Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis

Abstract

Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions.

Key Points

  • Patients with inflammatory rheumatic diseases have a substantially enhanced risk of venous thromboembolic events; in rheumatoid arthritis (RA), the risk seems to be increased by at least twofold

  • In patients with RA, a procoagulatory status is maintained by activated endothelial cells and platelets, as well as changes in coagulation and fibrinolysis factors, which correlate with immune activation

  • Coagulation factors prothrombin, fibrinogen and coagulation factor XIII define the quality of the fibrin network and influence the extent of immune activation and control inflammation

  • Citrullinated fibrinogen is an important autoantigen in RA, especially in patients carrying the HLA-DRβ1 shared epitope allele, and indicates a role for adaptive immune activation

  • Increased knowledge of coagulation and immune system interactions might lead to the development of therapeutics that target both systems and possibly reduce the burden of inflammation and vessel occlusions in inflammatory rheumatic disease

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Multiple functions of endothelial cells during immune activation, regulation of coagulation and fibrinolysis.
Figure 2: Activation pathways of fibrin generation and fibrinolysis.
Figure 3: Influence of fibrinogen and F13A genotypes on inflammatory processes.
Figure 4: Roles of fibrinogen in rheumatoid arthritis and inflammation.

Similar content being viewed by others

References

  1. Naranjo, A. et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res. Ther. 10, R30 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Symmons, D. P. & Gabriel, S. E. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat. Rev. Rheumatol. 7, 399–408 (2011).

    Article  PubMed  Google Scholar 

  3. Sawamura, A. et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb. Res. 124, 608–613 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Smeeth, L. et al. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet 367, 1075–1079 (2006).

    Article  PubMed  Google Scholar 

  5. Hoppe, B., Burmester, G. R. & Dörner, T. Heparin or aspirin or both in the treatment of recurrent abortions in women with antiphospholipid antibody (syndrome). Curr. Opin. Rheumatol. 23, 299–304 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Tripodi, A. de Groot, P. G. & Pengo, V. Antiphospholipid syndrome: laboratory detection, mechanisms of action and treatment. J. Intern. Med. 270, 110–122 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. Lim, W. Crowther, M. A. & Eikelboom, J. W. Management of antiphospholipid antibody syndrome: a systematic review. JAMA 295, 1050–1057 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Cervera, R. et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82, 299–308 (2003).

    Article  Google Scholar 

  9. Cervera, R. Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1,000 patients. Ann. Rheum. Dis. 68, 1428–1432 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Cohen, D., Berger, S. P., Steup-Beekman, G. M., Bloemenkamp, K. W. & Bajema, I. M. Diagnosis and management of the antiphospholipid syndrome. BMJ 340, c2541 (2010).

    Article  PubMed  Google Scholar 

  11. Solomon, D. H. et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107, 1303–1307 (2003).

    Article  PubMed  Google Scholar 

  12. Zöller, B., Li, X., Sundquist, J. & Sundquist, K. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 379, 244–249 (2012).

    Article  PubMed  Google Scholar 

  13. Busso, N. & Hamilton, J. A. Extravascular coagulation and the plasminogen activator/plasmin system in rheumatoid arthritis. Arthritis Rheum. 46, 2268–2279 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Sanchez-Pernaute, O. et al. A fibrin based model for rheumatoid synovitis. Ann. Rheum. Dis. 62, 1135–1138 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. So, A. K. et al. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J. Thromb. Haemost. 1, 2510–2515 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Matta, F., Singala, R., Yaekoub, A. Y., Najjar, R. & Stein, P. D. Risk of venous thromboembolism with rheumatoid arthritis. Thromb. Haemost. 101, 134–138 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Bacani, A. K., Gabriel, S. E., Crowson, C. S., Heit, J. A. & Matteson, E. L. Noncardiac vascular disease in rheumatoid arthritis: increase in venous thromboembolic events? Arthritis Rheum. 64, 53–61 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Choi, H. K., Hernan, M. A., Seeger, J. D., Robins, J. M. & Wolfe, F. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359, 1173–1177 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Micha, R. et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am. J. Cardiol. 108, 1362–1370 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Askling, J. & Dixon, W. Influence of biological agents on cardiovascular disease in rheumatoid arthritis. Ann. Rheum. Dis. 70, 561–562 (2011).

