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Clinical Rheumatology

, Volume 39, Issue 1, pp 19–26 | Cite as

Risk of bleeding events among patients with systemic sclerosis and the general population in the UK: a large population-based cohort study

  • Alexander MichelEmail author
  • Antonio González-Pérez
  • María E. Sáez
  • Luis A. García Rodríguez
Original Article
  • 102 Downloads
Part of the following topical collections:
  1. Updates in Systemic Sclerosis

Abstract

Introduction/objectives

To compare the risk of different bleeding outcomes between patients with systemic sclerosis (SSc) and the general population free of SSc.

Methods

Using UK electronic primary care data (2000–2012), 1314 patients with SSc and a matched SSc-free comparison cohort (n = 19,992) were followed until December 2013 to identify bleeding, confirmed following manual review of patient records including free text comments. Incidence rates were calculated and Cox regression used to estimate adjusted hazard ratios (HRs; SSc cohort vs. matched general population cohort) adjusted for confounders.

Results

One hundred and twenty-seven bleeding events occurred in the SSc cohort and 1762 in the general population cohort; incidence rates per 1000 person-years for the SSc cohort and general population cohort were 0.5 versus 0.3 for hemorrhagic stroke, 4.1 versus 3.3 for gastrointestinal bleeding, 2.5 versus 1.7 for pulmonary hemorrhage, 8.4 versus 7.5 for urogenital bleeding, and 15.5 versus 12.9 for any of the aforementioned bleedings. Adjusted HRs (95% confidence intervals) were 1.21 (1.00–1.46) for any bleeding, 1.51 (0.54–4.21) for hemorrhagic stroke, 1.50 (0.96–2.35) for pulmonary hemorrhage, 1.08 (0.75–1.54) for gastrointestinal bleeds, and 1.28 (1.00–1.64) for urogenital bleeds. HRs were more often higher in SSc patients with organ involvement than without organ involvement and in those with diffuse cutaneous SSc.

Conclusion

Our results are consistent with a moderately increased risk of bleeding in SSc patients. Further evidence from large SSc patient cohorts is needed to confirm this finding.

Key Points

The risk of experiencing a major bleed may be higher among patients with SSc than the general population.

Further large and well-designed studies are needed to corroborate our findings.

Keywords (MeSH)

Cohort studies Hemorrhage Scleroderma Systemic United Kingdom 

Notes

Acknowledgments

The authors acknowledge and thank Susan Bromley, EpiMed Communications Ltd. (Oxford, UK) for editorial support funded by Bayer AG.

Funding

This study was funded by Bayer AG.

Compliance with ethical standards

Conflict of interest

AM is a full-time employee of Bayer Consumer Care AG, Basel, Switzerland. LAGR, AG-P, and MES work for CEIFE, which have received research funding from Bayer AG. LAGR has received honoraria for serving on advisory boards for Bayer AG. The authors declare no non-financial conflict of interests.

Ethical standards

This study used anonymized primary care electronic health records. No clinical subjects were involved and therefore informed consent was not applicable.

Supplementary material

10067_2019_4588_MOESM1_ESM.docx (25 kb)
Supplementary Table 1 (DOCX 24 kb)
10067_2019_4588_MOESM2_ESM.docx (21 kb)
Supplementary Table 2 (DOCX 21 kb)
10067_2019_4588_MOESM3_ESM.docx (33 kb)
Supplementary Table 3 (DOCX 33 kb)
10067_2019_4588_MOESM4_ESM.docx (24 kb)
Supplementary Table 4 (DOCX 24 kb)

