Endothelial dysfunction in patients with hereditary spherocytosis and b-thalassemia

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

Download Full-text

Globin Chain Synthesis in the Marrow and Reticulocytes of Beta Thalassemia, Hemoglobin H Disease, and Beta Delta Thalassemia

Blood ◽

10.1182/blood.v40.1.105.105 ◽

1972 ◽

Vol 40 (1) ◽

pp. 105-111 ◽

Cited By ~ 18

Author(s):

Mordechai Shchory ◽

Bracha Ramot

Keyword(s):

Bone Marrow ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Globin Chain ◽

Thalassemia Intermedia ◽

Thalassemia Minor ◽

Order Of Magnitude ◽

Hb H Disease ◽

Chain Synthesis ◽

Globin Chain Synthesis

Abstract α, β, and γ globin chain synthesis in bone marrow and peripheral blood reticulocytes were studied in two patients with thalassemia major, two with thalassemia intermedia, one with thalassemia minor, one with Hb H disease, and one with homozygous βδ-thalassemia. Nine nonthalassemic patients served as controls. In thalassemia major, a marked imbalance of α- to β-chain synthesis was found in the bone marrow as well as in reticulocytes. The imbalance, however, was slightly more evident in the latter. In the patients with thalassemia intermedia and minor the α- to β-globin chain ratios in the reticulocytes were of the same order of magnitude, despite the marked clinical differences between thalassemia intermedia and minor. A balanced synthesis was found in the bone marrow of the patient with thalassemia minor. The bone marrow globin synthesis in thalassemia intermedia was not studied. Contrary to that in Hb H disease and βδ-thalassemia, the imbalance was more apparent in the bone marrow. In the latter, no evidence for imbalance was detected in the reticulocytes. These results point out the need for further studies on globin chain synthesis in the bone marrow and reticulocytes of patients With the various thalassemia syndromes and the effect of the free globin chain pool on those results.

Download Full-text

Incidence of Pulmonary Hypertension in Haemoglobinopathic Patients without Left Ventricular Disfunction.

Blood ◽

10.1182/blood.v106.11.2691.2691 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2691-2691 ◽

Cited By ~ 2

Author(s):

Giorgio Derchi ◽

Francesco Formisano ◽

Martina Lamagna ◽

Renzo Galanello ◽

Patrizio Bina ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Ventricular Dysfunction ◽

Thalassemia Major ◽

Left Ventricular ◽

Thalassemia Intermedia ◽

Normal Range ◽

Cross Sectional ◽

Jet Velocity ◽

Tricuspid Regurgitant Jet Velocity

Abstract Incidence of Pulmonary Hypertension (PH) has been described in haemoglobinopathic patients, ranging from 10% to 50%, depending on age, therapy, coexisting left ventricular dysfunction (LVD) and classification of the disease. To determine whether PH can occurs in haemoglobinopathic patients in absence of overt LVD, we studied 1121 pts from 7 Thalassemia Centers in Italy(485 Thalassemia Major (TM), 458 thalassemia intermedia (TI), 178 Sickle Cell or Sickle Thalassemia Disease (SCD),49% males, mean age 30 yrs, range 13–56 yrs). In all pts echocardiographic (Echo) defined ejection fraction (EF%) was > 45% and clinically overt LVD was excluded. A cross-sectional Echo study was performed in order to detect PH that was prospectively defined as mild with tricuspid regurgitant jet velocity (TRV)of at least 2.5 m per second and defined as severe with a TRV> 3.5 m per second. Severe PH was observed in 9 pts, 3 with TM, in 6 with TI and in 1 patients with SCD. Mild PH occurs in 46 patients with TM, in 57 patients with TI and 11 pts with SCD. In the remaining patients, PH was in the normal range (TM 89,9%, TI 86,2% and SCD 93,2% of pts, respectively). In the whole group of hemoglobinopathic pts the incidence of PH (mild plus severe) range from 6.5 % to 13.8% of pts. PH (mild to severe) particularly affects pts with TI (13,8% of pts). Incidence of PH in TM, TI and SCD Tricuspid Regurgitant Jet Velocity Thal Major 485 pts Thal Int 458 pts SCD 178 pts % pts TRV<2.5 m/sec 436 (89.9%) 395 (86.2%) 166 (93.2%) 89% 2,5<TRV<3.5 m/sec 46 (9.4%) 57 (12.5%) 11 (6.2%) 10.1% TRV>3.5 m/sec 3 (0.6%) 6 (1.3%) 1 (0.9%) 0.9% Our data support a significant presence of PH in haemoglobinopathic pts (6.2 to 13,8%) even though well treated and without LVD. Considering the pathophisiology of haemoglobinopathies a specific consideration to PH in these diseases is required in order to establish a preventive and therapeutic approach.

