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Background: Hematotoxicity is an underexplored end point of toxicity in most of the chemical exposures. An adverse effect on the hematological system arising out of xenobiotic exposure causes impaired hemostasis and coagulation leading to disease. BPA and acetaminophen are widely used synthetic chemicals the world over and both are known and have numerous toxic effects. Since both can be simultaneously exposed to humans over a period of time, we hypothesized that their exposure can cause hematotoxicity, which may be ameliorated by melatonin. Objective: In the current study, we aimed to find the effect of single and co-treatment of bisphenol A and acetaminophen on the RBC and coagulation factors in rats and amelioration of impairment by melatonin. Methods: Oxidative stress in red blood cells, bleeding time, blood clotting time, prothrombin time, and partial thromboplastin time, and fibrinogen levels were assessed as indicators of hematotoxicity. With treatment of bisphenol A and acetaminophen as single and co treatments and amelioration of the same by melatonin was evaluated. Results: An increase in RBC oxidative stress and decrease in bleeding time, blood clotting time, prothrombin time, and partial thromboplastin time along with an increase in fibrinogen levels was observed with bisphenol A and acetaminophen treatment, which was further aggravated with co-treatment of the two. Melatonin treatment, however, was seen to decrease the increase in oxidative stress and ameliorate the impairment in coagulation factors. Conclusion: Bisphenol A and acetaminophen cause an increase in oxidative stress in the red blood cells and cause a shift towards pro-coagulation, which is alleviated by treatment with melatonin.

Introduction Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still posing detrimental effects on people. An association between contracting COVID-19 and the ABO blood group type has been determined. However, factors that determine the severity of COVID-19 are not yet fully understood. Thus, the current study aimed to investigate whether the ABO blood group type has a role in the severity of complications due to COVID-19. Materials and methods Eighty-Six ICU-admitted COVID-19 patients and 80 matched-healthy controls were recruited in the study from Baish general hospital, Saudi Arabia. ABO blood grouping, complete blood count (CBC), CBC-derived inflammatory markers, coagulation profile, D-Dimer and anti-T antigen were reported. Results Our data showed that patients with blood groups O and B are more protective against severe complications from COVID-19, as compared to patients with blood groups A and AB. This could be partially attributed to the presence of anti-T in blood group A individuals, compared to non-blood group A. Conclusion The current study reports an association between the ABO blood group and the susceptibility to severe complications from COVID-19, with a possible role of anti-T in driving the mechanism of the thrombotic tendency, as it was also correlated with an elevation in D-dimer levels.

Background and Objective Transfusion-transmitted infectious agents are amongst the major health burden worldwide. The purpose of this study was to evaluate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among blood donors in Samtah General Hospital, Jazan region, Saudi Arabia. Material and Methods In this retrospective study, blood donation records of all blood donors recruited between January 2019 and August 2020 were included for data acquisition. A total of 4977 blood donors’ records were reviewed and data were analysed. Results Hepatitis B profile showed 0.60% blood donors positive for hepatis B surface antigen (HBsAg). Nucleic acid testing (NAT) showed the presence of HBV-DNA in 0.4% of the blood donors. Anti-HBs and anti-HBc antibodies were reactive in 3.34% and 7.31% blood donors’ units, respectively. Anti-HCV antibodies were reactive among 54 (1.09%) blood donors. Upon reviewing the NAT analysis results, 0.16% (08) blood donors showed the presence of HCV-RNA in their blood units. Anti-HIV antibodies were reactive in 8 (0.16%) blood donors. Conclusion It is concluded that the frequency of HBsAg is comparatively lower while anti-HCV positivity is higher in Samtah, Jazan as a region compared to other regions of the country. Further studies are warranted to evaluate the cause of HCV infection in this area. Frequency of HIV is uncommon in this area.

Aymen M Madkhali,1 Abdullah A Mobarki,1 Ahmad H Ghzwani,2 Hesham M Al-Mekhlafi,2 Ahmed Zhranei,1 Abdulrahman Osais,1 Ahmed Sohel,1 Basim Othman,3 Gasim Dobie,1 Hassan A Hamali1 1Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia; 2Medical Research Center, Jazan University, Gizan, Saudi Arabia; 3Department of Public Health, Faculty of Applied Medical Sciences, Albaha University, Albaha, Saudi ArabiaCorrespondence: Hassan A Hamali, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, P.O. Box 1906, Gizan, 45142, Saudi Arabia, Email hhamali@jazanu.edu.saBackground: Procoagulant microvesicles (MVs) are submicron membrane fragments released from activated cells and cells undergoing apoptosis. The procoagulant activity of MVs is enhanced in the presence of tissue factor (TF). MVs and TF are active mediators that induce pro-inflammatory response and prothrombotic tendency and have been linked to the severity of several disorders, including malaria infection. The current study aimed to measure the levels of circulating procoagulant MVs and TF-bearing MVs in malaria patients and correlate these levels with other hematological parameters and parasitemia.Materials and Methods: Levels of MVs and TF-bearing MVs in the plasma of children and adult patients infected with Plasmodium falciparum were measured alongside matched healthy controls.Results: Patients with Plasmodium falciparum infection had ~3.8 times MVs (p < 0.0001) and ~13.0 times TF-bearing MVs compared to the matched healthy controls. MVs showed inverse significant correlation with platelet count (p = 0.0055), hemoglobin (p = 0.0004) and parasitemia.Conclusion: Elevated levels of MVs and TF-bearing MVs could be useful biomarkers to evaluate the procoagulant activity, inflammatory response and parasitemia levels in malaria infection, aiding in better management of the disease.Keywords: procoagulant, microvesicles, tissue factor, malaria, prothrombotic inflammation

