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Published in: International Journal of Hematology 2/2018

01-08-2018 | Original Article

A characteristic flow cytometric pattern with broad forward scatter and narrowed side scatter helps diagnose immune thrombocytopenia (ITP)

Authors: Raita Araki, Ryosei Nishimura, Rie Kuroda, Toshihiro Fujiki, Shintaro Mase, Kazuhiro Noguchi, Yasuhiro Ikawa, Hideaki Maeba, Akihiro Yachie

Published in: International Journal of Hematology | Issue 2/2018

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Abstract

Various disorders cause severe thrombocytopenia, which can lead to critical hemorrhage. Procedures that rapidly support the diagnosis and risk factors for serious bleeding were explored, with a focus on immune thrombocytopenia (ITP). Twenty-five patients with thrombocytopenia, including 13 with newly diagnosed ITP, 3 with chronic ITP, 6 with aplastic anemia (AA), and 3 with other thrombocytopenia (one acute myeloid leukemia, one acute lymphoblastic leukemia, and one hemophagocytic lymphohistiocytosis), were reviewed. In addition to platelet-related parameters obtained by an automated hematology analyzer, flow cytometric analysis of platelets was performed. A characteristic flow cytometric pattern with broad forward scatter and narrowed side scatter, which is specific to ITP, but not other types of thrombocytopenia, was found. CD62P-positive platelets were increased in newly diagnosed ITP cases compared to control (P < 0.0001), AA (P = 0.0032). Moreover, detection of dramatic changes in these parameters on sequential monitoring may suggest internal hemorrhage, even absent skin or visible mucosal bleeding. The bleeding score for visible mucosae had a negative correlation with platelet count and a positive correlation with immature platelet fraction (%), forward scatter, and CD62P. This characteristic flow cytometric pattern makes it possible to distinguish ITP from other thrombocytopenic disorders.
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Literature
1.
go back to reference Vinholt PJ, Hvas AM, Nybo M. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients. Eur J Haematol. 2014;92:367–76.CrossRefPubMed Vinholt PJ, Hvas AM, Nybo M. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients. Eur J Haematol. 2014;92:367–76.CrossRefPubMed
2.
go back to reference Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E, et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol. 2005;128:698–702.CrossRefPubMed Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E, et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol. 2005;128:698–702.CrossRefPubMed
3.
go back to reference Bowles KM, Cooke LJ, Richards EM, Baglin TP. Platelet size has diagnostic predictive value in patients with thrombocytopenia. Clin Lab Haematol. 2005;27:370–3.CrossRefPubMed Bowles KM, Cooke LJ, Richards EM, Baglin TP. Platelet size has diagnostic predictive value in patients with thrombocytopenia. Clin Lab Haematol. 2005;27:370–3.CrossRefPubMed
4.
go back to reference Strauß G, Vollert C, von Stackelberg A, Weimann A, Gerhard G, Schulze H. Immature platelet count: a simple parameter for distinguishing thrombocytopenia in pediatric acute lymphocytic leukemia from immune thrombocytopenia. Pediatr Blood Cancer. 2011;57:641–7.CrossRefPubMed Strauß G, Vollert C, von Stackelberg A, Weimann A, Gerhard G, Schulze H. Immature platelet count: a simple parameter for distinguishing thrombocytopenia in pediatric acute lymphocytic leukemia from immune thrombocytopenia. Pediatr Blood Cancer. 2011;57:641–7.CrossRefPubMed
5.
go back to reference Connor DE, Ma DDF, Joseph JE. Flow cytometry demonstrates differences in platelet reactivity and microparticle formation in subjects with thrombocytopenia or thrombocytosis due to primary haematological disorders. Thromb Res. 2013;132:572–7.CrossRefPubMed Connor DE, Ma DDF, Joseph JE. Flow cytometry demonstrates differences in platelet reactivity and microparticle formation in subjects with thrombocytopenia or thrombocytosis due to primary haematological disorders. Thromb Res. 2013;132:572–7.CrossRefPubMed
