Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease.

Patients with sickle cell disease (SCD) appear to be at lower risk of endocrinopathies and cardiac dysfunction than those with thalassemia major (TM). Circulating redox active iron is lower in these patients, possibly due to increased systemic inflammation and circulating cytokines. Hepcidin synthesis is upregulated during chronic inflammation, reducing intestinal iron absorption and promoting retention of iron in the reticuloendothelial cells. Hence, we hypothesized that livers of patients with SCD would exhibit greater iron deposition in sinusoidal spaces relative to hepatocytes and less in portal tracts when compared to patients with TM. To test this hypothesis, iron scoring analysis was performed on 70 clinically indicated liver biopsy specimens from children and young adults with the two syndromes. Sinusoidal scores were lower in around 1 of 4 patients with TM but the relative iron loading in hepatocytes, and portal tracts was identical in both diseases. Sinusoidal iron burdens saturated at low hepatic iron concentration (HIC) while hepatocyte and portal iron depots increased proportionally to HIC. Liver fibrosis was increased in patients with TM regardless of their chronic hepatitis status. Overall, liver iron distribution was relatively insensitive to differences in disease type and to the presence or absence of hepatitis.

Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis.

In patients with sickle cell disease or beta-thalassemia receiving RBC transfusions for a long period, a precise knowledge of the liver iron concentration (LIC) is essential for treatment. Patients underwent LIC and liver pathology assessment by duplicate biopsies in 2 passes from the same local liver site. Fresh tissue cores in trace element-free containers and tissues from dissolved paraffin-embedded cores were analyzed. LIC measurements in each of 2 paraffin-embedded cores did not differ significantly (median, 12,455 vs 12,153 microg/g dry weight; n = 29). A significant difference was observed when 1 fresh tissue sample and 1 paraffin-embedded core were analyzed (median, 11,716 vs 12,864 microg/g dry weight; n = 16; P < .001) with a median disagreement between LIC measurements of 23.0%. We found high agreement in LICs between liver biopsy specimens processed by the paraffin-embedding technique but overestimation of LICs in comparison with desiccated fresh tissue samples.

Treatment of hepatitis C virus infection in thalassemia.

Treatment of hepatitis C virus (HCV) in the general population has improved over the last decade. Patients treated with peginterferon alfa (PegIFN) and ribavirin (RBV) combination therapy demonstrate overall 50-55% sustained viral response (SVR) with rates as high as 80% in patients with genotypes 2 and 3. Because RBV induces hemolysis and subsequently increases blood transfusion requirements, combination therapy has been considered contraindicated for hemoglobinopathies. This report reviews the response to interferon alfa and RBV (IFN/RBV) and PegIFN/RBV combination therapies in patients treated in the Northern California Comprehensive Thalassemia Center. A total of six thalassemia major patients were treated with IFN/RBV (n = 5; age: 4-38 years) or with PegIFN/RBV (n = 1; age: 26 years). Quantitative HCV RNA polymerase chain reaction and liver iron level assessment were completed. Transfusion volumes were obtained from patients' medical records. On IFN/RBV combination, four of five patients demonstrated SVR. The one patient on PegIFN/RBV showed end-treatment viral response after 6 months of therapy (genotype 3), but subsequently relapsed. Liver iron pretreatment level ranged from 0.2 to 22 mg/g dry weight, with a mean +/- SD of 7.9 +/- 7.7. Transfusion requirement increased by a median of 43.5% (range: 32-137%). Five of the six patients had liver iron measurements within 1 year following completion of treatment, with quantitative liver iron increasing in two patients by 2.5 mg/g dry weight, decreasing in two patients by 3 and 14 mg/g dry weight, and remaining unchanged in one patient. All patients were able to complete combination therapy, although dose reductions were required. Patients with thalassemia and high iron overload can obtain SVR after combination therapy with rates similar to those in the general population and without significant complications. Although transfusion requirements increased in most patients, iron burden was not necessarily increased.

Potential mechanisms for altered iron metabolism in human immunodeficiency virus disease.

Recently, anemia associated with human immunodeficiency virus (HIV) disease has received more attention as our understanding of the significance of anemia in this population has grown and more emphasis is placed on the quality of life of people living with HIV/AIDS. Although the diagnosis and treatment of anemia in HIV disease has been discussed in great detail, the prevalence and pathophysiology of the two most common forms of anemia, iron deficiency anemia (IDA) and the anemia of chronic disease (ACD), have not received much attention despite the difficulty and importance of differentiating between these two anemias. In addition, little attention has been given to iron overload, which has serious implications in individuals with HIV disease. This article proposes a model of altered iron metabolism in HIV disease as a basis for explaining the pathophysiology and implications of IDA, ACD, and iron overload in this population. Implications for clinical practice and recommendations for future research are discussed.

Caregiving time in sickle cell disease: psychological effects in maternal caregivers.

