Clinical and laboratory presentation of von Willebrand disease: Experience from a single center in Saudi Arabia.

Objectives: This study was aimed at assessing the clinical presentations and laboratory findings among patients diagnosed with vWD at a Saudi tertiary care unit. Methods: This retrospective study included 189 patients with vWD who were followed up in our unit over 4 years. Clinical and laboratory data were collected and analyzed in SPSS. Results: The median age of the study cohort was 30 years (range 11 months-56 years). The cohort had a female preponderance, with 32.30% males and 66.70% females. Bleeding from different sites was observed, mostly from the joints and muscles (23.90%), followed by the mucus membranes (14.60%), genitourinary areas (7.70%), ecchymoses (2.80%), and gastrointestinal areas (2.80%). A total of 48% of participants presented with more than one type of bleeding. A total of 105 (58.01%) participants had type 1; 29 (16.02%) had type 2; and 47 (25.96%) had type 3 vWD. Blood tests indicated the following mean value: hemoglobin, 116 ± 25.60 gm/L; ferritin, 75.80 ± 166.80 µg/L (median 28.5); vWAg, 0.40 ± 0.27IU/ml; and vWD:RCo, 0.32 ± 0.20IU/dL. The partial thromboplastin time was prolonged in 49.20% and normal in 50.80% of participants. Platelet function analysis values were prolonged in 92.90% and normal in 7.10% of participants. Comparative analysis of the O-type and non-O blood type showed that blood type O was significantly correlated with factor VIII (p-value = 0.013), vWF:RCo (p-value = 0.004), and vWF:Ag (p-value = 0.019). Conclusion: Joint and muscle bleeds were the most common clinical presentations in our cohort. Although type 1 vWD was most prevalent in our cohort, we observed a comparatively higher prevalence of type 3, possibly because of ethnic differences or referral bias. We found a significant difference between O and non-O blood type regarding FVIII and vWF:Ag, and observed a more pronounced difference for vWD activity measuresd by vWF:RCo with blood type O being the systematic factor.

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.