title: The international, prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention.
abstract: Standard treatment for Glanzmann thrombasthenia, a severe inherited bleeding disorder, is platelet transfusion. Recombinant factor VIIa is reported to be effective in Glanzmann thrombasthenia with platelet antibodies and/or refractoriness to platelet transfusions. We aimed to evaluate recombinant factor VIIa effectiveness and safety for the treatment and prevention of surgical bleeding in patients, with or without platelet antibodies and/or refractoriness, using data from the Glanzmann Thrombasthenia Registry, an international, multicenter, observational, post-marketing study of rFVIIa. Between 2007 and 2011, 96 patients were treated for 206 surgical procedures (minor 169, major 37). History of platelet antibodies was present in 43 patients, refractoriness in 23, antibodies+refractoriness in 17, while 47 had no confirmed antibodies/refractoriness. Treatments analyzed included antifibrinolytics, recombinant factor VIIa, recombinant factor VIIa+antifibrinolytics, platelets±antifibrinolytics and recombinant factor VIIa+platelets±antifibrinolytics. The most frequent treatment for minor procedures was recombinant factor VIIa+antifibrinolytics (n=65), and for major procedures, recombinant factor VIIa+platelets±antifibrinolytics (n=13). In patients without antibodies/refractoriness, recombinant factor VIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for minor and major procedures. The effectiveness of treatment for minor procedures in patients with antibodies and refractoriness was 88.9% for recombinant factor VIIa, 100% for recombinant factor VIIa+antifibrinolytics, 66.7% for platelets±antifibrinolytics and 100% for recombinant factor VIIa+platelets±antifibrinolytics. One of four adverse events reported for surgery was considered recombinant factor VIIa-treatment-related (non-fatal thromboembolic event in an adult female receiving recombinant factor VIIa+platelets+antifibrinolytics). For all patients, regardless of platelet antibody or refractoriness status, recombinant factor VIIa, administered with or without platelets (±antifibrinolytics), provided effective hemostasis with a low frequency of adverse events in surgical procedures in Glanzmann thrombasthenia patients. This trial was registered at clinicaltrials.gov identifier: 01476423.
authors.affiliation: Departments of Medicine, Pediatrics and Oncology, University of Calgary, Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, Foothills Hospital, Calgary, Canada mcpoon@ucalgary.ca.
authors.forename: Man-Chiu
authors.initials: MC
authors.lastname: Poon
authors.affiliation: Regional Reference Centre for Hemophilia and Constitutional Bleeding Disorders, Hôpital Bicêtre AP-HP, University Paris XI, Le Kremlin-Bicêtre, France.
authors.forename: Roseline
authors.initials: R
authors.lastname: d'Oiron
authors.affiliation: Center for Blood Coagulation and Transfusion Medicine (CBT), Dusseldorf, Germany.
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Zotz
authors.affiliation: Biostatistics, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Bindslev
authors.affiliation: Department of Clinical Medicine and Surgery, Regional Reference Center for Coagulation Disorders, Federico II University, Naples, Italy Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Matteo Nicola Dario
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: Department of Clinical Medicine and Surgery, Regional Reference Center for Coagulation Disorders, Federico II University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Minno
mesh_terms: D000293:Adolescent; D000328:Adult; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015942:Factor VIIa / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control / Q000601:surgery*; D006801:Humans; D008297:Male; D017713:Platelet Transfusion; D011994:Recombinant Proteins / Q000627:therapeutic use; D012042:Registries; D013915:Thrombasthenia / Q000150:complications* / Q000175:diagnosis; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa