Phenotypic and genotypic (exon 28) characterization of patients diagnosed with von Willebrand disease type 1 in Eastern Saudi Arabia.

Von Willebrand factor (VWF) is a plasma glycoprotein that plays a key role in hemostasis. Mutations in this protein can result in von Willebrand disease (VWD), the most common form of bleeding disorder in humans. Patients with type 1 VWD have a quantitative plasmatic deficiency of normal structural and functional VWF. Our study aimed to investigate the phenotypic and genotypic characteristics of VWD type 1 patients in eastern Saudi Arabia, focusing on exon 28. We included patients previously diagnosed with WWD type 1 at the King Fahad teaching hospital in Al Khobar and their family members. The correlations between various phenotypic data and genotypic (exon 28) were analyzed using statistical software (SPSS) version 21. While these variants were generally considered benign with minor clinical effects, our analysis did identify two pathogenic variants that could lead to severe VWD symptoms. Specifically, we found these two pathogenic variants in three VWD patients from Saudi Arabia, providing essential insights into pathogenic VWD mutations in this population. Our study, therefore, sheds light on the prevalence of VWF variants in the eastern province of the Kingdom and highlights the need for continued research into the genetic causes of VWD in this region.

Phenotypic and Genotypic Signatures of VWF Exon 18 in Eastern Saudi Patients Previously Diagnosed with Type 1 von Willebrand Disease.

Introduction: von Willebrand disease (VWD) is the most prevalent bleeding disease, which is associated with either low levels of von Willebrand factor (VWF) or abnormality in its structure. Three types of the disease have been described; type 1 (VWD1) and 3 (VWD3) are caused by deficiency of VWF and type 2 (VWD2) is caused by production of defective VWF. The aim of the current study was to characterize gene variants of VWF gene; exon 18 in particular, in a cohort of Saudi families as well as healthy control subjects. Methods: A total of 19 families comprising 60 subjects of type 1 VWD were enrolled in the study. Participants were divided into 22 index cases, 21 affected family members and 17 unaffected family members ranging in age from 6 to 70 years. Blood samples were collected from all participants to measure activated partial thromboplastin time test (APTT), von Willebrand antigen level (VWF:Ag), Factor VIII activity (FVIII:C) and ristocetin cofactor activity (VWF:RCo), platelet count, determining the ABO blood group and for genetic analysis by Sanger sequencing. Results: The results indicated that VWD1 patients have lower levels of VWF and factor VIII than the non-affected family members and the control subjects. In addition, five gene variants were reported in VWF exon 18; of these, c.2365A>G and c.2385T>C were more common in the control group and might be protective from VWD. Discussion: In conclusion, VWF levels are influenced by blood group, and there was no association between variants in exon 18 of VWF gene reported in all groups and the disease status; however, blood group analysis and genome-wide genotyping could help to highlight high-risk groups and improve clinical management of VWD.

Clinical outcome of pre-operative blood transfusion for sickle cell disease patients in post-operative complications.

BACKGROUND: Preoperative blood transfusion for patients with sickle cell disease is a debatable topic and it can be lifesaving. Sickle cell disease patients are at high risk for vaso-occlusive crisis due to the large concentration of sickle hemoglobin (HgbS) in their blood. Despite the current extensive research into this disease, there is still no consensus over whether blood transfusion is a preferable preoperative modality among patients undergoing elective surgical procedures. METHOD: A retrospective observational study, which enrolled 204 patients with Sickle cell disease who underwent surgery at King Fahad Hospital of the University (KFHU) over the last five years. The primary objective was to determine whether there is evidence that preoperative blood transfusion for SCD patients undergoing surgical procedures will reduce postoperative complications related to SCD. RESULTS: A total of 204 patients were included, of which 30% had preoperative blood transfusion. Majority of patient 44% had undergone cholecystectomy. On multivariate logistic regression analysis, patients who did not undergo blood transfusion had significantly higher risk to develop post-operative SCD complications (OR = 3.07, P value = 0.002). In addition, they had significantly prolonged hospitalization (OR = 2.22, P value = 0.08). In contrast, patients who received blood transfusion had lower risk for developing post-operative SCD-related complications (OR = 1.87, P value = 0.29), and decrease in the duration of hospitalization by (OR = 0.49, P value = 0.045). CONCLUSION: Our study showed that patients who had not undergone preoperative blood transfusion had higher risk to develop postoperative complications and prolonged hospital stay compared to those who underwent blood transfusion.

Does high serum iron level induce low bone mass in sickle cell anemia ?