Amr J Halawani,1 Abdullah A Mobarki,2 Ali H Arjan,3 Muhammad Saboor,2 Hassan A Hamali,2 Gasim Dobie,2 Khalaf F Alsharif4 1Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 3Department of Laboratory and Blood Bank, King Fahad Central Hospital, Ministry of Health, Jazan, Saudi Arabia; 4Department of Clinical Laboratory Science, College of Applied Medical Sciences, Taif University, Taif, Saudi ArabiaCorrespondence: Amr J Halawani, Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia, Email ajjhalawani@uqu.edu.saPurpose: Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require multiple blood transfusions, which may lead to alloimmunization because of mismatched blood group antigens. In this study, we examined the alloimmunization and autoimmunization rates in patients with SCD and thalassemia together with the involved antibodies.Patients and Methods: A cross-sectional study was conducted to review the transfusion history records of patients with SCD and thalassemia at Prince Mohammed bin Nasser Hospital, Jazan Province, Saudi Arabia.Results: Four-hundred thirty-eight patients (385 with SCD, 52 with β-thalassemia, and 1 with α-thalassemia) were received leukoreduced red cell transfusions. The alloimmunization and autoimmunization rates in patients with SCD were 12.98% and 0.52%, respectively. In patients with thalassemia, the alloimmunization and autoimmunization rates were 13.21% and 3.77%, respectively. The most prevalent antibodies in the study population were anti-E (17.19%) and anti-K (14.06%).Conclusion: The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fya, Fyb, Jka and Jkb antigens in the screening panel. This will benefit patients to ensure better transfusion practices.Keywords: red cell alloimmunization, sickle cell disease, thalassemia, autoimmunization

Ezeldine K Abdalhabib,1 Badr Alzahrani,1 Fehaid Alanazi,1 Abdulrahman Algarni,2 Ibrahim Khider Ibrahim,3 Hozifa A Mohamed,4,5 Hassan A Hamali,6 Abdullah A Mobarki,6 Gasim Dobie,6 Muhammad Saboor6,7 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia; 2Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 3Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 4Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Sudan International University, Khartoum, Sudan; 6Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad Saboor, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia, Tel +966 54 495 9029, Email msaboor@jazanu.edu.saPurpose: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and Methods: This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = < 0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42– 29.74, P < 0.001).Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.Keywords: GSTT1, GSTM1, polymorphism, acute lymphoblastic leukemia

Mohamed Moukhyer,1,2 Mohamed Salih Mahfouz,3 Mahmoud M Habibullah,4 Nouf Hussain Abuhadi,5 Nizar A Khamjan,4 Aymen M Madkhali,4 Ali O Hakamy,6 Hassan A Hamali,4 Mazharul Hoque,1 Mohtashim Lohani,1 Aziza Mukhayer7,8 1Emergency Medical Services, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2Public Health Programs, School of Medicine, University of Limerick, Limerick, Ireland; 3Department of Family and Community Medicine, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Medical Laboratory Technology Department, Jazan University, Jazan, Saudi Arabia; 5Diagnostic Radiology Technology Department, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 6Department of Respiratory Therapy, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Faculty of Medicine, Ahfad University for Women, Omdurman, Sudan; 8Department of Health Promotion, University of Maastricht, Maastricht, The NetherlandCorrespondence: Mohamed Moukhyer, Tel +966-568878291, Email mmoukhyer@jazanu.edu.saBackground: The emergence of COVID-19 posed a threat to millions of lives worldwide. The pandemic impacts extended to affect people’s psychological well-being, resulting in significant behavioural change. This study was designed to assess the knowledge regarding COVID-19 precautions among the College of Applied Medical Science students at Jazan University and to evaluate the general, psychosocial, and behavioral changes due to COVID-19.Methods: This is an observational study targeting 630 undergraduate students randomly selected during January 2020, using stratified random sampling. Data were collected using an online questionnaire. Linear regression models were used to evaluate the predictors of three outcome measures: knowledge, attitudes, and practice scores.Results: Knowledge of COVID-19 revealed that the students with correct answers ranged from 48.9 to 95%. Furthermore, significant gender differences are found regarding shortness of breath, fatigue, persistent chest discomfort, headache, and malaise (p < 0.05). Knowledge scores differed significantly across gender and academic level (p < 0.05) and so does attitude scores (p < 0.05). No significant difference was observed between practice scores according to socio-demographic background (p > 0.05). The linear regression model showed that females had significantly higher knowledge, attitudes, and practice scores (p < 0.05) as well as those within the 21– 23 age group and above (p < 0.05). Students residing in urban and semi-urban places had significantly higher scores for knowledge, attitudes, and practice (p < 0.05).Conclusion: The results demonstrated moderate knowledge about COVID-19 among study participants, with significant differences between the responses of males and females and among the urban and rural populations. Outcomes suggest the need for interventions to bridge students’ knowledge about COVID-19 and practice gaps. Students were concerned about basic life amenities and the inability to provide for their dear ones regarding behavioral changes.Keywords: COVID-19, health and safety, public health

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76 T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited metabolic abnormality of red blood cells (RBCs), affecting 400 million individuals worldwide. Patients with G6PD deficiency anemia might exhibit severe clinical manifestations, including acute hemolytic anemia (AHA), neonatal hyperbilirubinemia (jaundice), favism, and chronic non-spherocytic hemolytic anemia (CNSHA). The aim of the current review is to report the prevalence and genetic variants of G6PD deficiency anemia in Saudi Arabia. The scientific literature was reviewed for reports on G6PD deficiency in Saudi Arabia. The incidence rate of G6PD deficiency is very high in Saudi Arabia and varies from Province to Province. As reported by the Ministry of Health, the prevalence of G6PD deficiency in Saudi Arabia is 8.4% among males. The pattern and distribution of the genetic mutations also vary. Some of the genetic mutations of G6PD deficiency have been associated with clinical manifestations including hemolysis, especially in neonates. Several studies have reported known common variants such as Mediterranean and A-, as well as rare variants such as Nara, Sibiri, and Viangchan in the Saudi population. Early detection, characterization, and understanding of the phenotypic and molecular patterns of G6PD deficiency in Saudi Arabia are needed for better management and control of the disease. Thus, neonatal screening for G6PD deficiency, family counseling, and public awareness of the disease should be established.

Vitamin D has a pivotal role in maintaining healthy bones and in the modulation of multiple physiologic processes. Vitamin D deficiency has become a global burden that affects all members of society. This study aimed to investigate the prevalence and correlation of vitamin D deficiency with hematological and biochemical parameters in young adult college students. Hundred and fourteen students (77 men and 37 women) were recruited.The socio-demographic and clinicopathologic features of the students were evaluated using a pre-tested and validated questionnaire, and samples were collected for complete blood count (CBC), vitamin D, calcium, parathyroid hormone, and phosphorus measurements.Vitamin D deficiency was more prevalent in men (53.2%) than in women (48.7%). Calcium and parathyroid hormone levels were within the normal range, and 26% and 22% of male and female participants, respectively, had low phosphorus levels. Vitamin D showed a positive correlation with calcium in men (r=0.3927;Vitamin D deficiency is very prevalent among college students, therefore health education and public awareness campaigns on the consequences of vitamin D deficiency on health and well-being are required.

Rh and Kell blood group systems are amongst the most important blood group systems; being highly immunogenic after ABO system. The aim of this study was to evaluate the frequencies of Rh antigens, haplotypes and K antigen among blood donors belonging to various ethnicities in Samtah, Jazan, Saudi Arabia.This study was conducted during January 2019 and August 2020 at Samtah General Hospital, Samtah. Records of all blood donors recruited during this period were included for data acquisition. A total of 4977 blood donors' records were reviewed and data were analysed. A total of 3863 donors' results were considered in the final analysis.In comparison to Saudi blood donors, C antigen was less frequent in Sudanese donors (69.7% and 34.0%), the c antigen was less frequent in Indian (79.2% and 59.3%) and Philippine (79.2% and 40.0%) donors and more frequent in Sudanese (79.2% and 97.9%) donors, the E antigen was less frequent in Yemini (27.0% and 19.5%) and the e antigen was more frequent in Yemini (96.7% and 99.2%) donors. The DcE haplotype was less frequent (3.1% and 0.7%) and the ce haplotype was more frequent (4.3% and 7.6%) in Yemini donors. The K antigen was less frequent in Pakistani (11.9% and 4.1%; p = .041) and Indian (11.9% and 1.9%; p = .023) donors.Rh and K antigens showed marked variations in their frequencies among blood donors of different ethnicities. Utilization of blood from various ethnicities warrant extended phenotyping of Rh and K antigens to avoid the risk of alloimmunization in multiply transfused patients.

Background: The levels of procoagulant microvesicles (MVs) and tissue factor (TF)-bearing MVs may be increased in many conditions, including dengue fever (DF). This study aimed to measure the levels of MVs and TF-bearing MVs in patients with DF and matched healthy controls. Materials & methods: Levels of MVs and TF-bearing MVs in the plasma of patients with DF and matched healthy controls were measured using functional assay. Results: The patient group had significantly elevated levels of MVs (p

Purpose Anemia is one of the most common disorders affecting the population in both low-income and developing countries. This study aimed to determine the prevalence of anemia and iron deficiency in apparently normal male and female students of Jazan University, Saudi Arabia. Material and Methods This cross-sectional study was conducted at the Faculty of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia. One hundred thirty-four (85 males and 49 females) healthy students with no outward signs of illness were recruited. A specific questionnaire related to sociodemographic and health characteristics was designed and validated. The collected samples were analyzed for complete blood count, serum iron, and serum ferritin. Results In the male group, 81 participants (95.3%) were nonanemic with normal hemoglobin (14.99 ± 1.11g/dl), whereas only 4 males were anemic (hemoglobin

