Skip to main content
Top
Published in: International Journal of Hematology 6/2016

01-06-2016 | Original Article

Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies

Authors: Wendy J. Langeberg, W. Marieke Schoonen, Melissa Eisen, Laurence Gamelin, Scott Stryker

Published in: International Journal of Hematology | Issue 6/2016

Login to get access

Abstract

This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists.
Literature
1.
go back to reference Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93.CrossRefPubMed Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113:2386–93.CrossRefPubMed
2.
3.
go back to reference Kuhne T, Berchtold W, Michaels LA, Wu R, Donato H, Espina B, et al. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica. 2011;96:1831–7.CrossRefPubMedPubMedCentral Kuhne T, Berchtold W, Michaels LA, Wu R, Donato H, Espina B, et al. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica. 2011;96:1831–7.CrossRefPubMedPubMedCentral
4.
go back to reference Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.CrossRefPubMed Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.CrossRefPubMed
5.
6.
go back to reference Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:641–8.CrossRefPubMed Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:641–8.CrossRefPubMed
7.
go back to reference Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.CrossRefPubMed Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.CrossRefPubMed
8.
go back to reference Catalá-López F, Corrales I, de la Fuente-Honrubia C, González-Bermejo D, Martín-Serrano G, Montero D, Saint-Gerons DM. Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: an updated systematic review and meta-analysis of randomized controlled trials. Med Clin (Barc). 2015;145:511–19. Catalá-López F, Corrales I, de la Fuente-Honrubia C, González-Bermejo D, Martín-Serrano G, Montero D, Saint-Gerons DM. Risk of thromboembolism with thrombopoietin receptor agonists in adult patients with thrombocytopenia: an updated systematic review and meta-analysis of randomized controlled trials. Med Clin (Barc). 2015;145:511–19.
9.
go back to reference Nørgaard M. Thrombosis in patients with primary chronic immune thrombocytopenia. Thromb Res. 2012;130(suppl 1):S74–5.CrossRefPubMed Nørgaard M. Thrombosis in patients with primary chronic immune thrombocytopenia. Thromb Res. 2012;130(suppl 1):S74–5.CrossRefPubMed
10.
go back to reference Lowe GD. Common risk factors for both arterial and venous thrombosis. Br J Haematol. 2008;140:488–95.CrossRefPubMed Lowe GD. Common risk factors for both arterial and venous thrombosis. Br J Haematol. 2008;140:488–95.CrossRefPubMed
11.
go back to reference Previtali E, Bucciarelli P, Passamonti SM, Martinelli I. Risk factors for venous and arterial thrombosis. Blood Transfus. 2011;9:120–38.PubMedPubMedCentral Previtali E, Bucciarelli P, Passamonti SM, Martinelli I. Risk factors for venous and arterial thrombosis. Blood Transfus. 2011;9:120–38.PubMedPubMedCentral
12.
go back to reference Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.CrossRefPubMed Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.CrossRefPubMed
13.
go back to reference Sterne JAC, Bradburn MJ, Egger M. Meta-analysis in stata. In: Egger M, Smith GD, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. 2nd ed. London: BMJ; 2008. p. 347–69. Sterne JAC, Bradburn MJ, Egger M. Meta-analysis in stata. In: Egger M, Smith GD, Altman DG, editors. Systematic reviews in health care: meta-analysis in context. 2nd ed. London: BMJ; 2008. p. 347–69.
16.
go back to reference Severinsen MT, Engebjerg MC, Farkas DK, Jensen AØ, Nørgaard M, Zhao S, et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2011;152:360–2.CrossRefPubMed Severinsen MT, Engebjerg MC, Farkas DK, Jensen AØ, Nørgaard M, Zhao S, et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2011;152:360–2.CrossRefPubMed
17.
go back to reference Nørgaard M, Severinsen MT, Lund Maegbaek M, Jensen AØ, Cha S, Sørensen HT. Risk of arterial thrombosis in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2012;159:109–11.CrossRefPubMed Nørgaard M, Severinsen MT, Lund Maegbaek M, Jensen AØ, Cha S, Sørensen HT. Risk of arterial thrombosis in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol. 2012;159:109–11.CrossRefPubMed
18.
go back to reference Sarpatwari A, Bennett D, Logie JW, Shukla A, Beach KJ, Newland AC, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95:1167–75.CrossRefPubMedPubMedCentral Sarpatwari A, Bennett D, Logie JW, Shukla A, Beach KJ, Newland AC, et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica. 2010;95:1167–75.CrossRefPubMedPubMedCentral
19.
go back to reference Enger C, Bennett D, Forssen U, Fogarty PF, McAfee AT. Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol. 2010;92:289–95.CrossRefPubMed Enger C, Bennett D, Forssen U, Fogarty PF, McAfee AT. Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol. 2010;92:289–95.CrossRefPubMed
20.
go back to reference 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. 2012;379:244–9.CrossRefPubMed 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. 2012;379:244–9.CrossRefPubMed
21.
go back to reference Charlson ME, Pompei P, Ales KL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40:373–83.CrossRefPubMed Charlson ME, Pompei P, Ales KL, Mackenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40:373–83.CrossRefPubMed
22.
go back to reference Aledort LM, Hayward CP, Chen MG, Nichol JL, Bussel J, ITP Study Group. 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. 2004;76:205–13.CrossRefPubMed Aledort LM, Hayward CP, Chen MG, Nichol JL, Bussel J, ITP Study Group. 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. 2004;76:205–13.CrossRefPubMed
24.
go back to reference Rhee HY, Choi HY, Kim SB, Shin WC. Recurrent ischemic stroke in a patient with idiopathic thrombocytopenic purpura. J Thromb Haemost. 2010;30:229–32. Rhee HY, Choi HY, Kim SB, Shin WC. Recurrent ischemic stroke in a patient with idiopathic thrombocytopenic purpura. J Thromb Haemost. 2010;30:229–32.
25.
go back to reference Rand ML, Dean JA. Platelet function in autoimmune (idiopathic) thrombocytopenic purpura. Acta Paediatr Suppl. 1998;424:57–60.PubMed Rand ML, Dean JA. Platelet function in autoimmune (idiopathic) thrombocytopenic purpura. Acta Paediatr Suppl. 1998;424:57–60.PubMed
26.
go back to reference Kim KJ, Baek IW, Yoon CH, Kim WU, Cho CS. Thrombotic risk in patients with immune thrombocytopenia and its association with antiphospholipid antibodies. Br J Haematol. 2013;161:706–14.CrossRefPubMed Kim KJ, Baek IW, Yoon CH, Kim WU, Cho CS. Thrombotic risk in patients with immune thrombocytopenia and its association with antiphospholipid antibodies. Br J Haematol. 2013;161:706–14.CrossRefPubMed
27.
go back to reference Uthman I, Godeau B, Taher A, Khamashta M. The hematologic manifestations of the antiphospholipid syndrome. Blood Rev. 2008;22:187–94.CrossRefPubMed Uthman I, Godeau B, Taher A, Khamashta M. The hematologic manifestations of the antiphospholipid syndrome. Blood Rev. 2008;22:187–94.CrossRefPubMed
28.
go back to reference Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.CrossRefPubMed Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.CrossRefPubMed
29.
go back to reference Diz-Kucukkaya R. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98:1760–4.CrossRefPubMed Diz-Kucukkaya R. Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study. Blood. 2001;98:1760–4.CrossRefPubMed
30.
go back to reference Pierrot-Deseilligny Despujol C, Michel M, Khellaf M, Gouault M, Intrator L, Bierling P, et al. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol. 2008;142:638–43.CrossRefPubMed Pierrot-Deseilligny Despujol C, Michel M, Khellaf M, Gouault M, Intrator L, Bierling P, et al. Antiphospholipid antibodies in adults with immune thrombocytopenic purpura. Br J Haematol. 2008;142:638–43.CrossRefPubMed
31.
go back to reference Yang YJ, Yun GW, Song IC, Baek SW, Lee KS, Ryu HW, et al. Clinical implications of elevated antiphospholipid antibodies in adult patients with primary immune thrombocytopenia. Korean J Intern Med. 2011;26:449–54.CrossRefPubMedPubMedCentral Yang YJ, Yun GW, Song IC, Baek SW, Lee KS, Ryu HW, et al. Clinical implications of elevated antiphospholipid antibodies in adult patients with primary immune thrombocytopenia. Korean J Intern Med. 2011;26:449–54.CrossRefPubMedPubMedCentral
32.
go back to reference Ruggeri M, Tosetto A, Palandri F, Polverelli N, Mazzucconi MG, Santoro C, et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014;12:1266–73.CrossRefPubMed Ruggeri M, Tosetto A, Palandri F, Polverelli N, Mazzucconi MG, Santoro C, et al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost. 2014;12:1266–73.CrossRefPubMed
33.
go back to reference Al-Riyami AZ, Lee J, Connolly M, Shereck E. Cerebral sinus thrombosis following IV immunoglobulin therapy of immune thrombocytopenia purpura. Pediatr Blood Cancer. 2011;57:157–9.CrossRefPubMed Al-Riyami AZ, Lee J, Connolly M, Shereck E. Cerebral sinus thrombosis following IV immunoglobulin therapy of immune thrombocytopenia purpura. Pediatr Blood Cancer. 2011;57:157–9.CrossRefPubMed
34.
go back to reference Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood. 2013;121:4782–90.CrossRefPubMedPubMedCentral Boyle S, White RH, Brunson A, Wun T. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood. 2013;121:4782–90.CrossRefPubMedPubMedCentral
35.
36.
go back to reference Thachil J, Callaghan T, Martlew V. Thromboembolic events are not uncommon in patients with immune thrombocytopenia. Br J Haematol. 2010;150:496–7.PubMed Thachil J, Callaghan T, Martlew V. Thromboembolic events are not uncommon in patients with immune thrombocytopenia. Br J Haematol. 2010;150:496–7.PubMed
38.
go back to reference Thomsen RW, Schoonen WM, Farkas DK, Riis A, Fryzek JP, Sørensen HT. Risk of venous thromboembolism in splenectomized patients compared with the general population and appendectomized patients: a 10-year nationwide cohort study. J Thromb Haemost. 2010;8:1413–6.CrossRefPubMed Thomsen RW, Schoonen WM, Farkas DK, Riis A, Fryzek JP, Sørensen HT. Risk of venous thromboembolism in splenectomized patients compared with the general population and appendectomized patients: a 10-year nationwide cohort study. J Thromb Haemost. 2010;8:1413–6.CrossRefPubMed
Metadata
Title
Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies
Authors
Wendy J. Langeberg
W. Marieke Schoonen
Melissa Eisen
Laurence Gamelin
Scott Stryker
Publication date
01-06-2016
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 6/2016
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-016-1974-6

Other articles of this Issue 6/2016

International Journal of Hematology 6/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine