==== Front Orphanet J Rare Dis Orphanet J Rare Dis Orphanet Journal of Rare Diseases 1750-1172 BioMed Central London 37386449 2787 10.1186/s13023-023-02787-2 Position Statement Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders http://orcid.org/0000-0002-2526-8826 Fiore Mathieu mathieu.fiore@chu-bordeaux.fr 12 Giraudet Janine-Sophie 3 Alessi Marie-Christine 418 Falaise Céline 518 Desprez Dominique 6 d’Oiron Roseline 7 Voisin Sophie 8 Hurtaud Marie-Françoise 9 Boutroux Hélène 10 Saultier Paul 1118 Lavenu-Bombled Cécile 19 Bagou Gilles 12 Dubucs Xavier 13 Chauvin Anthony 14 Leroy Christophe 15 Meckert Francine 16 Kerbaul François 16 Giraud Nicolas 17 Pühler Ambra 3 Rath Ana 3 1 grid.42399.35 0000 0004 0593 7118 Laboratoire d’hématologie, Centre de Référence des Pathologies Plaquettaires, CHU de Bordeaux, Hôpital Cardiologique, Inserm U1034 – Biologie des Maladies Cardio-Vasculaires, Pessac, France 2 Centre de Référence des Pathologies Plaquettaires, Pessac, France 3 grid.458406.b ORPHANET, INSERM US14, Plateforme Maladies Rares, 96 Rue Didot, 75014 Paris, France 4 grid.411266.6 0000 0001 0404 1115 Laboratory of Hematology, Aix Marseille Univ, APHM, INSERM, INRAe, C2VN, La Timone Hospital, Marseille, France 5 grid.411266.6 0000 0001 0404 1115 Department of Pediatric Hematology, Immunology and Oncology, La Timone Children’s Hospital, Marseille, France 6 grid.412220.7 0000 0001 2177 138X Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU de Strasbourg, Strasbourg, France 7 grid.413784.d 0000 0001 2181 7253 Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU du Kremlin-Bicêtre, Le-Kremlin-Bicêtre, France 8 grid.411175.7 0000 0001 1457 2980 Laboratoire d’Hématologie, Centre de Référence des Pathologies Plaquettaires, CHU de Toulouse, Toulouse, France 9 grid.139510.f 0000 0004 0472 3476 Laboratoire d’Hématologie, CHU Robert Debré, Paris, France 10 grid.413776.0 0000 0004 1937 1098 Laboratoire d’Hématologie, Centre de Référence des pathologies Plaquettaires, CHU Armand Trousseau, Paris, France 11 grid.411266.6 0000 0001 0404 1115 Department of pediatric hematology, immunology and oncology, Aix Marseille Univ, APHM, INSERM, INRAe, C2VN, La Timone Children’s Hospital, Marseille, France 12 grid.412180.e 0000 0001 2198 4166 Anesthésiste-Réanimateur Urgentiste - SAMU-SMUR de Lyon - Hôpital Edouard-Herriot, 69437 Lyon Cedex 03, France 13 grid.411175.7 0000 0001 1457 2980 Pôle Médecine-Urgences, CHU de Toulouse, Toulouse, France 14 Président de la Commission des Référentiels de la SFMU (CREF), Chef de Service Adjoint - Service d’Accueil des Urgences/SMUR, CHU Lariboisière, Université de Paris, Paris, France 15 grid.50550.35 0000 0001 2175 4109 Médecin Urgentiste - Service de Gestion des Crises Sanitaires - Département Qualité Gestion des Risques, Assistance Publique-Hôpitaux de Paris, Paris, France 16 Direction Opérationnelle du Prélèvement et de la Greffe de l’Agence de la Biomédecine (ABM), Saint Denis, France 17 Association Française des Hémophiles, Paris, France 18 grid.414336.7 0000 0001 0407 1584 Reference Center of Platelet Disorders, APHM, Marseille, France 19 grid.413784.d 0000 0001 2181 7253 Service Hématologie Biologique, Centre de ressources et compétences MHEMO, CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de médecine Paris Saclay, Le Kremlin-Bicetre, France 29 6 2023 29 6 2023 2023 18 17113 3 2023 18 6 2023 © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients’ associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT. issue-copyright-statement© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023 ==== Body pmcBackground Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder caused by inherited defects of the platelet membrane αIIbβ3 glycoprotein [1]. This receptor is required for platelet aggregation, which culminates in the formation of a ‘plug’ that closes the damaged site of the blood vessel [2]. Therefore, absence of platelet αIIbβ3 glycoprotein prevents maintenance of vascular integrity in the case of injury leading to excessive bleeding [1, 3, 4]. GT is usually linked to quantitative, but sometimes qualitative, defects of the αIIbβ3 complex [5]. The disease is classically divided into three subtypes: type I disease defined as less than 5% αIIbβ3 expression; type II disease defined as residual αIIbβ3 expression (5–20%); and variant disease defined as qualitative defect with at least 20% residual expression [6, 7]. In very rare cases, acquired GT is defined as spontaneous inhibition of normally expressed αIIbβ3, which is most often associated with autoantibodies [8]. GT is usually suspected in cases with spontaneous or provoked mucocutaneous bleeding, such as epistaxis or heavy menstrual bleeding [9]. Symptoms may manifest shortly after birth, with purpura, umbilical stump haemorrhage and/or excessive bleeding following blood sampling for the Guthrie test. Nevertheless, in most patients, the diagnosis is made during childhood [7]. The laboratory criteria for diagnosis is based on the absence or severe decrease of platelet aggregation associated with reduced expression of αIIbβ3 on the platelet surface detected by flow cytometry [1, 10]. However, clinical observations suggest little or no correlation between the amount of residual αIIbβ3 expression and the severity of the disease [10]. Management of minor bleeding relies mostly on local haemostasis and/or the use of antifibrinolytics, whereas platelet transfusion remains the standard of care if bleeding cannot be controlled with these first measures or in cases of invasive procedures [11, 12]. Unfortunately, platelet transfusion therapy can be followed by an immune response that is directed against the deficient αIIbβ3 complex and/or the HLA class I system [13]. These antiplatelet antibodies occur in approximately 20–30% of patients and they are of much clinical concern as they can render platelet transfusions ineffective [14]. In addition, data from animal models suggest that the hemostatic efficacy of transfused platelets is much lower in the absence of thrombocytopenia, as is the case in GT, because dysfunctional platelets can interfere with the hemostatic activity of transfused platelets [15]. Correspondingly, a large series of cases with congenital platelet disorders [16] confirms that the median platelet transfusion dose is significantly higher (median of 5) in patients without thrombocytopenia (such as GT patients). Nonetheless, administration of recombinant activated factor VII is a therapeutic alternative when platelet transfusions are ineffective or when platelets are not rapidly accessible [17]. As GT leads to major platelet functional defects, severe bleeding can occur suddenly, requiring prompt management by healthcare professionals who may not be aware of disease-specific features and related difficulties of care. The objective of these recommendations is to provide information on the best clinical practice in emergency situations that may arise in patients with GT based on data from the literature and the practical expertise of the French Reference Center for Inherited Platelet Disorders. These guidelines are intended to provide support in decision making for patient management and surveillance of possible complications. Methodology Our working group identified a need for the development of recommendations for the management of GT patients in emergency situations, which are frequently encountered in this platelet disorder. Our aim was to make these recommendations easily accessible to medical practitioners working in emergency care on a daily basis. The elaboration of these standardised recommendations was coordinated by Orphanet [18] following a rigorous methodology. Since 2007, Orphanet has produced 112 recommendations for 447 different rare diseases [19], which are easily accessible through the websites of Orphanet or the French Society of Emergency Medicine and the Orphanet smartphone app. They also provide information for regulation by the emergency department in a single one-page table that can be read in 2–3 min by the emergency regulator and professionals sent to out-of-hospital sites. This report combines the outcomes of a literature review and a national survey on physicians’ practises, and was elaborated in collaboration with members of the French Reference Center for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients’ associations, and Orphanet. The production methodology of these recommendations was adapted from those elaborated by the French Authority for Health regarding good clinical practices. A prevalidated, standardised, and structured document was used as a draft, which included several different sections: Basic principles—these recommendations should be applicable by all emergency physicians regardless of the type of emergency department where the patient is receiving care; Specific emergency situations—divided into three different parts, i.e., emergency evaluation, immediate treatment and specific therapy; Orientation—recommendations regarding transport of the patient from home to the hospital, including where, how and when to transport; Precautions regarding co-medication and vaccination—discusses side effects or specific contraindications; Anaesthesia-related risks and specific precautions—specifies precautions related to tracheal intubation or other invasive procedures and anaesthetic drugs; and Organ and tissue donation—allows determination whether organ/tissue donation is possible based on current knowledge in collaboration with the French Biomedicine Agency. All of these recommendations were validated by a panel of expert authors and proofreaders. In view of the rarity of the disease, the recommendations presented here are largely based on the daily clinical practise of the expert authors. Draft recommendations were circulated to the working group for comments and final approval. However, these guidelines are general in nature and as every patient is unique, only the attending physician can judge the suitability of their application in each specific situation. Final recommendations are accessible in French within the Orphanet Emergency Guidelines collection and disseminated further through the Orphanet Guides app [20]. Basic principles It is imperative that health care professionals who may be unfamiliar with GT are made aware that GT patients are at high risk for bleeding [9]. Each patient or the parents/guardians of children with GT should possess a disease-specific emergency card as well as a logbook containing basic information on the disease and on GT-specific medical care [21]. Moreover, emergency practitioners should listen carefully to the patient, who will be intimately familiar his or her chronic disease. Some patients have undertaken therapeutic and educational programs regarding management of their disease [4]. Medical care should involve evaluation of the seriousness of the current situation based on clinical examination, and a specific protocol should be used for each patient in an emergency situation after asking for specialised advice from the referring centre involved in the patient’s ongoing care. The use of a peripheral venous line (see also ‘Anaesthesia-related risks and specific precautions’ section) should be preferred and rectal temperature should not be taken. Pre-transfusion screening blood tests should be performed and labile blood products in cooperation with the blood bank should be ordered, including in patients in clinically stable condition. It is recommended to monitor the evolution of bleeding as an indication for hospitalisation, and hospital discharge should be validated in consultation with an expert physician. Screening for antiplatelet antibodies should be performed on the day of admission and within 1–3 months following administration of blood products. Precautions regarding comedication and vaccination Except in special cases, medications that can increase bleeding risk (nonsteroidal anti-inflammatory drugs, such as aspirin, and anticoagulants) should be avoided. In the case of pain, the use of paracetamol and major analgesics should be preferred [9]. Except in special cases, intramuscular administration should be avoided. Emergency vaccinations (e.g., tetanus immunisation) should be administered by subcutaneous injection into the deltoid region using a thin needle, followed by local and prolonged compression with a compressive bandage [4]. The use of tranexamic acid in cases with a recent thromboembolic event, severe renal impairment (risk of accumulation), or past history of seizures should be avoided. Specific emergency situations Spontaneous and provoked bleeding or haemorrhage Emergency situations and specific appropriate therapies are described in Tables 1, 2 and 3. Hospitalisation is not mandatory in cases of minor bleeding.Table 1 Specific emergency situations in Glanzmann thrombasthenia and their definition Specific emergency situations Definition Life-threatening blood loss Severe drop of hemoglobin level, hemorrhagic shock. For instance, high risk situations of bleeding complications: polytrauma—accidents in public road traffic (also in low kinetic state)—psoas muscle hematoma, deep wound—fracture—severe uterine bleeding particularly in case of menarche—hematemesis, melena—hemoptysis Hemorrhage affecting functional prognosis Intracerebral hemorrhage—eye injury—spinal hematoma—hematoma of the floor of the mouth—compartment syndrome … Minor bleeding Moderate epistaxis—gynecological hemorrhage—gum bleedings—sores in the mouth (frenulum, tongue or lips laceration) -loss of temporary teeth—tooth extraction—suturing of a wound—sprain—dislocation—moderate or mild muscular hematoma—hemarthrosis—hematuria—arterial puncture Table 2 Details of emergency evaluation, immediate treatment and specific therapies that should be provided in case of severe bleeding in GT patients Emergency evaluation • Monitoring of vital parameters: blood pressure, heart and respiratory rates, oxygen saturation, temperature • Perform Whole Blood Count to evaluate the drop of hemoglobin level (platelet count is usually normal in GT) • Evaluate serum creatinine and ionogram • Perform routinely coagulation assay (results are expected to be normal in GT) • Pretransfusion blood screening test: blood group, rhesus, red cells phenotyping, detection of irregular agglutinins, anti-HLA and anti-αIIbβ3 antibodies (without waiting for results) Immediate treatment • Use local hemostatic means (compression if possible) and cryotherapy (15–20 min. every 6 h) • Give analgesics (avoid administration of non-steroidal anti-inflammatory drugs) • Give antibrinolytics by systemic route (1 g and 10 mg/kg every 8 h in adult patients and children, respectively) • Red blood cells administration if required Specific therapies • Ask for expert medical advice and discuss:   Platelet transfusion (HLA-matched concentrates if necessary)   rFVIIa in case of refractoriness to platelet transfusion or when platelets are not readily available (90 ug/kg every 2 h; at least 3 doses should be administered before concluding that the therapy has failed) Table 3 Recommended therapies in different and specific clinical situations Specific emergency situations Recommendations Skin injury • Prolonged compression of the skin lesion (at least 10 min) using compresses eventually soaked with tranexamic acid • Antiseptic solutions, excluding alcool products • Eventually use a hemostatic and compressive bandage Epistaxis • Reassure the patient • Place the patient in a semi seated position with the head bent forward • Ensure of the absence of posterior bleeding by examination of the throat, especially in children • Be aware of the possibility of blood ingestion or inhalation mimicking gastrointestinal bleeding or hemoptysis with respiratory distress • Blow the nose to evacuate blood clots and limit local fibrinolysis • Nasal compression maintained at least 10 min using both fingers • Apply cold (ice pack) if necessary • Give oral tranexamic acid during 7 to 10 days to avoid recurrence of bleeding In case of failure: • Bilateral packing anterior to the septum using hemostatic and absorbable compresses eventually soaked with tranexamic acid • Antibiotherapy is required during all the period of packing • Patient monitoring should be planned with an ENT specialist • If bleeding persists, the use of a balloon or a packing posterior to the septum will be discussed Loss of temporary teeth or gum bleeding • Prolonged compression of the gum and application of a hemostatic tissue sealant if necessary • Use oral antifibrinolytics during 10 days • Mandatory monitoring to adapt the treatment in case of failure • If bleeding persists, patient should see a dentist Heavy menstrual bleedings • Evaluate the severity of bleeding (drop of hemoglobin level) • Give oral tranexamic acid • The use of NSAIDs should be avoided • Consider the possible need for hospitalization in case of major bleeding that could require blood transfusions • Gynecological assessement is required: discuss the use of hormonal therapy with a monophasic pill containing at least 30 µg of ethinylestradiol • Treatment of iron deficiency Emergency surgery GT patients should be treated in a medical centre with availability of follow-up 24 h per day and easy access to blood products [12]. It is highly recommended to contact the referring centre involved in the patient’s ongoing care to define appropriate management [21]. Management must be supported by a multidisciplinary team (surgeon, anaesthetist, haematologist, pharmacist, and provider of blood products) after evaluating the patient’s bleeding history (spontaneous or provoked haemorrhagic syndrome, blood transfusions, and antiplatelet antibodies), results of urgent blood sampling, and type of surgery [22–24]. If possible, a written protocol should be established with details regarding the recommended haemostatic treatment, anaesthesia-related risks, and precautions that should be taken (see ‘Anaesthesia-related risks and specific precautions’ section) [25, 26]. Contact numbers of the medical team and referring specialists should also be included in the protocol [27]. After having taken into account the bleeding risk of surgery and that patient’s platelets may interfere with transfused ones, platelet concentrates should be administered 1 h before surgery and then every 12–24 h [16, 24]. In cases refractory to platelet transfusion or when platelets are not readily available, rFVIIa should be administered 10 min before surgery and then every 2–3 h [17, 23, 26]. Caution should be taken regarding the risk for thrombosis when using rFVIIa, and thrombosis prophylaxis should be decided on an individual basis [28–30]. Administration of intravenous or oral tranexamic acid may also be used [22]. Measures to improve local haemostasis, such as surgical haemostasis, surgical approaches, and local application of tranexamic acid or bioadhesives, should be applied. Perioperative blood loss must be evaluated regularly. Postoperative monitoring should be continued as long as the bleeding risk persists. Therefore, ambulatory care will be limited to conditions with a minor bleeding risk (e.g., dental care, cataract surgery, minor skin surgery). Emergency delivery Delivery should be in a maternity clinic capable of an adequate level of support [31]. The choice of delivery mode should first be determined according to obstetric conditions [32]. Caesarean section may, in some cases, be preferable for organisational reasons depending on the availability of blood products and local coordination [33]. The presence of antiplatelet antibodies should also be screened without waiting for final results [34, 35]. Choice of therapy should take into account recent or past history of platelet transfusion refractoriness. In the absence of a previously established medical care protocol, management should be similar between vaginal delivery and caesarean section, relying on the use of platelet concentrates and/or rFVIIa with or without tranexamic acid. The use of surgical drains in cases of caesarean section and regular monitoring of haemoglobin rates during the first 12–24 h will allow rapid detection of abnormal bleeding. Systematic assistance with delivery of the placenta is also recommended to limit blood loss and prevent postpartum haemorrhage [27, 33, 36]. The duration of therapy will depend on the clinical evolution. As GT is an autosomal recessive disorder, in the absence of consanguinity, the neonate will be an obligate asymptomatic heterozygous carrier [7]. However, the infant may be affected by neonatal immune thrombocytopaenia induced by the transplacental passage of maternal anti-αIIbβ3 antibodies that may require specific interventions [37, 38]. Anaesthesia-related risks and specific precautions Bleeding risk before any invasive procedure should be evaluated carefully [16, 39] and any invasive procedures should be performed by a qualified practitioner [27]. Epidural or spinal anaesthesia, locoregional anaesthesia, and analgesics