Bernard Soulier syndrome: a rare, frequently misdiagnosed and poorly managed bleeding disorder

Abstract

Bernard Soulier syndrome is a rare, congenital platelet bleeding disorder, with autosomal recessive inheritance. It is characterised by macrothrombocytopenia and platelet dysfunction, leading to mucocutaneous bleeding noted in early childhood. This entity poses an important diagnostic challenge, and blood smear and DNA sequencing are paramount for the correct diagnosis. Differential diagnosis includes May-Hegglin anomaly, Glanzmann Thrombasthenia and von Willebrand disease; it is also often misdiagnosed as idiopathic thrombocytopenic purpura. We report a 68-year-old man diagnosed with von Willebrand disease for three decades, admitted with gastrointestinal bleeding, anaemia and severe thrombocytopenia. Replacement with von Willebrand factor did not stop the haemorrhage, suggesting another aetiology for the bleeding disorder. Corticosteroids and intravenous immune globulin were also ineffective. Genetic sequencing showed a homozygous mutation in GP1BA gene, thus establishing the correct diagnosis.

Point‐of‐care platelet function testing results in a dog with Bernard–Soulier syndrome

“…In dogs, Bernard–Soulier syndrome has been associated with epistaxis, hematuria, melena, gingival bleeding, post‐mating bleeding, and postsurgical bleeding 7 . Fatal bleeding events have not been reported in dogs and are rare in humans 5–7 . Clinical bleeding in this case was predominantly urinary, which was associated with urinary tract infections.…”

“…7 Fatal bleeding events have not been reported in dogs and are rare in humans. [5][6][7] Clinical bleeding in this case was predominantly urinary, which was associated with urinary tract infections. The dog did not have a history of lower urinary tract signs or a bleeding tendency until 6 years of age, and it is likely that prostatitis or other urinary tract infection was the primary event with subsequent excessive bleeding.…”

“…It is classified as a giant platelet disorder (macrothrombocytopathia) due to the presence of an increased mean platelet volume, often associated with secondary thrombocytopenia with the preservation of a normal plateletcrit. [4][5][6] While humans and dogs with Bernard-Soulier syndrome have a low platelet count, the large size of platelets means that total platelet mass is preserved. 7 An apparent visual correlation between platelet count and MPV was seen in this dog (Figure 1).…”

“…9 In humans, Bernard-Soulier syndrome causes epistaxis, perioperative bleeding, bleeding gums, menorrhagia, and a predisposition to bruising. [4][5][6] In dogs, Bernard-Soulier syndrome has been associated with epistaxis, hematuria, melena, gingival bleeding, post-mating bleeding, and postsurgical bleeding. 7 Fatal bleeding events have not been reported in dogs and are rare in humans.…”

“…This receptor is crucial for the adhesion of platelets to damaged vascular walls under high‐shear conditions. It is classified as a giant platelet disorder (macrothrombocytopathia) due to the presence of an increased mean platelet volume, often associated with secondary thrombocytopenia with the preservation of a normal plateletcrit 4–6 . While humans and dogs with Bernard–Soulier syndrome have a low platelet count, the large size of platelets means that total platelet mass is preserved 7 .…”