BACKGROUND: Providing home care for a child with a chronic illness can be stressful for the family. The purpose of this paper is to examine patterns of caregiving and the associated psychological impact on maternal caregivers of children with sickle cell disease (SCD). PROCEDURE: Fourteen maternal caregivers of children with SCD were interviewed as part of a larger study of maternal caregivers of children with chronic illness. Forty-four caregivers of children with HIV and 36 caregivers of healthy children were included as comparison groups. Interviews included questions regarding amount of time spent providing care for the child (technical care, non-technical care, health care management), hospitalization, emergency room visits, illness stigma, and mental health of the caregiver. RESULTS: Children with SCD had significantly lower functional status and significantly more hospitalizations in the previous 3 months than children with HIV. Caregivers of children with SCD were more likely to work full-time and had higher incomes than caregivers of children with HIV. The three caregiving groups did not differ significantly on amount of total care, although caregivers of children with SCD and caregivers of children with HIV both reported significantly more time spent in technical care than caregivers of healthy children. Despite lower functional status of the children in the SCD group, when group comparisons on caregiving time variables were adjusted for child's functional status, the differences between groups increased. This appeared to be due to the fact that caregivers in the HIV group spent more time in all caregiving categories except skin, crisis, and other care. In terms of caregiver mental health, caregivers of children with HIV and SCD had significantly higher depressive mood scores than caregivers of healthy children but the groups did not differ on caregiving burden. CONCLUSIONS: The perceived care burden of caregivers of children with SCD may be related to the unpredictable nature of the crisis care they provide. Additional attention is warranted to developing adequate resources for caregivers of children with SCD to mitigate the stress of unexpected crises.

Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia.

Although it is life saving, transfusion therapy has resulted in the majority of sickle cell anemia and thalassemia patients being at risk for hemosiderosis-induced organ damage. It is unknown whether the complications of iron overload are affected by the underlying disease. In order to address this problem, we compared the prevalence of organ dysfunction in both groups of patients receiving chronic transfusion therapy (beta thalassemia, N = 30; sickle cell anemia, N = 43). Both groups had similar quantitative liver iron. Thalassemia patients had greater cardiac disease (20% vs. 0%), growth failure (27% vs. 9%), and endocrine failure (37% vs. 0%). The strongest predictors of combined endocrine and cardiac disease in multivariate analysis were duration of chronic transfusion (P = 0.03) and diagnosis (P = 0.03). Quantitative liver iron concentration on a single liver biopsy was not predictive of cardiac or endocrine injury. Viral hepatitis is the strongest predictor of hepatocellular damage (P = 0.009), while the development of liver fibrosis is more closely related to liver iron concentration (P = 0.04). In conclusion, sickle cell anemia and thalassemia differ in the prevalence of organ injury. This difference is related to the duration of iron exposure and the specific hemoglobinopathy. A prospective study with a larger number of subjects is needed to confirm the relationships between specific diagnosis, liver iron concentration over time, and organ dysfunction.

Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

OBJECTIVES: To evaluate the safety and efficacy of weekly treatment with human recombinant N-acetylgalactosamine 4-sulfatase (rhASB) in humans with mucopolysaccharidosis type VI (MPS VI). STUDY DESIGN: An ongoing Phase I/II, randomized, two-dose, double-blind study. Patients were randomized to weekly infusions of either high (1.0 mg/kg) or low (0.2 mg/kg) doses of rhASB. Six patients (3 male, 3 female; age 7-16 years) completed at least 24 weeks of treatment, five of this group have completed at least 48 weeks. RESULTS: No drug-related serious adverse events, significant laboratory abnormalities, or allergic reactions were observed in the study. The high-dose group experienced a more rapid and larger relative reduction in urinary glycosaminoglycan that was sustained through week 48. Improvements in the 6-minute walk test were observed in all patients with dramatic gains in those walking <100 meters at baseline. Shoulder range of motion improved in all patients at week 48 and joint pain improved in patients with significant pain at baseline. CONCLUSIONS: rhASB treatment was well-tolerated and reduced lysosomal storage as evidenced by a dose-dependent reduction in urinary glycosaminoglycan. Clinical responses were present in all patients, but the largest gains occurred in patients with advanced disease receiving high-dose rhASB.

Self-care for fatigue in patients With HIV.

PURPOSE/OBJECTIVES: To identify when fatigue is reported as a problem by people who are HIV positive, what the perception of fatigue is, and which self-care behaviors are used and with what efficacy. DESIGN: Multisite descriptive study. SETTING: University-based AIDS clinics, community-based organizations, and homecare agencies located in cities across the United States, in Norway, and through a university Web site. SAMPLE: Convenience sample of 422 self-identified people who are HIV positive. MAIN RESEARCH VARIABLES: Symptom description, symptom relief, symptom help, and self-care strategies. FINDINGS: The sixth most reported symptom in this study, fatigue, was treated with a variety of self-designed strategies. In only three instances was consultation with a healthcare provider (i.e., physician) or an injection (medication not defined) mentioned. The most frequently used interventions were supplements, vitamins, and nutrition followed by sleep and rest; exercise; adjusting activities, approaches, and thoughts; distraction; and complementary and alternative therapies. In addition to self-designed strategies, the media and friends and family were sources of information. CONCLUSIONS: Fatigue was reported less frequently in this study than in other HIV-, AIDS-, or cancer-related studies. This may be an artifact of the study design. The use of informal networks for assistance, let alone the prevalence of unrelieved fatigue, indicates the need for more attention to this problem among people with AIDS. IMPLICATIONS FOR NURSING: Careful assessment of the pattern of fatigue and its onset, duration, intervention, and resolution is required if the varied types of fatigue are to be identified and treated successfully.