Placenta growth factor in sickle cell disease: association with hemolysis and inflammation

Abstract Placenta growth factor (PlGF) is released by immature erythrocytes and is elevated in sickle cell disease (SCD). Previous data generated in vitro suggest that PlGF may play a role in the pathophysiology of SCD-associated pulmonary hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1. In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is significantly elevated in SCD compared with healthy control subjects. We found significantly higher levels of PlGF in SCD patients with PHT but observed no association of PlGF with the frequency of acute pain episodes or history of acute chest syndrome. The observed correlation between PlGF and various measures of red cell destruction suggests that hemolysis, and the resultant erythropoietic response, results in the up-regulation of PlGF. Although relatively specific, PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular cell adhesion molecule, has low predictive accuracy for the presence of PHT. Prospective studies are required to conclusively define the contribution of PlGF to the pathogenesis of PHT and other hemolytic complications in SCD.

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Prevalence and Risk Factors for Microalbuminuria in Children with Sickle Cell Disease in the King Abdulaziz University Hospital: A Retrospective Cross-sectional Study

10.21203/rs.2.14382/v1 ◽

2019 ◽

Author(s):

Yahya A Alzahrani ◽

Malak Ali Algarni ◽

Maryam Mohammed Alnashri ◽

Hanan Mohammad AlSayyad ◽

Khadijah Mohammed Aljahdali ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pediatric Population ◽

Cross Sectional Study ◽

University Hospital ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Cross Sectional ◽

King Abdulaziz University

Abstract Objectives Studies have not addressed microalbuminuria in the sickle cell disease (SCD) pediatric population in Jeddah, Saudi Arabia. This study aimed to determine the prevalence of microalbuminuria and to identify associated risk factors in children with SCD in the King Abdulaziz University Hospital.Results Overall, 42.5% of the patients enrolled were Saudi Arabian and 51% were boys. Patients’ mean age was 12.4 years, and the highest percentage (40%) was in the age group of 15–18 years. The prevalence of microalbuminuria was 9.6%, and hematuria was present in 8% of cases. The percentage of patients with hematuria in the microalbuminuria group (22.6%) was significantly higher than that in the non-microalbuminuria group (6.5%) (P=.007). The percentage of patients with acute chest syndrome was higher in the microalbuminuria group (26%) than in the non-microalbuminuria group (8%) (P=0.005). The percentage of patients with gallbladder stones was higher in the microalbuminuria group (13%) than in the non-microalbuminuria group (2.4%) (P=.014). The mean number of blood transfusions was higher in the non-microalbuminuria group than in the microalbuminuria group (P=.002). Sickle cell nephropathy manifests as microalbuminuria, begins in the early ages of life, occurs in all types of SCD, and is associated with disease severity.

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Prevalence and Risk Factors for Microalbuminuria in Children with Sickle Cell Disease at King Abdulaziz University Hospital: A Retrospective Cross-sectional Study

10.21203/rs.2.14382/v2 ◽

2019 ◽

Author(s):

Yahya A Alzahrani ◽

Malak Ali Algarni ◽

Maryam Mohammed Alnashri ◽

Hanan Mohammad AlSayyad ◽

Khadijah Mohammed Aljahdali ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cross Sectional Study ◽

University Hospital ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Cross Sectional ◽

King Abdulaziz University ◽

Associated Risk Factors

Abstract Objectives Previous studies have not addressed microalbuminuria in pediatric patients with sickle cell disease (SCD) in Jeddah, Saudi Arabia. This study aimed to determine the prevalence of microalbuminuria and identify associated risk factors in children with SCD at King Abdulaziz University Hospital.Results Overall, 42.5% of the patients enrolled were Saudi Arabian and 51% were male. The patients’ mean age was 12.4 years, and the highest percentage (40%) was in the age group of 15–18 years. The prevalence of microalbuminuria was 9.6%, and hematuria was present in 8% of cases. The percentage of patients with hematuria was significantly higher in the microalbuminuria group (22.6%) than in the non-microalbuminuria group (6.5%; P=.007). The percentage of patients with acute chest syndrome was also higher in the microalbuminuria group (26%) than in the non-microalbuminuria group (8%; P=0.005). The percentage of patients with gallbladder stones was higher in the microalbuminuria group (13%) than in the non-microalbuminuria group (2.4%; P=.014). However, the mean number of blood transfusions was higher in the non-microalbuminuria group than in the microalbuminuria group (P=.002). Sickle cell nephropathy manifests as microalbuminuria, begins at an early age, occurs in all types of SCD, and is associated with disease severity.