administered via the intramuscular route should be strictly avoided [27, 40]. If tracheal intubation or catheterisation is required, sedation will be necessary to limit traumatic injuries. Due to the bleeding risk during their placement or removal, the use of central venous lines should be avoided whenever possible (subclavian or femoral vein access). Central venous line insertion should be performed using ultrasound-guided access and after haemostatic correction. In cases of ophthalmic surgery, retrobulbar block is contraindicated and topical anaesthetics, such as eye drops, should be used [41, 42]. Orientation Transport from home to the emergency department Where to transport? Sometimes it may be necessary for the emergency medical dispatcher to guide the ambulance to an appropriate destination hospital according to bleeding risk and the type of emergency department available (e.g., emergency department for adults or children, intensive/critical care unit). This will be balanced by emergency management and the priority to guide the patient toward an institution where technical facilities and expertise are readily accessible. The patient will be admitted directly to the emergency department after prior agreement between practitioners in a medical centre where follow-up and ready access to blood products 24 h per day are possible. Expert medical advice from the referring practitioner should always be sought. How to transport? The emergency medical dispatcher may help to define the mode of medical transport with or without a fully equipped ambulance depending on the clinical situation. The type of transport (land or helicopter) will depend on where the patient is located (accessibility, distance to the healthcare centre) and the severity of the clinical situation. When to transport? The patient should be transported immediately in the case of life-threatening blood loss. Orientation following management by the emergency department Where to transport? The patient should be transported to the department of medicine/surgery or intensive/critical care unit depending on the severity of the clinical situation. How to transport? A fully equipped ambulance may or may not be required depending on the clinical situation. When to transport? The patient should be transported once the clinical situation has stabilised. Moreover, the patient should not leave the emergency department until expert advice has been obtained. Organ and tissue donation Current knowledge suggests that postmortem organ and tissue donation are possible depending on assessment of each patient’s situation. The referring centre or local biomedical agency should be contacted. These recommendations are based on those established by the French Biomedical Agency. Risk of disease transmission The disease can be transmitted by bone marrow donation, which is contraindicated. Specific risk related to the disease or medical treatment received There is a risk of transmission of viral infections linked to the history of blood product administration, but only HIV infection uncontrolled at the time of the donation is currently considered an absolute contraindication. Organ donation in patients with hepatitis B or C virus infection, even if currently active, is permitted under certain conditions. The decision regarding organ transplantation will be based on the risk incurred by the recipient compared to the expected benefit. Organ donation Organ donation is possible subject to the clinical and paraclinical evaluation of the donor, the organ, and treatment followed. Tissue donation Subject to individual evaluation, tissue donations (cornea, blood vessels, cardiac valves, skin, bone, etc.) are possible. Conclusion Different medical emergency situations and related complications can occur in GT patients due to the high risk of bleeding associated with this severe, inherited platelet disorder. Specifically, polytrauma, deep wounds, or severe uterine bleeding may result in life-threatening blood loss, whereas minor trauma can cause moderate bleeding that may worsen over time. These clinical situations require prompt treatment to reduce the period of required clinical management. Although acute management of