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Ischemic stroke/transient ischemic attack in adults with primary immune thrombocytopenia: a meta-analysis

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Abstract

Objective

To carry out a systematic review to help resolve the controversy of ischemic stroke (IS)/transient ischemic attack (TIA) in patients with primary immune thrombocytopenia (ITP).

Methods

A database search of PubMed and Ovid Embase was conducted for epidemiologic studies published up to December 17, 2019. The effective size was estimated by pooled prevalence, annualized incidence/risk, relative risk (RR), and their corresponding 95% confidence intervals (CIs).

Results

The systematic review included 14 eligible studies from 11 publications. The pooled annualized cumulative incidence was 0.15% (95% CI, 0.03–0.26%) per person-years. And the pooled annualized cumulative risk of IS/TIA of ITP was 0.86% (95% CI, 0.33–1.39%) per year based on 3 population-based cohort studies. There was a higher risk of incident IS/TIA in ITP patients than ITP-free subjects (pooled unadjusted or adjusted RR with 95% CI, 1.46 [1.22–1.74] or 1.50 [1.29–1.73]).

Conclusions

IS/TIA was not uncommon in patients with primary ITP. ITP patients have a higher risk of IS/TIA compared with the reference cohorts. Healthcare professionals should take into account the risk of IS/TIA when treating ITP patients with or without a history of IS/TIA.

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References

  1. Cooper N, Ghanima W (2019) Immune thrombocytopenia. N Engl J Med 381(10):945–955

    PubMed  Google Scholar 

  2. Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN (2010) The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 85(3):174–180

    PubMed  Google Scholar 

  3. Mihalov J, Timarova G (2016) A seeming paradox: ischemic stroke in the context of idiopathic thrombocytopenic purpura. Clinical & Applied Thrombosis/Hemostasis 22(2):115–120

    Google Scholar 

  4. Furlan JC, Fang J, Silver FL (2016) Outcomes after acute ischemic stroke in patients with thrombocytopenia or thrombocytosis. J Neurol Sci 362:198–203

    PubMed  Google Scholar 

  5. Fogarty PF, Segal JB (2007) The epidemiology of immune thrombocytopenic purpura. Curr Opin Hematol 14(5):515–519

    PubMed  Google Scholar 

  6. Ekstrand C, Linder M, Baricault B, Lafaurie M, Sailler L, Lapeyre-Mestre M, Kieler H, Moulis G, Bahmanyar S (2019) Impact of risk factors on the occurrence of arterial thrombosis and venous thromboembolism in adults with primary immune thrombocytopenia - results from two nationwide cohorts. Thromb Res 178:124–131

    CAS  PubMed  Google Scholar 

  7. Jy W, Horstman LL, Arce M, Ahn YS (1992) Clinical significance of platelet microparticles in autoimmune thrombocytopenias. Journal of Laboratory & Clinical Medicine 119(4):334–345

    CAS  Google Scholar 

  8. Sewify EM, Sayed D, Abdel Aal RF, Ahmad HM, Abdou MA (2013) Increased circulating red cell microparticles (RMP) and platelet microparticles (PMP) in immune thrombocytopenic purpura. Thromb Res 131(2):e59–e63

    CAS  PubMed  Google Scholar 

  9. Davizon P, Lopez JA (2009) Microparticles and thrombotic disease. Curr Opin Hematol 16(5):334–341

    PubMed  Google Scholar 

  10. Chandan JS, Thomas T, Lee S, Marshall T, Willis B, Nirantharakumar K, Gill P (2018) The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study. Journal of Thrombosis & Haemostasis 16(3):474–480

    CAS  Google Scholar 

  11. Nørgaard M, Cetin K, Maegbaek ML, Kristensen NR, Ghanima W, Bahmanyar S, Stryker S, Christiansen CF (2016) Risk of arterial thrombotic and venous thromboembolic events in patients with primary chronic immune thrombocytopenia: a Scandinavian population-based cohort study. Br J Haematol 174(4):639–642

    PubMed  Google Scholar 

  12. Enger C, Bennett D, Forssen U, Fogarty PF, McAfee AT (2010) Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol 92(2):289–295

    PubMed  Google Scholar 

  13. Sarpatwari A, Bennett D, Logie JW, Shukla A, Beach KJ, Newland AC, Sanderson S, Provan D (2010) Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom general practice research database. Haematologica 95(7):1167–1175

    PubMed  PubMed Central  Google Scholar 

  14. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Jama 283(15):2008–2012

    CAS  PubMed  Google Scholar 

  15. Zeng X, Zhang Y, Kwong JS et al (2015) The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med 8(1):2–10

    PubMed  Google Scholar 

  16. Moga C, Guo B, Schopflocher D, Harstall C (2012) Development of a quality appraisal tool for case series studies using a modified Delphi technique. http://www.iheca/documents/Case%20series%20studies%20using%20a%20modified%20Delphi%20technique.pdf. Accessed 11 Feburary, 2020

