Oral health and caries risk profile assessment using the the Cariogram in thalassemia patients with or without splenectomy: A cross-sectional study.

BACKGROUND: Splenectomy is performed in ß-thalassemia cases due to the destruction of red blood cells (RBCs), and the consequent splenomegaly. OBJECTIVES: The aim of the present study was to compare oral health and the caries risk between ß-thalassemia patients with or without splenectomy, using the Cariogram. MATERIAL AND METHODS: In a cross-sectional study carried out in both the Maternity and Children Hospital and the King Fahad Hospital, Al-Madinah al-Munawwarah, Saudi Arabia, interviews, salivary sampling and oral clinical examinations were performed on 60 children and adolescents with ß-thalassemia major (mean age: 13 ±3 years; 65% with splenectomy). The Cariogram program was used to calculate the caries risk. The main outcome measures were the number of decayed, missing due to caries, and filled teeth (DMFT), plaque and gingival indices, and the caries risk. RESULTS: Of individuals with and without splenectomy, tooth brushing was reported in 49% and 57%, respectively (p > 0.05). Individuals with splenectomy had lower plaque and gingival bleeding scores (p ≤ 0.05). Salivary secretion was identical in both groups. Caries experience and the caries risk were higher in individuals without splenectomy (p > 0.05 and p ≤ 0.05, respectively). CONCLUSIONS: Within the study limitations, children and adolescents with ß-thalassemia had high plaque and gingival bleeding scores, as well as caries experience and caries risk. Those with splenectomy demonstrated lower figures than those without. Individuals with ß-thalassemia, particularly those with splenectomy, need to be educated about the oral side effects of the disease and its treatment.

Genotype Hemophilia Screening Program Identified 2 Novel Variants Including a Novel Variant (c.5816-2A > G) Causing a Pathogenic Variant of the Factor 8 Gene.

Establishing a national screening program for hemophilia patients is highly encouraged by the World Health Organization and the World Federation of Hemophilia. Hence, this study aimed to analyze the variant spectrum of F8 and F9 genes in Arab hemophilia patients. Molecular genetic and sequencing studies were performed on a cohort of 135 Saudi hemophilia patients. Out of all screened hemophilia patients (97 hemophilia A and 39 hemophilia B), 15 (11.1%) were positive for inversion 22 and 4 (3%) for inversion 1. Out of a total of 32 (23.7%) substitution/deletion mutations, 2 novel variants were identified: a novel splice acceptor site missense mutation (c.5816-2A > G) causing a pathogenic variant of the F8 gene and another splicing site point mutation in intron/exon 23 (g.164496G > A). The frequent F8 variants were (c.409A > C, p.T137P) in exon 4, (c.760A > G) in exon 6, and (c.1835G > C, p.R612P) in exon 12, while the frequent F9 variants were (c.580A > G) in exon 6 and (c.880C > T) in exon 8. These study data will enrich the spectrum of the genetic databases in the Arab population that could be applied in the future for national genetic counseling.

Consensus recommendations on appropriate coagulation tests during emicizumab administration in Saudi Arabia.

INTRODUCTION: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests. METHODS: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring. RESULTS: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue. CONCLUSION: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).

Oral Health Profiles and Related Quality of Life in Thalassemia Children in Relation to Iron Overload: A Cross-Sectional Study.

The aim was to assess the oral health of children with ß-thalassemia major (BTM) and their oral health-related quality of life (OHRQoL) in relation to the serum ferritin level (SFL). Thirty-nine children with BTM underwent an interview, salivary sampling and an oral clinical examination. The Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess their OHRQoL. The mean age of the participants was 9 ± 3 years, with 62% females. The body mass index and salivary secretion rate were within normal ranges. The mean plaque index, gingival bleeding index and number of decayed, missing and filled tooth surfaces were 70 ± 29, 38 ± 25 and 3.2 ± 4, respectively, with no significant differences between individuals with SFL below or above 2000 ng/mL (p > 0.05). No significant differences were observed between the two groups in any of the ECOHIS questions (p > 0.05). The mean ECOHIS score was 4.2 ± 4. Individuals with SFL ≥2000 ng/mL had a significantly higher mean score in the family domain "Parent Distress" than those with lower SFL (p ≤ 0.05). Within the study limits, children with ß-thalassemia major generally had high dental caries experience and gingival inflammation, yet an acceptable OHRQoL. Those with high SFL had less favorable scores in the domain "Parent Distress".

First description of the molecular and clinical characterization of hereditary factor V deficiency in Saudi Arabia: report of four novel mutations.

