Amira Abdel Moneam Adly

Circulating platelet and erythrocyte microparticles in young children and adolescents with sickle cell disease: Relation to cardiovascular complications

Sickle cell disease (SCD) is characterized by a complex vasculopathy, consisting of endothelial dysfunction and increased arterial stiffness, with a global effect on cardiovascular function. The hypercoagulable state may result from chronic hemolysis and circulating cell-derived microparticles (MPs) originating mainly from activated platelets and erythrocytes. We measured the levels of platelet and erythrocyte-derived MPs (PMPs and ErMPs) in 50 young SCD patients compared with 40 age- and sex-matched healthy controls and assessed their relation to clinicopathological characteristics and aortic elastic properties. Patients were studied stressing on the occurrence of sickling crisis, transfusion history, hydroxyurea therapy, hematological, and coagulation profile as well as flow cytometric expression of PMPs (CD41b+) and ErMPs (glycophorin A+). Echocardiography was performed to assess aortic stiffness and distensibility, left ventricular function and pulmonary artery pressure. Both PMPs and ErMPs were significantly elevated in SCD patients compared with control group (p < 0.001). SCD patients had significantly elevated d-dimer and von Willebrand factor antigen (vWF Ag) levels with lower antithrombin III compared with controls (p < 0.001). Aortic stiffness index and pulmonary artery pressure were significantly higher in SCD (p < 0.001), whereas aortic strain and aortic distensibility were significantly lower (p < 0.001) compared with controls. MPs levels were significantly increased in SCD patients with pulmonary hypertension, acute chest syndrome, and stroke as well as those who had history of thrombosis or splenectomy (p < 0.001). Also, patients in sickling crisis during the study had higher PMPs and ErMPs levels than those in steady state (p < 0.001). Patients on hydroxyurea therapy had lower MPs levels than untreated patients (p < 0.001). PMPs and ErMPs were positively correlated with disease duration, transfusion index, white blood cell count, HbS, markers of hemolysis, serum ferritin, D-dimer, and vWF Ag, whereas negatively correlated with hemoglobin and HbF levels (p < 0.05). Both PMPs and ErMPs levels were positively correlated with aortic stiffness, pulmonary artery pressure, and tricuspid regurgitant velocity (p < 0.05) while negatively correlated with aortic distensibility. We suggest that PMPs and ErMPs overproduction may be considered a potential biological marker for vascular dysfunction and disease severity in SCD and may be implicated in the pathogenesis of coagulation abnormalities encountered in those patients. Their levels are closely related to sickling crisis, pulmonary hypertension, markers of hemolysis, fibrinolysis, and iron overload. Therefore, quantification of MPs in SCD may provide utility for identifying patients who are at increased risk of thrombotic events or cardiovascular abnormalities and would help to monitor response to hydroxyurea therapy.

Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients.

Minimal data are available on the combined two oral iron chelators in β‐thalassemia major (β‐TM). Comparison of safety, efficacy, compliance, treatment satisfaction, and quality of life (QoL) of two regimens: deferiprone (DFP) and deferoxamine (DFO) versus DFP and deferasirox (DFX) were studied.

Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia

Abstract Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p < 0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p < 0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p < 0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p < 0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients with a sensitivity of 88% and a specificity of 85.7%. We suggest that IPF may be a rapid and inexpensive automated marker for etiology of thrombocytopenia and can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. It may be considered as a potential prognostic marker for the development of chronic ITP.

BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis

Objective:  Although BIRC6/Apollon seems to play a critical role as an antiapoptotic regulator, its clinical relevance in acute leukemia remains largely elusive. Therefore, we aimed to investigate BIRC6 gene expression in childhood acute leukemia in relation to clinicopathological characteristics at presentation, therapeutic response, and prognosis.

Plasminogen activator inhibitor-1 (PAI-1) in children and adolescents With Type 1 Diabetes Mellitus: relation to diabetic micro-vascular complications and carotid intima media thickness

BACKGROUND Plasminogen activator inhibitor-1 (PAI-1) is a fast-acting inhibitor of fibrinolysis that has been linked to increase risk of thrombosis. We determined PAI-1 levels in 80 children and adolescents with type 1 diabetes (T1DM) compared with 40 healthy controls as a potential marker for micro-vascular complications and assessed the relation to carotid intima media thickness (CIMT) as a synergistic risk factor for development of atherosclerosis. METHODS Patients were divided into 2 groups according to micro-vascular complications. Hemoglobin A1c (HbA1c), urinary albumin excretion, fasting serum lipid profile and PAI-1 levels were measured. CIMT of the common carotid artery was assessed using high resolution ultrasonography. RESULTS PAI-1 levels were significantly elevated in the group with diabetes compared with control group (p<0.001). PAI-1 levels were also increased in patients with micro-vascular complications compared with those without (p<0.001). CIMT was significantly higher in patients, particularly those with micro-vascular complications than patients without complications or controls (p<0.001). Positive correlations were found between PAI-1 levels and random blood glucose, HbA1c, triglycerides, total cholesterol and CIMT (p<0.05). CONCLUSIONS Increased plasma PAI-1 may be involved in the state of hypofibrinolysis in patients with T1DM leading to the occurrence of micro-vascular complications and increased risk of atherosclerosis.