    Article  PubMed  Google Scholar 

  21. Greenberg, J. D. et al. Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular events among patients with rheumatoid arthritis. Ann. Rheum. Dis. 70, 576–582 (2011).

    Article  PubMed  Google Scholar 

  22. Ingegnoli, F. et al. Activation of inflammation, coagulation and fibrinolysis in patients with rheumatoid arthritis: inhibition by tumour necrosis factor alpha blockade [abstract]. Ann. Rheum. Dis. 67 (Suppl. 1), A30 (2008).

    Google Scholar 

  23. Ingegnoli, F. et al. Anti-tumor necrosis factor alpha therapy normalises fibrinolysis impairment in patients with active rheumatoid arthritis. Clin. Exp. Rheumatol. 28, 254–257 (2010).

    CAS  PubMed  Google Scholar 

  24. Ingegnoli, F. et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects of tumor necrosis factor-alpha blockade. J. Autoimmun. 31, 175–179 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Ingegnoli, F. et al. Reduction of haemostatic and inflammatory biomarkers by tumor necrosis factor-alpha blockade in patients with rheumatoid arthritis [abstract]. Ann. Rheum. Dis. 66 (Suppl. 1), A56 (2007).

    Google Scholar 

  26. Agirbasli, M., Inanc, N., Baykan, O.A. & Direskeneli, H. The effects of TNF alpha inhibition on plasma fibrinolytic balance in patients with chronic inflammatory rheumatical disorders. Clin. Exp. Rheumatol. 24, 580–583 (2006).

    CAS  PubMed  Google Scholar 

  27. Sarabi, Z. S. et al. Incidence rates of arterial and venous thrombosis after diagnosis of systemic lupus erythematosus. Arthritis Rheum. 53, 609–612 (2005).

    Article  PubMed  Google Scholar 

  28. Haga, H. J., Jacobsen, E. M. & Peen, E. Incidence of thromboembolic events in patients with primary Sjogren's syndrome. Scand. J. Rheumatol. 37, 127–129 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. Schramm, G. A. & Schrah, G. The efficacy and safety of an oral contraceptive containing chlormadinone acetate: results of a pooled analysis of noninterventional trials in adult and adolescent women. Contraception 84, 390–401 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Cushman, M. et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am. J. Med. 117, 19–25 (2004).

    Article  PubMed  Google Scholar 

  31. Hansson, P. O., Welin, L., Tibblin, G. & Eriksson, H. Deep vein thrombosis and pulmonary embolism in the general population—'The study of men born in 1913'. Arch. Intern. Med. 157, 1665–1670 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Merkel, P. A. et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's clinical occurrence of thrombosis (WeCLOT) study. Ann. Intern. Med. 142, 620–626 (2005).

    Article  PubMed  Google Scholar 

  33. Stassen, P. M., Derks, R. P., Kallenberg, C. G. & Stegeman, C. A. Venous thromboembolism in ANCA-associated vasculitis—incidence and risk factors. Rheumatology (Oxford) 47, 530–534 (2008).

    Article  CAS  Google Scholar 

  34. Smith, B. D. & La Celle, P. L. Blood-viscosity and thrombosis: clinical considerations. Prog. Hemost. Thromb. 6, 179–201 (1982).

    CAS  PubMed  Google Scholar 

  35. Murdaca, G. et al. Endothelial dysfunction in rheumatic autoimmune diseases. Atherosclerosis 224, 309–317 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. Dippold, W., Wittig, B., Schwaeble, W., Mayet, W. & Meyer zum Büschenfelde, K. H. Expression of intercellular-adhesion molecule-1 (ICAM-1, CD54) in colonic epithelial cells. Gut 34, 1593–1597 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Guillevin, L. & Dörner, T. Vasculitis: mechanisms involved and clinical manifestations. Arthritis. Res. Ther. 9 (Suppl. 2), S9 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Delvaeye, M. & Conway, E. M. Coagulation and innate immune responses: can we view them separately? Blood 114, 2367–2374 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. van Hinsbergh, V. W. Endothelium—role in regulation of coagulation and inflammation. Semin. Immunopathol. 34, 93–106 (2012).