these emergencies should follow the same basic principles as in non-GT patients, specific care should be taken to correct conditions unique to this disorder. The recommendations provided here should help nonspecialist physicians to safely and appropriately manage GT patients until expert advice can be obtained from the referring team [20]. Such expert advice can be obtained easily through the websites of Orphanet (15 million users per year) or the French Society of Emergency Medicine and the smartphone Orphanet app (possible use at patients’ bedside) (Fig. 1).Fig. 1 Screenshots of Orphanet website (A) and the French application of Orphanet for mobile phone (B) where emergency recommendations are easily accessible Abbreviations GT Glanzmann thrombasthenia Acknowledgements Not applicable. Author contributions MF wrote the main body of the text. MCA, CF, DD, RdO, SV, MFH, HB, PS, CLB and NG provided additional comments and suggestions for the text. JSG, AR, and AP gave input to the section on methodology, GB, XD, AC, CL provided assistance for the section on emergency situations; FM and NK provided assistance for the section on organ donation. All authors read and approved the final manuscript. Funding No funding was provided for the preparation of this paper. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ==== Refs References 1. Nurden AT Glanzmann thrombasthenia Orphanet J Rare Dis 2006 1 10 10.1186/1750-1172-1-10 16722529 2. Chaudhary PK Kim S Kim S An insight into recent advances on platelet function in health and disease Int J Mol Sci 2022 23 11 6022 10.3390/ijms23116022 35682700 3. Kaiser R Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI Blood 2022 140 2 121 139 10.1182/blood.2021014914 35472164 4. Di Minno G Glanzmann's thrombasthenia (defective platelet integrin alphaIIb-beta3): proposals for management between evidence and open issues Thromb Haemost 2009 102 6 1157 1164 10.1160/TH09-04-0225 19967146 5. Nurden AT Pillois X Wilcox DA Glanzmann thrombasthenia: state of the art and future directions Semin Thromb Hemost 2013 39 6 642 655 10.1055/s-0033-1353393 23929305 6. Fang J Therapeutic expression of the platelet-specific integrin, alphaIIbbeta3, in a murine model for Glanzmann thrombasthenia Blood 2005 106 8 2671 2679 10.1182/blood-2004-12-4619 15972454 7. Fiore M Clinical utility gene card for: Glanzmann thrombasthenia Eur J Hum Genet 2012 10.1038/ejhg.2012.151 22781097 8. Nurden AT Acquired Glanzmann thrombasthenia: from antibodies to anti-platelet drugs Blood Rev 2019 36 10 22 10.1016/j.blre.2019.03.004 31010659 9. Botero JP Glanzmann thrombasthenia: genetic basis and clinical correlates Haematologica 2020 105 4 888 894 10.3324/haematol.2018.214239 32139434 10. Nurden AT Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models Blood 2012 118 23 5996 6005 10.1182/blood-2011-07-365635 11. Poon MC New insights into the treatment of Glanzmann thrombasthenia Transfus Med Rev 2016 30 2 92 99 10.1016/j.tmrv.2016.01.001 26968829 12. Grainger JD Thachil J Will AM How we treat the platelet glycoprotein defects; Glanzmann thrombasthenia and Bernard Soulier syndrome in children and adults Br J Haematol 2018 182 5 621 632 10.1111/bjh.15409 30117143 13. Fiore M Anti-alphaIIb beta3 immunization in Glanzmann thrombasthenia: review of literature and treatment recommendations Br J Haematol 2018 181 2 173 182 10.1111/bjh.15087 29611179 14. Hod E Schwartz J Platelet transfusion refractoriness Br J Haematol 2008 142 3 348 360 10.1111/j.1365-2141.2008.07189.x 18510692 15. Lee RH Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: mechanisms and implications Sci Transl Med 2019 10.1126/scitranslmed.aay0203 31852801 16. Orsini S Bleeding risk of surgery and its prevention in patients with inherited platelet disorders Haematologica 2017 102 7 1192 1203 10.3324/haematol.2016.160754 28385783 17. Poon MC The use of recombinant activated factor VII in patients with Glanzmann's Thrombasthenia Thromb Haemost 2021 121 3 332 340 10.1055/s-0040-1718373 33124022 18. Orphanet, www.orpha.net. 19. Giraudet J et al. Les maladies rares aux urgences: « Orphanet Urgences ». Anesthésie & Réanimation, 2023. In Press. 10.1016/j.anrea.2023.01.006. 20. Orphanet-Urgences, Thrombasthénie de Glanzmann. https://www.orpha.net/data/patho/Emg/Int/fr/ThrombasthenieGlanzmann_FR_fr_EMG_ORPHA849.pdf, 2023. 21. Mathews N Rivard GE Bonnefoy A Glanzmann thrombasthenia: perspectives from clinical practice on accurate diagnosis and optimal treatment strategies J Blood Med 2021 12 449 463 10.2147/JBM.S271744 34149292 22. Lison S Spannagl M Heindl B Perioperative haemostatic management of Glanzmann thrombasthenia for abdominal surgery Blood Coagul Fibrinolysis 2009 20 5 371 373 10.1097/MBC.0b013e32832b280e 19367156 23. Hennewig U Bleeding and surgery in children with Glanzmann thrombasthenia with and without the use of recombinant factor VII a Klin Padiatr 2005 217 6 365 370 10.1055/s-2005-872523 16307424 24. Poon MC The international, prospective Glanzmann Thrombasthenia Registry: treatment and outcomes in surgical intervention Haematologica 2015 100 8 1038 1044 26001792 25. Park JB Shin YS Kim SH Anesthetic experience for orthopedic surgery on a patient with Glanzmann's thrombasthenia refractory to platelet transfusion: a case report Korean J Anesthesiol 2009 57 4 507 510 10.4097/kjae.2009.57.4.507 30625914 26. Yilmaz BT Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with Glanzmann thrombasthenia Pediatr Cardiol 2005 26 6 843 845 10.1007/s00246-004-0919-7 15690232 27. Bell JA Savidge GF Glanzmann's thrombasthenia proposed optimal management during surgery and delivery Clin Appl Thromb Hemost 2003 9 2 167 170 10.1177/107602960300900213 12812388 28. Phillips R Richards M Venous thrombosis in Glanzmann's thrombasthenia Haemophilia 2007 13 6 758 759 10.1111/j.1365-2516.2007.01555.x 17883405 29. Ten Cate H The role of platelets in venous thrombosis: a patient with Glanzmann's thrombasthenia and a factor V Leiden mutation suffering from deep venous thrombosis J Thromb Haemost 2003 1 2 394 395 10.1046/j.1538-7836.2003.00041.x 12871523 30. Gruel Y Severe proximal deep vein thrombosis in a Glanzmann thrombasthenia variant successfully treated with a low molecular weight heparin Blood 1997 90 2 888 890 10.1182/blood.V90.2.888 9226191 31. Anwer A Hanley J Kumarendran K Proposed management of pregnancy and labour in an inherited platelet disorder Glanzmann's thrombasthenia J Obstet Gynaecol 2007 27 4 421 423 10.1080/01443610701325705 17654200 32. Sherer DM Lerner R Glanzmann's thrombasthenia in pregnancy: a case and review of the literature Am J Perinatol 1999 16 6 297 301 10.1055/s-2007-993875 10586983 33. Fiore M Sentilhes L d'Oiron R How I manage pregnancy in women with Glanzmann thrombasthenia Blood 2022 139 17 2632 2641 10.1182/blood.2021011595 35286390 34. Ito K Antibody removal therapy used successfully at delivery of a pregnant patient with Glanzmann's thrombasthenia and multiple anti-platelet antibodies Vox Sang 1991 61 1 40 46 1949709 35. Kashyap R Pregnancy in a patient of Glanzmann's thrombasthenia with antiplatelet antibodies J Obstet Gynaecol Res 1997 23 3 247 250 10.1111/j.1447-0756.1997.tb00839.x 9255036 36. Huq FY Kadir RA Management of pregnancy, labour and delivery in women with inherited bleeding disorders Haemophilia 2011 17 Suppl 1 20 30 10.1111/j.1365-2516.2011.02561.x 21692925 37. Leticee N Kaplan C Lemery D Pregnancy in mother with Glanzmann's thrombasthenia and isoantibody against GPIIb-IIIa: Is there a foetal risk? Eur J Obstet Gynecol Reprod Biol 2005 121 2 139 142 10.1016/j.ejogrb.2005.02.011 16054952 38. Kaplan C Foetal and neonatal alloimmune thrombocytopaenia Orphanet J Rare Dis 2006 1 39 10.1186/1750-1172-1-39 17032445 39. Dupuis A Gachet C Inherited platelet disorders: management of the bleeding risk Transfus Clin Biol 2018 25 3 228 235 10.1016/j.tracli.2018.07.003 30077511 40. Monte S Lyons G Peripartum management of a patient with Glanzmann's thrombasthenia using Thrombelastograph Br J Anaesth 2002 88 5 734 738 10.1093/bja/88.5.734 12067020 41. Kamburoglu G Kiratli H Recurrent traumatic hyphema in a patient with Glanzmann thrombasthenia J Aapos 2006 10 2 186 187 10.1016/j.jaapos.2005.11.017 16678761 42. Dinakaran S Edwards MP Hampton KK Acquired Glanzmann's thrombasthenia causing prolonged bleeding following phacoemulsification Br J Ophthalmol 2003 87 9 1189 1190 10.1136/bjo.87.9.1189 12928299