Prolonged QTc in Sickle Cell Disease: A Potential Risk Factor for Early Death?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2476-2476
Author(s):  
Sean Lindstedt ◽  
Lynne Neumayr ◽  
Gregory Kurio ◽  
Claudia Morris ◽  
Shanda Robertson ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sudden Death ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Toxicity ◽  
Control Group ◽  
Cell Disease ◽  
Qtc Prolongation ◽  
Cardiac Iron

Abstract Background: Sudden unexplained death is one of the leading causes of mortality in sickle cell disease (SCD). Prolonged QTc has been associated with sudden death in older patients and in those with cardiac disease. Sudden death due to cardiac arrhythmias occurs in thalassemia (Thal) patients from cardiac iron toxicity, and recently, QTc prolongation has also been identified in this transfusion-dependent population. Chronic transfusion and iron overload have become more frequent in patients with SCD due to treatment regimens aimed at stroke prevention and treatment of stroke, pulmonary hypertension (PH) and recurrent vaso-occlusive crisis. Cardiac iron toxicity is thought to be rare in SCD but other factors such as anemia, PH, and hemolysis-associated nitric oxide dysregulation may predispose SCD to prolongation of the QTc interval. The purpose of this study was to examine the prevalence of QTc prolongation in chronically transfused and iron-overloaded SCD (txSCD) patients compared to a control group of non-transfused SCD patients. Methods: In this study, electrocardiograms (EKGs) were reviewed from SCD patients participating in the MCSIO, a five-year prospective study of the complications of iron toxicity in SCD and Thal. Using Bazett’s formula, a subset of 96 EKGs were analyzed for QTc prolongation, defined as ≥ 0.45 seconds and borderline as 0.44 to 0.449 seconds. Echocardiograms (ECHOs) obtained within an average of seven months were analyzed for left ventricular dysfunction (LVD) --which was defined as an ejection fraction < 55% or shortening fraction < 28% --and the presence of PH, defined as a tricuspid regurgitant jet velocity (TRJV) of ≥ 2.5 m/second. Results: There was no difference in mean age (25.3 ± 13.6) or gender (64% female) between the 65 txSCD and 31 control SCD patients. The txSCD group had been transfused 10 ± 6.2 years and their baseline ferritin was 3107 compared to 116 in the controls. QTc prolongation was present in 32% of the txSCD and 29% of the control group (n.s.); borderline prolongation was seen in an additional 17% and 13%, respectively. Mean QTc in txSCD was also not significantly different from the SCD controls: 0.45±.04 vs. 43±.03 (n.s.). None of the 68 patients with ECHOs had LVD. 36 patients had TRJV measured during the study: 50% of the txSCD had PH compared to 30% of non-transfused SCD (n.s.). The average QTc in PH patients was 0.45 ± .04 compared to 0.43 ± .04 in those without PH (p=.09). However, the frequency of either prolonged or borderline QTc was significantly higher in patients with PH (72% vs. 22%, p= .007). No correlations between QTc and age, gender, or baseline laboratory values (hemoglobin, white blood count, or platelets) were found. In the txSCD, QTc was not correlated to ferritin or years of transfusion. Conclusions: Overall, QTc prolongation was found in 31 % of SCD patients and borderline prolongation in an additional 16%. QTc intervals ≥ 0.44 were more common in patients with PH. Transfusion exposure and iron overload were not associated with QTc prolongation in this group of txSCD patients. The frequency of QTc prolongation is concerning in SCD patients, who often have pulmonary hypertension and are treated with medications known to contribute to QTc prolongation. Routine screening for QTc prolongation appears warranted with treatment of high-risk SCD patients.

scholarly journals Assessment of Iron Overload Impact on QTc Interval in Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3673-3673
Author(s):  
Gilbert Bader ◽  
Gregory J. Kato ◽  
Suvankar Majumdar ◽  
James Pollard ◽  
Jarrod Knudson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Research Funding ◽  
Iron Toxicity ◽  
Conduction Delay ◽  
P Value ◽  
Qtc Interval ◽  
Cell Disease ◽  
Qtc Prolongation

Abstract Ischemic injuries and subsequent degenerative myocardial and conduction system abnormalities occur in patients with sickle cell disease (SCD). This may lead to conduction and repolarization delays reflected as QTc prolongation. Patients with SCD have increased risk of cardiac death, the basis of which remains uncertain. QTc prolongation may be a contributing factor. We decided to examine factors that can potentiate QTc prolongation in this population. In particular, we studied effect of iron overload estimated by serum Ferritin level on QTc. We performed a cross-sectional study in SCD patients older than 18 years, in steady state, followed in our clinic. Patients with acute illness or vaso-occlusive crisis in prior 2 weeks, patients with bundle branch block, pacemaker or arrhythmia and patients unable to give consent were excluded. Prolonged QTC was defined as >450 and >460 ms in men and women respectively. Patients were divided into 3 groups corresponding to mild, moderate and severe iron overload with Ferritin < 1000, between 1000 and 3000 and > 3000 ng/mL respectively. QTc was prolonged in 25/177 patients (14%). Those were older (p=0.041), had lower hemoglobin (Hb) (p<0.001) and higher Ferritin (p=0.019). Their mean age was 33.8 years, Hb 8.26 g/dL and Ferritin 3167 ng/mL compared to 29.2, 9.58 and 1735 respectively in patients with normal QTc. Twenty eight % of patients with prolonged QTc had comorbidities compared to 9% of patients with normal QTc (p=0.004). There was no difference between the 2 groups regarding gender, weight, blood pressure, Lactate dehydrogenase, electrolytes, Reticulocytes count or use of medications known to prolong QTc. Mean QTC was 429, 438 and 440 ms in groups 1,2 and 3 respectively (p=0.013). Linear regression analysis showed that QTc is expected to be longer in groups 2 and 3 compared to group 1. We also estimated QTc prolongation corresponding to 500 unit increment in Ferritin. QTc is expected to get prolonged by 0.83 ms for each 500 unit increment of Ferritin with p value of 0.028 in unadjusted model and by 0.79 ms with p value of 0.035 and 0.67 ms with p value of 0.085 in models where age and comorbidities were adjusted for respectively. Hb was found to be inversely correlated with Ferritin. Correlation coefficient was -0.39 with p value < 0.001. Although there was no significant correlation between Ferritin and JTc, analysis showed that QRS is expected to increase by 0.33 ms for each 500 unit increment in Ferritin with p value of 0.022. Comorbidities including diabetes mellitus, kidney and heart disease are known independent factors that can cause QTC prolongation. QTc increases with age. However, this mainly applies to people older than 50 years (J Geriatric Cardiol 2016 Sep;13(9):740-8). We don't believe age is an independent QTc prolonging factor in our patients especially that mean age of patients with prolonged QTc was 33.87 years. Probably older patients had longer exposure to iron toxicity which may be the true contributing factor to QTc prolongation. Patients with prolonged QTc had lower Hb. However, no correlation was found between Hb and QTc in patients with anemia caused by conditions other than SCD (Chin Med J 2015 Dec 20;128(24):3385-6). In addition, major cause of tissue injury in SCD patients is intracellular polymerization of HbS. However, there is no correlation between Hb concentration and intracellular HbS polymer content (Blood 1998 Mar 1;91(5):1777-83). Thus, we don't think Hb is an independent QTc prolonging factor. Probably patients with lower Hb received more transfusions and subsequently had more pronounced iron overload which may be the direct contributing factor to QTc prolongation. The negative correlation between Hb and Ferritin supports our hypothesis. Thus, we think that the model where just comorbidities were adjusted for is the best to reflect the association between Ferritin and QTc. Iron overload reduces overshoot ( Circulation 1999 Aug 10;100(6):675-83) which will compromise propagation of cardiac impulse and result in conduction delay. Iron also leads to production of free radicals. That will cause chronic inflammation and fibrosis. We showed that QRS is expected to get prolonged with iron overload in SCD patients which is consistent with the physiology of iron toxicity. QTc prolongation seems to be associated with iron overload in SCD patients. Conduction delay manifested by prolonged QRS may be the main contributor rather than repolarization delay. Disclosures Bader: NIMHD: Research Funding. Majumdar:NIMHD: Research Funding. Maher:NIMHD: Research Funding.

Lack of Cardiac Iron in SCD Patients Despite Severe Iron Overload

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4943-4943
Author(s):  
Rasha I Ahmad ◽  
Sara Keyrouz ◽  
Mariam Arabi ◽  
Fadi Bitar ◽  
Wael al Jaroudi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Cardiac Involvement ◽  
Dry Weight ◽  
Iron Deposit ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Male Sibling

Abstract In sickle cell disease (SCD), transfusions improve blood flow by reducing the proportion of red cells capable of forming sickle hemoglobin polymer. The major and unavoidable complication of transfusions in SCD is iron overload. Patients with significant transfusion load and iron siderosis, often have iron deposit into multi organs, including liver, pancreas and heart. However, patients with SCD may be relatively protected from iron mediated cardiac toxicity as compared to patients with thalassemia and similar transfusion load. Nonetheless while patients with SCD have less iron deposition in the heart it is presumed that severe loading will eventually lead to cardiac involvement. We report here two patients with scd with severe iron overload who had no cardiac involvement. These are an 18 year old female and her 20 year old male sibling, known to have SCD (HbSS) with significant blood transfusions history, once a month or every two weeks for 12 years duration. Both had undergone splenectomy, and multiple hospitalizations for pain crises and acute chest syndrome. They had received intermittent iron chelation therapy for only 2 years. Examination revealed marked hepatomegaly and highly elevated ferritin levels, 11964ng/ml and 7098ng/ml respectively, suggestive of iron overload. Both patients had unremarkable electrocardiogram and echocardiogram. SGPT and SGOT are normal. Both patients are below the 5thpercentile for height, and l the 18 year old girl is pre-pubertal, has growth hormone deficiency and is on treatment. Cardiac, liver and pancreas magnetic resonance imaging with T2* showed normal cardiac structure and function without siderosis ( heart T2*32 ms and 35 ms in the female and male siblings, respectively [normal >20 ms]). There was however considerable liver siderosis with estimated liver iron content 16.6±4.4 mg/g dry weight (female sibling) and 13.9±1.8 mg/g dry weight (male sibling). The corresponding R2* were 646±165 HZ and 541±62 Hz, respectively. Also, there was mild to moderate pancreatic siderosis in the 18 year old female (R2* 111 HZ) and mild pancreatic siderosis in her sibling (R2* 55 Hz) These two cases while consistent with what has been reported are unusual because of the degree of iron ovreloead. It is an unexepected finding that despite such extensive iron deposits in the liver, there is no evidence of cardiac iron. It thus seems that in patients with sickle cell disease, even with extensive liver siderosis and endocrine dysfunction there is sparing of the heart. Collecting and studying such cases may shed light on the mecahins of cardiac protection from iron overload in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Alloimmunization in Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3251-3251
Author(s):  
Dipanjan Debnath ◽  
Hedy P Smith ◽  
Cathy Conry-Cantilena ◽  
Valentina Baez Sosa
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Health System ◽  
Sickle Cell ◽  
Organ Damage ◽  
Cell Disease ◽  
Academic Health ◽  
End Organ Damage ◽  
The Mean

