scholarly journals Total Serum Magnesium Levels and Calcium-To-Magnesium Ratio in Sickle Cell Disease

Medicina ◽  
2019 ◽  
Vol 55 (9) ◽  
pp. 547
Author(s):  
Antwi-Boasiako ◽  
Kusi-Mensah ◽  
Hayfron-Benjamin ◽  
Aryee ◽  
Dankwah ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Magnesium ◽  
Total Serum ◽  
Healthy Controls ◽  
Cell Disease ◽  
Flame Atomic Absorption ◽  
Significant Difference ◽  
Calcium Magnesium ◽  
Cell Dehydration

Background and objectives: Imbalance of calcium/magnesium ratio could lead to clinical complications in sickle cell disease (SCD). Low levels of magnesium have been associated with sickling, increased polymerization and vaso-occlusion (VOC) in sickle cell due to cell dehydration. The K-Cl cotransport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. The study evaluated total serum magnesium levels and computed calcium/magnesium ratio in SCD patients and “healthy” controls. Materials and methods: The study was a case-control cross-sectional one, involving 120 SCD patients (79 Haemoglobin SS (HbSS)and 41 Haemoglobin SC (HbSC)) at the steady state and 48 “healthy” controls. Sera were prepared from whole blood samples (n = 168) and total magnesium and calcium measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd., Melbourne, VIC, Australia). Calcium/magnesium ratios were calculated in patients and the controls. Results: The prevalence of hypomagnesemia and hypocalcaemia among the SCD patients was observed to be 39.17% and 52.50% respectively, higher than the controls (4.17% and 22.92%, for hypomagnesemia and hypocalcaemia, respectively). Level of magnesium was significantly lower in the SCD patients compared to their healthy counterparts (p = 0.002). The magnesium level was further reduced in the HbSS patients but not significantly different from the HbSC patients (p = 0.584). calcium/magnesium ratio was significantly higher in the SCD patients (p = 0.031). Although calcium/magnesium ratio was higher in the HbSC patients compared to those with the HbSS genotype, the difference was not significant (p = 0.101). Conclusion: The study shows that magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Although calcium/magnesium ratio is significantly higher in SCD patients compared with controls, there is no significant difference between patients with HbSS and HbSC genotypes. Magnesium supplementation may be required in sickle cell patients.

scholarly journals Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 180
Author(s):  
Charles Antwi-Boasiako ◽  
Gifty Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron-Benjamin ◽  
Alfred Doku ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Levels ◽  
Zinc Homeostasis ◽  
Healthy Controls ◽  
Cell Disease ◽  
Flame Atomic Absorption ◽  
Iron Copper ◽  
Copper And Zinc

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and “healthy” controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA “healthy” controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their “healthy” counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

scholarly journals Serum Potassium, Sodium, and Chloride Levels in Sickle Cell Disease Patients and Healthy Controls: A Case-Control Study at Korle-Bu Teaching Hospital, Accra

2019 ◽  
Vol 14 ◽  
pp. 117727191987388
Author(s):  
Charles Antwi-Boasiako ◽  
Yaw A Kusi-Mensah ◽  
Charles Hayfron-Benjamin ◽  
Robert Aryee ◽  
Gifty Boatemaah Dankwah ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Sodium ◽  
Serum Potassium ◽  
Serum Levels ◽  
Case Control ◽  
Healthy Controls ◽  
Cell Disease ◽  
Serum Electrolyte ◽  
Flame Atomic Absorption

The activity of Na+-K+ ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. This study evaluated the serum levels of sodium, potassium, and chloride in patients with SCD. The study was a case-control cross-sectional study involving 120 SCD patients in the steady state and 48 ‘healthy’ controls. The SCD patients were made up of 69 HbSS patients and 41 HbSC patients. Serum electrolyte levels (Na+, K+, and Cl−) were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS; Varian Australia Pty Ltd). Serum sodium levels were significantly lower in the sickle cell patients, compared with their ‘healthy’ counterparts ( P = .0001). Although the study found significantly higher serum levels of potassium in the SCD patients ( P = .0001), there was no significant difference in serum chloride levels between patients with SCD and the controls ( P = .098). Serum sodium and chloride levels were not significantly different in both HbSS and HbSC patients ( P = .197 and P = .553, respectively). The level of serum potassium in the HbSS patients was, however, significantly higher compared with those with the HbSC genotype ( P = .0001). There is higher efflux of K+ from the intracellular into the extracellular space in HbSS patients, which may lead to red cell membrane dysfunction and associated complications.

scholarly journals Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

2021 ◽  
Vol 11 (9) ◽  
pp. 870
Author(s):  
Pia Proske ◽  
Laura Distelmaier ◽  
Carmen Aramayo-Singelmann ◽  
Nikolaos Koliastas ◽  
Antonella Iannaccone ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Neonatal Outcomes ◽  
University Hospital ◽  
High Rate ◽  
Successful Outcome ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
Tract Infections

