Background/Purpose
Thrombosis occurs in 20% of patients with Behçet’s Syndrome (BS) and leads to significant morbidity. There is no robust association between thrombosis in BS and the presence of hereditary thrombophilia or raised inflammatory markers. It remains a challenge to distinguish those at risk of thrombosis potentially requiring aggressive preventative therapy and those whose therapy can be reduced. There is a clear need to develop biomarkers for diagnosis and risk management in BS.
Plasma cell membrane derived microparticles (MPs) are released from cells undergoing apoptosis or activation. MPs are known to promote thrombosis in malignancy and cardiovascular disease, as a result of surface expression of phosphatidylserine (PS) and other cell surface markers, in particular tissue factor (TF). The aim of this study was to assess whether MPs are associated with thrombosis in Behçet’s Syndrome (BS).
Methods
MPs were prepared following venepuncture of 88 BS patients who fulfilled International Study Group Criteria for diagnosis, 21 of whom had a history of thrombosis, and 39 healthy controls (HC). MPs were identified using flow cytometry by gating for particles less than 1µm in size and staining positively with Annexin V, which binds PS, giving a total MP count. Antibodies to CD14 (monocytes), TF, CD62P (platelets), CD144 (endothelial cells) and CD66b (neutrophils) were used to identify cellular origin. Endogenous thrombin potential (ETP) and peak thrombin (PT) were measured using calibrated automated thrombography, allowing analysis of the thrombotic potential of MPs.
Results
BS patients had higher total (4.3 x 105/ml vs 2.3 x 105/ml, p=0.0072), CD14+(2.7 x 105/ml vs 8.5 x 103/ml, p<0.0001), TF+ (4.5 x 104/ml vs 5.9 x 103/ml, p<0.0001) and CD14+TF+ (1.9 x 104/ml vs 4.5 x 103/ml, p<0.0001) MPs compared to HCs. Thrombotic BS (TBS) patients had higher total (8.8 x 105/ml vs 3.2 x 105/ml, p=0.0028), CD14+ (2.9 x 104/ml vs 2.5 x104/ml, p=0.042), TF+ (6.1 x 104/ml vs 4.3 x 104/ml, p=0.041) and CD14+ TF+ (2.6 x 104/ml vs 1.5 x 104/ml, p=0.047) than non-thrombotic BS (NTBS) patients.
BS patients also had higher CD62P+ (1.2 x 105/ml vs 4.7 x 104/ml, p=0.0152) and CD66b+ (1.9 x 104/ml vs 8.8 x 103/ml, p=0.0389) MPs than HCs. CD144 MPs were not significantly higher in BS patients than HCs (1.9 x 104/ml vs 1.1 x 104/ml, p=0.0769). TBS patients had higher CD62P+ (2.3 x 105/ml vs 7.1 x 104/ml, p=0.0111), CD144+ (3.8 x 104/ml vs 1.5 x 104/ml, p=0.0342) and CD66b+ (4.8 x 104/ml vs 1.7 x 104/ml, p=0.0237) MPs than NTBS patients.
ETP was significantly higher in BS patients than HCs (515.13 vs 383.52, p=0.013), but there was no difference in ETP between TBS and NTBS patients. PT was significantly higher in BS patients (20.08nM vs 9.92nM, p=0.0022) compared to HCs and in TBS (27.06nM vs 16.73nM, p=0.041) compared with NTBS patients, but did not correlate with MP numbers.
Conclusion
MPs are found in higher numbers in BS patients than in HCs, in particular in TBS patients. It is interesting that PT was raised in TBS compared with NTBS patients. These results suggest that MP counts and PT may be useful biomarkers in combination and may provide a scoring system for identifying patients at risk of thrombosis and risk management in patients with BS.
Disclosure:
E. Khan,
None;
N. Ambrose,
None;
M. A. Laffan,
None;
D. O. Haskard,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microparticles-may-play-a-role-in-causing-thrombosis-in-behcets-syndrome-and-act-as-a-biomarker-for-risk-management/