Purpose A2 and A2B are rare phenotypes of the ABO blood group system. Some individuals with A2 and A2B may have anti-A1 antibodies that may be clinically significant or insignificant. The aim of this study was to determine the frequency of A2, A2B phenotypes and anti-A1 antibodies in blood donors in Jazan, Saudi Arabia. This study also evaluated the reactivity potential of anti-A1 antibodies. Materials and methods Blood samples collected from 446 blood donors were typed for ABO (cell and serum grouping) and Rh D. Individuals with blood group A and AB were further subtyped by testing with anti-A1 lectin. In addition to the serum grouping using A1 red cells, A2 and A2B individuals were screened for the presence of anti-A1 in their sera against A1 red cells at 4°C, 22°C and 37°C to determine the thermal amplitude of the reacting anti-A1 antibody (if present). Results Among A and AB, A1 was the commonest phenotype (20.2%, n=90 out of 446) while A1B was found to be 1.8% (n=8) among AB phenotype. A2 and A2B were found to be 2.2% (n=10) and 0.9% (n=4), respectively. Only one individual with A2B blood type showed cold reactive anti-A1 antibody, the strength of which was 32. Conclusion A2 and A2B were the rarest among ABO phenotypes in the studied population. Although rare, anti-A1 antibody is not so uncommon. Care shall be taken during routine ABO grouping especially in cases of mix-field or weak positive reactions in A and AB phenotypes.

Abnormal levels of coagulation factors and their inhibitors have shown association with liver diseases. The objective of this study was to determine the qualitative and quantitive status of antithrombin (AT) in patients with chronic liver disease associated hepatitis C infection and their correlation with severity of liver fibrosis.In this study, 75 (43 male and 32 female) known patients with chronic liver disease associated hepatitis C infection were enrolled. AT activity and quantitative immunoassays were carried out using Stachrom AT reagent kit (Diagnostica Stago, France) and Liatest AT reagent (Diagnostica Stago, France), respectively. Hepatic biopsies were obtained and graded for liver fibrosis from all study participants.Of the 75 patients, 45 had normal AT while 30 showed lower activity of AT. Similarly, the quantitative assay showed reduced levels of AT in 30 patients and normal levels in 45 patients.In the early stages of liver fibrosis, AT activity and antigenic levels were found to be normal or minimally affected. While advanced stages of the disease showed markedly reduced levels of AT and activity. Hence, it can be concluded that the degree of fibrosis affects the status of AT.

Advanced mitochondrial multi-omics indicate a multi-facet involvement of mitochondria in the physiology of the cell, changing the perception of mitochondria from being just the energy-generating organelles to organelles that highly influence cell structure, function, signaling, and cell fate. This sets mitochondrial dysfunction in the centerstage of numerous acquired and genetic diseases. Sickle cell disease is also being increasingly associated with mitochondrial anomalies and the pathophysiology of sickle cell disease finds mitochondria at crucial intersections in the pathological cascade. Altered mitophagy, increased ROS, and mitochondrial DNA all contribute to the condition and its severity. Such mitochondrial aberrations lead to consequent mitochondrial retention in red blood cells in sickle cell diseases, increased oxidation in the cellular environment, inflammation, worsened vaso-occlusive crisis, etc. There are increasing studies indicating mitochondrial significance in sickle cell disease, consequently providing an opportunity to target it for improving the outcomes of treatment. Identification of the impaired mitochondrial attributes in sickle cell disease and their modulation by therapeutic interventions can impart a better management of the disease. This review aims to describe the mitochondria in the perspective of sicke cell disease so as to provide the reader an overview of the emerging mitochondrial stance in sickle cell disease.

Male contribution towards couple infertility is increasing but is less discussed. We aimed to assess the knowledge about iron deficiency anemia (IDA) as a contributor to male infertility in students at health colleges of Jazan University. A multicentric, cross-sectional survey included 910 participants and 768 participants qualified as per our inclusion criteria. The questions were categorized as: Model 1—knowledge about IDA-induced male infertility; Model 2—knowledge about IDA. The average knowledge of IDA causing male infertility is very low among students. The 18–20 years age group had a lesser score for either knowledge of IDA (M2; p-value = 0.047) or total (p-value < 0.0001) compared to the older group. In addition, female students were significantly more likely to be better in achieving higher total scores (p-value = 0.023) as well as M2 scores (p-value < 0.0001) when compared to the respective male category. On the other hand, males were significantly better in scoring for M1 (p-value = 0.004) compared to females. Awareness about iron deficiency anemia as a factor in male infertility may reduce the infertility burden, arising from a preventable factor, in the Jazan region.

Abdullah A Mobarki,1 Gasim Dobie,1 Muhammad Saboor,1,2 Aymen M Madkhali,1 Mohammad S Akhter,1 Ali Hakamy,3 Adel Humran,4 Yousof Hamali,5 Denise E Jackson,6 Hassan A Hamali1 1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia; 2Medical Research Center, Jazan University, Gizan, Saudi Arabia; 3Department of Respiratory Therapy, Faculty of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia; 4Respiratory Care Department, King Fahad Central Hospital, Gizan, Saudi Arabia; 5Radiodiagnostics and Medical Imaging Department, Prince Sultan Medical City, Riyadh, Saudi Arabia; 6Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology (RMIT) University, Bundoora, VIC, AustraliaCorrespondence: Hassan A HamaliDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, P.O. Box 1906, Gizan, 45142, Saudi ArabiaTel +966581155585Email hhamali@jazanu.edu.saObjective: The aims of the current study were to evaluate the importance of MPR and NLR as prognostic markers in ICU-admitted COVID-19 patients and to investigate the impact of COVID-19 on hematological and coagulation parameters in patients from Jazan region of Saudi Arabia.Methods: This retrospective study was conducted between October 2020 and January 2021 at King Fahad Central Hospital, Jazan region. Medical files, which included the results of complete blood count (CBC), calculated mean platelet volume to platelet count ratio (MPR) and neutrophils-to-lymphocytes ratio (NLR) parameters, coagulation profile and D-dimer test, of 96 (64 male and 32 female) COVID-19-infected patients admitted to the intensive care unit were reviewed. Associations between the test results and COVID-19 infection outcomes (discharged [DC] or passed away [PA]) were measured.Results: The results of the current study demonstrate overall significant differences in CBC parameters between PA group as compared to DC group (P < 0.05). The PA group had a significantly elevated MPR (10.15± 12.16 vs 4.04± 1.5; P < 0.01) and NLR (18.29± 19.82 vs 7.35± 9.68; P < 0.01) as compared to the DC group, suggesting an association between these parameters and mortality. Odds ratios analysis also showed that adjustment for demographic variables and comorbidities did not weaken the observed association.Conclusion: Elevated MPR and NLR are associated with poor prognosis in COVID-19 patients and could be useful as therapy management indicators.Keywords: COVID-19, NLR, MPR, ICU, CBC, mortality

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) accounting for 3%–10% of primary AML in childhood. Clinical manifestations of AML patients can include low grade of fever, diarrhea, easy bruising, failure to growth, and life-threatening clinical manifestations. Laboratory tests are very crucial to make a definitive diagnosis and treatment. We report here an uncommon case of AMKL in a 12-month-old boy who presented with general paleness and fatigue. Based on blood film investigation, bone marrow examination report, and immunophenotyping, he was diagnosed as a case of AMKL without Down syndrome.

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The pfmdr1 86Y mutation was found in 11.5% (26/227) of the isolates while the N86 wild allele was detected in 88.5%. Moreover, 184F point mutations dominated (86.3%) the instances of pfmdr1 polymorphism while no mutation was observed at codons 1034, 1042 and 1246. Three pfmdr1 haplotypes were identified, NFSND (74.9%), NYSND (13.7%) and YFSND (11.4%). Associations of the prevalence of 86Y mutation and YFSND haplotype with participants’ nationality, residency and parasitaemia level were found to be significant (P < 0.05). The findings revealed significant decline in the prevalence of the pfmdr1 86Y mutation in P. falciparum isolates from Jazan region over a decade after the implementation of ACT treatment. Moreover, the high prevalence of the NFSND haplotype might be indicative of the potential emergence of CQ-sensitive but artemether-lumefantrine-resistant P. falciparum strains since the adoption of ACT. Therefore, continuous monitoring of the molecular markers of antimalarial drug resistance in Jazan region is highly recommended.

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76 T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p 0.05). The findings provide evidence of the potential re-emergence of CQ-susceptible P. falciparum strains in Jazan region over a decade after CQ discontinuation, with about one third of the isolates analysed carrying the pfcrt K76 CQ-sensitive wild allele and the CVMNK ancestral wild haplotype. Although the reintroduction of CQ cannot be recommended at present in Saudi Arabia, these findings support the rationale for a potential future role for CQ in malaria treatment. Therefore, continuous molecular and in vitro monitoring mutations of pfcrt polymorphism in Jazan region is highly recommended.

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%), and CVMNT single-allele (8.5%) mutant haplotypes, and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate, and nationality of the patients as well as the parasitaemia level (P < 0.05). The findings provide evidence of the potential re-emergence of CQ-susceptible P. falciparum strains in Jazan region over a decade after CQ discontinuation, with about one third of the isolates analysed carrying the pfcrt K76 CQ-sensitive wild allele and the CVMNK ancestral wild haplotype. Although the reintroduction of CQ cannot be recommended at present in Saudi Arabia, these findings support the rationale for a potential future role for CQ in malaria treatment. Therefore, continuous molecular and in-vitro monitoring mutations of pfcrt polymorphism in Jazan region is highly recommended.

