Cost-Effectiveness of Hydroxyurea for Sickle Cell Anemia in a Low-Income African Setting: A Model-Based Evaluation of Two Dosing Regimens.

BACKGROUND AND OBJECTIVE: The disease burden of sickle cell anemia (SCA) in sub-Saharan African (SSA) countries is substantial, with many children dying without an established diagnosis or proper treatment. The global burden of SCA is increasing each year, making therapeutic intervention a high priority. Hydroxyurea is the only disease-modifying therapy with proven feasibility and efficacy suitable for SSA; however, no one has quantified the health economic implications of its use. Therefore, from the perspective of the health care provider, we estimated the incremental cost-effectiveness of hydroxyurea as a fixed-dose regimen or maximum tolerated dose (MTD) regimen, versus SCA care without hydroxyurea. METHODS: We estimated the cost of providing outpatient treatment at a pediatric sickle cell clinic in Kampala, Uganda. These estimates were used in a discrete-event simulation model to project mean costs (2021 US$), disability-adjusted life years (DALYs), and consumption of blood products per patient (450 mL units), for patients between 9 months and 18 years of age. We calculated cost-effectiveness as the ratio of incremental costs over incremental DALYs averted, discounted at 3% annually. To test the robustness of our findings, and the impact of uncertainty, we conducted probabilistic and one-way sensitivity analyses, scenario analysis, and price threshold analyses. RESULTS: Hydroxyurea treatment averted an expected 1.37 DALYs and saved US$ 191 per patient if administered at the MTD, compared with SCA care without hydroxyurea. In comparison, hydroxyurea at a fixed dose averted 0.80 DALYs per patient at an incremental cost of US$ 2. The MTD strategy saved 11.2 (95% CI 11.1-11.4) units of blood per patient, compared with 9.1 (95% CI 9.0-9.2) units of blood per patient at the fixed-dose alternative. CONCLUSIONS: Hydroxyurea at MTD is likely to improve quality of life and reduce the consumption of blood products for children with SCA living in Uganda. Compared with a fixed dose regimen, treatment dosing at MTD is likely to be a cost-effective treatment for SCA, using realistic ranges of hydroxyurea costs that are relevant across SSA. Compared with no use of the drug, hydroxyurea could lead to substantial net savings per patient, while reducing the disease morbidity and mortality and increasing quality of life.

Anemia and transfusion requirements among Ugandan children with severe malaria treated with intravenous artesunate.

Parenteral artesunate for the treatment of severe malaria in non-immune travelers is associated with late-onset hemolysis. In children in sub-Saharan Africa, the hematologic effects of malaria and artesunate are less well documented. Here we report a prospective case series of 91 children with severe malaria treated with parenteral artesunate, managed at a resource-poor hospital in Africa, with longitudinal data on hemoglobin (Hb), lactate dehydrogenase (LDH), haptoglobin, and erythrocyte morphology. The median (range) age was 2 (1-8) years and 43 (47%) were female. The median (IQR) admission Hb level was 69 (55-78) g/L and 20 patients (22%) had severe malarial anemia (Hb < 50 g/L). During hospitalization, 69 patients (76%) received one or more blood transfusions. Fatal outcome in 8 patients was associated with severe anemia in 6/8 cases. Follow-up Hb measurement was performed on 35 patients (38%) at day 14 after initial hospital admission; the remaining patients had no clinical evidence of anemia at the follow-up visit. The convalescent Hb was median (range) 90 (60-138) g/L, which was significantly higher than the paired admission levels (median increase +28 g/L, p < .001). Evidence of hemolysis (elevated LDH and low haptoglobin) was common at admission and improved by day 14. No patient met the standardized definition of post-artemisinin delayed hemolysis (PADH). In this cohort of young children with severe malaria treated with artesunate, anemia was common at admission, required one or more transfusions in a majority of patients, and markers of hemolysis had normalized by day 14.

Platelet transfusion therapy in sub-Saharan Africa: bacterial contamination, recipient characteristics, and acute transfusion reactions.

