Mutation Analysis and Clinical Sprectrum Of Patients With Glanzmann’s Thrombasthenia and Bernard Soulier Syndrome

Glanzmann’s thrombasthenia (GT) is an inherited disorder of platelet aggregation, resulting from defective glycoprotein IIb/IIIa on platelet surface. Bernard Soulier Syndrome (BSS) is also an inherited disorder of platelet adhesion and associated with defective glycoprotein Ib-V-IX on platelet surface. Both of these disorders usually present with mucocutaneous bleedings. We aimed to evaluate the clinical and genetic characteristics of the patients diagnosed as BSS and GT in department of pediatric hematology of Meram Faculty of Medicine, retrospectively.

Seven patients diagnosed with BSS and 20 patients diagnosed with GT were enrolled to the study. Medical records of patients were reviewed retrospectively. Glycoprotein IIb gen rearrangement was investigated in genetic department of Ankara University Medical School, Turkey. Mutational analysis for BSS was performed in Medicina Interna ed Oncologia Medica, Italy. The correlation between clinical outcome and genotyping was investigated.

Of 20 patients of GT, 8 were male and 12 were female. Of 7 patients of BSS, all of them were female. Glycoprotein IIB gene rearrangement was detected in 7 patient of GT. 5 of 7 were newly described mutations in published literature. Mutations in GpIBB and GpIBA gene were detected in 7 patients with BSS. No correlation was observed among the clinical and genotype characteristics of patients both with GT and BSS. The most common patterns of bleeding were epistaxis and gum bleeding. Life threatening bleeding was seen in 5 of GT patients (4 gastrointestinal bleeding, 1 mediastinal hematoma) and 2 of BSS patients (1 splenic rupture and 1 gastrointestinal bleeding). No patients had died due to major bleedings. One patient with GT experienced spontaneous duodenal intramural bleeding resulting duodenal obstruction. One patient with BSS experienced spontaneous mediastinal hematoma. Although the BSS, it is interesting that the patient was able to control of mediastinal hematoma. Further investigations revealed the patient has prothrombotic mutation (heterozygous FV Leiden).

The most common bleeding pattern in patients with thrombocyte dysfunction is mucocutaneous bleeding. Some patients may suffer from life-threatening bleedings. Our study contributes to the literature because of five newly described mutations in GT patients. It may be hypothesed that the presence of prothrombotic mutation in patients with thrombocyte dysfunction may reduce the severity of bleedings.

No relevant conflicts of interest to declare.