The international prospective Glanzmann Thrombasthenia Registry: treatment modalities and outcomes in non-surgical bleeding episodes in Glanzmann thrombasthenia patients

Abstract

© F e r r a t a S t o r t i F o u n d a t i o nMedicines Agency (EMA) for the treatment and prevention of bleeding episodes and in surgery or invasive procedures in GT patients with antibodies to GPIIb/IIIa and/or HLA, and a past or present history of platelet refractoriness to platelet transfusions. 20 To date, for GT patients who are not refractory, platelets are used as the first-line treatment.As part of the approval, the EMA required the collection of post-marketing pharmacovigilance data on rFVIIa in GT. The observational, international, multicenter, webbased Glanzmann's Thrombasthenia Registry (GTR) was, therefore, launched to prospectively gather and evaluate information on the different treatment modalities and their outcomes in "real-world" clinical practice. 21 Collection of such registry data is key to improving the understanding and management of rare diseases such as GT, for which randomized clinical trials are difficult to perform.This paper reports new, clinically relevant effectiveness and safety data on rFVIIa, as well as the other therapeutic options available (antifibrinolytics and platelets), for the treatment of non-surgical bleeds in patients with GT, using data obtained from the largest observational study of GT patients, the GTR. Methods PatientsFrom May 10, 2007, to December 16, 2011, prospectively collected online data were entered into the GTR on the effectiveness and safety (including thromboembolic events) of systemic hemostatic treatments used in clinics in patients with GT, including rFVIIa, platelet transfusions (P), and antifibrinolytics (AF) alone or in combination with other agents. All patients were treated according to local practices in an open-label manner, and no drugs were supplied for this registry. The main features of the GTR include: (i) standardized data collection using a customized webbased tool; (ii) a protocol-based registry conducted in accordance with general data protection laws and any local country requirements for conducting observational studies; and (iii) centralized data management overseen by an external expert panel composed of four physicians and by the international medical director of Novo Nordisk (the study sponsor). Protocol definitions and outcomes specified by the study sponsor, and post hoc classifications of bleed severity employed by the external expert panel (in response to requests by the EMA), are reported in Online Supplementary Table S1.Only patients with a diagnosis of congenital GT were included in the GTR (see Online Supplementary Table S1). Patients with acquired thrombasthenic states caused by autoimmune disorders or medications were excluded. Refractoriness and the presence of antibodies were coded initially and assessed periodically as deemed important by the investigator. As tests for antibodies may not have been available at all centers, antibodies may also have been present in some patients classified as having refractoriness only. Data handlingAs this was an observational study, treatment was based on local practice ...

Is there a role for antiangiogenic therapy, bevacizumab, in the treatment of recurrent digestive bleeding due to angiodysplasia in Glanzmann's thrombasthenia?

“…Indeed, the success rate to stop bleeding with these different treatments was ranged from 72% to 91% in the majority of moderate bleeding, with no blood transfusion. Treatment failure was documented in 18 cases (2.2% of the total) and re-bleeding in 6% [1]. Our patient had a relatively severe bleeding which required blood transfusion twice a week.…”

“…The different treatments are antifibrinolytic therapy, platelet transfusion, recombinant factor VIIa (rFVIIa) as well as local treatment. Seventy five percent of patients required blood and/or platelet transfusions at least once in their life, and recombinant factor VII has proven efficacy in patients with platelet antibodies refractory to platelet transfusions [1]. Nevertheless, treatment is more complicated when antiplatelet antibodies exist.…”

Independent adjudicator assessments of platelet refractoriness and rFVIIa efficacy in bleeding episodes and surgeries from the multinational Glanzmann's thrombasthenia registry

“…A detailed description of the GTR data collection process has been presented elsewhere . Briefly, the registry was a prospective, observational, multinational, Web‐based platform that collected safety and efficacy data regarding the use of systemic hemostatic treatments in patients with GT (see Supporting Information appendix for a list of data fields).…”

“…Briefly, the registry was a prospective, observational, multinational, Web‐based platform that collected safety and efficacy data regarding the use of systemic hemostatic treatments in patients with GT (see Supporting Information appendix for a list of data fields). Patients were eligible for participation in the GTR if they had a diagnosis of congenital GT and exhibited a normal platelet count and morphology . Congenital GT was defined by having a lifelong bleeding tendency characterized by impaired or absent platelet aggregation, impaired clot retraction and prolonged bleeding time, or prolonged platelet function analyzer closure time; optional diagnostic criteria were quantitative or qualitative evaluation of GPIIb/IIIa receptors, including flow cytometry and identification of gene defects .…”

“…The registry was initiated as a postmarketing surveillance commitment to the European Union's Committee for Medicinal Products for Human Use, following approval by the European Medicines Agency of rFVIIa for the treatment of GT . An external expert group monitored the registry and provided ongoing support of recruitment and analysis, including publication of primary data on the efficacy and safety of rFVIIa associated with specific patient events (bleeding episodes and surgeries) . Investigators found rFVIIa used alone to be effective in a majority of bleeding episodes (111 of 122; 91.0%) and surgical procedures (59 of 62; 95.2%).…”