RARE DISEASE
Bernard-Soulier syndrome
Bernard-Soulier syndrome
Bernard-Soulier syndrome
Synonyms: Giant platelet syndrome, Hemorrhagiparous thrombocytic dystrophy
Synonyms: Giant platelet syndrome, Hemorrhagiparous thrombocytic dystrophy
Synonyms: Giant platelet syndrome, Hemorrhagiparous thrombocytic dystrophy
Drug discovery
3
drugs
With orphan designations
Overview
Bernard-Soulier syndrome (BSS) is a rare autosomal recessive platelet disorder caused by mutations in GP1BA, GP1BB, or GP9 genes, leading to defective glycoprotein Ib-IX-V complex formation. This results in macrothrombocytopenia, impaired platelet adhesion, and bleeding manifestations such as epistaxis, menorrhagia, and prolonged post-traumatic hemorrhage. Diagnosis involves platelet aggregation studies (absent ristocetin response) and flow cytometry.
Burden
Lifelong bleeding risk requiring tailored interventions; 20–30% develop platelet transfusion refractoriness [3][8][12].
Frequent misdiagnosis as ITP, leading to inappropriate therapies (e.g., steroids, splenectomy) [5][15].
Quality-of-life impacts: activity restrictions (e.g., contact sports), iron deficiency anemia, and obstetric challenges [6][14].
Categories: rare genetic diseases, rare hematological diseases
Research Papers
138 drug discovery papers about Bernard-Soulier syndrome, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
138 drug discovery papers about Bernard-Soulier syndrome, with 4 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-05-07 | Genetic depletion in zebrafish uncovers requirement for septins in haematopoiesis
Abstract Haematopoiesis and differentiation of immune cells from haematopoietic stem and progenitor cells (HSPCs) are essential to core aspects of health and disease. A key player in haematopoiesis and HSPC differentiation is the cytoskeleton, which governs cell division and lineage bias. Despite insights using mouse models, regulation of haematopoiesis by the septin cytoskeleton is mostly unknown. Septins are unconventional filament forming proteins best known for roles in cell division and host defence. To investigate septin-mediated host defence in vivo , we generated septin-deficient zebrafish models for infection with Mycobacterium marinum . Unexpectedly, septin-deficient larvae were protected from mycobacterial infection due to significantly increased macrophage numbers, reduced cell death, and enhanced inflammatory responses. Underlying this, we found that septin-deficient larvae produce significantly more HSPCs and show myeloid lineage bias, establishing a requirement for septins in haematopoiesis. In agreement with classical HSPC hierarchy, increased myeloid production in septin-deficient larvae is at the expense of erythroid lineage production. Our findings that septins play a role in haematopoiesis is consistent with hallmarks of haematological disorders in which septin dysfunction has been implicated, including acute myeloid leukaemia, myelodysplastic syndrome, and platelet disorder Bernard-Soulier syndrome. These results highlight zebrafish as a new model to investigate septin-mediated haematopoiesis and application of septin-based medicines to treat blood disorders.
2026-04-08 | Congenital thrombopathies in southern Tunisia : A multicenter study.
congenital thrombopathies (CTs) are rare bleeding disorders resulting from platelet dysfunction which may also be associated with thrombocytopenia. To date, the prevalence of CT in Tunisia has not been established. The aim of this study was to describe the various types of CT and the associated hemorrhagic manifestations observed in a cohort from southern Tunisia. We retrospectively collected clinical and laboratory data of patients with CT who were followed up over 43 years (1982 - 2024) in the pediatric and hematology departements of a university hospital center in southern Tunisia. The diagnosis of thrombopathy was established based on flow cytometry analysis and/or light transmission aggregometry and/or molecular analysis. We identified 60 patients (35 men and 25 women). The mean age at diagnosis was 61.7 months (1 month-70 years). Consanguinity was noted in 71.6% of cases (n=43). A family history of thrombopathy was reported in 51.6% of cases (n=31). The presenting symptoms at diagnosis were spontaneous or provoked bleeding (n=56) and easy bruising associated with thrombocytopenia within the first 48 hours of life (n=1). The etiologies of the thrombopathies were as follows : Glanzmann thrombasthenia (n=54), Bernard Soulier syndrome (n=5) and Wiskott Aldrich syndrome (n=1). Glanzmann thrombasthenia was the most prevalent thrombopathy in our cohort, likely attributed to the high rate of consanguinity in our region.
2026-03-24 | Inherited Platelet Disorders During Pregnancy and Delivery: Overview of Management Strategies and Emerging Therapeutic Considerations.
