Relationship between Serum Ferritin and Outcomes in β-Thalassemia: A Systematic Literature Review

Abstract

Among the difficulties of living with β-thalassemia, patients frequently require blood transfusions and experience iron overload. As serum ferritin (SF) provides an indication of potential iron overload, we conducted a systematic literature review (SLR) to assess whether SF levels are associated with clinical and economic burden and patient-reported outcomes (PROs). The SLR was conducted on 23 April 2020 and followed by analysis of the literature. Dual-screening was performed at the title, abstract, and full-text levels using predefined inclusion and exclusion criteria. Ten studies identified by the SLR were eligible for inclusion in the analysis. Seven studies were conducted in Europe, and most were prospective or retrospective in design. The patient populations had a median age of 20.7–42.6 years, with a percentage of men of 38–80%. Sparse data were found on the correlation between SF levels and mortality, and hepatic, skeletal, and cardiac complications; however, in general, higher SF levels were associated with worsened outcomes. The bulk of the evidence reported on the significant association between higher SF levels and endocrine dysfunction in its many presentations, including a 14-fold increase in the risk of diabetes for patients with persistently elevated SF levels. No studies reporting data on PROs or economic burden were identified by the SLR. SF levels provide another option for prognostic assessment to predict a range of clinical outcomes in patients with β-thalassemia.

Glucose Homeostasis and Αssessment of Β-Cell Function by 3-Hour Oral Glucose Tolerance (Ogtt) in Patients With Β-Thalassemia Major With Serum Ferritin Below 1,000 Ng/Dl: Results From a Single Icet-a Centre

“…A significant association between persistently elevated SF levels and endocrine glands dysfunction has been documented; in particular, a 14-fold increased risk of diabetes has been reported in β-TM patient populations with a median age of 20.7 years. 27 ICT aims to balance the increased rate of iron input of blood transfusions by increasing iron excretion in urine and /or stools with effective chelating drugs. This requires a profound commitment from patients and parents to iron chelation protocols and recommendations to monitor efficiency and unwanted side effects for the individual patient.…”

“…Although SF is considered a reliable surrogate marker for total body iron load in β-TM patients, its elevation may also reflect other conditions not strictly linked to iron metabolisms, such as inflammation, liver damage, and steatohepatitis. 27 The average SF levels in healthy individuals range from 12 to 300 ng/mL in men and from 12 to 150 ng/mL in women. 27 Increased SF concentrations (> 300 ng/mL for men and > 200 ng/mL for women) in non-pathologic conditions, reflecting subclinical IOL, have been reported to be associated with insulin resistance (IR) and an increased risk of type 2 diabetes.…”

“…27 The average SF levels in healthy individuals range from 12 to 300 ng/mL in men and from 12 to 150 ng/mL in women. 27 Increased SF concentrations (> 300 ng/mL for men and > 200 ng/mL for women) in non-pathologic conditions, reflecting subclinical IOL, have been reported to be associated with insulin resistance (IR) and an increased risk of type 2 diabetes. 28,29 It has been shown that "normalizing" iron stores in β-TM patients, in the absence of chelator-mediated toxicity, prevents new morbidities and reverses many complications, such as cardiac failure, hypothyroidism, hypogonadism, and GD.…”

“…A significant association between persistently elevated SF levels and endocrine glands dysfunction has been documented; in particular, a 14-fold increased risk of diabetes has been reported in β-TM patient populations with a median age of 20.7 years. 27 …”

“…Although SF is considered a reliable surrogate marker for total body iron load in β-TM patients, its elevation may also reflect other conditions not strictly linked to iron metabolisms, such as inflammation, liver damage, and steatohepatitis. 27 …”