We investigated the protective and in vivo antioxidant effects of p-coumaric acid on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. The rats were orally pre-treated with p-coumaric acid (at 50 and 100 mg/kg body weight) for 15 days before the subcutaneous injection of carbon tetrachloride (1.5 mL/kg). Silymarin served as a positive control for hepatoprotection. Blood and tissue samples were obtained and used to assess the effects of p-coumaric acid using quantitative and qualitative histological evaluation, glutathione levels, protein determination, and liver enzymes. p-Coumaric acid treatment did not demonstrate any toxicological abnormalities in mice. p-Coumaric acid and silymarin reduced the extent of carbon tetrachloride-induced liver damage and preserved normal hepatic enzymes (P < 0.05). p-Coumaric acid pre-treatment led to a diminution in increased malondialdehyde and decreased glutathione following carbon tetrachloride administration (P < 0.05). Furthermore, p-coumaric acid restored changes in superoxide dismutase and caspase-3 gene expression as a result of carbon tetrachloride exposure. In conclusion, p-coumaric acid helps restore toxicant-induced liver injury in rats via avoidance of lipid peroxidation, inhibition of cell death and preservation of antioxidant mechanism.

Pulmonary embolism (PE) is a life-threatening complication arising from venous thromboembolism with a difficult diagnosis and treatment and is often associated with increased mortality and morbidity. PE had a significantly low incidence prior to the COVID-19 epidemic. This condition saw a sharp surge during the COVID-19 pandemic, indicating an evident viral influence on PE’s pathophysiology in COVID-19 patients. The hypercoagulable state induced by the viral load seems to be the major contributor, and the classical causative factors seem to play a lesser role. PE in COVID-19 infection has become a mammoth challenge since the diagnosis is quite challenging due to overlapping symptoms, lack of prior-known predisposing risk factors, limited resources, and viral transmittance risk. Numerous factors arising out of the viral load or treatment lead to an increased risk for PE in COVID-19 patients, besides the fact that certain unknown risk factors may also contribute to the incidence of PE in COVID-19 patients. The management of PE in COVID-19 infection mainly comprises thromboprophylaxis and anticoagulant therapy with mechanical ventilation, depending on the risk stratification of the patient, with a post-COVID-19 management that prevents recurrent PE and complications. This review aims to discuss various aspects of COVID-19-infection-associated PE and major differential aspects from non-COVID-19 PE.

Objective: To evaluate the frequency of alpha thalassemia and detect mutations in the alpha genes in individuals undergoing premarital screening. Methods: The cross-sectional study was conducted at King Fahad Central Hospital, Jazan, Sauid Arabia, from January 2018 to May 2019, and comprised blood samples of individuals visiting the premarital screening clinic. The samples were analyzed for complete blood counts and haemoglobin electrophoresis. Molecular analysis of samples suspected for alpha thalassemia was done using alpha–globin StripAssay kit. Data was anlaysed using SPSS 20. Results: Of the 3,970 samples analysed, 1,859(46.83%) were from males and 2,111(53.17%) from females. The overall frequency of suspected alpha thalassemia was 4.43% based upon haematological parameters including complete blood count and hemoglobin electrophoresis. Overall, 80 suspected samples were selected for genetic analyses, and, of them, 76 (95%) were positive for deletional and non-deletional mutations of alpha-globin genes, while 4 (5%) were negative for any of the 21 mutations tested. Conclusion: Alpha thalassemia was found to be highly prevalent in the study area. Key Words: Alpha thalassemia, –?3.7, –?IVS1, ? polyA1, premarital screening.

Background Sickle cell disease (SCD) is a common hematological genetic disorder in Saudi Arabia, Africa, the Mediterranean region, and India. The present study aimed to characterize βS haplotypes found in the Jazan region, Saudi Arabia. Methods One hundred sickle cell trait (SCT) individuals, diagnosed during their visit to the premarital screening clinic at King Fahad Central Hospital, were included in the study. Molecular analysis was carried out by polymerase chain reaction (PCR) and six polymorphic sites of the β-globin gene were analyzed using restriction endonucleases Hind II, Xmn-I, Hind III, and Ava II. Results The results of the current study revealed the presence of five typical haplotypes in which Benin, Bantu, and Senegal were found in homozygous state with 29%, 3% and 1% frequencies, respectively. Interestingly, 29% of the studied population showed atypical haplotypes in heterozygous state and 2% in homozygous state for the first time in Jazan region. Conclusions In addition to the typical haplotypes, high frequency of atypical haplotypes in this study indicates a diverse genetic mechanism that might have a crucial effect on the severity of SCD in this region. Therefore, considering this study in a cohort population with SCD in Jazan region may provide more indepth details about the correlation between haplotypes and the clinical manifestation of the disease.

