Treatment of alpha(0)-thalassemia (--(SEA)/--(SEA)) via serial fetal and post-natal transfusions: Can early fetal intervention improve outcomes?

OBJECTIVE AND IMPORTANCE: Homozygous Southeast Asian alpha-thalassemia mutation (--(SEA)/--(SEA)) results in deletion of all alpha-globin genes (alpha(0)-thalassemia). Since all alpha-globin chains are absent, hemoglobin F cannot be synthesized, and hemoglobin Bart's becomes the dominant fetal hemoglobin. Hemoglobin Bart's is a γ tetramer with a very high oxygen affinity, thus oxygen delivery to the tissues is poor. Clinical manifestations include severe fetal anemia, hydrops fetalis, fetal demise, and high risk of neurodevelopmental impairment in the rare survivors. CLINICAL PRESENTATION: A 39-year-old Vietnamese woman presented to our center at 28 0/7 weeks' gestation with fetal alpha(0)-thalassemia (--(SEA)/--(SEA) type deletion) and ultrasound markers suggestive of severe fetal anemia. INTERVENTION: The fetus was treated with four intrauterine transfusions followed by post-natal chronic transfusions. Formal neurodevelopmental testing (Battelle Developmental Inventory, Second Edition) was performed at 18 months of age, and the developmental quotient was 93 (32nd percentile) with all subdomains noted within normal limits, indicating overall intact neurodevelopment. CONCLUSION: We posit that earlier diagnosis and fetal treatment, prior to clinical findings suggestive of fetal anemia, may improve long-term outcomes by enhancing oxygen delivery to the tissues of the developing fetus.

Management of children with brain tumors in Paraguay.

BACKGROUND: Cure rates among children with brain tumors differ between low-income and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country. METHODS: Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asunción and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death. RESULTS: All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities. CONCLUSIONS: National and center-specific deficiencies in resources to manage pediatric brain tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain tumor programs in other low- and middle-income countries.

Thrombolytic therapy for central venous catheter occlusion.

BACKGROUND: Long-term central venous catheters have improved the quality of care for patients with chronic illnesses, but are complicated by obstructions which can result in delay of treatment or catheter removal. DESIGN AND METHODS: This paper reviews thrombolytic treatment for catheter obstruction. Literature from Medline searches using the terms "central venous catheter", "central venous access device" OR "central venous line" associated with the terms "obstruction", "occlusion" OR "thrombolytic" was reviewed. Efficacy of thrombolytic therapy, central venous catheter clearance rates and time to clearance were assessed. RESULTS: Alteplase, one of the current therapies, clears 52% of obstructed catheters within 30 min with 86% overall clearance (after 2 doses, when necessary). However, newer medications may have higher efficacy or shorter time to clearance. Reteplase cleared 67-74% within 30-40 min and 95% of catheters overall. Occlusions were resolved in 70 and 83% of patients with one and 2 doses of tenecteplase, respectively. Recombinant urokinase cleared 60% of catheters at 30 min and 73% overall. Alfimeprase demonstrated rapid catheter clearance with resolution in 40% of subjects within 5 min, 60% within 30 min, and 80% within 2 h. Additionally, urokinase prophylaxis decreased the incidence of catheter occlusions from 16-68% in the control group to 4-23% in the treatment group; in some studies, rates of catheter infections were also decreased in the urokinase group. CONCLUSIONS: Thrombolytic agents successfully clear central venous catheter occlusions in most cases. Newer agents may act more rapidly and effectively than currently utilized therapies, but randomized studies with direct comparisons of these agents are needed to determine optimal management for catheter obstruction.

Management of occlusion and thrombosis associated with long-term indwelling central venous catheters.

Long-term central venous catheters (CVCs) are important instruments in the care of patients with chronic illnesses, but catheter occlusions and catheter-related thromboses are common complications that can result from their use. In this Review, we summarise management of these complications. Mechanical CVC occlusions need cause-specific treatment, whereas thrombotic occlusions usually resolve with thrombolytic treatment, such as alteplase. Prophylaxis with thrombolytic flushes might prevent CVC infections and catheter-related thromboses, but confirmatory studies and cost-effectiveness analysis of this approach are needed. Risk factors for catheter-related thromboses include previous catheter infections, malposition of the catheter tip, and prothrombotic states. Catheter-related thromboses can lead to catheter infection, pulmonary embolism, and post-thrombotic syndrome. Catheter-related thromboses are usually diagnosed by Doppler ultrasonography or venography and treated with anticoagulation therapy for 6 weeks to a year, dependent on the extent of the thrombus, response to initial therapy, and whether thrombophilic factors persist. Prevention of catheter-related thromboses includes proper positioning of the CVC and prevention of infections; anticoagulation prophylaxis is not currently recommended.