High Prevalence of a Rare Bleeding Disorder: A Report from Glanzmann Thrombasthenia Registry of Al-Madinah, Saudi Arabia

Introduction

Glanzmann thrombasthenia (GT) is a hereditary bleeding disorder caused by a defect or deficiency of platelet glycoprotein IIbIIIa. Though GT is considered a rare bleeding disorder, some countries in the Middle East report a high prevalence of GT.

Aim

Description of GT patients' prevalence, demographic, clinical, and genetic features in AlMadinah, Saudi Arabia.

Methods

This is a 20-year report from the AlMadinah GT registry in the Madinah Hemophilia Comprehensive Care Center. The registry has included all patients with a confirmed diagnosis of GT. To label a patient as GT, He must have absence or abnormal response in all agonists except ristocetin plus absence or reduced expression of platelet glycoprotein IIbIIIa on Flowcytometry. Next-generation sequencing is used to target sequencing for Molecular testing. The extracted data underwent an analysis process, where 136 GT patients were identified. Only 125 cases have complete data in records. Statistical analysis made via a statistical package of social sciences (SPSS) version 23. The research and ethical committee approved the study.

Results

The prevalence of GT among Saudis in AlMadinah, Saudi Arabia, based on the Saudi population in 2022, is 1:10,000. One hundred twenty-five GT patients were studied: 67 (54%) females and 58 (46%) males. The median age at the time of the report was 16.5 (10 days to 56 years). Ninety-nine (79%) patients have type 1 GT. Out of 108 (86%) whose Consanguinity status was recorded, 106 (98%) GT patients are products of consanguineous marriage. Seventy (65%) patients were products of first-degree cousin parents. Family history of GT was reported in 107 (86%) cases. Twenty-five families have more than one sibling (2-5) with GT. A single tripe has 50 members with GT. The median age at presentation is 2 years (7 days to 11 years). The most common symptoms are gum bleeds, Epistaxis, and Bruises. Eighteen (16%) patients suffered from a severe bleeding course (defined as bleeding continued for more than 3 days, drop in hemoglobin for more than 2 g / L from the baseline, or needed admission to the intensive care unit). Forty (35%) patients had a moderate course (bleeding requiring hospital admission and not filling the criteria for severe one). Fifty-seven (50%) patients had a mild clinical course (bleeding can be stopped at home). Eighteen (17%) patients had bleeding episodes more than once a month, 34 (32%) had six or fewer bleeds per year, and 57 (52%) patients had one bleeding episode per year. Menorrhagia affected 35 (86%) ladies and girls. Hormonal therapy has been used at least once in their lives to interfere with the menstrual cycle in 39 (95 %) patients. Twenty-eight pregnancies were reported, producing 24 babies (13 girls and 11 boys). A postpartum hemorrhage took place after 18 deliveries (75%). Mild to moderate pregnancy-related bleeding occurred in 7 pregnancies. Iron deficiency anemia was found in 66 (66%) patients out of 100 whose iron status was reported. Eighteen mutations have been identified: 15 mutations in the ITGA2B gene and 3 mutations in the ITGB3 gene (table 1). The mutation ITGA2B:exon13:c.1210+5G>A is a novel mutation found only in one tripe, where all 12 GT patients in this tripe carry this mutation. The mutation ITGA2B: exon20:c.1879-2A>G is the most frequent mutation affecting one tribe only, and all 42 GT patients who descend from this tribe carry this mutation. The second frequent mutation is ITGB3:exon13:c.2112delC, involving 28 GT patients. Though we could not find a correlation between genotype and phenotype, we noticed GT patients carrying mutations exon13:c.2112delC and exon13:c.1210+5G>A running a more severe clinical course compared to patients affected by the mutation ITGA2B: exon20:c.1879-2A>G. Anti-platelet antibodies have been detected in 11 (9%) patients, 2 of them during pregnancy. Apart from Menorrhagia, 10 out of 15 GT patients running severe clinical courses improved when they reached puberty.

Conclusions

GT is the commonest bleeding disorder in AlMadinah, Saudi Arabia, with a prevalence of 1:10,000. With a high rate of menorrhagia and IDA. The high rate of consanguineous marriage could be a reason for the high prevalence of GT.