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

scholarly journals Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 252 ◽  
Author(s):  
Cadiele Oliana Reichert ◽  
Carolina Garcia de Macedo ◽  
Débora Levy ◽  
Bruno Carnevale Sini ◽  
Andréia Moreira Monteiro ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Protective Factor ◽  
Plasma Cholesterol ◽  
Transferrin Saturation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Healthy Controls ◽  
Cell Disease ◽  
Q192r Polymorphism

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

2020 ◽  
pp. 001857872095417
Author(s):  
Katherine Rector ◽  
Shelby Merchant ◽  
Rachel Crawford ◽  
Justin R. Arnall ◽  
James Symanowski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Cell Disease ◽  
Median Length ◽  
Significant Difference ◽  
Oral Group ◽  
Icd 10 ◽  
Secondary Endpoints ◽  
Group 2

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Whole Blood Tissue Factor Procoagulant Activity Is Elevated in Patients With Sickle Cell Disease

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4216-4223 ◽  
Author(s):  
Nigel S. Key ◽  
Arne Slungaard ◽  
Luke Dandelet ◽  
Stephen C. Nelson ◽  
Christopher Moertel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Tissue Factor ◽  
Mononuclear Cell ◽  
Sickle Cell ◽  
Whole Blood ◽  
Procoagulant Activity ◽  
Cell Disease ◽  
Blood Samples ◽  
Significant Difference ◽  
Whole Blood Samples

Abstract We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P &lt; .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.

Cell Free Fetal and Total DNA Levels in Pregnancies at Risk of Sickle Cell Disease and Significant Ethnic Variation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3791-3791
Author(s):  
Ageliki Gerovassili ◽  
Kypros H. Nicolaides ◽  
Swee Lay Thein ◽  
David Rees
Keyword(s):  
At Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Globin Gene ◽  
Cell Disease ◽  
Maternal Weight ◽  
Chromosome 11 ◽  
Significant Difference ◽  
African Caribbean

Abstract Cell free (cf) DNA in maternal circulation is increasingly investigated in pregnancy. We aimed to determine if sickle cell trait women had quantitative differences of cfDNA with controls and if there was an ethnic difference between the cfDNA levels of Northern European and African/African-Caribbean populations. Non-invasive prenatal diagnosis through quantification of fetal and total cfDNA was tested in 33 pregnant women at risk of carrying a fetus affected with sickle cell disease and 124 control pregnancies. Fetal cfDNA assays were based on two Y chromosome specific markers (SRY and DYS14) and total cfDNA was based on the β-globin gene on chromosome 11. Maternal age (MA), gestation age (GA), fetal sex, storage time prior to extraction, maternal weight and body mass index (BMI) before pregnancy were compared to the fetal and total cfDNA levels. No significant difference in the fetal or total cfDNA levels was found between any of the control pregnancies and the sickle cell trait mothers carrying HbAA, HbAS and HbSS fetuses. However, higher levels of total cfDNA, but lower fetal cfDNA levels were observed in the African/African-Caribbean population compared with the Nothern Europeans. A significant variation in cfDNA was found between ethnic groups, which should be taken under consideration in future studies measuring cfDNA.

Impact of Hydroxyurea on Thrombin Antithrombin Complex and Vaso-Occlusive Crisis in Pediatric Sickle Cell Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5525-5525
Author(s):  
Mohsen Saleh Elalfy ◽  
Ashraf M. Abdelmonem ◽  
Soha Youssef ◽  
Heba Ismail
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Coagulation System ◽  
P Value ◽  
Cell Disease ◽  
Significant Difference ◽  
Healthy Control ◽  
Pain Crisis

Abstract Background: Several studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD). Aim: To analyze the effect of HU on Thrombin-Antithrombin (TAT) as a marker of thrombin generation and hypercoagualbility in SCD and to find out the relation between TAT level and vaso-occusive crisis. Subjects and Method: we evaluated 37 child with sickle cell hemoglobinopathy (mean age 10.92±5.39 years) and 15 normal control children (mean age 9.75±6.34 years). Informed consent was obtained from patients and/or guardians and study approval by local IRB was obtained. Twenty-two patients (59.5%) were on HU, 15 (41.5%) patients did not receive HU, 7 (46.7%) of them were transfusion dependant. TAT assay was done in vitro using a sandwich enzyme immunoassay. Results: Mean patients’ age at institution of HU was 8.54± 3.85 years with median treatment duration of 4.5 years. Causes for initiating HU therapy were frequent blood transfusion in 11 patients (50%), frequent pain crisis (≥ 3/year) in 9 patients (41%), severe anemia and parents refusing blood transfusion in 1 patient (4.5%) and stroke in another patient (4.5%). HU dose was 20.82±4.95 mg/kg/day. We measured TAT in all patients and compared them to healthy control. There was significant difference in TAT level in sickle cell patients (198.86±185.7) compared to healthy control 2.91±0.94, [P value < 0.0001]. When the level of TAT was compared between the HU and non-HU groups we found that patients on HU had statistically significant lower TAT level (172.36 vs.225.37) [P=0.039]. There was also a significant negative correlation between HU dose and TAT level (p=0.03). A significant positive correlation between number of vaso-occlusive crisis/year [P=0.03], frequency of pain crisis/year [P=0.04], duration of pain crisis [P=0.03] and TAT level was observed. Conclusion: Hydroxyurea has significant inhibitory effect on thrombogenesis in sickle cell patients, which may be another mechanism for reducing vaso-occlusive crisis. Sickle cell children with higher TAT level had more frequent and severe vaso-occlusive crisis.

The Protein C Pathway in Human and Murine Sickle Cell Disease: Alterations in Protein C, Thrombomodulin (TM), and Endothelial Protein C Receptor (EPCR) at Baseline and during Acute Vaso-Occlusion

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 538-538 ◽  
Author(s):  
Yihe Guo ◽  
Teresa Uy ◽  
Nancy Wandersee ◽  
J. Paul Scott ◽  
Hartmut Weiler ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mouse Liver ◽  
Protein C ◽  
Coagulation System ◽  
Activity Levels ◽  
Healthy Controls ◽  
Cell Disease ◽  
Endothelial Protein C Receptor ◽  
Protein C Activity

Abstract The coagulation system is activated in sickle cell disease (SCD) and acute vaso-occlusion may heighten hypercoagulability. Protein C, a natural anticoagulant, has been reported to be low in individuals with SCD. Therefore, the natural anticoagulation pathway may be disrupted in SCD. The objective of this study is to more fully evaluate the protein C pathway in murine and human SCD by examining levels of: coagulation activation; protein C activity; thrombomodulin (TM); and endothelial protein C receptor (EPCR). In order to assess the level of activation of the coagulation system, we measured plasma thrombin/antithrombin (TAT) complex levels in humans and mice. TAT levels were elevated in 22 humans with SCD versus 9 healthy controls at baseline, and levels increased further in 15 individuals with SCD during acute vaso-occlusive events (5.6±1.2 vs. 2.4±0.2 vs. 9.2±1.8ug/L respectively, p=0.02). In order to study acute vaso-occlusive events in mice, we developed a model of acute vaso-occlusion by exposing Berkeley SCD mice to 3 hours of hypoxia (FI02 8–10%) followed by 2, 4, or 21 hours of reoxygenation in room air (HR2, HR4, HR21). In support of our human findings, TAT was elevated in SCD mice compared to HbA mice at baseline, and increased further in SCD mice exposed to HR2 (n=5–14 per group, p&lt;0.001). Assessment of protein C activity levels in plasma revealed that humans (n=8) with SCD have lower protein C activity levels than healthy controls (n=10) (78%±8.7% vs. 107%±5.3%, p=0.01). Additionally, we are the first to report that protein C activity levels decrease further during acute vaso-occlusive events (paired samples in 7 individuals, p=0.01). Another key protein of the PC pathway is TM, an endothelial-bound protein which activates protein C. TM is elevated in several chronic inflammatory diseases and acutely decreases in meningococcemia. We evaluated TM in mouse liver, an organ susceptible to vascular congestion, infarction, and inflammation in SCD mice. We first measured TM in mouse liver homogenates by ELISA. All SCD mice, at baseline and after HR, expressed elevated liver TM levels compared to HbA mice (n=6 per group, 1.7 to 2.9-fold increases in SCD livers, p&lt;0.05). Exposure to HR in SCD mice increased hepatic inflammation and ischemia and decreased hepatic TM levels compared to SCD mice at baseline (HR2 84%, HR4 60%, and HR21 85% of baseline SCD liver TM). In preliminary experiments, Western Blot analysis confirmed high TM expression in mouse SCD livers compared to HbA livers at baseline and after HR. Immunohistochemistry demonstrated widespread, increased TM staining in hepatic parenchymal vessels of SCD mice compared to HbA mice both at baseline and after HR, with decreased staining within mature infarcts. 4) Finally, we studied EPCR, a membrane-bound protein that binds circulating protein C and promotes both anti-thrombotic and anti-inflammatory functions. Similar to TM, immunohistochemical staining for EPCR was more prominent in hepatic parenchymal vessels of SCD mice compared to HbA mice at baseline and after HR (preliminary studies, n=3 per group). In summary, these data confirm that SCD is a prothrombotic state and suggest that the protein C pathway is altered in SCD. TAT levels are elevated in human and murine SCD, and increase further during vaso-occlusion, illustrating that SCD is a hypercoagulable state. Protein C activity levels are low in human SCD and decrease further during vaso-occlusive events, suggesting that protein C may be consumed both chronically and acutely. In SCD mice at baseline, elevated expression of TM and EPCR suggests that there may be a chronic, compensatory up-regulation of these proteins in SCD. Finally, an acute consumptive process could account for the transient, decreasing trend of these natural anticoagulant proteins in SCD mice after exposure to HR. Thus, targeted administration of activated protein C may provide a novel therapy to minimize tissue injury during acute vaso-occlusive events in SCD.

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