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Published in: Digestive Diseases and Sciences 11/2015

01-11-2015 | Original Article

Platelet Activation Markers Are Associated with Crohn’s Disease Activity in Patients with Low C-Reactive Protein

Authors: Hiroshi Takeyama, Tsunekazu Mizushima, Hideki Iijima, Shinzaki Shinichiro, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori

Published in: Digestive Diseases and Sciences | Issue 11/2015

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Abstract

Background

In assessing Crohn’s disease (CD) activity, C-reactive protein (CRP) is an important indicator of inflammation; however, it is not necessarily associated with the Crohn’s Disease Activity Index (CDAI), particularly in patients with low CRP. Recently, platelet activation factors have been recognized due to their importance in the inflammatory response. In this study, we examined associations between the CDAI and platelet factor 4 (PF-4), β-thromboglobulin (β-TG), and other coagulation and fibrinolysis factors.

Aims

We aimed to find a new marker for evaluating disease activity in patients with CD and low CRP.

Methods

Nine markers, including CRP, platelet count, white blood cell count, fibrin and fibrinogen degradation product, fibrinogen, thrombin–antithrombin complex, prothrombin fragments 1 + 2, PF-4, and β-TG were evaluated in 47 patients with CD and low CRP (<1.0 mg/dl). Patients were assigned to high or low disease activity groups, CDAI-H (CDAI ≥ 150) and CDAI-L (CDAI < 150), respectively.

Results

CDAI-H exhibited significantly higher PF-4 and β-TG levels than CDAI-L (P < 0.01). Other markers were not significantly different between groups. CDAI was positively correlated with the levels of PF-4 and β-TG (P = 0.0033 and 0.0024; r = 0.4202 and 0.4321, respectively). Receiver operating characteristic curve analyses of PF-4 and β-TG showed high sensitivity (61.9 and 81 %, respectively) and specificity (84.7 and 69.2 %, respectively) for diagnosing active CD.