Platelets microparticles as a link between micro- and macro-angiopathy in young patients with type 1 diabetes

Abstract The development of vasculopathies in diabetes involves multifactorial processes. Increased levels of platelets-derived microparticles (PMPs) have been reported in diseases associated with thrombotic risk, but few data are available in diabetes. We explored the level of PMPs in young patients with type 1 diabetes in relation to inflammation, glycemic control, micro-vascular complications and carotid intima media thickness (CIMT). Eighty children and adolescents with type 1 diabetes were divided into two groups according to the presence of micro-vascular complications and compared with 40 healthy controls. Patients were subjected to medical history, clinical examination and assessment of high-sensitivity C-reactive protein (hs-CRP), HbA1c, urinary albumin creatinine ratio (UACR), flow cytometric analysis for PMPs using anti-CD41b and CIMT. PMP levels were significantly increased in all patients with type 1 diabetes (2.92 ± 1.3%) whether with micro-vascular complications (3.46 ± 1.11%) or those without complications (2.37 ± 1.28%) compared with healthy controls (1.28 ± 0.64%; p < 0.001). CIMT was significantly elevated in all patients, and the highest levels were among those with micro-vascular complications (p < 0.001). Significant positive correlations were found between PMPs and body mass index, HbA1c, serum creatinine, total cholesterol, UACR, hs-CRP and CIMT (p < 0.05). Multiple linear regression analysis showed that HbA1c, UACR, hs-CRP and CIMT were independently related to PMPs levels in type 1 diabetes. According to Receiver operating characteristic curve analysis, the cutoff value of PMPs at 2.48% could differentiate patients with and without micro-vascular complications with a sensitivity of 80% and specificity of 73.3%. PMPs are elevated in patients with type 1 diabetes and can be considered as an early marker of micro-vascular complications and subclinical atherosclerosis.

Endothelial nitric oxide synthase gene intron 4 VNTR polymorphism in sickle cell disease: Relation to vasculopathy and disease severity

Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a common denominator in the pathogenesis of vasculopathy in sickle cell disease (SCD). Evidence indicates the contribution of 4a allele of endothelial NO synthase (eNOS) gene to cardiac and renal diseases. We studied the 27‐base pair tandem repeat polymorphism in intron 4 of eNOS gene in 51 patients with SCD compared with 55 healthy controls and evaluated its role in disease severity and hemolysis‐associated complications.

Soluble CD163 in young sickle cell disease patients and their trait siblings: a biomarker for pulmonary hypertension and vaso-occlusive complications.

CD163 is expressed on cells of monocyte–macrophage lineage and is the main hemoglobin–haptoglobin receptor. Inflammation and monocyte activation are predisposing factors to vaso-occlusion and pulmonary hypertension, which are serious complications in sickle cell disease (SCD). Siblings of SCD patients may have the same pathophysiology without displaying symptoms. We assessed soluble CD163 (sCD163) levels in 60 children with SCD and 30 sickle cell trait (SCT) siblings compared with 30 healthy controls as a potential marker for disease severity and treatment response. Patients were studied stressing on the presence of pulmonary hypertension by Dopplar-Echocardiography, sickling crisis, transfusion requirements, hydroxyurea response, hematological profile, high sensitivity C-reactive protein (hs-CRP) and serum sCD163. sCD163 was significantly elevated in SCD patients and SCT siblings compared with controls and the highest levels were in untreated SCD patients (P < 0.001). sCD163 was higher in patients with pulmonary hypertension, acute chest syndrome or stroke as well as in patients who developed sickling crisis during the study period (P < 0.05). Hydroxyurea-treated patients had lower sCD163 compared with untreated patients (P < 0.001). sCD163 was positively correlated to leukocyte count, HbS, hs-CRP, pulmonary artery pressure and tricuspid regurgitant velocity whereas inversely correlated to hemoglobin and HbF levels. The cut-off value of sCD163 at 1400 ng/ml could be considered a predictor for vaso-occlusive crisis in SCD with a sensitivity of 92.3% and specificity of 94.1%. sCD163 can be considered a biomarker for pulmonary hypertension, early crisis prediction and monitoring hydroxyurea response in SCD patients. Elevated sCD163 in trait siblings could reflect increased risk of sickling in challenging situations.

Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload

Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO).

Evoked potentails and neurocognitive functions in pediatric Egyptian Gaucher patients on enzyme replacement therapy: a single center experience

BackgroundEffectiveness of enzyme replacement therapy (ERT) in reverting hematologic, skeletal, and visceral symptoms in Gaucher disease (GD) has been demonstrated, although, its efficacy in neurologic involvement is still debated.AimWe evaluated the extent of neuro-cognitive dysfunction using brain stem evoked potential in GD3 patients, age-matched controls, and GD1 patients without neurological manifestations served as disease control group.MethodsStudy included 56 GD (36 had type 1, 20 had type 3) under ERT. Investigations included complete blood count, beta glucosidase assay in peipheral leucocytes, plasma chitotriosidase and bone marrow examination, electroencephalography, brain stem auditory (AEP), somatosensory (SSEP) and visual evoked potentials (VEP) as well as IQ testing.ResultsBoth types of GD showed significantly higher mean latency at 75 on left eye, lower PP amplitude ratio, higher latency at 75, 100, 145, lower amplitude, and higher Lat Diff LT-RT ms and Lt-Rt % compared to controls (p < 0.05) with no difference between both groups in other values of VEP. Both groups showed significantly prolonged latency of N 13–19 compared to controls (p < 0.05) with positive correlation between age and duration of therapy with parameters of SSEP (p < 0.01). Both groups of GD had significantly prolonged latency of the mean waves of AEP compared to controls (p < 0.05) with no significant difference between both groups. There was a negative correlation between age and waves II, III, I–III, I–V and threshold values of AEP. IQ level was positively correlated with AEP values. Severity scoring tool was positively correlated with AEP and SSEP values.ConclusionsElectrophysiological abnormalities were present in both types of GD and have been correlated to cognitive function and disease characteristics.