Coagulation factor V plays a significant role in the blood coagulation cascade as part of the prothrombinase complex. Factor V deficiency (FVD) is a rare autosomal recessive bleeding disorder with a variable phenotypic expression which varies from being asymptomatic-to-severe bleeding episodes. The aim of this study was to perform molecular and clinical characterization of FVD in patients originating from Saudi Arabia. Eleven patients (two males and nine females) with confirmed FVD were recruited in the study with ages ranging between 5 and 53 years. A next-generation sequencing-based hematology panel encompassing 393 known genes was used. A total of six sequence variations in F5 gene were identified, including four missense mutations (p.Pro189Leu, p.Trp2004Arg, p.Met2148Thr, p. Arg2202Cys), a deletion (p.Arg872Lysfs*12) and a splicing variant (c.1118+5G>T). Four variants were identified for the first time in this study. Three patients were homozygous for their respective mutations and seven patients were heterozygous. We were not able to identify a pathogenic variant in one patient of the cohort. In-silico and three-dimensional structural analyses were performed to predict the possible impact and functional consequences of the identified variants. To our knowledge, this is the first study addressing factor V mutations in patients with Arab ancestry. Results have helped in providing a definitive diagnosis to the patients and carrier detection in extended family members. Overall, the hematology panel assay was an efficient platform, demonstrating a formidable approach for the molecular diagnosis of other suspected bleeding disorders.

Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder. Around 490 mutations in ITGA2B and ITGB3 genes were reported. We aimed to use targeted next-generation sequencing (NGS) to identify variants in patients with GT. We screened 72 individuals (including unaffected family members) using a panel of 393 genes (SHGP heme panel). Validation was done by Sanger sequencing and pathogenicity was predicted using multiple tools. In 83.5% of our cohort, 17 mutations were identified in ITGA2B and ITGB3 (including 6 that were not previously reported). In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8. The SHGP heme panel can be used as a high-throughput molecular diagnostic assay to screen for mutations and variants in GT cases and carriers. Our findings expand the molecular landscape of GT and emphasize the robustness and usefulness of this panel.

The prevalence of factor VIII and IX inhibitors among Saudi patients with hemophilia: Results from the Saudi national hemophilia screening program.

Hemophilia A and B are X-linked diseases that predominantly affect male patients. Patients can develop coagulation factor inhibitors, which exponentially increases the treatment cost. However, the prevalence of factor VIII and IX inhibitors in Saudi Arabia is unclear.This study aimed to determine the Saudi prevalence of factor VIII and IX inhibitors.This 4-year, 7-center, cross-sectional study evaluated the Saudi prevalences of hemophilia A and B. We collected the patients' clinical data, evaluated their disease, and tested for factor inhibitors.We included 202 patients with hemophilia (median age at diagnosis: 0.13 years, range: birth-34.8 years). The patients included 198 male patients (98%), 148 patients with hemophilia A (73.3%), and 54 patients with hemophilia B (26.7%). The patients exhibited severe factor VIII activity (<1%; 121 patients; 5.2%), moderate activity (1-5%; 7 patients; 4.9%), and mild activity (14 patients; 9.9%). Among the patients with care-related data, most patients were treated for episodic bleeding (76.8%) or received prophylaxis (22.6%); 1 patient received both treatments. Among the patients with source-related data, the factor replacements were derived from plasma (48.4%), recombinant concentrates (22.9%), both sources (14.6%), or fresh frozen plasma (14.1%). Factor VIII inhibitors were observed in 43 (29.3%) of the 147 patients, and only 1 of the 54 patients developed factor IX inhibitors. Most patients who developed inhibitors had severe hemophilia (40/44; 90.9%), and inhibitors were also common among patients who received recombinant products (14/43; 32.6%).The Saudi prevalence of factor inhibitors was similar to those among other ethnic populations.

Assessment of cardiac functions in children with sickle cell anemia: doppler tissue imaging study.

BACKGROUND AND AIMS: The extent in which sickle cell anemia (SCA) impacts myocardial function in children is unclear. Doppler tissue imaging (DTI) was introduced as a new non-invasive echocardiographic method for assessment of ventricular systolic and diastolic functions. We undertook this study to assess subclinical impact of SCA on global myocardial performance in affected children using DTI and to correlate it with mean hemoglobin concentration. METHODS: Eighty five children with SCA (mean age 11.82 ± 3.7 years) was included as the study group and 55 age- and sex-matched healthy children as the control group. Conventional two-dimensional echocardiography was performed in both groups and DTI was used to determine right ventricular (RV) and left ventricular (LV) Tei indexes. Mean Hb concentration was correlated to the cardiac functions of SCA children. RESULTS: RV and LV Tei indexes were significantly higher in SCA group (mean ± SD: 0.54 ± 0.19 vs. 0.27 ± 0.01, p <0.0001 and 0.47 ± 0.09 vs. 0.30 ± 0.07, p <0.0001, respectively). Also, mean Hb concentration was correlated negatively with both LV Tei index (r = -0.611, p <0.0001) and with RV Tei index (r = -0.894, p <0.0001). On the contrary, fractional shortening (FS) did not correlate with mean Hb concentration (r = -0.044, p = 0.681). CONCLUSIONS: DTI technique appears to be more sensitive than conventional echocardiography in the early detection of myocardial dysfunction in children with SCA. This provides insights into the value of early screening and the potential for preventive therapy in children to avert cardiac morbidity and mortality in adults with SCA.