Hamostaseologie 2019; 39(03): 238-249
DOI: 10.1055/s-0039-1683416
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Epidemiology and Clinical Manifestations of Immune Thrombocytopenia

Rahil Kohli
1   Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
,
Shruti Chaturvedi
1   Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
› Author Affiliations
Further Information

Publication History

03 September 2018

05 February 2019

Publication Date:
13 March 2019 (online)

Abstract

Immune thrombocytopenia (ITP) occurs with an incidence rate of 1.6 to 3.9 per 100,000 patient-years, which increases with age and has a slight female preponderance. ITP is termed acute, persistent or chronic when its duration is <3 months, 3 to 12 months and >12 months, respectively. In this narrative review, we discuss the clinical manifestations of ITP in children and adults. ITP is asymptomatic in some patients; however, when present, bleeding is the most common symptom and can be mild as in petechiae, purpura and epistaxis, or severe and even life threatening in cases of intracranial haemorrhage, and massive gastrointestinal or urinary tract bleeding. A platelet count <10–20 × 109/L, advanced age and prior minor bleeding are risk factors for major bleeding, which is also more common in the months following a new diagnosis of acute ITP. Fatigue and impaired health-related quality of life are also manifestations of ITP that often improve with treatment and improvement in platelet counts. Over long-term follow-up, ITP is also associated with an increased risk of venous and arterial thromboembolism, haematologic malignancy and overall mortality than the general population.

Zusammenfassung

Die Immunthrombozytopenie (ITP) tritt mit einer Inzidenzrate von 1,6 bis 3,9 pro 100.000 Patientenjahre auf, die mit zunehmendem Alter zunimmt und ein geringes Überwiegen der Frauen aufweist. ITP wird als akut, persistent oder chronisch bezeichnet, wenn die Dauer <3 Monate, 3 bis 12 Monate bzw.> 12 Monate beträgt. In dieser narrativen Übersichtsarbeit diskutieren wir die klinischen Erscheinungsformen von ITP bei Kindern und Erwachsenen. ITP ist bei manchen Patienten asymptomatisch; Blutungen sind jedoch, wenn vorhanden, das häufigste Symptom und können mild sein, wie bei Petechien, Purpura und Epistaxis, oder sogar schwer oder gar lebensbedrohlich bei intrakraniellen Blutungen oder massiven Blutungen im Gastrointestinal- oder Harntrakt. Eine Thrombozytenzahl <10–20 × 109 / L, ein fortgeschrittenes Alter und frühere geringfügige Blutungen sind Risikofaktoren für starke Blutungen, die auch häufiger in den Monaten nach einer neuen Diagnose einer akuten ITP auftreten. Erschöpfung und Beeinträchtigung der gesundheitsbezogenen Lebensqualität sind auch Manifestationen von ITP, die sich häufig durch Behandlung und Erhöhung der Thrombozytenzahl verbessern. Im langjährigen Follow-Up ist ITP auch mit einem höheren Risiko für venöse und arterielle Thromboembolien, hämatologischer Malignität und Gesamtmortalität verbunden als in der allgemeinen Bevölkerung.

