Safety and efficacy of high dose intravenous desferrioxamine for reduction of iron overload in sickle cell disease.

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) desferrioxamine (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 have been utilized in non-compliant patients with heavy iron overload in small case series. PROCEDURE: We review our experience of high dose IV DFO in 27 patients with SCD who had significant iron overload and were noncompliant with subcutaneous (SQ) DFO. All patients were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hr every 2-4 weeks with a mean duration of 19.6 months. RESULTS: We observed a significant decrease in liver iron burden with high dose intermittent IV DFO. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Also there was significant improvement in liver enzymes (ALT, AST) after high dose IV DFO. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. CONCLUSIONS: In our cohort of patients with SCD 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.

Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease.

Sickle cell disease (SCD) is associated with a large spectrum of renal abnormalities, one of which, microalbuminuria/proteinuria (MA/P), is a known predictor of end-stage renal disease. We studied 90 children with SCD (57% male; mean age 11.4 +/- 5.2 years) to determine the prevalence and examine clinical correlates of MA/P. The average of two spot urine microalbumin-to-creatinine samples obtained 6 months apart was recorded. Medical records were reviewed for demographic and biochemical data. Medication use, resting office blood pressures (BP), vaso-occlusive pain crises (VOC), and monthly transfusions were recorded. Fourteen children (15.5%) had MA/P. Hemoglobin (Hb) levels were significantly lower in the children with MA than in those without MA/P (8.8 +/- 1.1 vs. 9.8 +/- 1.4 g/dL, respectively) and were significantly correlated with MA (rho = 0.24, p = 0.03). Children with MA were more likely to have abnormal BP (p = 0.058), with 5/14 being hypertensive or pre-hypertensive. In a multivariate logistic regression model of MA, both Hb and BP classification remained in the final model. MA is a simple screening biomarker of early kidney injury in children with SCD. Larger studies to evaluate predictive factors of MA and the relationship to BP are needed.

Clinical events after surgical splenectomy in children with sickle cell anemia.

PURPOSE: Despite advances in immune prophylaxis, sepsis remains the most feared complication following splenectomy for acute splenic sequestration crisis (ASSC) in children with sickle cell anemia (SCA). We seek to investigate the true prevalence of sepsis and other complications of splenectomy in this patient population. METHODS: We reviewed the records of children with SCA (HbSS) who underwent splenectomy for ASSC between 1993 and 2008 at a single institution. RESULTS: Fifty-eight patients (33 males) at a median age of 2 years at splenectomy were included with an average post-splenectomy follow-up of 6.4 years (range 6 months-14 years). Thirty-seven patients (64%) underwent laparoscopic splenectomy, and acute chest syndrome (ACS) was the most common post-operative complication (6.9%). There was no difference in the incidence of sepsis pre- and post-splenectomy. The occurrence of vaso-occlusive pain crises (VOC) and ACS was significantly higher after splenectomy. In addition, 14 patients (24%) developed stroke (n = 5) or an abnormal transcranial Doppler (TCD) (n = 9) after splenectomy. CONCLUSION: Our data suggest that splenectomy can be safely performed in children with SCA given a low risk of sepsis. However, the increased incidence of VOC, ACS, and stroke or abnormal TCDs after splenectomy remains a concern.

Liver biopsy results in patients with sickle cell disease on chronic transfusions: poor correlation with ferritin levels.

BACKGROUND: Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion. PROCEDURE: Forty-four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin. RESULTS: Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r = 0.46). The correlation of duration of transfusion with serum ferritin (r = 0.40) and with liver iron content (r = 0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin >/=2500 ng/ml predicted high liver iron content (>/=7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%. CONCLUSION: We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients.

Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events.

We conducted a retrospective study to determine whether the presence of moyamoya collaterals influenced the risk of recurrence of cerebrovascular events (CVEs: stroke or transient ischemic attack) in patients with sickle cell disease placed on chronic transfusions after a stroke. Forty-three patients with homozygous sickle cell anemia (HbSS) and 1 with HbSO(Arab) (16 females, 28 males) who had suffered strokes while under the age of 18 were studied. All patients had been on transfusions aimed at maintaining the sickle hemoglobin (HbS) level below 30%. They were followed for a mean of 6.6 years (2.2 to 20.4 years). The presence of collaterals was diagnosed based on either magnetic resonance angiography or conventional angiography. Eighteen (41%) of the 44 patients suffered recurrent CVEs. Nineteen (43%) (6 females, 13 males) patients had moyamoya collaterals. Eleven (58%) of these 19 experienced 21 total recurrent CVEs, including 4 strokes in 4 patients (21%). In comparison, 7 (28%) of 25 patients without moyamoya collaterals experienced 9 recurrent CVEs (P <.05) with only 1 recurrent stroke (4%). Moyamoya patients were also more likely to have 2 recurrent CVEs (42% vs 8%, P <.05) as well as poorer neuropsychological testing results. A proportional hazards regression analysis indicated that patients with moyamoya were more than twice as likely to incur a subsequent CVE (hazard ratio, 2.40; 95% confidence interval, 0.85, 6.75). We conclude that up to 41% of patients with sickle cell disease experience recurrent CVEs after an initial stroke despite chronic transfusions and that the risk of recurrence is significantly higher for those who have moyamoya collaterals.