Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective,single arm,open label,dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy‐three pediatric patients with severe β thalassemias, age range 3.2–19 years, were recruited to a 1‐year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty‐four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.1±4.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml^?1. Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml^?1 had the most significant fall of SF at 1 year. A subgroup analysis by MRI‐T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug‐related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251–260, 2013. © 2013 Wiley Periodicals, Inc.     

The use of dengue nonstructural protein 1 antigen for the early diagnosis during the febrile stage in patients with dengue infection

BACKGROUND: To evaluate the use of dengue nonstructural protein 1 (NS1) antigen for the early diagnosis during the febrile stage in patients with dengue infection. METHODS: A total of 445 sera obtained from 165 patients [dengue fever (DF): 42, dengue hemorrhagic fever (DHF) grade I: 50, II: 63, III and IV: 10] and 8 other febrile illnesses 5-15 years of age, were assayed for the NS1 antigen, dengue-specific Ig M and Ig G antibodies. RESULTS: The positive rates of NS1 antigen among patients with either DF or DHF was 100% (7 of 7) on day 2, 92.3% (12 of 13) on day 3, 76.9% (40 of 52) on day 4, 56.5% (61 of 108) on day 5 of fever; and declined to 43.1% (59 of 137) on day 6 with defervescence and 29.8% (25 of 84) on day 7 (1 day after defervescence). The positive rates of patients with DF were higher than those with DHF but no statistically significant difference was found. However, patients with primary DHF infection had significantly higher positive rates than those with secondary DHF infection. The positive rates of Ig M antibodies were in reverse proportion to those of NS1 antigen. The additional Ig M antibody determination increased the positive rates to 90.4% (47 of 52) on day 4, 83.3% (90 of 108) on day 5 of fever; 95.6% (131 of 137) on day 6 with defervescence, and 88.1% (74 of 84) on day 7. CONCLUSIONS: Dengue NS1 antigen testing is suggested as a helpful tool for the early diagnosis of dengue infection after the onset of fever. The additional Ig M antibody determination increased the diagnostic rates.     

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection

Dengue virus (DENV) infection is considered one of the most important mosquito‐borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV‐infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56^hi CD16^? and CD56^lo CD16⁺ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56^hi CD16^? subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56^lo CD16⁺ subset compared with those in the CD56^hi CD16^? subset. Moreover, although the CD56^lo CD16⁺ subset contained a high frequency of cells expressing skin‐homing markers, the CD56^hi CD16^? subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.     

Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection

Two hundred twenty samples obtained from 104 patients with dengue infection (n = 89) and other febrile illnesses (n = 15) were assayed for dengue nonstructural protein 1 (NS1) antigen by enzyme immunoassay and by an immunochromatography (lateral flow) test strip. The sensitivity and the specificity of dengue NS1 antigen strip were 98.9% and 90.6%, respectively.     

Essential issues of laboratory investigation for patients with haemophilia and bleeding disorders

Summary.  Apart from history-taking and physical examination, laboratory investigation is one of the essential issues for the definite diagnosis of haemophilia and bleeding disorders. The limited resources of medical personnel, equipment and reagents should be shared among several departments in the hospital, especially for serving patients with common genetic diseases such as thalassemia and haemoglobinopathies. Medical personnel require appropriate training to expand their skills in laboratory techniques. Laboratory procedures can be created, modified and simplified using locally produced and shared equipment. Molecular genetic studies can also be set up at different levels of hospital service using simple, rapid and low-cost methods. Finally, a system of periodic external quality control will guarantee the accuracy of laboratory results.     

VENOUS THROMBOEMBOLISM IN THAI CHILDREN

This is a retrospective study of 24 pediatric venous thromboembolism (VTE) patients with or without pulmonary embolism, conducted in Bangkok, Thailand, between 1981 and 2005. The incidence rate of VTE in Thai children was 3.9/10,000 hospital admissions per year. The median age was 11.7 years. Seventy-five percent of the patients had at least one associated medical condition accounting for the VTE; the two most common conditions, however, were infection and malignancy. Pulmonary embolism occurred in 29% of patients. Observed outcomes of VTE in this series included death (13%), postphlebitic syndrome (13%), and recurrence (26%). Genetic risk factors were explored in 19 patients, and no factor V Leiden or prothrombin 20210 mutations were detected. Protein C deficiency was found in 4 patients.