Background Iron deficiency anemia (IDA) is one of the commonest clinical scenarios especially in children, women of childbearing age, and elders. The crux of this review was revisiting iron homeostasis, mechanism of iron absorption, causes, laboratory diagnosis, and management of IDA. Methods This narrative review is compiled after a relevant literature search from electronic databases including, but not limited to, Google, Google Scholar, PMC, PubMed, Science Direct, and Scopus. The key words used for searching relevant literature include iron, iron deficiency, iron deficiency anemia, iron metabolism, hepcidin, transferrin, causes of iron deficiency anemia, and laboratory diagnosis of iron deficiency anemia. Reference hema-tology books were also consulted. Results According to the published literature, about one mg of iron is required daily which equals its loss, although the iron requirement increases in pregnancy and lactating mothers. Dietary non heme iron (oxidized Fe3+) is reduced to the ferrous (Fe2+) form by ferrireductase present in the brush border of duodenal enterocytes. Ferrous iron is absorbed in the brush border of duodenal enterocytes through a carrier protein, divalent metal transporter 1 (DMT1). Heme iron is absorbed by the duodenal enterocytes through a mechanism that is not well understood or a receptor yet to be discovered. Transferrin receptor helps in the internalization of iron in the cells. Hepcidin acts as a gatekeeper and controls iron absorption by enterocytes and macrophages. IDA may be caused by decreased intake of iron, increased iron requirements or loss of iron from the body. Conclusions Iron deficiency anemia is the most common nutritional anemia that affects large numbers of people in developed as well as in developing countries. It is estimated that approximately 2 billion people around the world have IDA. Microcytosis with marked reduction in serum iron, decreased % saturation of transferrin, low ferritin, and reduced or even undetectable hepcidin are the laboratory features of IDA. In addition, total iron binding capacity and soluble transferrin receptors increase significantly in IDA. Management of IDA is incomplete if the underlying cause is not ruled out and left untreated.

Purpose A2 and A2B are rare phenotypes of the ABO blood group system. Some individuals with A2 and A2B may have anti-A1 antibodies that may be clinically significant or insignificant. The aim of this study was to determine the frequency of A2, A2B phenotypes and anti-A1 antibodies in blood donors in Jazan, Saudi Arabia. This study also evaluated the reactivity potential of anti-A1 antibodies. Materials and Methods Blood samples collected from 446 blood donors were typed for ABO (cell and serum grouping) and Rh D. Individuals with blood group A and AB were further subtyped by testing with anti-A1 lectin. In addition to the serum grouping using A1 red cells, A2 and A2B individuals were screened for the presence of anti-A1 in their sera against A1 red cells at 4°C, 22°C and 37°C to determine the thermal amplitude of the reacting anti-A1 antibody (if present). Results Among A and AB, A1 was the commonest phenotype (20.2%, n=90 out of 446) while A1B was found to be 1.8% (n=8) among AB phenotype. A2 and A2B were found to be 2.2% (n=10) and 0.9% (n=4), respectively. Only one individual with A2B blood type showed cold reactive anti-A1 antibody, the strength of which was 32. Conclusion A2 and A2B were the rarest among ABO phenotypes in the studied population. Although rare, anti-A1 antibody is not so uncommon. Care shall be taken during routine ABO grouping especially in cases of mix-field or weak positive reactions in A and AB phenotypes.

Objectives: To evaluate the prevalence of undiagnosed hemoglobinopathies among individuals visiting the premarital screening Centre. Methods: This study was conducted at Premarital Screening Centre, King Fahad Central Hospital and Research Centre, Jazan, between January 2018 and October 2018. A total of 3,970 (male n =1,859 and female n = 2,111) individuals were included in the study. Data of complete blood count, hemoglobin electrophoresis and sickling tests of all individuals recruited in the study were obtained and statistically analyzed. Results: One thousand three hundred and twelve individuals had abnormal complete blood counts or hemoglobin electrophoresis results, that include sickle cell trait (13.5%), sickle cell disease (0.7%), β thalassemia with sickle cell trait (2.46%), β thalassemia trait (1.51%), β thalassemia major (0.075%), suspected α thalassemia or other hemoglobinopathies (4.43%), hemoglobin H (0.3%), hemoglobin E (0.075%), undiagnosed cases (0.91%) and iron deficient (7.23%). Conclusion: A high percentage of individuals are suspected for α thalassemia or other hemoglobinopathies that needs to be diagnosed. Further investigations shall be included in the premarital screening program to diagnose these inconclusive cases. Coexistence iron deficiency with thalassemia shall also be ruled out during premarital screening program.

