Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


The Correlation between Circulating Microparticles and Platelet Aggregation and Disease Activity in Wegener Granulomatosis.

Hajj-Ali3,  Rula, Silverstein1,  Roy, Hoffman1,  Gary, Zhang1,  Li, Imrey1,  Peter, Langford2,  Carol A.

Cleveland Clinic
Cleveland Clinic Foundation, Cleveland, OH
Clevelnad Clinic, Cleveland, OH

Background:

The objective of this study is to determine whether there are correlations between platelet aggregation and/ or circulating microparticles (MP) and disease activity in Wegener's granulomatosis (WG)

Methods:

Eligible consenting adult patients who met the ACR 1990 classification criteria for WG were enrolled from the Cleveland Clinic Center for Vasculitis Care and Research. Controls were subjects who did not have WG or other chronic inflammatory diseases. Exclusion criteria for patients and controls included acute or chronic infection within the past 3 months, NSAID or aspirin use within a week of platelet and MP studies, or diagnosis of a chronic inflammatory diseases, an autoimmune disease, or thrombophilia. Data on WG disease activity was captured by BVAS-WG.

Platelet aggregation was assessed turbidometrically with a dual channel aggregometer using graded doses of ADP (1, 2, 5, and 10 mM). The change in light transmission after addition of ADP was recorded and expressed as a percentage of maximum deflection. MP counts were assessed by flow cytometry from platelet poor plasma. MP were stained by Annexin V and further characterized for cellular origin using specific antibodies to endothelial cells (CD105, CD144), platelets (CD41), leukocytes (CD18), neutrophils (CD16b) and monocytes (CD14). Each marker was assessed separately.

Results:

46 patients were included; 38 in remission and 8 during acute disease relapse. The two groups did not differ in age or gender. Subjects in relapse had

1- a significant increase in leukocyte derived MP compared to those in remission, and

2- platelets with increased sensitivity to activation by ADP (Table 1).

Table 1. Comparison of MP counts and platelet aggregation between flare and remission groups

FactorFlare (N=8)Remission (N=38)P value
Age (years)61 ± 1354 ± 130.20
Female5 (63)17 (45)0.45
CD14 - MP counts477 (386, 797)249 (67, 409)0.030*
CD16 - MP counts182 (127, 219)56 (26, 100)0.006*
CD18 - MP counts257 (210, 314)63 (36, 106)0.002*
Platelet aggregation (1mM ADP)28 (18, 38)5 (2, 10)0.005*
Platelet aggregation (2 mM ADP)49 (43, 71)19 (7, 26)0.005*
Platelet aggregation (5 mM ADP)82 (78, 98)36 (26, 57)0.009*
Platelet aggregation (10 mM ADP)87 (78, 92)51 (38, 70)0.008*
Normally distributed data were expressed as mean ± SD and analyzed with the P from the T-test; Non-normally distributed data were expressed as median (25th, 75th) percentiles and analyzed with the P from the Wilcoxon rank sum test. N and percentage for categorical variables with Fisher exact test.

We also assessed the association of MP levels to platelet aggregation in WG vs. healthy controls (N=21). There were moderately positive linear relationships between levels of CD14, CD16 and CD18 expressing MP and platelet aggregation responses in WG patients. There were no statistically significant associations in the control group (Table 2).

Table 2. Correlation of Platelet aggregation and MP counts in WG and healthy controls

 Platelet aggregationMPNrho95%CIP value
WG PatientsADP 1mMCD14410.43(0.14, 0.65)0.006
  CD16410.47(0.19, 0.68)0.002
  CD18410.64(0.41, 0.79)<0.001
 ADP 2 mMCD14440.38(0.09, 0.61)0.011
  CD16440.40(0.12, 0.63)0.007
  CD18440.54(0.28, 0.72)<0.001
 ADP 5 mMCD14440.35(0.06, 0.58)0.021
  CD16440.31(0.01, 0.55)0.042
  CD18440.45(0.18, 0.66)0.002
 ADP 10 mMCD14410.32(0.02, 0.57)0.039
  CD16410.30(-0.01, 056)0.058
  CD18410.43(0.14, 0.65)0.005
ControlsADP 1 mMCD14190.31(-0.11, 0.84)0.13
  CD16190.25(-0.18, 0.79)0.13
  CD18190.28(-0.21, 0.77)0.25
 ADP 2 mMCD14210.25(-0.21, 0.72)0.27
  CD16210.18(-0.29, 0.65)0.43
  CD18210.28(-0.18, 0.74)0.22
 ADP 5 mMCD14210.41(-0.03, 0.85)0.067
  CD16210.37(-0.08, 0.81)0.1
  CD18210.44(0.01, 0.87)0.046
 ADP 10 mMCD14200.08(-0.41, 0.58)0.73
  CD16200.07(-0.43, 0.56)0.78
  CD18200.15(-0.33, 0.64)0.52

Conclusions:

Levels of leukocyte derived MP and sensitivity of platelets to ADP-induced aggregation correlate with disease flares in WG. The correlation between MP counts and platelet reactivity seen in WG but not controls suggest that elevated levels of leukocyte-derived MP generated during chronic inflammation may sensitize platelets to activation and contribute to athero-thrombotic complications. Whether these events also contribute to injury in WG is worthy further studies.

To cite this abstract, please use the following information:
Hajj-Ali, Rula, Silverstein, Roy, Hoffman, Gary, Zhang, Li, Imrey, Peter, Langford, Carol A.; The Correlation between Circulating Microparticles and Platelet Aggregation and Disease Activity in Wegener Granulomatosis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2047
DOI: 10.1002/art.29812

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