References

  1. 1.
    Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP et al (2015) Systemic sclerosis. Nat Rev Dis Primers 1:15002CrossRefGoogle Scholar
  2. 2.
    Duchini A, Sessoms SL (1998) Gastrointestinal hemorrhage in patients with systemic sclerosis and crest syndrome. Am J Gastroenterol 93:1453–1456CrossRefGoogle Scholar
  3. 3.
    Sarac H, Telarovic S, Zarkovic K (2015) Multiple intracerebral hemorrhages in a patient with systemic sclerosis sine scleroderma. Acta Neurol Belg 115:151–152CrossRefGoogle Scholar
  4. 4.
    Nakamura K, Yoshizaki A, Takahashi T, Saigusa R, Taniguchi T, Asano Y, Gonoi W, Hinata M, Shinozaki-Ushiku A, Sato S (2016) The first case report of fatal acute pulmonary dysfunction in a systemic sclerosis patient treated with rituximab. Scand J Rheumatol 45:249–250CrossRefGoogle Scholar
  5. 5.
    Bhangoo MS, Hein P, Nicholson L, Carter C (2014) Spontaneous subdural haemorrhage in a patient with scleroderma renal crisis. BMJ Case Rep 2014:bcr2014205471CrossRefGoogle Scholar
  6. 6.
    Griffin MT, Robb JD, Martin JR (1990) Diffuse alveolar haemorrhage associated with progressive systemic sclerosis. Thorax 45:903–904CrossRefGoogle Scholar
  7. 7.
    Chaer RA, Massad MG, Evans A, Olopade C, Varga J (2001) Systemic sclerosis complicated by diffuse alveolar hemorrhage. Med Sci Monit 7:1013–1015PubMedGoogle Scholar
  8. 8.
    Lewis JD, Schinnar R, Bilker WB, Wang X, Strom BL (2007) Validation studies of the health improvement network (thin) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf 16:393–401CrossRefGoogle Scholar
  9. 9.
    Stuart-Buttle CD, Read JD, Sanderson HF, Sutton YM (1996) A language of health in action: Read codes, classifications and groupings. Proc AMIA Annu Fall Symp 1996:75–79Google Scholar
  10. 10.
    NHS Digital. Read codes. https://digital.nhs.uk/article/1104/Read-Codes. Accessed 26 November 2018
  11. 11.
  12. 12.
    Garcia Rodriguez LA, Gonzalez-Perez A, Michel A, et al. (2018) Contemporary epidemiology of systemic sclerosis: a population-based cohort study in the United Kingdom. Semin Arthritis Rheum doi:  https://doi.org/10.1016/j.semarthrit.2018.11.002 CrossRefGoogle Scholar
  13. 13.
    Gaist D, Wallander MA, Gonzalez-Perez A, Garcia-Rodriguez LA (2013) Incidence of hemorrhagic stroke in the general population: validation of data from the health improvement network. Pharmacoepidemiol Drug Saf 22:176–182CrossRefGoogle Scholar
  14. 14.
    García Rodríguez LA, Barreales Tolosa L (2007) Risk of upper gastrointestinal complications among users of traditional nsaids and coxibs in the general population. Gastroenterology 132:498–506CrossRefGoogle Scholar
  15. 15.
    González-Pérez A, Sáez ME, Johansson S, Himmelmann A, García Rodríguez LA (2016) Risk of bleeding after hospitalization for a serious coronary event: a retrospective cohort study with nested case-control analyses. BMC Cardiovasc Disord 16:164CrossRefGoogle Scholar
  16. 16.
    Margulis AV, García Rodríguez LA, Hernandez-Diaz S (2009) Positive predictive value of computerized medical records for uncomplicated and complicated upper gastrointestinal ulcer. Pharmacoepidemiol Drug Saf 18:900–909CrossRefGoogle Scholar
  17. 17.
    Akkara Veetil BM, Schimmer BM (2009) A case of limited systemic sclerosis with p-anca, complicated by multiple cerebral hemorrhages. Rheumatol Int 29:325–329CrossRefGoogle Scholar
  18. 18.
    Goh KG, Ong SG (2015) Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome. Lupus 24:90–93CrossRefGoogle Scholar
  19. 19.
    Wutzl AL, Foley RN, O'Driscoll BR, Reeve RS, Chisholm R, Herrick AL (2001) Microscopic polyangiitis presenting as pulmonary-renal syndrome in a patient with long-standing diffuse cutaneous systemic sclerosis and antibodies to myeloperoxidase. Arthritis Rheum 45:533–536CrossRefGoogle Scholar
  20. 20.
    Yamada T, Nakajima H, Tanaka E, Nakajima A, Terai C, Hara M, Kamatani N (2003) Case of systemic sclerosis presenting with alveolar hemorrhage and positive anti-neutrophil cytoplasmic myeloperoxidase antibody (mpo-anca) without pathological renal involvement. Ryumachi 43:690–695PubMedGoogle Scholar
  21. 21.
    El-Gendy H, Shohdy KS, Maghraby GG, Abadeer K, Mahmoud M (2017) Gastric antral vascular ectasia in systemic sclerosis: where do we stand? Int J Rheum Dis 20(12):2133–2139CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Alexander Michel
    • 1
    Email author
  • Antonio González-Pérez
    • 2
    • 3
    • 4
  • María E. Sáez
    • 2
    • 3
  • Luis A. García Rodríguez
    • 2
  1. 1.Epidemiology, Division PharmaceuticalsBayer Consumer Care AGBaselSwitzerland
  2. 2.Spanish Centre for Pharmacoepidemiologic Research (CEIFE)MadridSpain
  3. 3.Andalusian Bioinformatics Research Centre (CAEBi)SevilleSpain
  4. 4.Pharmacoepidemiology Research GroupInstitute for Health Research IRYCISMadridSpain

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