectomy.

METHODS: Fifty-seven patients meeting diagnostic criteria of ITP were studied. Excluded were those with HIV, viral hepatitis, or lupus anticoagulant. Fifteen had splenectomy (ITPs) while 42 had not (ITPns). The ITPs group comprised 11F, 4M, while ITPns group had 28F, 14M. The 2 groups were comparable in sex, ages and platelet counts. In the latter, 9 failed to undergo remission, having active ITP (ITPs-A) while the other 6 were in remission (ITPs-R) following splenectomy. In the ITPns group, 23 responded poorly to therapies (ITPns-A) while the remaining 19 were in remission (ITPns-R). CBC and platelet counts, blood chemistry and PT, aPTT were measured. Flow-cytometry was employed to assay cell-derived MP from platelets (PMP) by anti-CD41, from leukocytes (LMP) by anti-CD45, from red cells (RMP) by anti-glycophorin, and from endothelial cells (EMP) by anti-CD31+/anti-CD41-. All patients were followed and incidence of thrombotic events was evaluated.

RESULTS: Data are summarized in Table 1. Mean values of EMP, LMP, PMP and RMP were all significantly higher except PMP in ITPs compared to ITPns: RMP (p=0.002), EMP (p=0.008), LMP (p=0.03). In addition, aPTT was significantly shortened in ITPs vs ITPns (p=0.0059), as well as in ITPs-A vs. ITPns-A (p=0.0025). In the ITPs-R group, the aPTT was shorter than ITPns-R but did not reach statistical significance. Thrombotic events were recorded in 6 of the 15 ITPs group (40%) but in only 4 of the 42 ITPns (10%), p<0.001. Of the 6 ITPs with thrombosis, 5 had TIA and one DVT. Of the 4 with ITPns, 3 had TIA and 1 DVT.

CONCLUSIONS: (i) Cell-derived MP, which are known to be procoagulant and implicated in the pathogenesis of thrombosis and inflammation, are significantly elevated, (ii) along with significantly shortened aPTT and (iii) thrombotic events were more prevalent in those without spleen compared to those with spleen among ITP patients. These observations support the hypothesis that spleen is the main site of clearance of procoagulant MP, and that accumulation of procoagulant MP may increase risk of thrombotic complications following splenectomy. A larger-scale study is warranted to clarify the long term safety of splenectomy in ITP and other disorders.

Table 1 ITPs (no spleen) ITPns (with spleen) p value Patients; n= 15 42 EMP 730 323 0.008 PMP 16147 10995 0.11 LMP 1810 1238 0.03 RMP 2777 1759 0.002 aPTT 22.5 25.7 0.006 Thrombosis 40% 10% 0.002