 
  • References

  • 1 Bakchoul T, Sachs UJ. Platelet destruction in immune thrombocytopenia. Understanding the mechanisms. Hamostaseologie 2016; 36 (03) 187-194
  • 2 van Leeuwen EF, van der Ven JT, Engelfriet CP, von dem Borne AE. Specificity of autoantibodies in autoimmune thrombocytopenia. Blood 1982; 59 (01) 23-26
  • 3 He R, Reid DM, Jones CE, Shulman NR. Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura. Blood 1994; 83 (04) 1024-1032
  • 4 Audia S, Santegoets K, Laarhoven AG. , et al. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia. Clin Exp Immunol 2017; 188 (02) 275-282
  • 5 Roark JH, Bussel JB, Cines DB, Siegel DL. Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation. Blood 2002; 100 (04) 1388-1398
  • 6 Kuwana M, Okazaki Y, Kaburaki J, Kawakami Y, Ikeda Y. Spleen is a primary site for activation of platelet-reactive T and B cells in patients with immune thrombocytopenic purpura. J Immunol 2002; 168 (07) 3675-3682
  • 7 Kuwana M, Kawakami Y, Ikeda Y. Suppression of autoreactive T-cell response to glycoprotein IIb/IIIa by blockade of CD40/CD154 interaction: implications for treatment of immune thrombocytopenic purpura. Blood 2003; 101 (02) 621-623
  • 8 McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004; 103 (04) 1364-1369
  • 9 Chang M, Nakagawa PA, Williams SA. , et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 2003; 102 (03) 887-895
  • 10 Olsson B, Andersson PO, Jernås M. , et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9 (09) 1123-1124
  • 11 Lilleyman JS. Chronic childhood idiopathic thrombocytopenic purpura. Best Pract Res Clin Haematol 2000; 13 (03) 469-483
  • 12 Watts RG. Idiopathic thrombocytopenic purpura: a 10-year natural history study at the childrens hospital of alabama. Clin Pediatr (Phila) 2004; 43 (08) 691-702
  • 13 Cohn J. Thrombocytopenia in childhood: an evaluation of 433 patients. Scand J Haematol 1976; 16 (03) 226-240
  • 14 Lilleyman JS. ; Paediatric Haematology Forum of the British Society for Haematology. Intracranial haemorrhage in idiopathic thrombocytopenic purpura. Arch Dis Child 1994; 71 (03) 251-253
  • 15 Zeller B, Helgestad J, Hellebostad M. , et al. Immune thrombocytopenic purpura in childhood in Norway: a prospective, population-based registration. Pediatr Hematol Oncol 2000; 17 (07) 551-558
  • 16 Zeller B, Rajantie J, Hedlund-Treutiger I. , et al; NOPHO ITP. Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease. Acta Paediatr 2005; 94 (02) 178-184
  • 17 Sutor AH, Harms A, Kaufmehl K. Acute immune thrombocytopenia (ITP) in childhood: retrospective and prospective survey in Germany. Semin Thromb Hemost 2001; 27 (03) 253-267
  • 18 Bolton-Maggs PH, Moon I. Assessment of UK practice for management of acute childhood idiopathic thrombocytopenic purpura against published guidelines. Lancet 1997; 350 (9078): 620-623
  • 19 Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood 1999; 94 (03) 909-913
  • 20 Moulis G, Palmaro A, Montastruc JL, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood 2014; 124 (22) 3308-3315
  • 21 Abrahamson PE, Hall SA, Feudjo-Tepie M, Mitrani-Gold FS, Logie J. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol 2009; 83 (02) 83-89
  • 22 Koylu A, Pamuk GE, Uyanik MS, Demir M, Pamuk ON. Immune thrombocytopenia: epidemiological and clinical features of 216 patients in northwestern Turkey. Ann Hematol 2015; 94 (03) 459-466
  • 23 Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. ; Northern Region Haematology Group. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003; 122 (06) 966-974
  • 24 Schoonen WM, Kucera G, Coalson J. , et al. Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database. Br J Haematol 2009; 145 (02) 235-244
  • 25 Yong M, Schoonen WM, Li L. , et al. Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database. Br J Haematol 2010; 149 (06) 855-864
  • 26 Rand ML, Wright JF. Virus-associated idiopathic thrombocytopenic purpura. Transfus Sci 1998; 19 (03) 253-259
  • 27 Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113 (26) 6511-6521
  • 28 Rodeghiero F, Stasi R, Gernsheimer T. , 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 (11) 2386-2393
  • 29 Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4 (11) 2377-2383