Conclusion

Among eight potential markers, PF-4 and β-TG were the most highly correlated with CDAI in patients with CD and low CRP. PF-4 and β-TG levels showed promise as new markers for assessing CD in patients with low CRP.
Literature
1.
go back to reference Kiss LS, Szamosi T, Molnar T, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011;34:911–922.CrossRefPubMed Kiss LS, Szamosi T, Molnar T, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011;34:911–922.CrossRefPubMed
2.
go back to reference Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn’s Disease Activity Index (CDAI). Gastroenterology. 1979;77:843–846.PubMed Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn’s Disease Activity Index (CDAI). Gastroenterology. 1979;77:843–846.PubMed
3.
go back to reference Chamouard P, Richert Z, Meyer N, et al. Diagnostic value of C-reactive protein for predicting activity level of Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4:882–887.CrossRefPubMed Chamouard P, Richert Z, Meyer N, et al. Diagnostic value of C-reactive protein for predicting activity level of Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4:882–887.CrossRefPubMed
4.
go back to reference Jones J, Loftus EV Jr, Panaccione R, et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2008;6:1218–1224.CrossRefPubMed Jones J, Loftus EV Jr, Panaccione R, et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2008;6:1218–1224.CrossRefPubMed
5.
go back to reference Diaz-Jimenez D, Nunez LE, Beltran CJ, et al. Soluble ST2: a new and promising activity marker in ulcerative colitis. World J Gastroenterol. 2011;17:2181–2190.PubMedCentralCrossRefPubMed Diaz-Jimenez D, Nunez LE, Beltran CJ, et al. Soluble ST2: a new and promising activity marker in ulcerative colitis. World J Gastroenterol. 2011;17:2181–2190.PubMedCentralCrossRefPubMed
6.
go back to reference Filik L, Dagli U, Ulker A. C-reactive protein and monitoring the activity of Crohn’s disease. Adv Ther. 2006;23:655–662.CrossRefPubMed Filik L, Dagli U, Ulker A. C-reactive protein and monitoring the activity of Crohn’s disease. Adv Ther. 2006;23:655–662.CrossRefPubMed
7.
go back to reference Husain N, Tokoro K, Popov JM, et al. Neopterin concentration as an index of disease activity in Crohn’s disease and ulcerative colitis. J Clin Gastroenterol. 2013;47:246–251.CrossRefPubMed Husain N, Tokoro K, Popov JM, et al. Neopterin concentration as an index of disease activity in Crohn’s disease and ulcerative colitis. J Clin Gastroenterol. 2013;47:246–251.CrossRefPubMed
8.
go back to reference Rodgers AD, Cummins AG. CRP correlates with clinical score in ulcerative colitis but not in Crohn’s disease. Dig Dis Sci. 2007;52:2063–2068.CrossRefPubMed Rodgers AD, Cummins AG. CRP correlates with clinical score in ulcerative colitis but not in Crohn’s disease. Dig Dis Sci. 2007;52:2063–2068.CrossRefPubMed
9.
go back to reference Desai D, Faubion WA, Sandborn WJ. Review article: biological activity markers in inflammatory bowel disease. Aliment Pharmacol Ther. 2007;25:247–255.CrossRefPubMed Desai D, Faubion WA, Sandborn WJ. Review article: biological activity markers in inflammatory bowel disease. Aliment Pharmacol Ther. 2007;25:247–255.CrossRefPubMed
10.
go back to reference Denis MA, Reenaers C, Fontaine F, et al. Assessment of endoscopic activity index and biological inflammatory markers in clinically active Crohn’s disease with normal C-reactive protein serum level. Inflamm Bowel Dis. 2007;13:1100–1105.CrossRefPubMed Denis MA, Reenaers C, Fontaine F, et al. Assessment of endoscopic activity index and biological inflammatory markers in clinically active Crohn’s disease with normal C-reactive protein serum level. Inflamm Bowel Dis. 2007;13:1100–1105.CrossRefPubMed
11.
go back to reference Florin TH, Paterson EW, Fowler EV, et al. Clinically active Crohn’s disease in the presence of a low C-reactive protein. Scand J Gastroenterol. 2006;41:306–311.CrossRefPubMed Florin TH, Paterson EW, Fowler EV, et al. Clinically active Crohn’s disease in the presence of a low C-reactive protein. Scand J Gastroenterol. 2006;41:306–311.CrossRefPubMed
12.
go back to reference Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375:657–663.CrossRefPubMed Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375:657–663.CrossRefPubMed
13.
go back to reference Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut. 2004;53:542–548.PubMedCentralCrossRefPubMed Miehsler W, Reinisch W, Valic E, et al. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism? Gut. 2004;53:542–548.PubMedCentralCrossRefPubMed
15.
go back to reference Hayat M, Ariens RA, Moayyedi P, et al. Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002;14:249–256.CrossRefPubMed Hayat M, Ariens RA, Moayyedi P, et al. Coagulation factor XIII and markers of thrombin generation and fibrinolysis in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2002;14:249–256.CrossRefPubMed
16.
go back to reference Irving PM, Pasi KJ, Rampton DS. Thrombosis and inflammatory bowel disease. Clin Gastroenterol Hepatol. 2005;3:617–628.CrossRefPubMed Irving PM, Pasi KJ, Rampton DS. Thrombosis and inflammatory bowel disease. Clin Gastroenterol Hepatol. 2005;3:617–628.CrossRefPubMed
17.
go back to reference Thornton M, Solomon MJ. Crohn’s disease: in defense of a microvascular aetiology. Int J Colorectal Dis. 2002;17:287–297.CrossRefPubMed Thornton M, Solomon MJ. Crohn’s disease: in defense of a microvascular aetiology. Int J Colorectal Dis. 2002;17:287–297.CrossRefPubMed
18.
go back to reference Bernhard H, Deutschmann A, Leschnik B, et al. Thrombin generation in pediatric patients with Crohn’s disease. Inflamm Bowel Dis. 2011;17:2333–2339.CrossRefPubMed Bernhard H, Deutschmann A, Leschnik B, et al. Thrombin generation in pediatric patients with Crohn’s disease. Inflamm Bowel Dis. 2011;17:2333–2339.CrossRefPubMed
19.
go back to reference Danese S, de la Motte C, Fiocchi C. Platelets in inflammatory bowel disease: clinical, pathogenic, and therapeutic implications. Am J Gastroenterol. 2004;99:938–945.CrossRefPubMed Danese S, de la Motte C, Fiocchi C. Platelets in inflammatory bowel disease: clinical, pathogenic, and therapeutic implications. Am J Gastroenterol. 2004;99:938–945.CrossRefPubMed
21.
go back to reference Vrij AA, Rijken J, Van Wersch JW, et al. Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis. Eur J Clin Invest. 2000;30:188–194.CrossRefPubMed Vrij AA, Rijken J, Van Wersch JW, et al. Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis. Eur J Clin Invest. 2000;30:188–194.CrossRefPubMed
22.
go back to reference Kasperska-Zajac A, Rogala B. Platelet function in anaphylaxis. J Investig Allergol Clin Immunol. 2006;16:1–4.PubMed Kasperska-Zajac A, Rogala B. Platelet function in anaphylaxis. J Investig Allergol Clin Immunol. 2006;16:1–4.PubMed
23.
go back to reference Kasperska-Zajac A, Rogala B. Platelet activation during allergic inflammation. Inflammation. 2007;30:161–166.CrossRefPubMed Kasperska-Zajac A, Rogala B. Platelet activation during allergic inflammation. Inflammation. 2007;30:161–166.CrossRefPubMed
25.
go back to reference Rosenberg L, Nanda KS, Zenlea T, et al. Histologic markers of inflammation in patients with ulcerative colitis in clinical remission. Clin Gastroenterol Hepatol. 2013;11:991–996.PubMedCentralCrossRefPubMed Rosenberg L, Nanda KS, Zenlea T, et al. Histologic markers of inflammation in patients with ulcerative colitis in clinical remission. Clin Gastroenterol Hepatol. 2013;11:991–996.PubMedCentralCrossRefPubMed
26.
go back to reference Sandborn WJ, Feagan BG, Hanauer SB, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–530.CrossRefPubMed Sandborn WJ, Feagan BG, Hanauer SB, et al. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn’s disease. Gastroenterology. 2002;122:512–530.CrossRefPubMed
27.
go back to reference Gear AR, Camerini D. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation. 2003;10:335–350.CrossRefPubMed Gear AR, Camerini D. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation. 2003;10:335–350.CrossRefPubMed
Metadata
Title
Platelet Activation Markers Are Associated with Crohn’s Disease Activity in Patients with Low C-Reactive Protein
Authors
Hiroshi Takeyama
Tsunekazu Mizushima
Hideki Iijima
Shinzaki Shinichiro
Mamoru Uemura
Junichi Nishimura
Taishi Hata
Ichiro Takemasa
Hirofumi Yamamoto
Yuichiro Doki
Masaki Mori
Publication date
01-11-2015
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 11/2015
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3745-2

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