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Abstract Number: 3044

Microparticles (MPs) Derived from Cell Plasma Membranes Are Increased in Behcet’s Syndrome (BS) and a Low Ratio of Tissue Factor Pathway Inhibitor Positive Mps to Tissue Factor Positive Mps (TFPI/TF) Is Associated with Thrombosis

Emon Khan1, Nicola Ambrose1, Miles Stanford2, Michael A. Laffan3 and Dorian O. Haskard4, 1Department of Vascular Sciences, National Heart and Lung Institute, Imperial College, London, United Kingdom, 2Ophthalmology, Guy's and St. Thomas' Hospital, London, United Kingdom, 3Department of Haemostasis and Thrombosis, Imperial College, London, United Kingdom, 4Rheumatology, Imperial College, London, United Kingdom

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Behcet's syndrome, microparticles and thrombosis

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Session Information

Date: Tuesday, November 10, 2015

Title: Vasculitis Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Thrombosis occurs in
around 20% of Behçet’s Syndrome (BS) patients and
causes substantial morbidity.  There is a clear need for better biomarkers
of thrombotic risk in BS to inform treatment decisions.  MPs are released from
cells undergoing activation and/or apoptosis and express phosphatidylserine
(PS) on their surface. MP that also express Tissue Factor (TF) provide a
stimulus for blood coagulation, whereas Tissue Factor Pathway Inhibitor (TFPI)
expressed by MP may be protective.  We tested the hypothesis that
imbalance between TF+ and TFPI+ MPs provides a biomarker for thrombotic risk in
BS.

Methods: MPs were prepared from peripheral
blood from 88 BS patients (who fulfilled International Study Group diagnostic
criteria), and 72 age- and sex- matched healthy controls.  The BS group
was composed of 21 patients with a history of thrombosis (Th+)
and 67 patients with no history of thrombosis (Th-).
 MPs were identified using flow cytometry by size (<1µm) and binding to
Annexin V (to PS). MP were further characterized by
binding of monoclonal antibodies to CD14 (a monocyte marker), TF and TFPI.

 

Results: Total numbers of plasma MPs and
also CD14+, TF+ and CD14+TF+ MPs were increased in BS compared to HC (all p
< 0.0001), and also in Th+ compared to Th– BS patients (p ≤ 0.0002). TFPI+ MPs were
higher in BS patients than HC (medians: 3.60 x 104/ml vs.
2.15 x 103/ml, p < 0.0001), but not between Th+
and Th– BS patients (medians: 3.09 x 104/ml
vs. 3.74 x 104/ml, p = 0.6660).  The TFPI/TF ratio was
higher in BS patients than HCs (medians: 0.49 vs. 0.20, p < 0.0001) and in Th– compared to Th+
patients (medians: 0.85 vs. 0.23, p =
0.0002). Strikingly, a TFPI/TF ratio > 0.7 conferred freedom from thrombosis
(Figure).

Conclusion: Monocyte-derived MP
expressing TF were increased in BS patients and more so in those with a history
of thrombosis.  Discrimination between BS patients with and without a
history of thrombosis was improved by also measuring TFPI+ MPs and generating a
TFPI/TF ratio. The data suggest that the balance between TF+ and TFPI+ MPs is
important for thrombotic risk in BS and raise the possibility that the TFPI /TF
MP ratio may allow the identification and appropriate treatment of BS patients
with a low risk of thrombosis.

 


Disclosure: E. Khan, None; N. Ambrose, None; M. Stanford, None; M. A. Laffan, None; D. O. Haskard, None.

To cite this abstract in AMA style:

Khan E, Ambrose N, Stanford M, Laffan MA, Haskard DO. Microparticles (MPs) Derived from Cell Plasma Membranes Are Increased in Behcet’s Syndrome (BS) and a Low Ratio of Tissue Factor Pathway Inhibitor Positive Mps to Tissue Factor Positive Mps (TFPI/TF) Is Associated with Thrombosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/microparticles-mps-derived-from-cell-plasma-membranes-are-increased-in-behcets-syndrome-bs-and-a-low-ratio-of-tissue-factor-pathway-inhibitor-positive-mps-to-tissue-factor-positive-mps-tfpitf/. Accessed .
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