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Faculty Opinions recommendation of High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.720029502.793510079 ◽

2015 ◽

Author(s):

Marilyn Telen

Keyword(s):

Pulmonary Hypertension ◽

Growth Factor ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Placenta Growth Factor

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Placenta Growth Factor (PlGF), a Novel Inducer of Plasminogen Activator Inhibitor-1 (PAI-1) in Sickle Cell Disease (SCD)

Journal of Biological Chemistry ◽

10.1074/jbc.m110.101691 ◽

2010 ◽

Vol 285 (22) ◽

pp. 16713-16722 ◽

Cited By ~ 25

Author(s):

Nitin Patel ◽

Nambirajan Sundaram ◽

Mingyan Yang ◽

Catherine Madigan ◽

Vijay K. Kalra ◽

...

Keyword(s):

Growth Factor ◽

Sickle Cell Disease ◽

Plasminogen Activator ◽

Sickle Cell ◽

Plasminogen Activator Inhibitor ◽

Cell Disease ◽

Placenta Growth Factor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

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Endothelial Barrier Integrity Is Disrupted In Vitro by Heme and by Serum From Sickle Cell Disease Patients

Frontiers in Immunology ◽

10.3389/fimmu.2020.535147 ◽

2020 ◽

Vol 11 ◽

Author(s):

Vanessa Araujo Gomes Santaterra ◽

Maiara Marx Luz Fiusa ◽

Bidossessi Wilfried Hounkpe ◽

Francine Chenou ◽

Wouitchekpo Vincent Tonasse ◽

...

Keyword(s):

Sickle Cell Disease ◽

Healthy Volunteers ◽

Sickle Cell ◽

Endothelial Barrier ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Experimental Conditions ◽

Cell Monolayers ◽

Junction Protein

Free extracellular heme has been shown to activate several compartments of innate immunity, acting as a danger-associated molecular pattern (DAMP) in hemolytic diseases. Although localized endothelial barrier (EB) disruption is an important part of inflammation that allows circulating leukocytes to reach inflamed tissues, non-localized/deregulated disruption of the EB can lead to widespread microvascular hyperpermeability and secondary tissue damage. In mouse models of sickle cell disease (SCD), EB disruption has been associated with the development of a form of acute lung injury that closely resembles acute chest syndrome (ACS), and that can be elicited by acute heme infusion. Here we explored the effect of heme on EB integrity using human endothelial cell monolayers, in experimental conditions that include elements that more closely resemble in vivo conditions. EB integrity was assessed by electric cell-substrate impedance sensing in the presence of varying concentrations of heme and sera from SCD patients or healthy volunteers. Heme caused a dose-dependent decrease of the electrical resistance of cell monolayers, consistent with EB disruption, which was confirmed by staining of junction protein VE-cadherin. In addition, sera from SCD patients, but not from healthy volunteers, were also capable to induce EB disruption. Interestingly, these effects were not associated with total heme levels in serum. However, when heme was added to sera from SCD patients, but not from healthy volunteers, EB disruption could be elicited, and this effect was associated with hemopexin serum levels. Together our in vitro studies provide additional support to the concept of heme as a DAMP in hemolytic conditions.

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The Practices of Anaesthesiologists in the Management of Patients with Sickle Cell Disease: Empirical Evidence from Cameroon

Healthcare ◽

10.3390/healthcare9121617 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1617

Author(s):

Dominique Djomo Tamchom ◽

Aristide Kuitchet ◽

Raymond Ndikontar ◽

Serge Nga Nomo ◽

Hermine Fouda ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Perioperative Management ◽

Treatment Guideline ◽

Binary Logistic Regression ◽

Cross Sectional Study ◽

Cell Disease ◽

Binary Logistic Regression Model ◽

Cross Sectional ◽

Elective Surgical Procedures

Patients with sickle cell disease are more likely to undergo surgery during their lifetime, especially given the numerous complications they may develop. There is a paucity of data concerning the management of patients with sickle cell disease by anaesthesiologists, especially in Africa. This study aimed to describe the practices of anaesthesiologists in Cameroon concerning the perioperative management of patients with sickle cell disease. A cross-sectional study was carried out over four months and involved 35 out 47 anaesthesiologists working in hospitals across the country, who were invited to fill a data collection form after giving their informed consent. The data were analysed using descriptive statistics and a binary logistic regression model. Among the 35 anaesthesiologists included in the study, most (29 (82.9%)) had managed patients with sickle cell disease for both emergency and elective surgical procedures. Most of them had never asked for a haematology consultation before surgery. Most participants (26 (74.3%)) admitted to having carried out simple blood transfusions, while 4 (11.4%) carried out exchange transfusions. The haemoglobin thresholds for transfusion varied from one practitioner to another, between < 6 g/dl and < 9 g/dl. Only 6 (17.1%) anaesthesiologists had a treatment guideline for the management of patients with sickle cell disease in the hospitals where they practiced. Only 9 (25.7%) prescribed a search for irregular agglutinins. The percentage of haemoglobin S before surgery was always available for 5 (14.3%) of the participants. The coefficient (0.06) of the occurrence of a haematology consultation before surgery had a significant influence on the probability of management of post-operative complications (coefficient 0.06, 10% level of probability). This study highlights the fact that practices in the perioperative management of patients with sickle cell disease in Cameroon vary greatly from one anaesthesiologist to another. We disclosed major differences in the current recommendations, which support the fact that even in Sub-Saharan countries, guidelines applicable to the local settings should be published.

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Sexual Maturity in Adolescents Suffering from Sickle Cell Disease: A Cross-sectional Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47287.14981 ◽

2021 ◽

Author(s):

Vijay Shah ◽

Akash Patel ◽

Praful Bambharoliya ◽

Jigisha Patadia

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sexual Maturity ◽

Tanner Stage ◽

Cross Sectional Study ◽

Reproductive Capacity ◽

Sectional Study ◽

Cell Disease ◽

Cross Sectional ◽

The Mean

Introduction: Sickle Cell Disease (SCD) is an inherited chronic haemolytic anaemia. The diseased person suffers from various complications such as anaemia, frequent infection, fever, hand-foot syndrome, stroke, etc. Puberty changes includes the appearance of the secondary sexual characteristics, increase in height, change in body composition and development of reproductive capacity. Aim: To study the sexual maturity and effect of multiple blood transfusions in adolescents suffering from SCD. Materials and Methods: It was a cross-sectional study conducted on 35 adolescents of age group 11 to 15 years, suffering from SCD. Study was conducted over a period of six months from March 2018 to September 2018 at Department of Paediatrics. SCD was diagnosed by Haemoglobin (Hb) electrophoresis. Weight and height were measured of all the participants. For assessing the sexual maturity, Tanners staging was used. Unpaired t-test was done for data analysis. Results: The mean age of the patients was 13.03±1.7 years. There were 25 males and 10 females. The mean age of male patients between Tanner stage 2(14.63±0.52 years) and Tanner stage 3 (14.75±0.5 years) was significantly higher than the Indian data for males (11.3 and 12.8 years, respectively). The mean age of female patients between Tanner stages 2 (13.5±2.12 years) and Tanner stage 3 (14.33±1.16 years) was higher than the Indian reference data for girls (10.2 and 11.6 years respectively). Conclusion: This study concluded that adolescents with SCD were significantly shorter in height and weight than the standard reference population. Sexual maturity is delayed in adolescents with sickle cell anaemia.

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Asymmetric Dimethyl Arginine Level in Children with Sickle Cell Disease: A Cross Sectional Study

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i1831059 ◽

2021 ◽

pp. 93-98

Author(s):

Seham Fathy Khedr ◽

Mohamed Hosny El Bradaey ◽

Hala Mohamed Nagy ◽

Mohamed Ramadan El-Shanshory ◽

Eslam Elhawary

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Cross Sectional Study ◽

Sectional Study ◽

Cell Disease ◽

Adma Level ◽

Cross Sectional ◽

Asymmetric Dimethyl Arginine ◽

Dimethyl Arginine

Background: Sickle cell disease (SCD) consists of a group of hemoglobinopathies in which individuals inherit hemoglobin variants derived from single point mutations. Asymmetric dimethylarginine (ADMA) contributes to limiting Nitric Oxide (NO) bioavailability in SCD. The aim of the present study was to assess the level of the Asymmetric Dimethyl Arginine in children with sickle cell. Methods: This cohort cross-sectional study was carried out on 60 children which were divided in to 3 equal groups. Group I: SCD children with sickle retinopathy. Group II: SCD children without retinopathy. Group III: healthy control children who were selected from the outpatient clinic. Results: There was a significant increase in ADMA level among participants withSCD. There was a positive significant correlation between ADMA level and family history as well as the incidence of hepatomegaly. There was no significant correlation between ADMA level and demographic and laboratory parameters except LDH. Conclusions: The level of ADMA is elevated in children with sickle cell anemia. High plasma ADMA level is a risk for hepatomegaly in children with sickle cell anemia.

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