  17. Nyaga VN, Arbyn M, Aerts M (2014) Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health 72(1):39

    PubMed  PubMed Central  Google Scholar 

  18. Harris RJ, Deeks JJ, Altman DG, Bradburn MJ, Harbord RM, Sterne JA (2008) Metan: fixed-and random-effects meta-analysis. Stata J 8(1):3–28

    Google Scholar 

  19. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. Bmj 327(7414):557–560

    PubMed  PubMed Central  Google Scholar 

  20. Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1(2):97–111

    PubMed  Google Scholar 

  21. Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23(9):1351–1375

    PubMed  Google Scholar 

  22. Zhang T, Zhong W (2012) Applied methodology for evidence-based medicine. Central South University Press, Changsha, Hunan Province

    Google Scholar 

  23. Nørgaard M, Jensen AO, Engebjerg MC, Farkas DK, Thomsen RW, Cha S, Zhao S, Sørensen HT (2011) Long-term clinical outcomes of patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Blood 117(13):3514–3520

    PubMed  Google Scholar 

  24. Sinkovic A, Majal M (2015) The impact of thrombocytopenia on outcome in patients with acute coronary syndromes: a single center retrospective study. Biomed Res Int 2015:907304

    PubMed  PubMed Central  Google Scholar 

  25. Moret C, Tichelli A, Wieland-Greguare-Sander A, Angelillo-Scherrer A, Rovo A (2017) Prevalence and risk factors for thrombosis in adult ITP patients. Haematologica 102 (supplement 2): 594

  26. Sico JJ, Phipps MS, Concato J, Wells CK, Lo AC, Nadeau SE, Williams LS, Peixoto AJ, Gorman M, Boice JL, Bravata DM (2013) Thrombocytopenia and in-hospital mortality risk among ischemic stroke patients. Journal of Stroke & Cerebrovascular Diseases 22(7):e99–e102

    Google Scholar 

  27. Ekstrand C, Baricault B, Linder M, et al. (2017) Prevalence of cardiovascular risk factors and incidence of venous and arterial thrombosis in non-splenectomized immune thrombocytopenia adult patients in sweden and france. results from two nationwide studies. Blood Conference: 59th Annual Meeting of the American Society of Hematology, ASH 130 (Supplement 1)

  28. Yang YJ, Yun GW, Song IC, Baek SW, Lee KS, Ryu HW, Lee MW, Lee HJ, Yun HJ, Kim S, Jo DY (2011) Clinical implications of elevated antiphospholipid antibodies in adult patients with primary immune thrombocytopenia. Korean J Intern Med 26(4):449–454

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Pierrot-Deseilligny Despujol C, Michel M, Khellaf M, Gouault M, Intrator L, Bierling P, Godeau B (2008) Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol 142(4):638–643

    PubMed  Google Scholar 

  30. Stasi R, Stipa E, Masi M, Cecconi M, Scimò MT, Oliva F, Sciarra A, Perrotti AP, Adomo G, Amadori S, Papa G (1995) Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura. Am J Med 98(5):436–442

    CAS  PubMed  Google Scholar 

  31. Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR (2003) Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 122(6):966–974

    PubMed  Google Scholar 

  32. Jimenez JJ, Jy W, Mauro LM, Horstman LL, Fontana V, Ahn YS (2008) Transendothelial migration of leukocytes is promoted by plasma from a subgroup of immune thrombocytopenic purpura patients with small-vessel ischemic brain disease. Am J Hematol 83(3):206–211

    PubMed  Google Scholar 

  33. Kaya E, Erkurt MA, Aydogdu I, Kuku I, Ozhan O, Oner RI, Ulutas O (2007) Retrospective analysis of patients with idiopathic thrombocytopenic purpura from eastern Anatolia. Med Prin Pract 16(2):100–106

    Google Scholar 

  34. Bidot L, Jy W, Bidot C Jr, Jimenez JJ, Fontana V, Horstman LL, Ahn YS (2008) Microparticle-mediated thrombin generation assay: increased activity in patients with recurrent thrombosis. Journal of Thrombosis & Haemostasis 6(6):913–919

    CAS  Google Scholar 

  35. Moulis G, Baricault B, Ekstrand C, et al. (2018) Risk factors of thrombosis in adults with primary immune thrombocytopenia. a french nationwide cohort study. Blood Conference: 60th Annual Meeting of the American Society of Hematology, ASH 132 (Suppl. 1)

  36. Enger C, Bennett D, Forssen U, McAfee AT (2009) Risk of thromboembolic events among persons with chronic idiopathic thrombocytopenia purpura. Pharmacoepidem DRS 18(S1):S217

    Google Scholar 

  37. Feudjo-Tepie MA, Le Roux G, Beach KJ, Bennett D, Robinson NJ (2009) Comorbidities of idiopathic thrombocytopenic purpura: a population-based study. Adv Hematol 2009:963506

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Aledort LM, Hayward CP, Chen MG, Nichol JL, Bussel J (2004) Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies. Am J Hematol 76(3):205–213

    CAS  PubMed  Google Scholar 

  39. Machin N, Ragni MV, Comer DM, Yabes JG (2018) Prevalence and correlates of thrombosis in adults with immune thrombocytopenia: an NIS study. Thromb Res 172:80–85

    CAS  PubMed  Google Scholar 

  40. Diz-Küçükkaya R, Hacıhanefioğlu A, Yenerel M, Turgut M, Keskin H, Nalçacı M, Īnanç M (2001) Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood 98(6):1760–1764

    PubMed  Google Scholar 

  41. Gadenstatter M, Lamprecht B, Klingler A, Wetscher GJ, Greil R, Schmid T (2002) Splenectomy versus medical treatment for idiopathic thrombocytopenic purpura. Am J Surg 184(6):606–609 discussion 609-610

    PubMed  Google Scholar 

  42. Kim KJ, Baek IW, Yoon CH, Kim WU, Cho CS (2013) Thrombotic risk in patients with immune thrombocytopenia and its association with antiphospholipid antibodies. Br J Haematol 161(5):706–714

    CAS  PubMed  Google Scholar 

  43. Ruggeri M, Tosetto A, Palandri F, Polverelli N, Mazzucconi MG, Santoro C, Gaidano G, Lunghi M, Zaja F, de Stefano V, Sartori R, Fazi P, Rodeghiero F, the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Anemia and Thrombocytopenias Working Party. GIMEMA Study ITP0311 (2014) Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. Journal of Thrombosis & Haemostasis 12(8):1266–1273

    CAS  Google Scholar 

  44. Khare S (2016) Risk factors of transient ischemic attack: an overview. J Mid-life Health 7(1):2–7

    Google Scholar 

  45. Weimar C, Diener HC, Alberts MJ, Steg PG, Bhatt DL, Wilson PW, Mas JL, Röther J, REduction of Atherothrombosis for Continued Health Registry Investigators (2009) The Essen stroke risk score predicts recurrent cardiovascular events: a validation within the REduction of Atherothrombosis for continued health (REACH) registry. Stroke 40(2):350–354

    PubMed  Google Scholar 

  46. Lee YJ, Jy W, Horstman LL, Janania J, Reyes Y, Kelley RE, Ahn YS (1993) Elevated platelet microparticles in transient ischemic attacks, lacunar infarcts, and multiinfarct dementias. Thromb Res 72(4):295–304

    CAS  PubMed  Google Scholar 

  47. Ichijo M, Ishibashi S, Ohkubo T, Nomura S, Sanjo N, Yokota T, Mizusawa H (2014) Elevated platelet microparticle levels after acute ischemic stroke with concurrent idiopathic thrombocytopenic purpura. Journal of Stroke & Cerebrovascular Diseases 23(3):587–589

    Google Scholar 

  48. Thachil J, Callaghan T, Martlew V (2010) Thromboembolic events are not uncommon in patients with immune thrombocytopenia. Br J Haematol 150(4):496–497

    PubMed  Google Scholar 

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Funding

This study was supported by the Jiangxi Project of Health Commission (no. 20204733 and 20197487) and the Yichun Project of Science and Technology (no. JXYC2018KSB032).

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Authors and Affiliations

  1. School of Clinical Medicine, Yichun Vocational Technical College, 399 West Zhong Shan Road, Yichun, 336000, Jiangxi Province, People’s Republic of China

    Lishou Pan

  2. Department of Neurology, The People’s Hospital of Yichun City, Yichun University, 1061 Jinxiu Road, Yichun, 336000, Jiangxi Province, People’s Republic of China

    Huilin Leng & Ningyan Xia

  3. Department of Pharmacology, The People’s Hospital of Yichun City, Yichun University, 1061 Jinxiu Road, Yichun, 336000, Jiangxi Province, People’s Republic of China

    Yin Huang

  4. Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, People’s Republic of China

    Lingjin Jin

  5. Departments of Neuroscience and Behavioral Medicine & Psychiatry, the Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, WV, 26506, USA

    Han-Ting Zhang

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  1. Lishou Pan
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Correspondence to Huilin Leng.

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Approval from an ethics committee was not required because all data used in the present study were extracted from publications.

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Pan, L., Leng, H., Huang, Y. et al. Ischemic stroke/transient ischemic attack in adults with primary immune thrombocytopenia: a meta-analysis. Neurol Sci 42, 2013–2020 (2021). https://doi.org/10.1007/s10072-020-04746-2

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