Iron overload is quite common in patients suffering from hemoglobinopathies causing arthropathies, endocrinal affection and neuropathies. Recently low bone mass was added to the list of complications. This study is conducted to find any correlation between serum iron level and low bone mass in sickle cell anemia (SCA). Patients ≥18 years of age with sickle cell anemia, who attended outpatient clinics or admitted to King Fahd University Hospital, Al Khobar, Saudi Arabia,between 1st September 2006 and August 2007 were the subjects of this study. Patients age and sex were documented and body mass index was calculated. Apart from routine hematological tests, serum ferritin, serum Iron level, total estradiol, testosterone level was done. Bone mineral density measurement was done using dual energy X-ray absorptiometry (DEXA) at upper femur and lumbar spine. The data of 100 patients was analyzed, 48 males and 52 females. The mean age was 27.5 ± 6.1 years. In 64 patients (32 males and 32 females) serum iron level was 319.35 µg/dl and the mean serum ferritin level in males and females was within the normal range. Sixty-eight percent of females and 71.8% of males patients in whom serum iron was high had lower bone mass P = < 0.001. Our study shows that SCA patients in whom serum iron level was higher than normal effected bone mass. Further studies are needed to confirm this as a cause of osteoporosis in SCA patients.

Three-factorial Genetic Thrombophilia with Recurrent Thrombotic Events in a Saudi Patient: A Case Report.

Thrombophilia is caused by several genetic and acquired factors. Existence of more than one genetic factor may increase the risk of developing recurrent thrombotic events. Here, we present a case of a 48-year-old male with a known history of deep venous thrombosis and a known mutation in factor V Leiden combined with mild protein S deficiency, who presented with a painful swelling in the left leg. Moreover, the patient had a history of diabetes, dyslipidemia and obesity. Prothrombin time and platelet count were within the normal range. The international normalized ratio and activated partial thromboplastin time were 3.21 and 36.7 s, respectively. The Doppler study showed a thrombus in the saphenous vein, and complementary genetic screening investigations revealed heterozygous mutation for prothrombin (G20210A). A diagnosis of multifactorial genetic thrombophilia was established. The patient was treated with warfarin, which resulted in significant improvement in the follow-ups, and at the time of reporting this case, there were no clinical or biological signs of thrombosis. The presence of multiple hereditary and acquired thrombophilic factors is a rare clinical presentation that requires close monitoring, for which a lifelong anticoagulation therapy should be discussed based on the clinical response of the patient.

Secondary osteoporosis due to sickle cell anemia: do sex steroids play a role?

BACKGROUND: The exact cause of osteoporosis in patients with sickle cell disease (SCD) is not known, and various hypotheses have been put forward. AIM: To assess the effect of sex steroids on bone mass in SCD patients. SETTINGS AND DESIGN: In King Fahd Hospital of the university, Alkhobar, Saudi Arabia, a cross-sectional study was carried out. MATERIALS AND METHODS: All patients known to suffer from SCD attending the hospital between August 2006 and August 2007 were subjects of the study. Blood was extracted for serum level of androgens, gonadotropins, thyroid stimulating hormone (TSH), calcium, phosphorus, and alkaline phosphatase. Measurement of bone mineral density (BMD) of hip and spine was done using dual-energy X-ray absorptiometry (DEXA). All tests were performed using SPSS (Statistical Package for Social Sciences), version 14.0, Chicago, Illinois, with P value of < 0.05 being statistically significant with confidence interval (CI) of 95%. RESULTS: One hundred three consecutive patients with an average age of 27.83 years were studied. Forty-five were males; and 58, females. Low bone mass (osteoporotic/osteopenic) was found in 62.2% of the patients in the male group and 67.06% in the female group. In males, testosterone level was not significant between different groups, but total estradiol levels were significantly lower in the osteopenic and osteoporotic patients (P < 0.003 and < 0.01 respectively). In female patients, estradiol and testosterone levels were lower in osteoporotic patients in comparison to non-osteoporotic patients (P = 0.05 and 0.001). CONCLUSIONS: Our study indicates that sex steroids play a major role in the development of osteopenia and osteoporosis in patients with SCD.

Influence of androgens on bone mass in young women with sickle cell anemia.

OBJECTIVE: To evaluate the relationship between the gender hormonal levels and bone mineral density in premenopausal women suffering with sickle cell disease. METHODS: A cross-sectional study including consecutive female adult patients with sickle cell anemia attending the outpatient hematology/orthopaedic clinics, or admitted to King Fahd University Hospital, Al-Khobar, Saudi Arabia, between August 2006 and June 2007. Patient's age was documented, and body mass index was calculated. Blood was drawn for complete blood picture, biochemistry, and hormonal profile including total estradiol E2 and total testosterone Te. Bone mineral density BMD was measured for all patients using dual energy x-ray absorptiometry scan at the hip and lumbar spine. RESULTS: We analyzed the data of 51 patients with an average age of 26+/-3.1 years. Patients were divided into 2 groups group A and group B. Group A had normal BMD and group B with low BMD. Thirty-one (60.8%) were in group A and 20 (39.2%) were in group B. The E2 level was not statistically different between the 2 groups, while Te level was significantly lower in women with low BMD 38+/-11.8 versus 22.3+/-11.7 ng/dl, p<0.001. CONCLUSION: Our study indicates that in premenopausal female patients with sickle cell anemia, testosterone may play a role in the preservation of bone mass.