Download Full-text

Unbound Amino Acids in the Plasma and Erythrocytes of Children with Various Anemias and with Erythroblastosis Fetalis

Blood ◽

10.1182/blood.v26.1.91.91 ◽

1965 ◽

Vol 26 (1) ◽

pp. 91-99 ◽

Cited By ~ 8

Author(s):

MARIA NICOLAIDOU ◽

CHARLES C. LUND ◽

RAPIER H. MCMENAMY

Keyword(s):

Amino Acid ◽

Hemolytic Anemia ◽

Hereditary Spherocytosis ◽

Reduced Glutathione ◽

Thalassemia Major ◽

Deficiency Anemia ◽

Hemoglobin Content ◽

Disease Category ◽

Thalassemia Minor ◽

Amino Acid Concentrations

Abstract The unbound amino acid concentrations in the plasma and erythrocytes of 24 children with anemias of various types have been determined by the method of salt-saturated paper chromatography (iron deficiency anemia— 8 subjects; sickle cell anemia—3 subjects; hereditary spherocytosis—3 subjects; erythroblastosis fetalis—4 subjects; and 1 subject each for thalassemia minor, thalassemia major, unstable reduced glutathione, acquired hemolytic anemia, autoimmune hemolytic anemia, S & F hemoglobinopathy). Anemia per se was found to have little effect on the plasma amino acid concentrations, although a marked increase in the erythrocyte concentrations of every amino acid determined was found. In multiple regression and correlation analyses, the unbound amino acid concentrations in the erythrocytes were found to be a function of both the reticulocyte counts and the blood hemoglobin content, with a somewhat greater dependence on the latter. No recognizable distinction as to the disease category was evident in the unbound amino acid patterns of the anemia patients. The extent of the unbound amino acid elevations in the erythrocytes was largely a reflection of the severity of the anemia. The subjects with erythroblastosis fetalis were in a category different from those with anemia. Their erythrocyte amino acid concentrations were probably the same as those of normal babies during the first few hours after birth.

Download Full-text

Endothelial dysfunction in obstructive sleep apnea patients

Sleep And Breathing ◽

10.1007/s11325-021-02382-4 ◽

2021 ◽

Author(s):

Michał Harańczyk ◽

Małgorzata Konieczyńska ◽

Wojciech Płazak

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Endothelial Dysfunction ◽

Right Ventricular ◽

Contractile Function ◽

Sleep Apnea Syndrome ◽

Apnea Hypopnea Index ◽

Endothelin 1 ◽

Obstructive Sleep

Abstract Purpose Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial dysfunction and thrombosis biomarkers and to evaluate the effect of treatment with continuous positive airway pressure (CPAP) on biomarker levels. Methods NT-proBNP, sICAM-1, endothelin-1, von Willebrand factor, D-dimers, and thrombin-antithrombin complex (TAT) were measured in 50 patients diagnosed with moderate-to-severe OSAS. All patients underwent transthoracic echocardiography, and 38 months after the inclusion, 16 CPAP users and 22 non-CPAP users were reassessed. Results Sleep-related indices of apnea-hypopnea index (AHI) and mean SpO2 were associated with higher sICAM-1 levels (AHI < 30: 7.3 ± 4.7 vs. AHI ≥ 30: 19.5 ± 19.4 mg/ml, p = 0.04; SpO2 ≥ 90%: 11.9 ± 9.3 vs. SpO2 < 90%: 23.6 ± 25.8, p = 0.04). sICAM-1 levels were significantly higher in obese patients, particularly with BMI ≥ 40. Plasma levels of TAT were significantly correlated with the increased right ventricular size (right ventricular diameter ≤ 37 mm: 0.86 ± 0.70 vs. > 37 mm: 1.96 ± 1.20 ng/ml, p = 0.04). Endothelin-1 levels were higher in patients with decreased right ventricular function (right ventricle TDI-derived S′ ≥ 12 cm/s: 11.5 ± 10.9 vs. < 12 cm/s: 26.0 ± 13.2 pg/ml, p = 0.04). An increase in NT-proBNP was related to impaired parameters of the right ventricular contractile function. There were no correlations between long-term CPAP therapy and the levels of biomarkers. Conclusion Severe OSAS influences endothelial damage as manifested by an increase in sICAM-1 levels. Changes in right ventricular structure and function, observed mainly in patients with higher TAT and endothelin-1 levels, are also manifested by an increase in NT-proBNP levels. Long-term CPAP treatment does not seem to influence biomarkers in patients with moderate-to-severe OSAS, which may help to explain the lack of influence of CPAP on cardiovascular risk reduction.