6.
go back to reference Dovlatova N. Current status and future prospects for platelet function testing in the diagnosis of inherited bleeding disorders. Br J Haematol. 2015;170:150–61.CrossRefPubMed Dovlatova N. Current status and future prospects for platelet function testing in the diagnosis of inherited bleeding disorders. Br J Haematol. 2015;170:150–61.CrossRefPubMed
7.
go back to reference Shirahata A, Ishii E, Eguchi H, Okawa H, Ohta S, Kaneko T, et al. Consensus guideline for diagnosis and treatment of childhood idiopathic thrombocytopenic purpura. Int J Hematol. 2006;83:29–38.CrossRefPubMed Shirahata A, Ishii E, Eguchi H, Okawa H, Ohta S, Kaneko T, et al. Consensus guideline for diagnosis and treatment of childhood idiopathic thrombocytopenic purpura. Int J Hematol. 2006;83:29–38.CrossRefPubMed
8.
go back to reference Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013;121:2596–606.CrossRefPubMed Rodeghiero F, Michel M, Gernsheimer T, Ruggeri M, Blanchette V, Bussel JB, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013;121:2596–606.CrossRefPubMed
9.
go back to reference Neunert C, Buchanan GR, Imbach PA, Bolton-Maggs PHB, Bennett CM, Neufeld E, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia (ITP): data from the intercontinental cooperative ITP study group. Blood. 2009;114:4457–63. Neunert C, Buchanan GR, Imbach PA, Bolton-Maggs PHB, Bennett CM, Neufeld E, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia (ITP): data from the intercontinental cooperative ITP study group. Blood. 2009;114:4457–63.
10.
go back to reference Hama A, Takahashi Y, Muramatsu H, Ito M, Narita A, Kosaka Y, et al. Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine. Haematologica. 2015;100:1426–33.CrossRefPubMedPubMedCentral Hama A, Takahashi Y, Muramatsu H, Ito M, Narita A, Kosaka Y, et al. Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine. Haematologica. 2015;100:1426–33.CrossRefPubMedPubMedCentral
11.
go back to reference Hézard N, Potron G, Schlegel N, Amory C, Leroux B, Nguyen P. Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children. Thromb Haemost. 2003;90:116–23.CrossRefPubMed Hézard N, Potron G, Schlegel N, Amory C, Leroux B, Nguyen P. Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children. Thromb Haemost. 2003;90:116–23.CrossRefPubMed
12.
go back to reference Yip C, Linden MD, Attard C, Monagle P, Ignjatovic V. Platelets from children are hyper-responsive to activation by thrombin receptor activator peptide and adenosine diphosphate compared to platelets from adults. Br J Haematol. 2015;168:526–32.CrossRefPubMed Yip C, Linden MD, Attard C, Monagle P, Ignjatovic V. Platelets from children are hyper-responsive to activation by thrombin receptor activator peptide and adenosine diphosphate compared to platelets from adults. Br J Haematol. 2015;168:526–32.CrossRefPubMed
13.
go back to reference Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Platelets at work in primary hemostasis. Blood Rev. 2011;25:155–67.CrossRefPubMed Broos K, Feys HB, De Meyer SF, Vanhoorelbeke K, Deckmyn H. Platelets at work in primary hemostasis. Blood Rev. 2011;25:155–67.CrossRefPubMed
14.
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;115:168–87.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;115:168–87.CrossRefPubMed
15.
go back to reference Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. 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. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.CrossRefPubMed
16.
go back to reference Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol. 2014;166:592–600.CrossRefPubMed Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol. 2014;166:592–600.CrossRefPubMed
17.