Abstract INTRODUCTION Blood transfusion is an essential therapeutic and prophylactic component in the management of sickle cell disease (SCD) and associated complications. Prolonged transfusion therapy can lead to the development of antibodies to the donor's RBC antigens (alloimmunization), causing complications such as delayed hemolytic transfusion reactions, hyperhemolysis, worsening vaso-occlusive episodes, and end-organ damage. There have been only a few case series highlighting the impact of RBC alloimmunization on SCD morbidity and mortality, proposing a pathway involving RBC alloimmunization and decreased survival associated with hemolytic reactions or difficulty obtaining compatible blood when needed. However, apart from the consequences of iron overload, there is no long-term data for alloimmunization highlighting the clinical consequences, multiorgan damage, or associated morbidity in sickle cell patients. AIM The primary aim is to investigate the incidence of alloimmunization in SCD patients in an academic health system. The secondary aim is to elucidate the differences in demographics, frequency of vaso-occlusive crisis, end-organ damage, and inflammatory markers between alloimmunized and non-alloimmunized SCD patients. METHODS We conducted a retrospective multicentric descriptive study, including all sickle cell patients treated in an academic health system from January 1st, 2009, to December 31st, 2020, in Maryland, Virginia, and Washington, DC. An exemption from the Institutional Review Board for obtaining individual subjects' consent was procured. Patients included in the study were older than 18 years and diagnosed with sickle cell disease. Patients who did not have sickle cell disease were excluded from the study. Statistical analysis was reported using means for descriptive data, t-test for continuous variables, and chi-square for categorical variables. RESULTS A total of 94 patients with sickle cell disease were included in the study. Of these, 24 (25.5%) patients were found to have alloimmunization, whereas 70 (74.4%) patients did not. Of the alloimmunized patients, the average age, BMI and BSA were 30.15 years (p=0.037), 23.15 kg/m2 (p=0.040), and 1.65 m2 (p=0.003) compared to 37.07 years, 26.17 kg/m2 and, 1.84 m2 respectively among the non-alloimmunized group. 83% of the alloimmunized patients had sickle cell anemia (Hb SS), and 17% had a sickle thalassemia phenotype (p=0.005). A lower baseline hemoglobin (Hb) value of 8.01 g/dL was seen among alloimmunized patients compared to a higher Hb value of 9.63 g/dL (p=0.001) among the non-alloimmunized. Alloimmunized patients had an average of 5.55 alloantibodies. The average number of vaso-occlusive crises per year and related hospitalizations was statistically significantly higher in the alloimmunized group with 4.82 and 3.78, respectively, compared to 2.34 (p=0.035) 1.01 (p=0.0005) in the non-alloimmunized group. Similarly, the incidence of other sickle cell-related complications were higher among the alloimmunized patients, such as priapism (29% vs. 9%; p=0.0139), pulmonary hypertension (38% vs. 9%; p=0.0038) with no statistical difference in the iron overload (25% vs. 11%; p=0.150) or ferritin levels (. 83% of alloimmunized patients had a history of narcotic use vs. 34% among the non-alloimmunized (p=0.0001). Higher use of disease-modifying therapies including hydroxyurea (71% vs. 31%; p=0.0009) and voxelotor (13%vs0; p=0.0029), were also seen among alloimmunized patients. While no statistically significant difference was seen in the mean number of lifetime transfusions, there was a difference in the mean number of lifetime exchanges (3.67 vs. 0.0; p=0.0208). CONCLUSION The prevalence of alloimmunization in sickle cell patients in our study population (25.5%) was higher than in the literature (7- 59%) and the general population (2%). An increase in alloimmunization was associated with an increased number of exchanges but not with simple transfusions. Independent from the iron overload, alloimmunization was associated with increasing end-organ damage and sickle cell complications such as priapism, pulmonary hypertension. Strategies to decrease alloimmunization are needed to prevent these complications. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its correlation to myocardial iron overload

2020 ◽  
Author(s):  
Tamer Hassan ◽  
Mohamed Badr ◽  
Mohamed Arafa ◽  
Doaa Abdel Rahman ◽  
Manar Fathy ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Restrictive Cardiomyopathy ◽  
Myocardial Iron ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in LV remodeling. We aimed to detect plasma levels of MMP-9 in patients with SCD and its correlation to myocardial iron overload. A case control study was carried out on 50 patients with SCD and 50 age and sex matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using ELISA. SCD patients had significantly higher levels of MMP-9 than controls. There was highly significant correlation between plasma levels of MMP-9 and serum ferritin. Patients with vaso-occlusive crises (VOC) > 5/year had significantly higher levels of MMP-9 than those with VOC ≤ 5 /year. No significant correlation was found between MMP-9 and cardiac T2*. MMP-9 seems to be a useful marker in SCD patients. Patients with serum ferritin > 1000 ng/ml, recurrent VOC > 5 /year had significantly higher MMP-9 serum levels than others.

Cardiac Iron Overload In Sickle-Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1013-1013
Author(s):  
Antonella Meloni ◽  
Mammen Puliyel ◽  
Alessia Pepe ◽  
Massimo Lombardi ◽  
Vasilios Berdoukas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Clinical Characteristics ◽  
Transferrin Saturation ◽  
Thalassemia Major ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Introduction Chronically transfused sickle cell disease (SCD) patients have lower risk of endocrine and cardiac iron overload load than comparably transfused thalassemia major patients. The mechanisms for this protection remain controversial but likely reflects lower transferrin saturation and circulating labile iron pools because of chronic inflammation and regeneration of apotransferrin through erythropoiesis. However, cardioprotection is incomplete; we have identified 6 patients out of the 201 patients (3%) followed at our Institution who have prospectively developed cardiac iron. We present the clinical characteristics of these patients to identify potential risk factors for cardiac iron accumulation. Methods Cardiac, hepatic, and pancreatic iron overload were assessed by R2* Magnetic Resonance Imaging (MRI) techniques as extensively described by our laboratory. The medical records of the selected patients were reviewed for demographic data, for transfusion and chelation history and for hematologic and biochemical parameters. Results Table 1 describes clinical characteristics of the six patients at the time they developed detectable cardiac iron (R2* ≥ 50 ms). Patient 6 was included because he showed a R2* of 49 Hz that was increasing rapidly. Five of the six patients were managed on simple transfusions. Five patients had been on chronic transfusion for more than 11 years. The three patients who developed cardiac iron the earliest (3.7 – 14 years of transfusions) had more efficient suppression of endogenous red cell production (HbS levels 2-5%) compared with patients who required longer transfusional exposure (HbS levels 13.3 – 41%). All patients had qualitatively poor chelation compliance (<50%), based upon their prescription refill rate. All patients had serum ferritin levels exceeding 4600 and liver iron concentration (LIC) greater than 22 mg/g. Pancreatic R2* was greater than 100 Hz in every patient studied (5/6). Figure 1 shows the longitudinal relationship between iron overload in the heart and in the other organs for each patient; initial iron levels are shown in black. Cardiac R2* appears increase dramatically once a critical LIC “threshold” is reached, qualitatively similar to the 18 mg/g threshold observed in thalassemia major patients. Cardiac R2* rose proportionally to pancreas R2*, similar to thalassemia major patients, with all of the patients having pancreas R2* > 100 Hz at the time cardiac iron was detected. Conclusions Cardiac iron overload occurs in a small percentage of chronically transfused SCD patients and is only associated with exceptionally poor control of total body iron stores. Duration of chronic transfusion is clearly important but other factors, such as levels of effective erythropoiesis, may also contribute to cardiac risk. The relationship between cardiac iron and pancreas R2* suggests that pancreas R2* can serve as a valuable screening tool for cardiac iron in SCD patients. Disclosures: Berdoukas: ApoPharma inc: Consultancy. Coates:ApoPharma inc, Novartis, Shire: Consultancy. Wood:Novartis: Consultancy, Honoraria; Shire: Consultancy, Research Funding; ApoPharma: Consultancy, Honoraria, Use of deferiprone in myocardial infarction, Use of deferiprone in myocardial infarction Patents & Royalties.

scholarly journals Cardiac Iron Overload in Sickle Cell Disease: When to Screen and How to Intervene

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 528-528
Author(s):  
Amy Y Tang ◽  
Cassandra D Josephson ◽  
Kristina Lai ◽  
Peter A. Lane ◽  
Ross M. Fasano
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Clinical Characteristics ◽  
Iron Loading ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Cardiac Iron ◽  
Cardiac Iron Overload

Abstract Background Iron overload is a recognized consequence of chronic transfusion therapy in patients with sickle cell disease (SCD), but most of the focus to date has been on the effects of increased liver iron concentration (LIC) with increasing transfusion burden. Even though there is a robust body of literature concerning cardiac iron overload (CIO) in patients with thalassemia major, there remains a paucity of data in how to detect and treat CIO in patients with SCD, particularly in the pediatric and young adult population. While CIO is seen less commonly in sickle cell disease than in thalassemia, patients with SCD remain at risk, with recent studies demonstrating an incidence of 2-5% of CIO in chronically transfused patients with SCD. We performed a retrospective chart review of patients with cardiac MRIs (cMRIs) and LICs by Ferriscan performed at our institution to identify risk factors for CIO, as well as to characterize institutional practice for assessing cardiac iron in the absence of defined practice guidelines. Methods We reviewed clinical characteristics of all patients with SCD who had cMRIs performed at Children's Healthcare of Atlanta between June 2012 and December 2017. We then queried our institutional sickle cell database for patients who were at least 3 years old in 2010, genotype SS or S Beta zero thalassemia, were on chronic transfusions for at least 5 years by 2017, and had not undergone a cMRI. Patients who were status post bone marrow transplant were excluded. For comparison of age, average ferritin, and transfusion duration, significance among means between patients with and without CIO was calculated using a two-tailed unpaired t-test. For comparison of LIC, significance among medians was calculated using the Mann Whitney test. A p value of <0.05 was considered significant. Statistical analyses were performed using Prism 6 (GraphPad Software, Inc.). Results Of 36 evaluable patients who had undergone cMRI, there were 11 with CIO, as defined by a T2* < 20ms. Clinical characteristics are shown in Figure 1. Patients were 7-28 years of age, and had received chronic transfusion therapy for a range of 22 months to 228 months. Between patients who did and did not have CIO, there was no significant difference in average 1-year ferritin level (6786 vs 6373 ng/mL, p=0.79), transfusion duration (103 vs 123 months, p=0.41), or age (15 vs 18 years, p=0.12). There was a higher median LIC by Ferriscan of > 43 mg/g in those with CIO vs 34 mg/g in those without CIO, although this was not statistically significant (Figure 1). Interestingly, CIO was seen as young as 7 years of age and after as little as 22 months of chronic transfusions, and with concurrent LIC values as low as 8.1 mg/g. Of the 11 patients with CIO, 6 had follow-up cMRI data available, and all 6 had normalization of cardiac iron (T2* > 20ms) on subsequent MRIs (Figure 2 and Table 2). There was 1 patient who did not have full transfusion and chelation history available for analysis. Of the remaining 5, 5/5 had increased or more aggressive chelation added, including 2 who were started on high-dose IV Desferal every 2 weeks; 3/5 also had partial manual exchange (PME) added to their chronic transfusion regimens. There were 80 patients who were on chronic transfusions but did not have a cMRI performed; as a group, they had a median LIC of 17 mg/g (range: 1.7 - >43 mg/g), an average 1-year ferritin of 3641 ng/mL (range: 520 - 8478 ng/mL), and had been on chronic transfusions for a mean of 87 months at time of Ferriscan study (range: 14 - 192 months). Overall, these patients had a lower transfusion burden than those who received cMRIs, but there were several in this group who had significant iron overload, including 10 who had LIC values of > 43mg/g. Conclusion CIO in SCD may be a more salient issue, and occur earlier, than previously described. We did not find a strong relationship between CIO and ferritin levels or LIC by Ferriscan, but we did find that CIO was reversible with more aggressive chelation or the addition of PME. While guidelines for monitoring for CIO in SCD are largely extrapolated from thalassemia data, the rate and physiology of iron loading may be completely different. Due to a paucity of information in this area, more studies are needed to guide screening and to fully assess risk factors that may put certain individuals more at risk for cardiac iron loading. Disclosures No relevant conflicts of interest to declare.

scholarly journals Iron overload parameters and early detection of cardiac disease among Egyptian children and young adults with β-thalassaemia major and sickle cell disease: a cross-sectional study

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1108
Author(s):  
Khaled Salama ◽  
Amina Abdelsalam ◽  
Hadeel Seif Eldin ◽  
Eman Youness ◽  
Yasmeen Selim ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Iron Overload ◽  
Sickle Cell ◽  
Systolic Pulmonary Artery Pressure ◽  
Thalassaemia Major ◽  
Cell Disease ◽  
Cardiac Iron ◽  
Diastolic Velocity ◽  
Egyptian Children

Background: Cardiac, hepatic and pancreatic T2* measured by magnetic resonance imaging (MRI) has been proven to be an accurate and non-invasive method for measuring iron overload in iron overload conditions. There is accumulating evidence that pancreatic iron can predict cardiac iron in young children because the pancreas loads earlier than the heart. The aim of our study was to investigate cardiac function and cardiac iron and their relation to pancreatic iron among patients with β-thalassaemia major (βTM) and sickle cell disease (SCD). Methods: 40 βTM and 20 transfusion-dependant SCD patients were included along with 60 healthy age-matched controls. Echocardiography and Tissue Doppler Imaging were performed for all subjects as well as the control group.  Hepatic, cardiac and pancreatic iron overload in cases were assessed by MRI T2*. Results: The study group consisted of 40 βTM and 20 transfusion dependant SCD patients with mean age 13.7 years and mean frequency of transfusion/year 12. Mean cardiac T2* was 32.9 ms and mean myocardial iron concentration was 0.7 mg/g; One patient had cardiac iron overload of moderate severity. Mean pancreatic T2* was 22.3 ms with 20 patients having mild pancreatic iron overload. Pancreatic T2* correlated positively with main pulmonary artery diameter (p=0.046), peak late diastolic velocity at septal mitral annulus (p=0.038), peak early diastolic velocity at tricuspid annulus (p=0.001) and mitral annular plane systolic excursion (p=0.01); and negatively with end systolic pulmonary artery pressure (p=0.007). We couldn’t test the predictability of pancreatic T2* in relation to cardiac T2* as only one patient had cardiac T2*<20 ms. Conclusion: Assessment of pancreatic T2* in multi-transfused patients with βTM and SCD can predict myocardial dysfunction. No direct relation between pancreatic iron and cardiac siderosis was detected.

Mortality in Sickle Cell Patient Transitioning from Pediatric to Adult Program: 10 Years Grady Comprehensive Sickle Cell Center Experience.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1426-1426 ◽  
Author(s):  
Si mbo O Aduloju ◽  
Sheila Palmer ◽  
James R. Eckman
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Mortality Rate ◽  
Sudden Death ◽  
Iron Overload ◽  
Organ Failure ◽  
Cause Of Death ◽  
Sickle Cell ◽  
Cell Disease ◽  
Adult Care

Abstract Over the last three decades there has been improvement in survival in children with sickle cell disease. Overall survival from birth to age 18 of 86% and 95% has been reported in children with sickle cell anemia (HbSS) and sickle hemoglobin C (Hb SC) disease respectively. These encouraging results are secondary to initiation of preventive measures like newborn screening, penicillin prophylaxis, immunization and stroke prevention and other supportive therapies. Ballas (Blood2004;104 supl:Abstr 3743) reported high death rate for young adults with the disease. To determine the death rates and cause of death in our population, we did a retrospective review of our patients who had recently transitioned into adult care. Mortality rate and circumstances of death in a 10 year period of transition from pediatric to adult program in Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital between 1996 and 2006 were determined. Total number of deaths was obtained from the clinical database. Death, autopsy and medical records were reviewed to determine the cause and circumstances of death. Between 1996 and 2006, 387 young adults with sickle cell disease (HbSS, HbSC, HbS beta thalassemia) transitioned to the adult program at age 18. Twenty two (5.8%) patients died during their first 10 years of transition. Mean age at death was 23.4 (range 21.6–26) and male to female ratio was 1.2 to 1. Ten patients (45%) died due to chronic organ failure all due to chronic iron overload (end stage liver disease in 8 and congestive heart failure in 2). Eight patients (36%) died due to complications of acute vaso-occlusive crisis (sudden death in 4, acute chest/multi-organ failure in 4) while 4 patients (18%) died of non-sickle related causes. Three of four who died of sudden death has documented pulmonary hypertension. Our mortality rate is lower than those reported by Ballas with the most common cause of death being complications of iron overload in chronically transfused patients. Specific interventions targeted at improving management of iron overload need to be developed for the increasing numbers of patients on chronic transfusion transitioning into adult care.

Placental Growth Factor Is Elevated in Patients with Sickle Cell Disease and Associated with Pulmonary Hypertension, Hemolysis, Inflammation, Iron Overload, and Hepatic Dysfunction.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1531-1531
Author(s):  
Laurel Mendelsohn ◽  
Anitaben Tailor ◽  
Gregory J Kato
Keyword(s):  
Pulmonary Hypertension ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Hepatic Dysfunction ◽  
Transferrin Saturation ◽  
Placental Growth Factor ◽  
Cell Disease ◽  
Pulmonary Pressure

Abstract Abstract 1531 Poster Board I-554 Placental Growth Factor (PlGF) is a functional cytokine in the vascular endothelial growth factor (VEGF) family that generally promotes angiogenesis, depending on the specific context, and can also promote atherogenesis. Produced in erythroid cells, its level in patients with sickle cell disease (SCD) has been previously related to the rate of erythropoiesis. We evaluated PlGF plasma levels in SCD patients by ELISA, and related it to biomarkers of pulmonary hypertension (PH), an emerging and serious complication of SCD linked to early mortality. We find that PlGF levels are significantly higher in SCD (n=95) than healthy African American control subjects (n=19) (median 16.6 vs. 2.1 pg/mL, p<0.001). PlGF levels were higher in SCD patients with elevated pulmonary pressure (normal pulmonary pressure vs. mildly elevated vs. highly elevated: medians 13.7 vs. 16.7 vs. 19.8 pg/mL, p<0.0001). Supporting a linkage to rate of hemolysis, PlGF correlated with LDH (p=0.001) and inversely with hemoglobin level (p<0.0001). Suggesting a link to inflammation, PlGF correlated significantly with C-reactive protein (p=0.001) and erythrocyte sedimentation rate (p<0.001). PlGF correlated with markers of iron overload, including ferritin, transferrin saturation and inversely with transferrin (all p<0.001). Finally, PlGF correlated with markers of hepatic dysfunction, including low albumin and high direct bilirubin (p<0.001). We found significantly higher PlGF levels in SCD patients taking hydroxyurea compared to those not taking it (median 17.4 vs. 14.0 pg/ml, p<0.01). Confirming that hydroxyurea increases PlGF levels, in a separate cohort of seven patients, PlGF levels rose significantly from their baseline values after initiating hydroxyurea (median approx 22 vs. 27, p<0.05). Our data suggest that elevated PlGF level is associated with PH in patients with SCD, and PlGF is correlated with severity of hemolysis, inflammation, iron overload and hepatic dysfunction. Considering the variable evidence in the literature for either stimulating or inhibiting angiogenesis, it is not clear whether pathologic elevation of PlGF may be mediating pulmonary hypertension, or perhaps conversely providing an adaptive response to vascular damage. It has been suggested by Perelman et al. that PlGF may mediate leukocyte activation that might promote disease severity in SCD. However, hydroxyurea, which tends to ameliorate SCD complications, stimulates PlGF level in an unexpected manner, possibly related to the ability of hydroxyurea to stimulate erythropoietin production, which might in turn induce PlGF. Further research is needed to reconcile the role of PlGF in PH in SCD. Disclosures Tailor: Mesoscale: Employment.

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