  • 30 Terrell DR, Beebe LA, Neas BR, Vesely SK, Segal JB, George JN. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol 2012; 87 (09) 848-852
  • 31 Bennett D, Hodgson ME, Shukla A, Logie JW. Prevalence of diagnosed adult immune thrombocytopenia in the United Kingdom. Adv Ther 2011; 28 (12) 1096-1104
  • 32 Neunert CE, Buchanan GR, Imbach P. , et al; Intercontinental Cooperative ITP Study Group Registry II Participants. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013; 121 (22) 4457-4462
  • 33 Imbach P, Kühne T, Müller D. , et al. Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer 2006; 46 (03) 351-356
  • 34 Donato H, Picón A, Martinez M. , et al. Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina. Pediatr Blood Cancer 2009; 52 (04) 491-496
  • 35 Kühne T, Buchanan GR, Zimmerman S. , et al; Intercontinental Childhood ITP Study Group; Intercontinental Childhood ITP Study Group. A prospective comparative study of 2540 infants and children with newly diagnosed idiopathic thrombocytopenic purpura (ITP) from the Intercontinental Childhood ITP Study Group. J Pediatr 2003; 143 (05) 605-608
  • 36 Treutiger I, Rajantie J, Zeller B, Henter JI, Elinder G, Rosthøj S. ; NOPHO ITP Study Group. Does treatment of newly diagnosed idiopathic thrombocytopenic purpura reduce morbidity?. Arch Dis Child 2007; 92 (08) 704-707
  • 37 Edslev PW, Rosthøj S, Treutiger I, Rajantie J, Zeller B, Jonsson OG. ; NOPHO ITP Working Group. A clinical score predicting a brief and uneventful course of newly diagnosed idiopathic thrombocytopenic purpura in children. Br J Haematol 2007; 138 (04) 513-516
  • 38 Chotsampancharoen T, Sripornsawan P, Duangchoo S, Wongchanchailert M, McNeil E. Predictive factors for resolution of childhood immune thrombocytopenia: Experience from a single tertiary center in Thailand. Pediatr Blood Cancer 2017; 64 (01) 128-134
  • 39 Glanz J, France E, Xu S, Hayes T, Hambidge S. A population-based, multisite cohort study of the predictors of chronic idiopathic thrombocytopenic purpura in children. Pediatrics 2008; 121 (03) e506 –e512
  • 40 Revel-Vilk S, Yacobovich J, Frank S. , et al. Age and duration of bleeding symptoms at diagnosis best predict resolution of childhood immune thrombocytopenia at 3, 6, and 12 months. J Pediatr 2013; 163 (05) 1335-1339.e1 , 2
  • 41 Rosthøj S, Hedlund-Treutiger I, Rajantie J. , et al; NOPHO ITP Working Group. Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: a prospective Nordic study of an unselected cohort. J Pediatr 2003; 143 (03) 302-307
  • 42 Heitink-Pollé KMJ, Uiterwaal CSPM, Porcelijn L. , et al; TIKI Investigators. Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood 2018; 132 (09) 883-891
  • 43 Bussel JB, Lee CS, Seery C. , et al. Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration. Haematologica 2014; 99 (07) 1264-1271
  • 44 Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC. , et al. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood 2014; 123 (25) 3906-3908
  • 45 Schattner A. Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine 2005; 23 (30) 3876-3886
  • 46 Feusner JH, Slichter SJ, Harker LA. Mechanisms of thrombocytopenia in varicella. Am J Hematol 1979; 7 (03) 255-264
  • 47 Takahashi T, Yujiri T, Shinohara K. , et al. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura. Br J Haematol 2004; 124 (01) 91-96
  • 48 Nardi M, Karpatkin S. Antiidiotype antibody against platelet anti-GPIIIa contributes to the regulation of thrombocytopenia in HIV-1-ITP patients. J Exp Med 2000; 191 (12) 2093-2100
  • 49 Zhang W, Nardi MA, Borkowsky W, Li Z, Karpatkin S. Role of molecular mimicry of hepatitis C virus protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia. Blood 2009; 113 (17) 4086-4093
  • 50 Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of “hypersplenic” thrombocytopenia. J Clin Invest 1966; 45 (05) 645-657
  • 51 Bordin G, Ballaré M, Zigrossi P. , et al. A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion?. Clin Exp Rheumatol 1995; 13 (Suppl (Suppl. 13) S39 –S43
  • 52 Zucker-Franklin D, Termin CS, Cooper MC. Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1). Am J Pathol 1989; 134 (06) 1295-1303