go back to reference McDonnell A, Bride KL, Lim D, Paessler M, Witmer CM, Lambert MP. Utility of the immature platelet fraction in pediatric immune thrombocytopenia: differentiating from bone marrow failure and predicting bleeding risk. Pediatr Blood Cancer. 2017; 65(2):e26812. https://doi.org/10.1002/pbc.26812.CrossRef McDonnell A, Bride KL, Lim D, Paessler M, Witmer CM, Lambert MP. Utility of the immature platelet fraction in pediatric immune thrombocytopenia: differentiating from bone marrow failure and predicting bleeding risk. Pediatr Blood Cancer. 2017; 65(2):e26812. https://​doi.​org/​10.​1002/​pbc.​26812.CrossRef
19.
go back to reference Casonato A, Fabris F, Boscaro M, Girolami A. Increased factor VIII/von Willebrand factor levels in patients with reduced platelet number. Blut. 1987;54:281–8.CrossRefPubMed Casonato A, Fabris F, Boscaro M, Girolami A. Increased factor VIII/von Willebrand factor levels in patients with reduced platelet number. Blut. 1987;54:281–8.CrossRefPubMed
21.
go back to reference Álvarez-Román MT, Fernández-Bello I, Jiménez-Yuste V, Martín-Salces M, Arias-Salgado EG, Rivas Pollmar MI, et al. Procoagulant profile in patients with immune thrombocytopenia. Br J Haematol. 2016;175:925–34.CrossRefPubMed Álvarez-Román MT, Fernández-Bello I, Jiménez-Yuste V, Martín-Salces M, Arias-Salgado EG, Rivas Pollmar MI, et al. Procoagulant profile in patients with immune thrombocytopenia. Br J Haematol. 2016;175:925–34.CrossRefPubMed
23.
24.
go back to reference Mangalpally KKR, Siqueiros-Garcia A, Vaduganathan M, Dong JF, Kleiman NS, Guthikonda S. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. J Thromb Thrombolysis. 2010;30:251–62.CrossRefPubMed Mangalpally KKR, Siqueiros-Garcia A, Vaduganathan M, Dong JF, Kleiman NS, Guthikonda S. Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. J Thromb Thrombolysis. 2010;30:251–62.CrossRefPubMed
25.
go back to reference Neunert C, Noroozi N, Norman G, Buchanan GR, Goy J, Nazi I, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost. 2015;13:457–64.CrossRefPubMedPubMedCentral Neunert C, Noroozi N, Norman G, Buchanan GR, Goy J, Nazi I, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review. J Thromb Haemost. 2015;13:457–64.CrossRefPubMedPubMedCentral
27.
go back to reference 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;114:4777–83.CrossRefPubMedPubMedCentral 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;114:4777–83.CrossRefPubMedPubMedCentral
28.
go back to reference Imbach P, Kühne T, Müller D, Berchtold W, Zimmerman S, Elalfy M, 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;46:351–6.CrossRefPubMed Imbach P, Kühne T, Müller D, Berchtold W, Zimmerman S, Elalfy M, 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;46:351–6.CrossRefPubMed
29.
go back to reference Frelinger AL, Grace RF, Gerrits AJ, Berny-Lang MA, Brown T, Carmichael SL, et al. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. Blood. 2015;126:873–9.CrossRefPubMedPubMedCentral Frelinger AL, Grace RF, Gerrits AJ, Berny-Lang MA, Brown T, Carmichael SL, et al. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP. Blood. 2015;126:873–9.CrossRefPubMedPubMedCentral
30.
go back to reference Bhoria P, Sharma S, Varma N, Malhotra P, Varma S, Luthra-Guptasarma M. Effect of steroids on the activation status of platelets in patients with immune thrombocytopenia (ITP). Platelets. 2015;26:119–26.CrossRefPubMed Bhoria P, Sharma S, Varma N, Malhotra P, Varma S, Luthra-Guptasarma M. Effect of steroids on the activation status of platelets in patients with immune thrombocytopenia (ITP). Platelets. 2015;26:119–26.CrossRefPubMed
Metadata
Title
A characteristic flow cytometric pattern with broad forward scatter and narrowed side scatter helps diagnose immune thrombocytopenia (ITP)
Authors
Raita Araki
Ryosei Nishimura
Rie Kuroda
Toshihiro Fujiki
Shintaro Mase
Kazuhiro Noguchi
Yasuhiro Ikawa
Hideaki Maeba
Akihiro Yachie
Publication date
01-08-2018
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 2/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-018-2454-y

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