BACKGROUND: Little data are available on bacterial contamination (BC) of platelet units or acute transfusion reactions to platelet transfusions (PTs) in sub-Saharan Africa (SSA). STUDY DESIGN AND METHODS: This prospective, observational study evaluated the rate of BC in whole blood-derived platelet units (WB-PUs), the utility of performing Gram stains to prevent septic reactions, characteristics of patients receiving PTs, and the rate of acute reactions associated with PTs at the Uganda Cancer Institute in Kampala, Uganda. An aliquot of each WB-PU studied was taken to perform Gram stains and culture using the Bactec 9120 instrument. Study participants were monitored for reactions. RESULTS: In total, 337 WB-PUs were evaluated for BC, of which 323 units were transfused in 151 transfusion episodes to 50 patients. The frequency of BC ranged from 0.3% to 2.1% (according to criteria used to define BC). The Gram stain had high specificity (99.1%) but low sensitivity to detect units with BC. The median platelet count before PT was 10,900 cells/µL (interquartile range, 6000-18,900 cells/µL). Overall, 78% of PTs were given to patients with no bleeding. Acute reactions occurred in 11 transfusion episodes, involving 13 WB-PUs, for a rate of 7.3% (95% confidence interval, 3.7%-12.7%) per transfusion episode. All recipients of units with positive bacterial cultures were receiving antibiotics at the time of transfusion; none experienced a reaction. CONCLUSIONS: The rate of BC observed in this study is lower than previously reported in SSA, but still remains a safety issue. Because Gram staining appears to be an ineffective screening tool, alternate methods should be explored to prevent transfusing bacterially contaminated platelets in sub-Saharan Africa.

Cryoprecipitate use in 25 Canadian hospitals: commonly used outside of the published guidelines.

BACKGROUND: Canadian Blood Services' disposition reports suggested considerable variation in cryoprecipitate use and prompted this national audit. STUDY DESIGN AND METHODS: Thirty-one institutions were invited to participate in a 2-month audit. Patient information and relevant laboratory and transfusion data were collected. Cryoprecipitate transfusions were categorized as appropriate if a fibrinogen level (taken 6 hr before/after transfusion) was not more than 1.0 g per L and inappropriate if the pretransfusion fibrinogen level was more than 1.0 g per L and posttransfusion fibrinogen level was more than 1.0 g per L or not performed. Appropriateness was categorized as undetermined if the pretransfusion fibrinogen level was not performed and the posttransfusion fibrinogen level was more than 1.0 g per L or not performed. RESULTS: Overall, 25 of 31 invited hospitals agreed to participate. A total of 4370 units of cryoprecipitate were transfused in 603 events to 453 patients representing 62 percent of cryoprecipitate issued to hospitals during the time period. Comparison of the number of units of cryoprecipitate per 100 units of red blood cells (RBCs) transfused by each institution showed significant variation in practice (mean, 9 per 100 RBCs; range, 2 to 27 units). The single most common indication for cryoprecipitate was cardiac surgery (45.4% of events). Overall, 24 percent of cryoprecipitate transfusions were considered to be appropriate (pretransfusion fibrinogen level

Complications of apheresis in children.

BACKGROUND: Although the frequency of complications in adults undergoing therapeutic apheresis is low, there are little data in children. STUDY DESIGN AND METHODS: A retrospective study of 186 children who had undergone a total of 1632 apheresis procedures between 1994 and 2002 was conducted. Adverse reactions were prospectively documented. The procedures were plasma exchange (67%), hematopoietic progenitor cell collection (18%), red blood cell exchange (6.9%), leukodepletion (0.7%), and plasma exchange with immunoadsorption (6.7%). RESULTS: Adverse reactions, most minor, were reported in 55 percent of procedures in 82 percent of patients. The most frequent complications, per procedure and per patient during an entire course of therapy, were hypotension (14 and 48.4%), hypotension requiring fluid bolus (4.8 and 26.9%), symptomatic hypocalcemia (9.7 and 28.5%), allergic reactions (4.4 and 5.9%), catheter-related thrombosis (1.7 and 12.4%), catheter-related infection (2.1 and 16.1%), and severe anemia (hemoglobin [Hb] level, <7 g/dL; 2.5 and 17.2%). There were two deaths (1% of patients). Risk factors for complications by multivariate analysis were lower body weight, lower preapheresis Hb level, apheresis in a critical care unit, and number of procedures per patient. The 55 percent incidence of complications per procedure in our pediatric cohort is much higher than the 4.3 to 28 percent incidence reported in adults. The excess of adverse reactions in children are mostly related to citrate toxicity, higher relative vascular volume shifts, and the need for vascular access. CONCLUSION: Pediatric apheresis presents unique challenges and is associated with higher complication rate compared to adults. It is recommended that this procedure be performed in specialized centers.

Perioperative blood transfusion therapy in pediatric patients.

In general, transfusion guidelines for non-neonatal pediatric patients are similar to those for adults. However, some differences do exist and certain precautions may be necessary particularly in the setting of massive transfusions. We review these differences as they apply to general pediatric surgery outside of the neonatal period, with respect to the transfusion of red blood cells (RBCs), platelets, fresh-frozen plasma (FFP), and cryoprecipitate. We include a discussion of the indications for transfusion and practical considerations such as dosing and administration. Finally, we briefly review the use of directed donations and specialized (irradiated, CMV seronegative) blood components.