Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.
© 2002 S. Karger AG, Basel
- Inflammatory bowel disease
- Grip O, Svensson PJ, Lindgren S: Inflammatory bowel disease promotes venous thrombosis earlier in life. Scand J Gastroenterol 2000;35:619–623.
- Lake AM, Stauffer JQ, Stuart MJ: Hemostatic alterations in inflammatory bowel disease: Response to therapy. Am J Dig Dis 1978;23:897–902.
- Edwards RL, Levine JB, Green R, Duffy M, Mathews E, Brande W, Rickles FR: Activation of blood coagulation in Crohn’s disease. Increased plasma fibrinopeptide A levels and enhanced generation of monocyte tissue factor activity. Gastroenterology 1987;92:329–337.
- Kjeldsen J, Lassen JF, Brandslund I, Schaffalitzky de Muckadell OB: Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease. Scand J Gastroenterol 1998;33:637–643.
- Hudson M, Hutton RA, Wakefield AJ, Sawyerr AM, Pounder RE: Evidence for activation of coagulation in Crohn’s disease. Blood Coagul Fibrinolysis 1992;3:773–778.
- Souto JC, Martinez E, Roca M, Mateo J, Pujol J, Gonzalez D, Fontcuberta J: Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease. Dig Dis Sci 1995;40:1883–1889.
- Stouthard JM, Levi M, Hack CE, Veenhof CH, Romijn HA, Sauerwein HP, Van der Poll T: Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost 1996;76:738–742.
- Heits F, Stahl M, Ludwig D, Stange EF, Jelkmann W: Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease. J Interferon Cytokine Res 1999;19:757–760.
- Rosendaal FR: Venous thrombosis: A multicausal disease. Lancet 1999;353:1167–1173.
- van Boven HH, Olds RJ, Thein SL, Reitsma PH, Lane DA, Briet E, Vandenbroucke JP, Rosendaal FR: Hereditary antithrombin deficiency. Heterogeneity of the molecular basis and mortality in Dutch families. Blood 1994;84:4209–4213.
- Esmon CT: The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989;264:4743–4746.
- Dahlbäck B: Protein S and C4b-binding protein: Components involved in the regulation of the protein C anticoagulant system. Thromb Haemost 1991;66:49–61.
- Koutroubakis IE, Sfiridaki A, Mouzas IA, Maladaki A, Kapsoritakis A, Roussomoustakaki M, Kouroumakis EA, Manousos ON: Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease. Am J Gastroenterol 2000;95:190–194.
- Santhosh-Kumar CR, Yohannan MD, Higgy KE, al Mashhadani SA: Thrombocytosis in adults. Analysis of 777 patients. J Intern Med 1991;229:493–495.
- Vila N, Reverter JC, Yague J, Chamorro A: Interaction between interleukin-6 and the natural anticoagulant system in acute stroke. J Interferon Cytokine Res 2000;20:325–329.
- Singleton JW: Clinical activity assessment in inflammatory bowel disease. Dig Dis Sci 1987;32:42S–45S.
- Salas A, Sans M, Soriano A, Reverter JC, Anderson DC, Pique JM, Panes J: Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism. Gut 2000;47:88–96.
- Collins CE, Rampton DS: Review article: Platelets in inflammatory bowel disease – pathogenetic role and therapeutic implications. Aliment Pharmacol Ther 1997;11:237–247.
- Carty E, MacEy M, Rampton DS: Inhibition of platelet activation by 5-aminosalicylic acid in inflammatory bowel disease. Aliment Pharmacol Ther 2000;14:1169–1179.
Torben Bjerregaard Larsen, MD, PhD
Department of Clinical Biochemistry, Section for Thrombosis and Hemostasis
Aalborg Hospital, Hobrovej 18–22, PO Box 365
DK–9100 Aalborg (Denmark)
Tel. +45 9932 3180, Fax +45 9813 1196, E-Mail email@example.com
Received: Received: January 2, 2002
Accepted in revised form: April 3, 2002
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 3, Number of References : 19
Pathophysiology of Haemostasis and Thrombosis
Official Journal of the ‘Mediterranean League against Thromboembolic Diseases’
Vol. 32, No. 2, Year 2002 (Cover Date: March-April 2002 (Released July 2002))
Journal Editor: H.C. Hemker, Maastricht
ISSN: 1424–8832 (print), 1424–8840 (Online)
For additional information: http://www.karger.com/journals/pht
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.