Bernard-Soulier syndrome is a rare inherited disorder of coagulation, with only about 100 cases reported and prevalence rates of less than 1 in 1,000,000 individuals [1] [2] [3] [4]. The pathogenesis stems from autosomal recessive mutations that cause a deficiency of receptors located on the surfaces of platelets [1] [2] [3] [4]. Specifically, the deficiency of the glycoprotein (GP) Ib-IX-V complex impairs the binding of von Willebrand factor (VWF), ultimately resulting in an insufficient coagulatory response [1] [4] [5] [6] [7]. The clinical presentation of Bernard-Soulier syndrome strongly depends on the extent of mutations, ranging from asymptomatic and mild (typical for heterozygotes) to severe and life-threatening (characteristic for homozygous individuals ) [1] [3] [5] [6] [7]. Symptoms appear as early as in infancy and childhood, with main findings being epistaxis, gingival bleeding, purpura, trauma-associated hemorrhage, and pronounced cutaneous bruising [1] [2] [4]. Post-procedural bleeding (for example after tonsillectomies, dental procedures, appendectomies, splenectomies, etc.) is an important manifestation in patients with more severe phenotypes, whereas hematuria and gastrointestinal bleeding are less common presentations [1] [4] [7]. In women, excessive menorrhagia is a common manifestation [1] [4] [7].

• Easy Bruising

  Another patient presented with easy bruising. Peripheral blood smears showed giant platelets. [ncbi.nlm.nih.gov]

  bruising, nosebleeds, mucosal bleeding, menorrhagia and, occasionally, gastrointestinal bleeding. [patient.info]

  • Easy bruising. • Epistaxis (nose bleed). • Abnormally large bleed from small injuries. [mypharmacyvisit.com]

  Bernard Soulier Syndrome Patient with Bernard Soulier syndrome may present with symptoms and signs such as prolonged bleeding time,epistaxis, dental bleeding, menorrhagia and easy bruising. [medicalrealm.net]

  Easy bruising, nose bleeds and mucocutaneous bleeding were the most frequent symptoms. [caspjim.com]

• Pharyngitis

  The 22q11.2 deletion syndrome (22q11.2DS) is caused by a microdeletion on chromosome 22, which includes the GPIbβ gene, and is characterized by abnormal development of the pharyngeal apparatus and heart. [ncbi.nlm.nih.gov]

• Gagging

  One allele contained a novel four base-pair deletion (TGAG) that eliminated the last base of the codon for Ser39 (AGT) and the entire codon for Glu40 (GAG), causing a reading frame shift that yielded a stretch of 51 amino acids before a premature stop [ncbi.nlm.nih.gov]

The diagnosis of Bernard-Soulier syndrome might be difficult to attain, primarily because of the very rare occurrence of this disorder. For this reason, the physician must conduct a detailed patient history that determines the onset and progression of symptoms, followed by a physical examination. As soon as suspicion of a coagulation disorder is raised, laboratory studies need to be employed. A complete blood count (CBC) with a peripheral blood smear can provide vital clues toward a more specific diagnosis [1] [5] [7]. Thrombocytopenia, although being variable from patient to patient, is virtually always present, and is accompanied by the appearance of very large platelets that may sometimes resemble lymphocytes [5] [7]. In fact, some authors recommend manual counting of these large platelets, as they are often mistaken as lymphocytes by automatic counters [4]. In addition to these findings, prolonged skin bleeding time is also a constitutive feature of Bernard-Soulier syndrome [1] [7]. However, more advanced studies that assess the surface glycoproteins on platelets, such as flow cytometry, immunoblotting, and surface-labeling of washed platelets, but also VWF assessment, are sometimes necessary to solidify the diagnosis [4] [5] [7]. Molecular genetic testing serves as a definitive diagnostic method [1] [4].

• Small Platelets

  platelets) X-linked thrombocytopenia (small platelets) May-Hegglin syndrome (giant platelets) Sebastian syndrome (giant platelets) Fechtner syndrome (giant platelets) Epstein syndrome (giant platelets) Idiopathic thrombocytopenic purpura (ITP)- most [wikidoc.org]

  For example, presence of small platelets is typical of Wiscott-Aldrich syndrome and X-linked thrombocytopenia. [dx.doi.org]

• Anisocytosis

  We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x109/L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis. [ncbi.nlm.nih.gov]

• Antinuclear Autoantibodies

  We suggest that the patient had an immunocomplex-mediated leukocytoclastic vasculitis accompanied by production of antinuclear autoantibodies as well as the presence of an autoantibody against GPIb. [ncbi.nlm.nih.gov]

1. López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood. 1998;91(12):4397-4418.
2. Berndt MC, Andrews RK. Bernard-Soulier syndrome. Haematologica. 2011;96(3):355-359.
3. Savoia A, Pastore A, De Rocco D, et al. Clinical and genetic aspects of Bernard-Soulier syndrome: searching for genotype/phenotype correlations. Haematologica. 2011;96(3):417-423.
4. Lanza F. Bernard-Soulier syndrome (Hemorrhagiparous thrombocytic dystrophy). Orphanet J Rare Dis. 2006;1:46.
5. Kanaji S, Kuether EL, Fahs SA, et al. Correction of Murine Bernard–Soulier Syndrome by Lentivirus-mediated Gene Therapy. Mol Ther. 2012;20(3):625-632.
6. Savoia A, Kunishima S, De Rocco D, et al. Spectrum of the mutations in Bernard-Soulier syndrome. Hum Mutat. 2014;35(9):1033-1045.
7. Pham A, Wang J. Bernard-Soulier syndrome: an inherited platelet disorder. Arch Pathol Lab Med. 2007;131(12):1834-1836.