  • 53 Verdonck LF, van Heugten H, de Gast GC. Delay in platelet recovery after bone marrow transplantation: impact of cytomegalovirus infection. Blood 1985; 66 (04) 921-925
  • 54 Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science 2003; 301 (5638): 1374-1377
  • 55 Hehle V, Fraser LD, Tahir R. , et al. Immunoglobulin kappa variable region gene selection during early human B cell development in health and systemic lupus erythematosus. Mol Immunol 2015; 65 (02) 215-223
  • 56 Praituan W, Rojnuckarin P. Faster platelet recovery by high-dose dexamethasone compared with standard-dose prednisolone in adult immune thrombocytopenia: a prospective randomized trial. J Thromb Haemost 2009; 7 (06) 1036-1038
  • 57 Neunert C, Noroozi N, Norman G. , et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost 2015; 13 (03) 457-464
  • 58 Kühne T, Berchtold W, Michaels LA. , et al; Intercontinental Cooperative ITP Study Group. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group. Haematologica 2011; 96 (12) 1831-1837
  • 59 Neunert CE, Buchanan GR, Imbach P. , et al; Intercontinental Childhood ITP Study Group Registry II Participants. Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura. Blood 2008; 112 (10) 4003-4008
  • 60 Altomare I, Cetin K, Wetten S, Wasser JS. Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US. Clin Epidemiol 2016; 8: 231-239
  • 61 Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 2000; 160 (11) 1630-1638
  • 62 Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology (Am Soc Hematol Educ Program) 2015; 2015: 237-242
  • 63 Neunert CE, Buchanan GR, Blanchette V. , et al. Relationships among bleeding severity, health-related quality of life, and platelet count in children with immune thrombocytopenic purpura. Pediatr Blood Cancer 2009; 53 (04) 652-654
  • 64 Arnold DM, Lim W. The use and abuse of surrogate endpoints in clinical research in transfusion medicine. Transfusion 2008; 48 (08) 1547-1549
  • 65 Neunert CE. Individualized treatment for immune thrombocytopenia: predicting bleeding risk. Semin Hematol 2013; 50 (Suppl (Suppl. 01) S55-S57
  • 66 Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991; 77 (01) 31-33
  • 67 Tsuda H, Tsuji T, Tsuji M, Yamasaki H. Life-threatening bleeding episodes in primary immune thrombocytopenia: a single-center retrospective study of 169 inpatients. Ann Hematol 2017; 96 (11) 1915-1920
  • 68 Psaila B, Petrovic A, Page LK, Menell J, Schonholz M, Bussel JB. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood 2009; 114 (23) 4777-4783
  • 69 Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol 2003; 25 (08) 660-664
  • 70 Gaydos LA, Freireich EJ, Mantel N. The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med 1962; 266: 905-909
  • 71 Slichter SJ, Harker LA. Thrombocytopenia: mechanisms and management of defects in platelet production. Clin Haematol 1978; 7 (03) 523-539
  • 72 Rosthøj S, Rajantie J, Treutiger I, Zeller B, Tedgård U, Henter JI. ; NOPHO ITP Working Group. Duration and morbidity of chronic immune thrombocytopenic purpura in children: five-year follow-up of a Nordic cohort. Acta Paediatr 2012; 101 (07) 761-766
  • 73 Pansy J, Minkov M, Dengg R. , et al. Evaluating bleeding severity in children with newly diagnosed immune thrombocytopenia: a pilot study. Klin Padiatr 2010; 222 (06) 374-377
  • 74 Khellaf M, Michel M, Schaeffer A, Bierling P, Godeau B. Assessment of a therapeutic strategy for adults with severe autoimmune thrombocytopenic purpura based on a bleeding score rather than platelet count. Haematologica 2005; 90 (06) 829-832
  • 75 Page LK, Psaila B, Provan D. , et al. The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding in patients with ITP. Br J Haematol 2007; 138 (02) 245-248
  • 76 Rand ML, Dean JA. Platelet function in autoimmune (idiopathic) thrombocytopenic purpura. Acta Paediatr Suppl 1998; 424: 57-60
  • 77 Middelburg RA, Carbaat-Ham JC, Hesam H, Ragusi MA, Zwaginga JJ. Platelet function in adult ITP patients can be either increased or decreased, compared to healthy controls, and is associated with bleeding risk. Hematology 2016; 21 (09) 549-551
  • 78 Panzer S, Rieger M, Vormittag R, Eichelberger B, Dunkler D, Pabinger I. Platelet function to estimate the bleeding risk in autoimmune thrombocytopenia. Eur J Clin Invest 2007; 37 (10) 814-819