Download Full-text

Cardiac Involvement in β‐Thalassemia Major and β‐Thalassemia Intermedia

Hemoglobin ◽

10.1081/hem-120034248 ◽

2004 ◽

Vol 28 (2) ◽

pp. 123-129 ◽

Cited By ~ 6

Author(s):

Mara Ferrara ◽

Sofia M. R. Matarese ◽

Barbara Borrelli ◽

Angelo Perrotta ◽

Gelsomina Simeone ◽

...

Keyword(s):

Cardiac Involvement ◽

Thalassemia Major ◽

Thalassemia Intermedia

Download Full-text

STUDY OF THALASSEMIA MINOR IN THREE GENERATIONS OF AN ITALIAN FAMILY

Blood ◽

10.1182/blood.v3.4.449.449 ◽

1948 ◽

Vol 3 (4) ◽

pp. 449-456

Author(s):

ROBERT W. HEINLE ◽

MARGARET RUTH READ

Keyword(s):

Life Expectancy ◽

General Health ◽

Hypochromic Anemia ◽

Thalassemia Major ◽

Genetic Studies ◽

Italian Family ◽

Three Generations ◽

Thalassemia Minor ◽

Hypotonic Saline

Abstract 1. Three generations of a family of Italian descent were studied. Nine of 13 members were found to have thalassemia minor. 2. Genetic studies indicate that this mild, microcytic hypochromic anemia characterized by the presence of target and elliptical cells and other bizarre forms and by increased resistance to hypotonic saline, results from heterozygosity of an inherited factor, which, when homozygous, produces thalassemia major or Cooley’s Mediterranean anemia. 3. If individuals heterozygous for this factor (thalassemia minor) marry other heterozygous individuals, one quarter of the offspring can be expected to be homozygous (thalassemia major), one half heterozygous (thalassemia minor) and one quarter free of the trait. 4. The presence of thalassemia minor apparently did not interfere with the general health of affected members of this family and did not appear to shorten life expectancy. The importance of the condition lies in its relation to thalassemia major.

Download Full-text

P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty

European Heart Journal ◽

10.1093/eurheartj/ehz745.1061 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

W Magon ◽

J Stepniewski ◽

K Jonas ◽

M Waligora ◽

P Podolec ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Serum Concentration ◽

Systemic Inflammation ◽

Interleukin 6 ◽

C Reactive Protein ◽

Pulmonary Hemodynamics ◽

Endothelin 1 ◽

Reactive Protein ◽

Balloon Pulmonary Angioplasty

Abstract Introduction Pulmonary endarterectomy leads to a decrease in systemic inflammation and improvement in endothelial function in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in patients with inoperable CTEPH. Aim To assess changes in systemic inflammation and endothelial dysfunction after a single BPA session and after completion of the treatment. Methods We enrolled consecutive, inoperable CTEPH patients who underwent BPA. Interleukin 6, 10 (IL-6, IL-10), and C-reactive protein (hsCRP) constituted markers of systemic inflammation. Endothelin-1 (ET-1) served as a marker of endothelial dysfunction. Serum concentration of selected markers was assessed in every patient before, 24 hours after the first BPA session and 6 months after completion of the BPA treatment. Age- and sex-matched healthy subjects served as a control group. Results We recruited 20 patients with inoperable CTEPH (6 males [30%]), aged 67 [61–74] years in New York Heart Association class III (n=19 [95%]) and II (n=1 [5%]). BPA treatment was completed with a median of 5 [2–8] BPA sessions per patient. Before starting the treatment CTEPH patients, as compared to controls (n=10), had raised serum level of IL-6 (3.82 [2.75 - 6.03] vs. 2.64 [0.88 - 4.75] pg/ml; p=0.04), hsCRP (2.47 [0.93 - 4.27] vs. 1.23 [0.48–3.21] ng/ml; p=0.02) and ET-1 (2.68 [2.24 - 3.64] vs. 1.47 [1.4 - 1.82] pg/ml; p=0.004). There was no difference in IL-10 level. 24 hours after a BPA session we observed an increased level of IL-6, IL-10 and hsCRP. (Tab.) 6 months after completion of the BPA treatment there was a reduced level of IL-6, hsCRP and ET-1 (Tab.) Table 1. Changes (Δ) in serum concentration of analyzed markers 24 hours after a single BPA session and at 6-months assessment after completion of the BPA treatment (n=20) Initial Δ at 24 hours after single BPA p Δ at 6-months follow-up p ET-1 [pg/ml] 2.68 [2.24; 3.64] −0.2 [−0.5; 0.23] 0.21 −0.47 [−0.96; 0.05] 0.004 IL-6 [pg/ml] 3.82 [2.75; 6.03] 3.67 [1.41; 7.16] 0.008 −0.82 [−3.11; 0.54] 0.04 IL-10 [pg/ml] 0.53 [0.44; 0.58] 0.32 [0.21; 0.87] 0.006 −0.11 [−0.33; 0.14] 0.94 hsCRP [ng/ml] 2.47 [0.93; 4.27] 5.4 [3.96; 10.59] 0.008 −0.36 [−0.94; 0.16] 0.02 ET-1, endothelin 1; hsCRP, C-reactive protein; IL-6, interleukin 6; IL-10, interleukin 10. Conclusions Patients with inoperable CTEPH, as compared to healthy controls, exhibit an increased systemic inflammation and endothelial dysfunction, which both improve after completion of the BPA treatment. At short-term follow-up after single BPA session there is an increase in systemic inflammatory response.

Download Full-text

The Role of Endothelial Dysfunction in the Development of Cardiotoxic Action of Cytostatics in Patients with Lymphoproliferative Diseases

Kardiologiia ◽

10.18087/cardio.2019.4.10251 ◽

2019 ◽

Vol 59 (4) ◽

pp. 64-66 ◽

Cited By ~ 2

Author(s):

D. A. Budanova ◽

Yu. N. Belenkov ◽

I. Ya. Sokolova ◽

O. N. Antyufeeva ◽

V. I. Ershov ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Normal Values ◽

Clear Understanding ◽

Age Group ◽

Lymphoproliferative Diseases ◽

Endothelin 1 ◽

Vasoconstrictor Effect ◽

Before And After ◽

Chemotherapy Cardiotoxicity

Understanding mechanisms of chemotherapy cardiotoxicity is an important problem due to the lack of clear understanding of its occurrence. Development of endothelial dysfunction is considered to be one of possible ways in implementation of these side effects. The analysis of endothelin-1 and e-selectin levels in 26 patients with lymphoproliferative diseases before and after the completion of the treatment program was been performed. The results of the study showed normal values of E-selectin level and increased level of endothelin-1 in the whole group of patients before treatment. After completion of chemotherapy program, in the whole group, there was a decrease of these two markers. However, values of level of endothelin-1 with vasoconstrictor effect remained high even after the end of therapy. It is imp ortant that at detailed analysis the dynamics of investigated markers in patients of older age group (median age 64 years) was associated with worsening of endothelial dysfunction.

Download Full-text

Current Perspective of Beta Thalassemia and Its Treatment Strategies

10.20944/preprints201907.0277.v1 ◽

2019 ◽

Author(s):

Shaukat Ali ◽

Shumaila Mumtaz ◽

Hafiz Abdullah Shakir ◽

Hafiz Muhammad Tahir ◽

Tafail Akbar Mughal

Keyword(s):

Genetic Testing ◽

Blood Transfusion ◽

Dna Analysis ◽

Complete Blood Count ◽

Globin Gene ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Beta Globin ◽

Hematopoietic Stem ◽

Thalassemia Minor

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

Download Full-text

Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4353462 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

Sebastian Steven ◽

Matthias Oelze ◽

Moritz Brandt ◽

Elisabeth Ullmann ◽

Swenja Kröller-Schön ◽

...

Keyword(s):

Oxidative Stress ◽

Pulmonary Hypertension ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Whole Blood ◽

Pulmonary Arteries ◽

Vascular Wall ◽

Pentaerythritol Tetranitrate ◽

Endothelin 1 ◽

Pulmonary Arterial

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined.Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells.Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.

Download Full-text