Inherited platelet disorders (IPDs) comprise a heterogeneous group of rare conditions that present particular challenges during pregnancy, with bleeding risk increasing during labor and the immediate postpartum period. These disorders require coordinated, multidisciplinary management to mitigate maternal and neonatal bleeding risk. Although data remains limited, individuals with IPD, including Bernard-Soulier syndrome, Glanzmann thrombasthenia, MYH9-related disorders, Hermansky-Pudlak syndrome, and platelet storage pool disorders, are at an increased risk for obstetrical bleeding, with the degree of risk varying by underlying diagnosis. In severe inherited platelet disorders such as Glanzmann thrombasthenia, peripartum hemorrhage is common, with up to half of the deliveries in some series requiring red cell or platelet transfusion. Because these conditions are congenital, the fetus may also be affected, placing neonates at risk for serious bleeding complications, including intracranial hemorrhage, although available data is limited. Despite the considerable morbidity and mortality risk associated with inherited platelet disorders, management strategies during pregnancy and delivery remain poorly defined. This stands in contrast to other bleeding disorders, such as factor deficiencies, for which multiple therapeutic approaches have been evaluated in the peripartum setting. In this review, we summarize the available evidence and current management strategies for individuals with inherited platelet disorders during pregnancy and delivery.
2026-02-26 | Hemostatic rescue with rFVIIa in Bernard-Soulier syndrome refractory to HLA-matched platelet transfusion.
We report the case of a man in his 50’s diagnosed with Bernard-Soulier syndrome (BSS) in childhood who developed refractory gluteal bleeding following a fall accident. The patient underwent four hematoma evacuation procedures and multiple platelet transfusions, including HLA (human leukocyte antigen) -matched platelet concentrates, without achieving sustained hemostatic control. Given the lack of response to platelet transfusion and ongoing bleeding risk, Eptacog Alfa (recombinant activated factor VII; rFVIIa) was administered for 4 days, following the dosing regimen recommended for Glanzmann thrombasthenia in surgical bleeding settings. Hemostasis was achieved shortly after rFVIIa administration, and no further surgical evacuation was necessary. Importantly, no thromboembolic complications occurred despite the use of rFVIIa. This case demonstrates that rFVIIa can serve as an effective adjunctive hemostatic therapy in patients with BSS who are refractory to platelet transfusions. We reviewed the existing literature on rFVIIa use in patients with BSS and summarized the clinical contexts, dosing strategies, efficacy, and safety outcomes. Our experience suggests that early consideration of rFVIIa may help prevent repeated surgical interventions and reduce bleeding-related morbidity in complex cases.
2026-02-01 | Immune-mediated platelet dysfunction with spontaneous formation of aggregates in pediatric end-stage liver disease: A case report
Introduction A 12-year-old girl with Alagille syndrome was admitted with progressive liver failure and subsequently listed for liver transplantation. Furthermore, the patient was born with tetralogy of Fallot, for which corrective surgery was performed. Eleven years after surgery, a stent was implanted in the pulmonary artery due to progressive pulmonary stenosis. As expected in advanced hepatic insufficiency, she developed thrombocytopenia (baseline 100-120 Tsd/µl) and reduced vitamin K-dependent clotting factors. In May, platelet counts suddenly became immeasurable due to pronounced spontaneous platelet aggregation, fluctuating over time. Pseudothrombocytopenia was excluded. Light transmission aggregometry revealed absent aggregation in response to arachidonic acid and ristocetin 1mg/ml, consistent with a Bernard–Soulier- and Aspirin-like phenotype. Since the glycoprotein profile was normal, it appeared to be an acquired disorder, even though there was no solid evidence of any specific antibodies. In order to demonstrate the presumed antibodies indirectly, mixing studies were performed. When donor platelets were combined with the patient’s plasma, aggregation responses to ristocetin 1M and arachidonic acid improved, followed by gradual desaggregation. However, donor plasma combined with the patient’s platelets did not improve aggregation, suggesting that antibodies were primarily platelet-bound. Peripheral blood smears showed fragmented erythrocytes and complement activity was elevated, indicating microangiopathy. During pre-transplant evaluation, acquired von Willebrand syndrome was also diagnosed, as expected following stent angioplasty. Method Light transmission aggregometry Glycoprotein-specific ELISA Results Subsequent to liver transplantation, the patient was treated with von-Willebrand-Factor-containing factor VIII concentrate and regular platelet transfusions regardless of the absolute count. Tranexamic acid was avoided because of possible microangiopathy. Standard anticoagulation with unfractionated heparin was administered perioperatively. The liver transplantation proceeded without bleeding or thrombotic complications. Within one week after the last platelet transfusion, platelet count had normalized completely, and light transmission aggregometry confirmed full recovery of platelet function. Conclusion This case illustrates the complex coagulation abnormalities observed in end-stage liver disease, where hemostatic impairment may extend beyond reduced clotting factors to include Bernard–Soulier-like phenotype, and microangiopathy. Despite severe preoperative coagulopathy, precise perioperative management with targeted replacement therapy and cautious avoidance of prothrombotic agents enabled successful transplantation without bleeding events. Liver transplantation not only resolved hepatic failure but also led to rapid normalization of platelet counts and function, highlighting the reversible nature of these coagulation disorders once hepatic function is restored. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