  • 79 van Bladel ER, Laarhoven AG, van der Heijden LB. , et al. Functional platelet defects in children with severe chronic ITP as tested with 2 novel assays applicable for low platelet counts. Blood 2014; 123 (10) 1556-1563
  • 80 Tantawy AA, Matter RM, Hamed AA, Shams El Din El Telbany MA. Platelet microparticles in immune thrombocytopenic purpura in pediatrics. Pediatr Hematol Oncol 2010; 27 (04) 283-296
  • 81 Newton JL, Reese JA, Watson SI. , et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011; 86 (05) 420-429
  • 82 Hill QA, Newland AC. Fatigue in immune thrombocytopenia. Br J Haematol 2015; 170 (02) 141-149
  • 83 Frith J, Watson S, Bolton Maggs PH, Newton JL. Cognitive symptoms are common in immune thrombocytopenia and associate with autonomic symptom burden. Eur J Haematol 2012; 88 (03) 224-228
  • 84 McMillan R, Bussel JB, George JN, Lalla D, Nichol JL. Self-reported health-related quality of life in adults with chronic immune thrombocytopenic purpura. Am J Hematol 2008; 83 (02) 150-154
  • 85 Flores A, Klaassen RJ, Buchanan GR, Neunert CE. Patterns and influences in health-related quality of life in children with immune thrombocytopenia: a study from the Dallas ITP Cohort. Pediatr Blood Cancer 2017;64(08)
  • 86 Klaassen RJ, Blanchette VS, Barnard D. , et al. Validity, reliability, and responsiveness of a new measure of health-related quality of life in children with immune thrombocytopenic purpura: the Kids' ITP Tools. J Pediatr 2007; 150 (05) 510-515 , 515.e1
  • 87 Kuter DJ, Mathias SD, Rummel M. , et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol 2012; 87 (05) 558-561
  • 88 George JN, Mathias SD, Go RS. , et al. Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials. Br J Haematol 2009; 144 (03) 409-415
  • 89 Mathias SD, Li X, Eisen M, Carpenter N, Crosby RD, Blanchette VS. A phase 3, randomized, double-blind, placebo-controlled study to determine the effect of romiplostim on health-related quality of life in children with primary immune thrombocytopenia and associated burden in their parents. Pediatr Blood Cancer 2016; 63 (07) 1232-1237
  • 90 Severinsen MT, Engebjerg MC, Farkas DK. , et al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2011; 152 (03) 360-362
  • 91 Nørgaard M, Severinsen MT, Lund Maegbaek M, Jensen AO, 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 (01) 109-111
  • 92 Enger C, Bennett D, Forssen U, Fogarty PF, McAfee AT. Comorbidities in patients with persistent or chronic immune thrombocytopenia. Int J Hematol 2010; 92 (02) 289-295
  • 93 Sarpatwari A, Bennett D, Logie JW. , et al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica 2010; 95 (07) 1167-1175
  • 94 Langeberg WJ, Schoonen WM, Eisen M, Gamelin L, Stryker S. Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies. Int J Hematol 2016; 103 (06) 655-664
  • 95 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 (06) 1413-1416
  • 96 Ruggeri M, Tosetto A, Palandri F. , et al; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Anemia and Thrombocytopenias Working Party. GIMEMA Study ITP0311. 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 (08) 1266-1273
  • 97 Rørholt M, Ghanima W, Farkas DK, Nørgaard M. Risk of cardiovascular events and pulmonary hypertension following splenectomy - a Danish population-based cohort study from 1996-2012. Haematologica 2017; 102 (08) 1333-1341
  • 98 Thai LH, Mahévas M, Roudot-Thoraval F. , et al. Long-term complications of splenectomy in adult immune thrombocytopenia. Medicine (Baltimore) 2016; 95 (48) e5098
  • 99 Rodeghiero F, Stasi R, Giagounidis A. , et al. Long-term safety and tolerability of romiplostim in patients with primary immune thrombocytopenia: a pooled analysis of 13 clinical trials. Eur J Haematol 2013; 91 (05) 423-436
  • 100 Saleh MN, Bussel JB, Cheng G. , et al; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood 2013; 121 (03) 537-545
  • 101 Frederiksen H, Maegbaek ML, Nørgaard M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol 2014; 166 (02) 260-267
  • 102 Kirsch M, Klaassen RJ, De Geest S, Matzdorff A, Ionova T, Dobbels F. Understanding the importance of using patient-reported outcome measures in patients with immune thrombocytopenia. Semin Hematol 2013; 50 (Suppl (Suppl. 01) S39-S42