Objectives: To evaluate the prevalence of undiagnosed hemoglobinopathies among individuals visiting the premarital screening Centre. Methods: This study was conducted at Premarital Screening Centre, King Fahad Central Hospital and Research Centre, Jazan, between January 2018 and October 2018. A total of 3,970 (male n =1,859 and female n = 2,111) individuals were included in the study. Data of complete blood count, hemoglobin electrophoresis and sickling tests of all individuals recruited in the study were obtained and statistically analyzed. Results: One thousand three hundred and twelve individuals had abnormal complete blood counts or hemoglobin electrophoresis results, that include sickle cell trait (13.5%), sickle cell disease (0.7%), β thalassemia with sickle cell trait (2.46%), β thalassemia trait (1.51%), β thalassemia major (0.075%), suspected α thalassemia or other hemoglobinopathies (4.43%), hemoglobin H (0.3%), hemoglobin E (0.075%), undiagnosed cases (0.91%) and iron deficient (7.23%). Conclusion: A high percentage of individuals are suspected for α thalassemia or other hemoglobinopathies that needs to be diagnosed. Further investigations shall be included in the premarital screening program to diagnose these inconclusive cases. Coexistence iron deficiency with thalassemia shall also be ruled out during premarital screening program. doi: https://doi.org/10.12669/pjms.35.6.976 How to cite this:Hamali HA, Saboor M. Undiagnosed Hemoglobinopathies: A potential threat to the premarital screening program. Pak J Med Sci. 2019;35(6):1611-1615. doi: https://doi.org/10.12669/pjms.35.6.976 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Apoptosis in megakaryocytes results in the formation of platelets. The role of apoptotic pathways in platelet turnover and in the apoptotic-like changes seen after platelet activation is poorly understood. ABT-263 (Navitoclax), a specific inhibitor of antiapoptotic BCL2 proteins, which is currently being evaluated in clinical trials for the treatment of leukemia and other malignancies, induces a dose-limiting thrombocytopenia. In this study, the relationship between BCL2/BCL-XL inhibition, apoptosis, and platelet activation was investigated. Exposure to ABT-263 induced apoptosis but repressed platelet activation by physiologic agonists. Notably, ABT-263 induced an immediate calcium response in platelets and the depletion of intracellular calcium stores, indicating that on BCL2/BCL-XL inhibition platelet activation is abrogated because of a diminished calcium signaling. By comparing the effects of ABT-263 and its analog ABT-737 on platelets and leukemia cells from the same donor, we show, for the first time, that these BCL2/BCL-XL inhibitors do not offer any selective toxicity but induce apoptosis at similar concentrations in leukemia cells and platelets. However, reticulated platelets are less sensitive to apoptosis, supporting the hypothesis that treatment with ABT-263 induces a selective loss of older platelets and providing an explanation for the transient thrombocytopenia observed on ABT-263 treatment.

Here, a group of specific lipids, comprising phosphatidylethanolamine (PE)- or phosphatidylcholine (PC)-esterified 12S-hydroxyeicosatetraenoic acid (12S-HETE), generated by 12-lipoxygenase was identified and characterized. 12S-HETE-PE/PCs were formed within 5 min of activation by thrombin, ionophore, or collagen. Esterified HETE levels generated in response to thrombin were 5.85 +/- 1.42 (PE) or 18.35 +/- 4.61 (PC), whereas free was 65.5 +/- 17.6 ng/4 x 10(7) cells (n = 5 separate donors, mean +/- S.E.). Their generation was stimulated by triggering protease-activated receptors-1 and -4 and signaling via Ca(2+) mobilization secretory phospholipase A2, platelet-activating factor-acetylhydrolase, src tyrosine kinases, and protein kinase C. Stable isotope labeling showed that they form predominantly by esterification that occurs on the same time scale as free acid generation. Unlike free 12S-HETE that is secreted, esterified HETEs remain cell-associated, with HETE-PEs migrating to the outside of the plasma membrane. 12-Lipoxygenase inhibition attenuated externalization of native PE and phosphatidylserine and HETE-PEs. Platelets from a patient with the bleeding disorder, Scott syndrome, did not externalize HETE-PEs, and liposomes supplemented with HETE-PC dose-dependently enhanced tissue factor-dependent thrombin generation in vitro. This suggests a role for these novel lipids in promoting coagulation. Thus, oxidized phospholipids form by receptor/agonist mechanisms, not merely as an undesirable consequence of vascular and inflammatory disease.

Introduction: Sickle cell disease (SCD) is an inherited genetic disorder characterized by various complications, including thrombosis. Increased levels of circulating microvesicles (MVs) and tissue factor (TF)- bearing MVs have been reported in SCD. Objectives: The present study compares the levels of circulating MVs and TF- bearing MVs in steady state SCD children with age- and gender- matched healthy controls using an indirect ELISA. Citrated whole blood was collected from 54 SCD patients homozygous for sickle haemoglobin (HbSS) (aged from 2 to 12 years-old) and 34 healthy controls. Results: SCD patients showed significantly higher levels of MVs in their plasma as compared to the controls (P = 0.0095). Although the TF activity on MVs was low in both groups, there was a significant difference between them P

Cardiovascular (CV) death remains the largest cause of mortality in dialysis patients, unexplained by traditional risk factors. Endothelial microvesicles (EMVs) are elevated in patients with traditional CV risk factors and acute coronary syndromes while platelet MVs (PMVs) are associated with atherosclerotic disease states. This study compared relative concentrations of circulating MVs from endothelial cells and platelets in two groups of dialysis patients and matched controls and investigated their relative thromboembolic risk. MVs were isolated from the blood of 20 haemodialysis (HD), 17 peritoneal dialysis (PD) patients and 20 matched controls. Relative concentrations of EMVs (CD144(+ ve)) and PMVs (CD42b(+ ve)) were measured by Western blotting and total MV concentrations were measured using nanoparticle-tracking analysis. The ability to support thrombin generation was measured by reconstituting the MVs in normal plasma, using the Continuous Automated Thrombogram assay triggered with 1µM tissue factor. The total concentration of MVs as well as the measured sub-types was higher in both patient groups compared to controls (p0.3). Dialysis patients have higher levels of circulating procoagulant MVs than healthy controls. This may represent a novel and potentially modifiable mediator or predictor of occlusive cardiovascular events in these patients.