Salwa Hindawi

Clinical biomarkers in sickle cell disease.

Sickle cell disease (SCD) is a hereditary blood disorder caused by a single gene. Various blood and urine biomarkers have been identified in SCD which are associated with laboratory and medical history. Biomarkers have been proven helpful in identifying different interconnected disease-causing mechanisms of SCD, including hypercoagulability, hemolysis, inflammation, oxidative stress, vasculopathy, reperfusion injury and reduced vasodilatory responses in endothelium, to name just a few. However, there exists a need to establish a panel of validated blood and urine biomarkers in SCD. This paper reviews the current contribution of biochemical markers associated with clinical manifestation and identification of sub-phenotypes in SCD.

Thrombin Generating Capacity and Phenotypic Association in ABO Blood Groups

Individuals with blood group O have a higher bleeding risk than non-O blood groups. This could be explained by the lower levels of FVIII and von Willebrand Factor (VWF) levels in O individuals. We investigated the relationship between blood groups, thrombin generation (TG), prothrombin activation and thrombin inactivation. Plasma levels of VWF, FVIII, antithrombin, fibrinogen, prothrombin and α2Macroglobulin (α2M) levels were determined. TG was measured in platelet rich (PRP) and platelet poor plasma (PPP) of 217 healthy donors and prothrombin conversion and thrombin inactivation were calculated. VWF and FVIII levels were lower (75% and 78%) and α2M levels were higher (125%) in the O group. TG is 10% lower in the O group in PPP and PRP. Less prothrombin was converted in the O group (86%) and the thrombin decay capacity was lower as well. In the O group, α2M plays a significantly larger role in the inhibition of thrombin (126%). In conclusion, TG is lower in the O group due to lower prothrombin conversion, and a larger contribution of α2M to thrombin inactivation. The former is unrelated to platelet function because it is similar in PRP and PPP, but can be explained by the lower levels of FVIII.

A putative association of interleukin-10 promoter polymorphisms with cardiovascular disease

Interleukin‐10 (IL‐10) is an anti inflammatory cytokine involved in the ongoing coronary inflammation and related patho‐physiological processes. The piece of work presented herein is aimed at investigating possible association of polymorphisms in IL‐10 promoter with Saudi cardiovascular disease (CVD) patients. The study included 80 confirmed CVD patients with diabetes and 75 healthy control individuals both men and women. Concentration of IL‐10 in the serum samples were measured by ELISA method. For single nucleotide polymorphism (SNP) analysis, Sanger method of DNA sequencing was followed. The IL‐10 level was found to be significantly elevated in CVD patients (P < 0.001) and its associated complications viz. ST‐elevation myocardial infarction [STEMI] (P <0.01), non ST‐elevation myocardial infarction [NSTEMI] (P < 0.05), and unstable angina [UA] (P < 0.001). We also observed a significant association between polymorphisms in IL‐10 promoter at −1082 and −819 locus with Saudi CVD patients. Moreover, at −1082 A/G locus, AA haplotype was found to be less frequent in the CVD patients compared with control individuals. On the other hand, highly significant rise in heterozygous (A/G genotype) condition was observed in patient samples compared with control ones (P < 0.001). Similarly, the genotypic frequencies at −819 C/T locus were also found to be significantly associated (P < 0.001) with CVD patients compared with control individuals. Our study provides the status of polymorphism in IL‐10 promoter and its association with CVD risk in Saudi population. As per our information, ours is the first article that shows the genetic diversity in IL‐10 promoters and its level in the Saudi CVD patients.

Estimation of Interleukin‐1β Promoter (‐31 C/T & ‐511 T/C) Polymorphisms and its Level in Coronary Artery Disease Patients

Interleukin‐1β (IL‐1β) is an inflammation‐causing cytokine that exerts several unique biological effects and could lead to future adverse events of CAD. The piece of work presented herein is aimed at investigating possible association of IL‐1β levels to its polymorphic site viz. −511 and −31 at promoter region in Saudi CAD patients. The study included 155 confirmed CAD patients and 80 healthy control individuals both men and women. Concentration of IL‐1β in the patients’ serum was measured by ELISA method. For single nucleotide polymorphism (SNP) analysis, sanger method of DNA sequencing was followed. We observed variable numbers of SNPs at −31 C/T and −511 T/C promoter regions in Saudi patients suffering from CAD in comparison to the control set of individuals. However, the changes in the number of SNP‐hotspots were determined to be non‐significant with reference to the control set. The haplotype analysis at −31 and −511 also did not show any significant changes between control and CAD patients. Moreover, serum IL‐1β levels were observed to be expressively higher in patients suffering from CAD (P < 0.001) and its associated complications viz. STEMI (P < 0.001), NSTEMI (P < 0.001), and UA (P < 0.001). Our study provides the status of SNPs at IL‐1β promoter in Saudi population. As per our information, ours is the first article that shows the genetic diversity in IL‐1β promoters and its level in the Saudi CAD patients. J. Cell. Biochem. 118: 2977–2982, 2017.

Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease

ABSTRACT Background: Natural killer (NK) cells are the potential modulators of inflammatory reactions that exert several unique biological effects and could lead to future adverse events of coronary artery disease (CAD). Hypothesis: The purpose of this study was to find out the possible association of modulation in NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-α) in CAD patients and various forms of myocardial infarction. Methods: The present study included total 190 subjects (98 confirmed CAD patients both men and women and 92 healthy control individuals). Serum concentration of TNF-α was measured by ELISA method. For the measurement of various immune cells, viz., NK cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed. Results: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was observed in CAD patients. Moreover, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable angina (UA), and combined UA + NSTEMI group also showed a significant decline in NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA + NSTEMI group did not show any significant change in TNK cells. On the other hand, the level of TNF-α was found to be significantly elevated in CAD, STEMI, and UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant change in TNF-α level. Conclusion: Current study provides an insight toward the association of immune cells and inflammation with CAD.