    Article  CAS  PubMed  Google Scholar 

  40. Foster, W., Carruthers, D., Lip, G. Y. & Blann, A. D. Inflammation and microvascular and macrovascular endothelial dysfunction in rheumatoid arthritis: effect of treatment. J. Rheumatol. 37, 711–716 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Egerer, K. et al. sE-selectin for stratifying outcome in rheumatoid arthritis. Arthritis Rheum. 49, 546–548 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Schouten, M., Wiersinga, W. J., Levi, M. & van der Poll, T. Inflammation, endothelium, and coagulation in sepsis. J. Leukoc. Biol. 83, 536–545 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Peters, M. J., Nurmohamed, M. T., van Eijk, I. C., Verkleij, C. J. & Marx, P. F. Thrombin-activatable fibrinolysis inhibitor and its relation with inflammation in rheumatoid arthritis. Ann. Rheum. Dis. 68, 1232–1233 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Carmeliet, P. et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368, 419–424 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Nurden, A. T. Platelets, inflammation and tissue regeneration. Thromb. Haemost. 105 (Suppl. 1), S13–S33 (2011).

    CAS  PubMed  Google Scholar 

  46. Boilard, E. et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 327, 580–583 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Esmon, C. T. Coagulation and inflammation. J. Endotoxin Res. 9, 192–198 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Undas, A. et al. Thrombin generation in rheumatoid arthritis: dependence on plasma factor composition. Thromb. Heamost. 104, 224–230 (2010).

    Article  CAS  Google Scholar 

  49. Monroe, D. M., Hoffman, M. & Roberts, H. R. Platelets and thrombin generation. Atherioscler. Thromb. Vasc. Biol. 22, 1381–1389 (2002).

    Article  CAS  Google Scholar 

  50. Morris, R., Winyard, P. G., Blake, D. R. & Morris, C. J. Thrombin in inflammation and healing: relevance to rheumatoid arthritis. Ann. Rheum. Dis. 53, 72–79 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Petaja, J. Inflammation and coagulation. An overview. Thromb. Res. 127 (Suppl. 2), S34–S37 (2011).

    Article  PubMed  CAS  Google Scholar 

  52. Marty, I. et al. Amelioration of collagen-induced arthritis by thrombin inhibition. J. Clin. Invest. 107, 631–640 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Varisco, P. A. et al. Effect of thrombin inhibition on synovial inflammation in antigen induced arthritis. Ann. Rheum. Dis. 59, 781–787 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Flick, M. J. et al. The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A. Blood 117, 6326–6337 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Danckwardt, S. et al. The prothrombin 3′ end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations. Blood 104, 428–435 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Hoppe, B., Burmester, G. R. & Häupl, T. Prothrombin 20210G>A genotype and C-reactive protein level. Blood 118, 4495–4496 (2011).

    Article  CAS  PubMed  Google Scholar 

  57. Mosesson, M. W. Fibrinogen and fibrin structure and functions. J. Thromb. Haemost. 3, 1894–1904 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Lanir, N. et al. Macrophage migration in fibrin gel matrices. II. Effects of clotting factor XIII, fibronectin, and glycosaminoglycan content on cell migration. J. Immunol. 140, 2340–2349 (1988).

    CAS  PubMed  Google Scholar 

  59. Loof, T. G. et al. Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense. Blood 118, 2589–2598 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Hoppe, B. et al. Fibrinogen and factor XIII A-subunit genotypes interactively influence C-reactive protein levels during inflammation. Ann. Rheum. Dis. 71, 1163–1169 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Lim, B. C., Ariëns, R. A., Carter, A. M., Weisel, J. W. & Grant, P. J. Genetic regulation of fibrin structure and function: complex gene–environment interactions may modulate vascular risk. Lancet 361, 1424–1431 (2003).

