Thrombophilia genetic mutations and their relation to disease severity among patients with COVID-19.

OBJECTIVES: Patients with COVID-19 infection appear to develop virus-induced hypercoagulability resulting in numerous thrombotic events. The aim of the present study was to determine the relationship between the thrombophilia genes mutations (prothrombin G20210A, factor V Leiden, and methyltetrahydrofolate reductase (MTHFR)) and the severity of COVID-19 patients. DESIGN: Prospective cross-sectional study. METHOD: One hundred and forty patients (80 adults and 60 children) were included in the current study. They were divided into the severe COVID-19 group and the mild COVID-19 group, with each group comprising 40 adults and 30 children. The patients were assessed for FV R506Q, FV R2H1299R, MTHFR A1298C, MTHFR C677T, and prothrombin gene G20210A polymorphisms. CBC, D-dimer, renal and liver function tests, hs-CRP, ferritin, and LDH were also assessed. Thrombotic events were clinically and radiologically documented. RESULTS: Severe COVID-19 cases were significantly more frequent to have a heterozygous mutation for all the studied genes compared to mild COVID-19 cases (p<0.05 for all). Being mutant to gene FV R506Q carried the highest risk of developing a severe disease course (p<0.0001). Patients with abnormally high D-dimer levels were significantly more frequent to be heterozygous for FV R506Q, FV R2H1299R, and prothrombin gene G20210A (p = 0.006, 0.007, and 0.02, respectively). CONCLUSION: We concluded that there is an evident relationship between severe COVID-19 and inherited thrombophilia. In the current study, FV R506Q gene mutation carried the highest risk of developing a severe COVID-19 disease course.

OPG/RANK/RANKL axis relation to cardiac iron-overload in children with transfusion-dependent thalassemia.

OPG/RANK/RANKL axis was reportedly involved in initiating various diseases, especially bone and cardiovascular diseases. This study aimed to assess the relationship between some OPG, RANK, and RANKL polymorphisms and alleles and iron-overload-induced cardiomyopathy in children with transfusion-dependent thalassemia (TDT). This study included 80 TDT children and 80 age and sex-matched controls. Real-time PCR was done for rs207318 polymorphism for the OPG gene and rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, and rs9594782 and rs2277438 polymorphisms for the RANKL gene. Cardiac T2* MRI and ejection fraction (EF) were done to assess the myocardial iron status and cardiac function. In this study, there were no significant differences in frequencies of the studied polymorphisms between cases and controls (p > 0.05 in all). In TDT children, OPG rs2073618 (G > C) had a significant relation to myocardial iron overload (p = 0.02). Its C allele had significantly more frequent normal EF than its G allele (p = 0.04). RANK rs75404403 (C > DEL) had a significant relation to cardiac dysfunction (p = 0.02). Moreover, the C allele of that gene had significantly more frequent affected EF than its DEL allele (p = 0.02). The A allele of RANKL rs2277438 (G > A) had significantly less frequent severe cardiac iron overload than the G allele (p = 0.04). In conclusion, the OPG/ RANK/RANKL genes may act as genetic markers for iron-induced cardiomyopathy in TDT children. Some of the studied genes' polymorphisms and alleles were significantly related to myocardial iron overload and cardiac dysfunction in TDT children.

Association of Thrombotic Markers With Severity of Pediatric-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To assess the relation of thrombotic markers, thrombomodulin and D-dimer levels to the disease severity in pediatric onset systemic lupus erythematosus (p-SLE) measured by the Systemic Lupus Erythematous Disease Activity Index (SLEDAI). METHODS: 40 children with p-SLE were grouped according to SLEDAI into: low activity SLE group (laSLE) and moderate-high activity SLE group (mhaSLE). 40 healthy children were included as control group. Serum thrombomodulin, and D-dimer levels were measured for all enrolled children. RESULTS: The low activity and moderate-high activity SLE groups had significantly higher mean (SD) thrombomodulin [7.2 (1.83) mg/mL and 9.86 (3.29) mg/mL, respectively vs 5.85 (1.41) mg/mL; P<0.001] and D-dimer (r=0.42, P=0.006) levels than controls. Furthermore, the mhaSLE group had significantly higher thrombomodulin levels and D-dimer (r = 0.42, P= 0.006) levels than the laSLE group (P=0.008 and 0.006). Thrombomodulin and D-dimer had significant positive correlations with SLEDAI. CONCLUSION: Thrombomodulin and D-dimer are valuable markers for p-SLE activity, discriminating children with severe disease activity from those with low disease activity.

RANK/RANKL/OPG axis genes relation to cognitive impairment in children with transfusion-dependent thalassemia: a cross-sectional study.

BACKGROUND: RANK/RANKL/OPG axis was implicated in many pathological conditions. The study aimed to assess the relationship between the studied RANK, RANKL, and OPG polymorphisms and alleles and cognitive impairment in children with transfusion-dependent thalassemia (TDT). METHODS: This study included 60 TDT children. Real-time PCR was done for: rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, rs9594782 and rs2277438 polymorphisms for the RANKL gene, and rs207318 polymorphism for the OPG gene. The intelligence quotient (IQ) was assessed using the Wechsler Intelligence Scale for Children-Third Edition. RESULTS: TDT children had a low average total IQ, verbal IQ, and borderline performance IQ. RANK rs1805034 (C > T) had a significant effect on total IQ (p = 0.03). Its TT polymorphism and the CT polymorphism of RANKL rs9494782 (C > T) had a significantly lower total IQ (p = 0.01 for both). The G allele of the RANKL rs2277438 (G > A) had a significantly lower total IQ (p = 0.02). RANK rs1805034 (C > T) and RANKL rs2277438 (G > A) significantly affected verbal IQ (p = 0.01 and 0.03). TT genotype of RANK rs1805034 (C > T) had significantly lower verbal IQ (p = 0.002). Furthermore, the GG genotype of RANKL rs2277438 (G > A) had a significantly lower verbal and performance IQ than the AA genotype (p = 0.04 and 0.01 respectively), and its G allele had a significantly lower performance IQ than the A allele (p = 0.02). CONCLUSION: TDT children had low average total and verbal IQ while their performance IQ was borderline. The RANK/RANKL/OPG pathway affects cognition in TDT children, as some of the studied genes' polymorphisms and alleles had significant effects on total, verbal, and performance IQ of the studied TDT children.

Macular microvascular changes in children with transfusion-dependent beta-thalassemia.

BACKGROUND: To investigate the effect of iron overload on macular perfusion among transfusion-dependent thalassemia (TDT) patients using optical coherence tomography angiography (OCTA) METHODS: The study is a prospective observational case-control study. It included 27 eyes from 27 children with transfusion-dependent ß-thalassemia and 25 eyes from 25 age-matched controls. All participants were evaluated clinically and with OCTA Avanti RTVue-XR system (Optovue) to assess macular microvascular changes, by measuring vessels density (VDs) and foveal avascular zone (FAZ) area, at both superficial and deep retinal plexuses and at choriocapillaris level. RESULTS: Foveal and parafoveal zones were significantly thinner among thalassemia patients, with significantly larger FAZ area at the level of both superficial and deep retinal plexuses when compared with control group. The thalassemia group showed significant lower values compared with the controls regarding whole-image, foveal, and parafoveal deep VD. There were significant negative correlations between serum ferritin and deep (whole image and parafoveal) VD (r = - 0.429, P = 0.026, and r = - 0.452, P = 0.018, respectively). Choriocapillaris VDs (whole image and foveal) showed significant negative correlations with serum ferritin levels (r = - 0.390, P = 0.044 and r = - 0.401, P = 0.038, respectively) CONCLUSIONS: Macular microvascular changes were detected by OCTA examination in patients with TDT, mostly due to iron overload effect, as we selected patients on iron-chelating agent with the least harmful effect on the retina. The most affected layer is the DCP. Changes at the deep layer could be used as a sensitive biomarker for early macular perfusion changes in those patients. TRIAL REGISTRATION: Study registration number is UMIN000042657, date of registration: 2020/12/04 (retrospectively registered).

Association between oxidative stress and cord serum lipids in relation to delayed cord clamping in term neonates.

BACKGROUND: Although delayed cord clamping (DCC) is a recent WHO recommendation, early cord clamping (ECC) is still a routine practice in many countries. Limited researches studied the effect of delayed cord clamping on oxidative stress in term neonates; In this study we aim to assess the influence of cord clamping either early or late on oxidative stress in term neonates and to evaluate the association of oxidative stress and cord blood lipids. METHODS: One-hundred mothers and their term neonates were included in the present study. Umbilical cord blood samples were collected from the umbilical vein and umbilical artery immediately following labor. RESULTS: Total cholesterol, total triglycerides and phospholipids levels were significantly higher in the ECC group than the DCC group (p < 0.001 in all). Plasma total antioxidant status was higher in the DCC group than the ECC group (p < 0.001). While, plasma hydroperoxides were lower in the DCC group than the ECC group (p < 0.001). Levels of erythrocytes catalase cytosol, superoxide dismutase and glutathione peroxidase were significantly higher in the DCC group than the ECC group (p < 0.001). CONCLUSION: DCC was associated with a decrease in cord blood lipids and an augmented antioxidant activity. This suggests the protective effect of DCC on the future health of the term neonates and supports the application of DCC in active management of 3rd stage of labor in term neonates.

Assessment of platelets morphological changes and serum butyrylcholinesterase activity in children with diabetic ketoacidosis: a case control study.

BACKGROUND: Many studies indicated that mean platelet volume (MPV) and platelet distribution width (PDW) may be valuable in the diagnosis and management of clinical disorders; also, serum butyrylcholinesterase activity (BChE) was suggested to be linked to systemic inflammation and oxidative stress. Limited studies measured these readily available markers in children with diabetic ketoacidosis (DKA). Our objectives were to measure MPV, PDW and BChE in children with DKA; and to assess if any of these markers reflects the severity of DKA. METHODS: Our study included: 30 children with DKA (DKA group), 30 diabetic children (Non-DKA group) and 30 apparently healthy children (control group). MPV, PDW and BChE were measured in all children. Additional blood samples were withdrawn from the DKA group to assess these markers at discharge from hospital. RESULTS: MPV, PDW and BChE were significantly altered in the DKA group than the other two groups; and their levels improved significantly at discharge of the DKA group (p < 0.05). The three markers were found to equally to predict the presence of DKA, but MPV was the most suitable risk marker for DKA diagnosis (OR = 4.251, CI 95% =1.463-12.351, p = 0.003). Regarding their relation with DKA severity, they did not correlate significantly with arterial PH or serum HCO3- (p > 0.05). CONCLUSION: DKA in children is associated with changes in MPV, PDW and BChE activity, which improve after resolution of the condition. Elevated MPV can be a suitable risk marker for DKA. None of the studied markers correlated with the severity of DKA.