Poor Access to Care Is a Risk Factor for Iron Overload in Adults with Sickle Cell Disease in Southern California

Abstract The lack of access to quality comprehensive care is a major problem for adults with sickle cell disease (SCD) and contributes to increased morbidity and mortality. This problem is especially acute in Los Angeles where the average lifespan is 10 years shorter than the national average. Without access to disease modifying therapies, patients utilize Emergency Department services and are repeatedly hospitalized. During inpatient stays many may be inappropriately transfused. The result can be severe iron overload, a significant cause of morbidity and mortality. Inattention to iron chelation in patients who are not cared for by knowledgeable SCD providers perpetuates this issue. In 2016 we cared for a new patient at our clinic in South Los Angeles who previously had a liver transplant due iron overload. This patient received multiple transfusions during her lifetime and was never seen in a comprehensive SCD clinic. This experience prompted us to evaluate our population of clinic patients to assess how lack of access to care might be a risk factor for iron overload. Methods: We performed a chart review of all patients with SCD who presented to either of two adult sickle cell clinics in Southern California: MLK Jr. Outpatient Center in Los Angeles and Center for Inherited Blood Disorders (CIBD) in Orange. We examined records from 2013-2018 from CIBD and from 2016-2018 from MLK. Patients were considered evaluable if they had a least one visit to clinic with labs that included iron studies and /or MRI. Iron saturations greater than 50% and /or a ferritin greater than 1000 was deemed indicative of iron overload when combined with a history of prior transfusions. Lack of access was defined as the absence of appropriate care for SCD for at least 12 months prior to the initial visit in our clinics. Patients were deemed in good SCD care if they had been transitioned from a pediatric SCD program or another adult SCD program where they received team based comprehensive services. Results: 74 patients were able to be evaluated. (Table 1). 53 patients were Hgb SS. Of those, 27 (50.9%) were not receiving appropriate SCD care for the prior 12 months when they first presented, 20 (74.1%) of those patients were iron overloaded. There were 9 patients with Hgb S/beta thalassemia 0 or +. Five (55.6%) of those patients were not receiving appropriate SCD care for the prior 12 months; one (35.6%) was iron overloaded. 12 patients had Hgb SC. Although 5 (41.7%) were not receiving appropriate SCD care at the time of presentation, none had evidence of iron overload. Using these data, the odds ratio of having iron overload if a patient was out of appropriate SCD care for the 12 months prior to evaluation was 6.8 (95% confidence interval 2,23.13), indicating that being out of good care is a risk factor for iron overload. Discussion: Although guidelines exist to prevent unnecessary transfusions in adult patients with SCD; lack of access to knowledgeable providers both in the inpatient and outpatient setting places them at a nearly 7 times higher risk for iron overload, a serious and preventable comorbidity. Our study indicates that many adults with SCD are not appropriately monitored or treated for transfusion related iron overload using guideline-based care, placing avoidable burdens on individual health and adding to healthcare costs. Further education of providers to address this issue is warranted. Disclosures Baker: Genentech: Research Funding.

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Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease

Seminars in Hematology ◽

10.1053/shem.2001.20142 ◽

2001 ◽

Vol 38 (1, Suppl 1) ◽

pp. 30-36 ◽

Cited By ~ 14

Author(s):

Samir K. Ballas

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Adult Patients ◽

Morbidity And Mortality ◽

Cell Disease

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Transfusional Iron Overload In An Adult Sickle Cell Disease Population: Epidemiology, Prevalence, and Management

Blood ◽

10.1182/blood.v122.21.1005.1005 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1005-1005 ◽

Cited By ~ 1

Author(s):

James Son ◽

Hongyan Xu ◽

Nadine J Barrett ◽

Leigh G Wells ◽

Latanya Bowman ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Chelation Therapy ◽

Organ Damage ◽

Morbidity And Mortality ◽

Genotype Distribution ◽

Cell Disease ◽

The Mean

Abstract Transfusional iron (Fe) overload remains a significant problem among patients with chronic, transfusion dependent anemias, especially in transfusion dependent ß-thalassemia (Thal) syndromes. If not treated vigorously with chelation, Fe overload in Thal is associated with significant organ damage, especially with chronic liver disease and cardiac abnormalities which can contribute to morbidity and mortality. In recent decades, the significance of Fe overload in sickle cell disease (SCD) has also been recognized especially among pediatric patients on chronic transfusion regimens predominantly for primary and secondary prevention of stroke. The prevalence and significance of this problem among adult SCD patients is less clear, although it is widely believed that episodic, mostly unnecessary transfusion practices play a more prominent role in this patient population. There have been reports of an association between iron overload and increased morbidity and mortality among adult SCD patients; it has also been speculated that the chronic inflammatory state that exists in SCD affords some degree of protection against severe organ damage through upregulation of hepcidin and sequestration of Fe in these patients. We performed a retrospective review of 635 adult SCD patients followed at our Center to define and ascertain the epidemiology, prevalence, etiology, and clinical correlates of transfusional Fe overload. Fe overload was defined as two consecutive serum ferritin values of > 1000 ng/ml. 80 patients (12.6%) met this criterion. Of these, 38 were male and 42 were female. Genotype distribution was: 73 SS, 3 S-β+ thal, 2 S-β0 thal and 2 SC. The mean age was 35.9 (range 18-69). Out of the 80 patients with transfusional Fe overload, 24 (30%) were/had been on a chronic transfusion regimen (23 for secondary or primary stroke prevention and one for childhood cardiomyopathy). Seventy percent of the patients (n=56) developed Fe overload from episodic transfusions predominantly performed at outlying community hospitals. The mean highest ferritin value was 4991 ng/ml (range 1,052-16,500). There was no correlation between ferritin levels and the number of hospitalizations or painful episodes (p=0.9). Thirty seven patients (46.2%) had a history of chelation therapy (with desferoxamine, deferasirox, or both). In 25 patients who have been on deferasirox for a period of 6 months or more, serum ferritin levels decreased from 4452.3 to 3876.6 ng/ml (p=0.3239). Our retrospective study shows that transfusional Fe overload is not rare among adults with SCD and develops predominantly as a result of episodic blood transfusions. This underscores the importance of the development and dissemination of evidence based guidelines, especially for episodic transfusions in SCD. A careful study of the extent and degree of organ damage associated with transfusional Fe overload in SCD and why less than half (46.2%) of patients are exposed to chelation therapy needs to be done. These studies should include liver iron concentration (LIC), cardiac iron and liver histology, when indicated, in parallel with serum hepcidin levels. The fact that the reduction in serum ferritin levels with deferasirox did not reach statistical significance in this cohort can be explained by the relatively small number of patients as well as by the short period (6 months) of exposure to chelation therapy. Disclosures: No relevant conflicts of interest to declare.

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Disseminated Mycobacterium avium infection in a young woman with sickle cell disease and iatrogenic iron overload

Case Reports in Internal Medicine ◽

10.5430/crim.v8n2p5 ◽

2021 ◽

Vol 8 (2) ◽

pp. 5

Author(s):

Pouria Hosseini ◽

Yogamaya Mantha ◽

Shannon J Koh ◽

Gebre K Tseggay ◽

Jyothi K Baby ◽

...

Keyword(s):

Risk Factor ◽

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Case Reports ◽

Recurrent Pain ◽

Cell Disease ◽

Increased Risk ◽

Avium Infection ◽

Immunosuppressed Patients

A 29-year-old woman with known sickle cell disease (SCD) and iatrogenic iron overload presented to the emergency department with a recurrent pain crisis and fever. Blood cultures obtained at a recent prior admission for the same complaints grew M avium. Bone marrow biopsy revealed non-caseating granulomas, but stains for mycobacteria and fungi were negative. Disseminated non-tuberculous mycobacterial infections (NTMIs) occur almost exclusively in immunosuppressed patients. SCD is not considered a risk factor for the development of disseminated NTMIs, making diagnosis challenging in this population. However, a number of case reports describing disseminated NTMIs in patients with SCD have been published. This case adds to the current literature, suggesting SCD with iatrogenic iron overload is a possible risk factor for disseminated NTMIs. Potential mechanisms for this increased risk include 1) functional asplenia, 2) iatrogenic iron overload, 3) chronic indwelling central venous catheters, and 4) hydroxyurea use. Further investigation is required to describe the strength and mechanism of the relationship between SCD and disseminated NTMIs.

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Hidden Brain iron content in Sickle cell disease: Impact on Neurocognitive Functions

10.21203/rs.3.rs-399346/v1 ◽

2021 ◽

Author(s):

Mohsen Saleh ElAlfy ◽

Ahmed Samir Ibrahim ◽

Ghada Samir Ibrahim ◽

Hanaa Midhat Abdel Gader Hussein ◽

Hend Galal Eldeen Mohammed ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Brain Mri ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Brain Iron ◽

Cell Disease ◽

Neurocognitive Dysfunction ◽

Neurocognitive Functions

Abstract Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30±0.12 mg/kg/day. 68.9% of SCD had under- threshold IQ, 12.5% had moderate to severe anxiety and 60.8% had depression. There was no differences between SCD, BTM and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p=0.032). Mean right caudate R2* was higher in female than male (p=0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, negative correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients. Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload.

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Outcomes of Chronic Automated RBC Exchange Program in Omaha, Nebraska 2015-2020

Blood ◽

10.1182/blood-2020-136308 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 21-22

Author(s):

Aleh Bobr ◽

Scott A Koepsell ◽

Julie Eclov ◽

Omar Abughanimeh ◽

Steven Ebers ◽

...

Keyword(s):

Sickle Cell Disease ◽

Blood Cell ◽

Iron Overload ◽

Sickle Cell ◽

Red Blood Cell ◽

Beta Thalassemia ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Before And After ◽

Ed Visits

Background: Red blood cell exchange (RBCX) is an effective therapy in the treatment of different hemoglobinopathies. The University of Nebraska Medical Center (UNMC) established a chronic RBCX program in November 2015, which took care of patients with multiple hemoglobinopathies. In this study, we aim to evaluate the outcomes of this program. Methods: This is a retrospective study. After an IRB approval, we reviewed the charts of patients who were enrolled in the chronic RBCX program between 11/2015-7/2020 at UNMC. Data was collected to evaluate indications of RBCX, types of hemoglobinopathies, hemoglobinopathies' complications before and after the enrollment in the program, and assessment of hospital visits before and after enrollment in the program. Results: In November 2015, the chronic RBCX program was established in Nebraska. Since the start, 24 patients came through the program and 20 patients are still actively enrolled and undergoing regular exchange transfusions. The four patients who left the program did it for the following reasons: moving out of state, stem cell transplant and change to different treatment modality. Four of 24 patients were beta thalassemia patients (two of them with combined HbE/beta thalassemia). Twenty patients had sickle cell disease with two of them having combined beta thalassemia and HbS and one with alpha thalassemia and HbS. The indications ranged from history of stroke, intracranial vascular stenosis, acute chest syndrome (ACS), iron overload, multiple vascular occlusive crises (VOC) and intolerance of medications with most of the patients having multiple indications from the list above (Figure 1). There are several positive outcomes from being on the program. In the patients who had been on the program for at least one year (n=11), nine started the program with iron overload and all of them had a significant decrease in serum ferritin (average 751 ng/mL) with three patients returning to normal range. In the patients who had been in the program at least six months (n=16), 13 patients started with iron overload with five returning to normal range and average decrease in ferritin of 585 ng/mL. Another positive outcome is the number of emergency department (ED) visits for pain crisis. We noted reduction in ED visits in all patients who were in the program for at least six months (n=14), with the exception of one patient where the visits were likely the part of drug seeking behavior. In fact 12 of 13 patients had one or no ED visits within one year after starting on the chronic exchange program having had from 2-11 visits a year prior. None of the patients in the program experienced more severe complications of sickle cell disease, like stroke and acute chest syndrome, while on the program. Due to high volumes of transfusion, there is a big concern about developing red blood cell antibodies in sickle cell disease patients who in general have higher red blood cell antibody burden. Out of 24 patients in the program, six had pre-existing antibodies. For the duration of the program, no new alloantibodies were discovered in the chronically exchanged patients despite high transfusion volumes (range 14L-30L/year). The transfused blood was matched for Rh and Kell antigens for the patients with no antibody history. The patients with previous antibody history had additional matching for the antigen to which antibody was directed. Conclusion:Automated chronic RBCX transfusion program is safe to perform. It leads to significant reduction in volume overload and ED visits. Performing high volume transfusions outside of acute sickle cell crisis and with Rh and Kell matched units prevents formation of RBC antibodies Disclosures Gundabolu: BioMarin:Consultancy;Bristol Myers Squibb pharmaceuticals:Consultancy.

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