2026-05-07 | Genetic depletion in zebrafish uncovers requirement for septins in haematopoiesis
Abstract Haematopoiesis and differentiation of immune cells from haematopoietic stem and progenitor cells (HSPCs) are essential to core aspects of health and disease. A key player in haematopoiesis and HSPC differentiation is the cytoskeleton, which governs cell division and lineage bias. Despite insights using mouse models, regulation of haematopoiesis by the septin cytoskeleton is mostly unknown. Septins are unconventional filament forming proteins best known for roles in cell division and host defence. To investigate septin-mediated host defence in vivo , we generated septin-deficient zebrafish models for infection with Mycobacterium marinum . Unexpectedly, septin-deficient larvae were protected from mycobacterial infection due to significantly increased macrophage numbers, reduced cell death, and enhanced inflammatory responses. Underlying this, we found that septin-deficient larvae produce significantly more HSPCs and show myeloid lineage bias, establishing a requirement for septins in haematopoiesis. In agreement with classical HSPC hierarchy, increased myeloid production in septin-deficient larvae is at the expense of erythroid lineage production. Our findings that septins play a role in haematopoiesis is consistent with hallmarks of haematological disorders in which septin dysfunction has been implicated, including acute myeloid leukaemia, myelodysplastic syndrome, and platelet disorder Bernard-Soulier syndrome. These results highlight zebrafish as a new model to investigate septin-mediated haematopoiesis and application of septin-based medicines to treat blood disorders.
2026-04-08 | Congenital thrombopathies in southern Tunisia : A multicenter study.
congenital thrombopathies (CTs) are rare bleeding disorders resulting from platelet dysfunction which may also be associated with thrombocytopenia. To date, the prevalence of CT in Tunisia has not been established. The aim of this study was to describe the various types of CT and the associated hemorrhagic manifestations observed in a cohort from southern Tunisia. We retrospectively collected clinical and laboratory data of patients with CT who were followed up over 43 years (1982 - 2024) in the pediatric and hematology departements of a university hospital center in southern Tunisia. The diagnosis of thrombopathy was established based on flow cytometry analysis and/or light transmission aggregometry and/or molecular analysis. We identified 60 patients (35 men and 25 women). The mean age at diagnosis was 61.7 months (1 month-70 years). Consanguinity was noted in 71.6% of cases (n=43). A family history of thrombopathy was reported in 51.6% of cases (n=31). The presenting symptoms at diagnosis were spontaneous or provoked bleeding (n=56) and easy bruising associated with thrombocytopenia within the first 48 hours of life (n=1). The etiologies of the thrombopathies were as follows : Glanzmann thrombasthenia (n=54), Bernard Soulier syndrome (n=5) and Wiskott Aldrich syndrome (n=1). Glanzmann thrombasthenia was the most prevalent thrombopathy in our cohort, likely attributed to the high rate of consanguinity in our region.
2026-03-24 | Inherited Platelet Disorders During Pregnancy and Delivery: Overview of Management Strategies and Emerging Therapeutic Considerations.
Inherited platelet disorders (IPDs) comprise a heterogeneous group of rare conditions that present particular challenges during pregnancy, with bleeding risk increasing during labor and the immediate postpartum period. These disorders require coordinated, multidisciplinary management to mitigate maternal and neonatal bleeding risk. Although data remains limited, individuals with IPD, including Bernard-Soulier syndrome, Glanzmann thrombasthenia, MYH9-related disorders, Hermansky-Pudlak syndrome, and platelet storage pool disorders, are at an increased risk for obstetrical bleeding, with the degree of risk varying by underlying diagnosis. In severe inherited platelet disorders such as Glanzmann thrombasthenia, peripartum hemorrhage is common, with up to half of the deliveries in some series requiring red cell or platelet transfusion. Because these conditions are congenital, the fetus may also be affected, placing neonates at risk for serious bleeding complications, including intracranial hemorrhage, although available data is limited. Despite the considerable morbidity and mortality risk associated with inherited platelet disorders, management strategies during pregnancy and delivery remain poorly defined. This stands in contrast to other bleeding disorders, such as factor deficiencies, for which multiple therapeutic approaches have been evaluated in the peripartum setting. In this review, we summarize the available evidence and current management strategies for individuals with inherited platelet disorders during pregnancy and delivery.
