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Bernard-Soulier Syndrome

Bernard-Soulier syndrome is a very rare autosomal recessive disorder of impaired clotting. Depending on the phenotype, patients present with bleeding episodes of variable severity. Epistaxis, cutaneous hemorrhage, pronounced post-traumatic bleeding, and severe menorrhagia are typically encountered. Certain cases could manifest with post-procedural bleeding. Thrombocytopenia, very large platelets, and a prolonged skin bleeding time are some of the main findings, but genetic studies and the use of techniques that examine the platelet expression of surface glycoproteins are necessary to confirm the diagnosis.


Presentation

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]
  • Other symptoms of people affected with Bernard-Soulier syndrome are bleeding gums (the area around your teeth), easy bruising, and heavy menstrual periods.[diseaseinfosearch.org]
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]

Workup

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

Treatment

  • These three admissions highlight the potential of rFVIIa for the treatment of severe bleeds in patients with BSS.[ncbi.nlm.nih.gov]
  • This case illustrates the utility of using octreotide for the long-term treatment of children with bleeding disorders and angiodysplasia.[ncbi.nlm.nih.gov]
  • Although platelet transfusion was omitted, haemostasis was regarded excellent in all of these treatment episodes.[ncbi.nlm.nih.gov]
  • Surgical treatment should be considered if the general condition can tolerate a surgical procedure.[ncbi.nlm.nih.gov]
  • Another woman with BSS later also received the same rFVIIa and fibrinogen treatment prophylactically after delivery without any postpartum bleeding.[ncbi.nlm.nih.gov]

Prognosis

  • The prognosis is usually good with adequate supportive care but severe bleeding episodes can occur with menses, trauma and surgical procedures. Treatment of bleeding or prophylaxis during surgical procedures usually requires platelet transfusion.[ncbi.nlm.nih.gov]
  • Prognosis The tendency to bleed easily lasts for life but may decrease as the patient gets older. [ 3 ][patient.info]
  • […] heterozygous for BSS mutations have lower platelet counts, more mucocutaneous bleeding, and higher vWF levels than do controls without these mutations, although bleeding is much milder than in persons who are homozygous for BSS. [7] Epidemiology and Prognosis[emedicine.medscape.com]

Etiology

  • This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management.[books.google.com]
  • Pathophysiology and Etiology The underlying biochemical defect in BSS is the absence or decreased expression of the GPIb/IX/V complex on the surface of the platelets. [2, 3, 4, 5] This complex is the receptor for von Willebrand factor (vWF), and the result[emedicine.medscape.com]

Epidemiology

  • This has been found to be caused by mutation in the GP1BA gene, the GP1BB gene, or the GP9 gene. [ 1 ] It is familial with autosomal recessive inheritance. [ 2 ] Epidemiology The syndrome is rare - estimated prevalence is less than 1 per million. [ 3[patient.info]
  • […] individuals who are heterozygous for BSS mutations have lower platelet counts, more mucocutaneous bleeding, and higher vWF levels than do controls without these mutations, although bleeding is much milder than in persons who are homozygous for BSS. [7] Epidemiology[emedicine.medscape.com]
Sex distribution
Age distribution

Pathophysiology

  • This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management.[books.google.com]
  • However, the study of the pathophysiology has led to a better understanding of platelet biochemistry and physiology.[impact-r.com]
  • Pathophysiology and Etiology The underlying biochemical defect in BSS is the absence or decreased expression of the GPIb/IX/V complex on the surface of the platelets. [2, 3, 4, 5] This complex is the receptor for von Willebrand factor (vWF), and the result[emedicine.medscape.com]

Prevention

  • Treatment of the Bernard soulier syndrome mainly depends upon supportive measures and you may adopt the preventive measures to prevent yourself from any life threatening complication. • Prevention of major injury. • Transfusion of the factor 8 precipitate[mypharmacyvisit.com]
  • In this case, we successfully performed adenoidectomy and tonsillectomy and circumcision surgery concurrently under the preventive and intermittent transfusion of platelets.[ncbi.nlm.nih.gov]
  • For those rare few afflicted with this disease, we present a combined systemic and topical approach that may be helpful in the control and prevention of perioperative hemorrhage in this and other similar platelet disorders.[ncbi.nlm.nih.gov]
  • Patients suffering from BSS may require platelet transfusion in prevention and management of severe bleeding. However, recent publications have suggested that recombinant factor VIIa (rFVIIa) infusion may support haemostasis in BSS.[ncbi.nlm.nih.gov]
  • In this case we successfully performed both an interventional examination as well as mastectomy with axillary lymph node dissection, under the preventive and intermittent transfusion of platelets.[ncbi.nlm.nih.gov]

References

Article

  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.

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Last updated: 2019-06-28 10:24