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CC BY 4.0 · TH Open 2019; 03(03): e286-e294
DOI: 10.1055/s-0039-1696657
Original Article
Georg Thieme Verlag KG Stuttgart · New York

The International Prospective Glanzmann Thrombasthenia Registry: Pediatric Treatment and Outcomes

Rainer B. Zotz
1   Institute for Laboratory Medicine, Blood Coagulation and Transfusion Medicine (LBT), Düsseldorf, Germany
2   Department of Hemostasis, Hemotherapy and Transfusion Medicine, Heinrich Heine University Medical Centre, Düsseldorf, Germany
,
Man-Chiu Poon
3   Departments of Medicine, Pediatrics and Oncology, University of Calgary, Calgary, Alberta, Canada
4   Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Medical Centre, Calgary, Alberta, Canada
,
Giovanni Di Minno
5   Department of Clinical Medicine and Surgery, Regional Reference Center for Coagulation Disorders, Federico II University, Naples, Italy
,
Roseline D'Oiron
6   Center for Hemophilia and Rare Congenital Bleeding Disorders, University Hospitals Paris-Sud, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre, France
,
for the Glanzmann Thrombasthenia Registry Investigators › Author Affiliations
Further Information

Publication History

04 February 2019

25 July 2019

Publication Date:
12 September 2019 (online)

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Abstract

Background Standard treatment for Glanzmann thrombasthenia (GT), a severe inherited bleeding disorder, is platelet transfusion. Recombinant activated factor VII (rFVIIa) is reported to be effective in GT with platelet antibodies and/or refractoriness to platelet transfusions.

Methods We evaluated rFVIIa effectiveness and safety for the treatment and prevention of surgical and nonsurgical bleeding in children <18 years old, with or without platelet antibodies and/or refractoriness, as reported in the GT Registry (GTR). Data were used from the GTR, an international, multicenter, observational, postmarketing study of rFVIIa that prospectively collected data on the treatment and outcomes of bleeds in patients with GT. Only patients with a diagnosis of congenital GT were included in the registry.

Results Between 2007 and 2011, 27 children were treated for 44 surgical procedures (minor: 36; major: 8); nonsurgical bleeds occurred in 104 patients (599 episodes: severe, 145; moderate, 454; spontaneous, 423; posttraumatic, 176). The effectiveness of treatment for minor procedures, major procedures, nonsurgical bleeds was 6/6, 1/1, and 75/84 for rFVIIa, 6/6, 2/2, and 64/76 for rFVIIa + antifibrinolytics (AF), 11/12, 1/1, and 162/214 for platelets ± AF, and 5/6, 0/3, and 33/45 for rFVIIa + platelets ± AF. In all, 25 adverse events were reported in children; no thromboembolic events were reported.

Conclusion For all patients, regardless of platelet antibody or refractoriness status, rFVIIa, administered with or without platelets (± AF), provided effective hemostasis with a low frequency of adverse events in surgical, as well as nonsurgical, bleeding in patients with GT.

clinicaltrials.gov identifier: NCT01476423.

Keywords

recombinant activated factor VII - Glanzmann thrombasthenia - autosomal dominant - pediatric - registry - observational study

Authors' Contributions

R. B. Zotz drafted, reviewed, and approved the article. M.-C. Poon, G. Di Minno, and R. d'Oiron reviewed and approved the article content.


Data Sharing Statement

The trial sponsor's policy on data sharing may be found at https://www.novonordisk-trials.com/how-access-clinical-trial-datasets.


Supplementary Material

 

  • References

  • 1 Bellucci S, Caen J. Molecular basis of Glanzmann's thrombasthenia and current strategies in treatment. Blood Rev 2002; 16 (03) 193-202
    CrossrefPubMedGoogle Scholar
  • 2 George JN, Caen JP, Nurden AT. Glanzmann's thrombasthenia: the spectrum of clinical disease. Blood 1990; 75 (07) 1383-1395
    CrossrefPubMedGoogle Scholar
  • 3 Toogeh G, Sharifian R, Lak M, Safaee R, Artoni A, Peyvandi F. Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran. Am J Hematol 2004; 77 (02) 198-199
    CrossrefPubMedGoogle Scholar
  • 4 Poon MC, D'Oiron R, Von Depka M. , et al; International Data Collection on Recombinant Factor VIIa and Congenital Platelet Disorders Study Group. Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey. J Thromb Haemost 2004; 2 (07) 1096-1103
    CrossrefPubMedGoogle Scholar
  • 5 Di Minno G, Zotz RB, d'Oiron R, Bindslev N, Di Minno MN, Poon MC. ; Glanzmann Thrombasthenia Registry Investigators. The international, prospective Glanzmann Thrombasthenia Registry: treatment modalities and outcomes of non-surgical bleeding episodes in patients with Glanzmann thrombasthenia. Haematologica 2015; 100 (08) 1031-1037
    PubMedGoogle Scholar
  • 6 Poon MC, d'Oiron R, Zotz RB, Bindslev N, Di Minno MN, Di Minno G. ; Glanzmann Thrombasthenia Registry Investigators. The international, prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention. Haematologica 2015; 100 (08) 1038-1044
    PubMedGoogle Scholar
  • 7 Novo Nordisk. NovoSeven summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000074/WC500030873.pdf . Accessed April 4, 2016
    PubMed
  • 8 Brand A, Claas FH, Voogt PJ, Wasser MN, Eernisse JG. Alloimmunization after leukocyte-depleted multiple random donor platelet transfusions. Vox Sang 1988; 54 (03) 160-166
    CrossrefPubMedGoogle Scholar
  • 9 Legler TJ, Fischer I, Dittmann J. , et al. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol 1997; 74 (04) 185-189
    CrossrefPubMedGoogle Scholar
  • 10 Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1997; 337 (26) 1861-1869
    CrossrefPubMedGoogle Scholar
  • 11 Ito K, Yoshida H, Hatoyama H. , et al. Antibody removal therapy used successfully at delivery of a pregnant patient with Glanzmann's thrombasthenia and multiple anti-platelet antibodies. Vox Sang 1991; 61 (01) 40-46
    PubMedGoogle Scholar
  • 12 Vivier M, Treisser A, Naett M. , et al. Glanzmann's thrombasthenia and pregnancy. Contribution of plasma exchange before scheduled cesarean section [in French]. J Gynecol Obstet Biol Reprod (Paris) 1989; 18 (04) 507-513
    PubMedGoogle Scholar
  • 13 Martin I, Kriaa F, Proulle V. , et al. Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies. Br J Haematol 2002; 119 (04) 991-997
    CrossrefPubMedGoogle Scholar
  • 14 NiaStase RT®. Product Monograph. Available at: http://www.novonordisk.ca/content/dam/Canada/AFFILIATE/www-novonordisk-ca/OurProducts/PDF/niastase-product-monograph.pdf . Accessed November 8, 2017
    PubMed
  • 15 Schulman S, Kearon C. ; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 16 Chitlur M, Ewing N, Kraut EH. , et al. Recombinant factor VIIa (rFVIIa) use in Glanzmann's thrombasthenia (GT) and other platelet disorders (OPDS): Hemophilia and Thrombosis Research Society (HTRS) registry data. [abstract]. J Thromb Haemost 2011; 9 (Suppl. 2): 340
    PubMedGoogle Scholar
  • 17 Lak M, Scharling B, Blemings A. , et al. Evaluation of rFVIIa (Novo-Seven) in Glanzmann patients with thromboelastogram. Haemophilia 2008; 14 (01) 103-110
    PubMedGoogle Scholar