Inactivation of Middle East respiratory syndrome-coronavirus in human plasma using amotosalen and ultraviolet A light: MERS-CoV INACTIVATION IN PLASMA

Middle East respiratory syndrome‐coronavirus (MERS‐CoV) is a novel zoonotic pathogen. Although the potential for MERS‐CoV transmission through blood transfusion is not clear, MERS‐CoV was recognized as a pathogen of concern for the safety of the blood supply especially after its detection in whole blood, serum, and plasma of infected individuals. Here we investigated the efficacy of amotosalen and ultraviolet A light (UVA) to inactivate MERS‐CoV in fresh‐frozen plasma (FFP).

The use of transfusion quality indicators as a tool for hemovigilance system implementation at a tertiary care center in Saudi Arabia

Objectives: To report 2-years experience of using transfusion-related quality indicators as a tool in hemovigilance system implementation. Methods: The study was carried out between 2012 and 2013. Blood transfusion service data were prospectively collected at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Donor reactions, transfusion reactions, fresh frozen plasma (FFP) in-date wastage, incidents, and errors pertaining to orders, or requests were collected quarterly and prospectively and forwarded to the Hospital Transfusion Committee (HTC) for review. Results: Donor population consisted of 23,132 donors. One hundred and forty-eight donor reactions were reported, resulting in a rate of 0.6%. Eighty-four transfusion reactions were reported and most were allergic reactions (79.7%). Errors or incidents were reported with approximately 0.3% of the total number of submitted samples/request forms. The FFP in-date wastage was 21.3% of the total FFP wastage. The HTC regularly reviewed the hemovigilance data and reporting; and safety improvements were implemented. Conclusion: The use of quality indicators as a tool for developing and implementing a hemovigilance system provided a better understanding of improvement areas for continuous progress in quality and safety, and is expected to enhance these features along the blood transfusion chain.

Allelic variance among ABO blood group genotypes in a population from the western region of Saudi Arabia

Background Characterization of the ABO blood group at the phenotype and genotype levels is clinically essential for transfusion, forensics, and population studies. This study elucidated ABO phenotypes and genotypes, and performed an evaluation of their distribution in individuals from the western region of Saudi Arabia. Methods One-hundred and seven samples underwent standard serological techniques for ABO blood group phenotype analysis. ABO alleles and genotypes were identified using multiplex polymerase chain reaction, and electrophoretic analysis was performed to evaluate the highly polymorphic ABO locus. Results A phenotype distribution of 37.4%, 30.8%, 24.3%, and 7.5% was found for blood groups O, A, B, and AB respectively in our study cohort. Genotype analysis identified 10 genotype combinations with the O01/O02 and A102/O02 genotypes being the most frequent with frequencies of 33.6% and 14.95%, respectively. Common genotypes such as A101/A101, A101/A102, A101/B101, B101/B101, and O01/O01 were not detected. Similarly, the rare genotypes, cis-AB01/O02, cis-AB01/O01, and cis-AB01/A102 were not found in our cohort. The most frequently observed allele was O02 (35.98%) followed by the A102 allele (17.76%). Furthermore, our findings are discussed in reference to ABO allele and genotype frequencies found in other ethnic groups. Conclusion The study has a significant implication on the management of blood bank and transfusion services in Saudi Arabian patients.

Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus

Skin auto fluorescence (SAF) is used as a proxy for the accumulation of advanced glycation end products (AGEs) and has been proposed to stratify patients into cardiovascular disease (CVD) and diabetes mellitus (DM) risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian) and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens’d) is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.

Validation of a Scoring System for Prediction of Clinical Outcome in the Offlabel Use of Recombinant Factor VIIa

Background and Objectives: Recombinant factor VIIa (rFVIIa) is approved for treatment of inhibitors in hemophilia but has also been used for numerous off-label indications. Type of study: This study aims to validate a modified Biss scoring system in patients who received recombinant factor rFVIIa in Jeddah, Saudi Arabia. Materials and Methods: We included 70 patients who received rFVIIa for off-label indications over 12 months. Characteristics of survivor and non-survivor groups were compared including demographics, laboratory and clinical data. Using a modified Biss prognostic scoring system, based on the original scoring system used by Biss and Hanley, patients were divided into low (<1), intermediate (1-2) and high (≥3) score groups. Results: The mean age of patients was 46.1(±18.6) years. The most common off-label indications for rFVIIa treatment were to control bleeding associated with cardiac surgery (33%) and management of intracranial hemorrhage (18.8%). Forty three patients (61.6%) were at low risk, 20(28.6%) were at intermediate risk, and 7 (10%) were at high risk. Survivors were younger than non-survivors and less likely to have coagulopathy, or renal impairment at the time of treatment. The total prognostic score correlated to survival outcome (P ≤ 0.042); 73.2%, 22%, 4.9% of survivors had a low, intermediate and high score, respectively. Conclusions: Our results suggest that a modified Biss score could help predict survival of patients receiving rFVIIa. Prospective studies are needed to further validate the utility of this scoring system.