2026-02-26 | Hemostatic rescue with rFVIIa in Bernard-Soulier syndrome refractory to HLA-matched platelet transfusion.
We report the case of a man in his 50’s diagnosed with Bernard-Soulier syndrome (BSS) in childhood who developed refractory gluteal bleeding following a fall accident. The patient underwent four hematoma evacuation procedures and multiple platelet transfusions, including HLA (human leukocyte antigen) -matched platelet concentrates, without achieving sustained hemostatic control. Given the lack of response to platelet transfusion and ongoing bleeding risk, Eptacog Alfa (recombinant activated factor VII; rFVIIa) was administered for 4 days, following the dosing regimen recommended for Glanzmann thrombasthenia in surgical bleeding settings. Hemostasis was achieved shortly after rFVIIa administration, and no further surgical evacuation was necessary. Importantly, no thromboembolic complications occurred despite the use of rFVIIa. This case demonstrates that rFVIIa can serve as an effective adjunctive hemostatic therapy in patients with BSS who are refractory to platelet transfusions. We reviewed the existing literature on rFVIIa use in patients with BSS and summarized the clinical contexts, dosing strategies, efficacy, and safety outcomes. Our experience suggests that early consideration of rFVIIa may help prevent repeated surgical interventions and reduce bleeding-related morbidity in complex cases.
2026-02-01 | Immune-mediated platelet dysfunction with spontaneous formation of aggregates in pediatric end-stage liver disease: A case report
Introduction A 12-year-old girl with Alagille syndrome was admitted with progressive liver failure and subsequently listed for liver transplantation. Furthermore, the patient was born with tetralogy of Fallot, for which corrective surgery was performed. Eleven years after surgery, a stent was implanted in the pulmonary artery due to progressive pulmonary stenosis. As expected in advanced hepatic insufficiency, she developed thrombocytopenia (baseline 100-120 Tsd/µl) and reduced vitamin K-dependent clotting factors. In May, platelet counts suddenly became immeasurable due to pronounced spontaneous platelet aggregation, fluctuating over time. Pseudothrombocytopenia was excluded. Light transmission aggregometry revealed absent aggregation in response to arachidonic acid and ristocetin 1mg/ml, consistent with a Bernard–Soulier- and Aspirin-like phenotype. Since the glycoprotein profile was normal, it appeared to be an acquired disorder, even though there was no solid evidence of any specific antibodies. In order to demonstrate the presumed antibodies indirectly, mixing studies were performed. When donor platelets were combined with the patient’s plasma, aggregation responses to ristocetin 1M and arachidonic acid improved, followed by gradual desaggregation. However, donor plasma combined with the patient’s platelets did not improve aggregation, suggesting that antibodies were primarily platelet-bound. Peripheral blood smears showed fragmented erythrocytes and complement activity was elevated, indicating microangiopathy. During pre-transplant evaluation, acquired von Willebrand syndrome was also diagnosed, as expected following stent angioplasty. Method Light transmission aggregometry Glycoprotein-specific ELISA Results Subsequent to liver transplantation, the patient was treated with von-Willebrand-Factor-containing factor VIII concentrate and regular platelet transfusions regardless of the absolute count. Tranexamic acid was avoided because of possible microangiopathy. Standard anticoagulation with unfractionated heparin was administered perioperatively. The liver transplantation proceeded without bleeding or thrombotic complications. Within one week after the last platelet transfusion, platelet count had normalized completely, and light transmission aggregometry confirmed full recovery of platelet function. Conclusion This case illustrates the complex coagulation abnormalities observed in end-stage liver disease, where hemostatic impairment may extend beyond reduced clotting factors to include Bernard–Soulier-like phenotype, and microangiopathy. Despite severe preoperative coagulopathy, precise perioperative management with targeted replacement therapy and cautious avoidance of prothrombotic agents enabled successful transplantation without bleeding events. Liver transplantation not only resolved hepatic failure but also led to rapid normalization of platelet counts and function, highlighting the reversible nature of these coagulation disorders once hepatic function is restored. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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Drug Discovery Landscape
3 orphan drug designations for Bernard-Soulier syndrome.
3 orphan drug designations for Bernard-Soulier syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
induced pluripotent stem cell (iPSC)-derived platelet injection | cell therapies | FDA | 2025-12-19 | — | HemaCell Biotechnology Inc. |
platelets produced in vitro from proplatelets derived from peripheral blood | cell therapies | FDA | 2025-04-25 | — | HemaCell Biotechnology Inc. |
umbilical cord blood derived megakaryocyte injection | cell therapies | FDA | 2025-04-04 | — | HemaCell Biotechnology Inc. |
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