    Article  CAS  PubMed  Google Scholar 

  62. Reiner, A. P. et al. Association between patterns of nucleotide variation across the three fibrinogen genes and plasma fibrinogen levels: the Coronary Artery Risk Development in Young Adults (CARDIA) study. J. Thromb. Haemost. 4, 1279–1287 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Siegerink, B., Rosendaal, F. R. & Algra, A. Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. J. Thromb. Haemost. 7, 385–390 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Ariens, R. A., Lai, T. S., Weisel, J. W., Greenberg, C. S. & Grant, P. J. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood 100, 743–754 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Van Meegeren, M. E., Roosendaal, G., Barten-van Rijbroek, A.D., Mastbergen, S.C. & Lafeber, F. P. Intra-articular blood coagulation aggravates joint damage after a bleed in a canine in vivo model [abstract]. Osteoarthritis Cartilage 20, S49 (2012).

    Article  Google Scholar 

  66. Senior, R. M., Skogen, W. F., Griffin, G. L. & Wilner, G. D. Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B. J. Clin. Invest. 77, 1014–1019 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Persson, K., Russell, W., Mörgelin, M. & Herwald, H. The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides. J. Biol. Chem. 278, 31884–31890 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Sokolove, J., Zhao, X. & Robinson, W. Citrullinated fibrinogen stimulates TNF release via TLR-4 and citrullinated fibrinogen immune complexes co-stimulate through TLR-4 and the Fc gamma receptor [abstract]. Clin. Immunol. 135 (Suppl.), S38 (2010).

    Article  Google Scholar 

  69. Sokolove, J., Zhao, X., Chandra, P. E. & Robinson, W. H. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fc gamma receptor. Arthritis Rheum. 63, 53–62 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Flick, M. J. et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J. Clin. Invest. 113, 1596–1606 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Flick, M. J. et al. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J. Clin. Invest. 117, 3224–3235 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Klareskog, L., Rönnelid, J., Lundberg, K., Padyukov, L. & Alfredsson, L. Immunity to citrullinated proteins in rheumatoid arthritis. Annu. Rev. Immunol. 26, 651–675 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Kuhn, K. A. et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J. Clin. Invest. 116, 961–973 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hill, J. A., Al-Bishri, J. Gladman, D. D., Cairns, E. & Bell, D. A. Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis. J. Rheumatol. 33, 2115–2119 (2006).

    CAS  PubMed  Google Scholar 

  75. Sokolove, J. et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS ONE 7, e35296 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hill, J. A. et al. Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-I E transgenic mice. J. Exp. Med. 205, 967–979 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Belkin, A. M. et al. Transglutaminase-mediated oligomerization of the fibrin(ogen) alphaC domains promotes integrin-dependent cell adhesion and signaling. Blood 105, 3561–3568 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Liu, X. F. & Piela-Smith, T. H. Fibrin(ogen)-induced expression of ICAM-1 and chemokines in human synovial fibroblasts. J. Immunol. 165, 5255–5261 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Skogen, W. F., Senior, R. M., Griffin, G. L. & Wilner, G. D. Fibrinogen-derived peptide B beta 1–42 is a multidomained neutrophil chemoattractant. Blood 71, 1475–1479 (1988).

    CAS  PubMed  Google Scholar 

  80. Gaitonde, S. D. & Ballou, S. P. Deep venous thrombosis in dermatomyositis. J. Rheumatol. 35, 2288 (2008).

    Article  PubMed  Google Scholar 

  81. Selva-O'Callaghan, A., Fernandez-Lugue, A., Martinez-Gomez, X., Labirua-Ituburu, A. & Vilardell-Tarres, M. Venous thromboembolism in patients with dermatomyositis and polymyositis. Clin. Exp. Rheumatol. 29, 846–849 (2011).

    PubMed  Google Scholar 

  82. Weidner, S. Hafezi-Rachti, S. & Rupprecht, H. D. Thromboembolic events as a complication of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 55, 146–149 (2006).

    Article  PubMed  Google Scholar 

  83. Allenbach, Y. et al. High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener's granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1,130 patients. Ann. Rheum. Dis. 68, 564–567 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Both authors have contributed equally to researching the data for the article, to discussions of the content, and to writing, reviewing and editing the manuscript before submission.

Corresponding author

Correspondence to Thomas Dörner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoppe, B., Dörner, T. Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis. Nat Rev Rheumatol 8, 738–746 (2012). https://doi.org/10.1038/nrrheum.2012.184

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2012.184

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing