Abstract

Background: Patients with sickle cell disease (SCD) receiving chronic blood transfusions are at risk of developing iron overload and organ toxicity. Chelation therapy with either subcutaneous (SQ) desferoxamine (DFO) or oral deferasirox is effective in preventing and reducing iron overload but poses significant challenges with patient compliance. Intravenous (IV) infusions of high dose DFO (HDD) have been utilized in non compliant patients with heavy iron overload in small case series. We review our experience of high dose IV DFO in a large cohort of SCD patients with significant iron overload who are non compliant with SQ DFO.

Methods: The medical records of SCD patients who received HDD in our center between 1993 and 2004 were reviewed. All of them were on chronic transfusion, had significant iron overload defined by serum ferritin > 1500 and/or liver iron concentration (LIC) more than 10 μg/g of liver tissue and were non-compliant with SQ DFO. All patients underwent annual ophthalmologic, hearing, pulmonary and cardiac evaluation. Demographic data, treatment details, serum ferritin levels, liver iron concentration (LIC), liver enzymes, renal function tests, audiogram and other relevant clinical data were collected.

Results: There were 27 patients (19 males, 8 females), 19 patients were on transfusion for history of cerebrovascular accident, 5 for abnormal transcranial Doppler flow velocity, 2 for transient ischemic attack and one for recurrent pain crises. All continued to receive packed red blood cell transfusions aimed to keep HbS levels below 30 or 50% during this time. They were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hrs every 2 weeks (20 patients), 3 weeks (4 patients) and 4 weeks (3 patients). The mean age at start of high dose regimen was 14.6 years (range 9–27 years). The mean duration of HDD treatment was 8.9 months (range 3–49 months). Fourteen patients had LIC determined by liver biopsy. Significant reductions in LIC were observed after HD (table I). This was more pronounced in patients who had higher LIC and received at least 6 months of HDD. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Four patients had portal triaditis initially which resolved after starting HDD therapy. Also there was significant improvement in liver enzymes (ALT, AST) after HDD. There was a trend in decreasing ferritin levels after HDD but this did not achieve statistical significance. All patients tolerated HDD without any major reactions. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. Blood urea nitrogen remained normal in all patients after HDD but there was mild increase in serum creatinine. One patient had high serum creatinine (1.2 mg/dL) after two doses HDD. This patient had focal segmental glomeurosclerosis which was most probably the cause for the rise in creatinine. There was no significant increase in serum creatinine in our series when this patient was excluded.

Conclusions: In our cohort of SCD patients we observed a significant decrease in liver iron burden with high dose IV DFO. Our patients tolerated the therapy well without any major toxicity. This regimen is safe and may be an option for poorly compliant patients with significant iron overload. In addition, combination of this regimen with oral iron chelators may be of benefit to patients with significant iron overload and organ dysfunction.

Table 1: Laboratory characteristics of sickle cell patients before and after high dose IV DFO

Parameter No. of Patients Mean (SD) prior to HDD Mean (SD)after HDD p Value* 
* Changes in mean levels analyzed using two-tailed Paired T Test with significant p value ≤ 0.05. 
SD – Standard deviation 
+ See text 
Liver iron (μg/g of liver tissue ) 14 16864 (10903) 12681 (8298) 0.04 
Liver iron min of 6 months of HDD (μg/g of liver tissue ) 18677 (8319) 9362 (4521) 0.01 
Liver iron >10 mg & minimum 6 months of HDD (μg/g of liver tissue) 21181 (7054) 10092 (4443) 0.01 
Grade of liver iron storage 14 3.57 (0.9) 3.07 (1) 0.05 
Serum Ferritin (ng/mL) 27 3842 (2619) 3238 (1780) 0.06 
Serum AST (IU/L) 27 54.1 (27.2) 44.6 (17.6) 0.04 
Serum ALT (IU/L) 27 39.2 (36) 27.5 (14.2) 0.01 
Blood urea nitrogen (mg/dL) 27 8.9 (2.9) 9.5 (4.3) 0.20 
Serum Creatinine (mg/dL)+ 26 0.50 (0.1) 0.55 (0.2) 0.07 
Parameter No. of Patients Mean (SD) prior to HDD Mean (SD)after HDD p Value* 
* Changes in mean levels analyzed using two-tailed Paired T Test with significant p value ≤ 0.05. 
SD – Standard deviation 
+ See text 
Liver iron (μg/g of liver tissue ) 14 16864 (10903) 12681 (8298) 0.04 
Liver iron min of 6 months of HDD (μg/g of liver tissue ) 18677 (8319) 9362 (4521) 0.01 
Liver iron >10 mg & minimum 6 months of HDD (μg/g of liver tissue) 21181 (7054) 10092 (4443) 0.01 
Grade of liver iron storage 14 3.57 (0.9) 3.07 (1) 0.05 
Serum Ferritin (ng/mL) 27 3842 (2619) 3238 (1780) 0.06 
Serum AST (IU/L) 27 54.1 (27.2) 44.6 (17.6) 0.04 
Serum ALT (IU/L) 27 39.2 (36) 27.5 (14.2) 0.01 
Blood urea nitrogen (mg/dL) 27 8.9 (2.9) 9.5 (4.3) 0.20 
Serum Creatinine (mg/dL)+ 26 0.50 (0.1) 0.55 (0.2) 0.07 

Disclosures: No relevant conflicts of interest to declare.

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