Effect of acetylsalicylic acid on thalassemia with pulmonary arterial hypertension

Nonlawan Chueamuangphan,1,2 Wattana Wongtheptian,2 Jayanton Patumanond,3 Apichard Sukonthasarn,4 Suporn Chuncharunee,5 Chamaiporn Tawichasri,6 Weerasak Nawarawong4 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Medicine, Chiang Rai Hospital, Chiang Rai, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand Objective: To compare pulmonary artery systolic pressure (PASP) between thalassemic patients with pulmonary arterial hypertension (PAH) for whom acetylsalicylic acid (ASA) was and was not prescribed after 1 year. Methods: A retrospective cohort study was conducted at the hematological outpatient clinic at Chiang Rai Hospital, Chiang Rai, Thailand. All new cases of thalassemia with PAH from January 2007 to January 2012 were studied at the first month and at 12 months. The patients were classified into two groups. In one group, ASA 81 mg daily was prescribed for 1 year, whereas in another group no ASA was prescribed, due to its contraindications, which included bleeding, gastrointestinal side effects, and thrombocytopenia. PASP, estimated by a Doppler echocardiography, was measured by the same cardiologist. Propensity score adjustment was used to control confounding variables by indication and contraindication. Multivariable regression analysis was used to evaluate the effects of ASA. Results: Of the 63 thalassemia patients with PAH, there were 47 (74.6%) in the ASA group and 16 (25.4%) in the no ASA group. ASA, as compared with no ASA, did not significantly reduce PASP (adjusted difference -0.95; 95% confidence interval -16.99 to 15.10; P=0.906). Conclusion: Low-dose ASA may not have a beneficial effect on PASP after 1 year of treatment of PAH in thalassemia. Keywords: thalassemia, pulmonary arterial hypertension, acetylsalicylic aci

Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia

Summary: Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non-transfusion-dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade® in non-transfusion-dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron-overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041). © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd

Approaching low liver iron burden in chelated patients with non-transfusion-dependent thalassemia: The safety profile of deferasirox

Objective: Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload and related complications, and may require iron chelation. However, the risk of over-chelation emerges as patients reach low, near-normal body iron levels and dose adjustments may be needed. In the THALASSA study, the threshold for chelation interruption was LIC <3 mg Fe/g dw (LIC<3); 24 patients receiving deferasirox for up to 2 yr reached this target. A post hoc analysis was performed to characterize the safety profile of deferasirox as these patients approached LIC<3. Methods: THALASSA was a randomized, double-blind, placebo-controlled study of two deferasirox regimens (5 and 10 mg/kg/d) versus placebo in patients with NTDT. Patients randomized to deferasirox or placebo in the core could enter a 1-yr extension, with all patients receiving deferasirox (extension starting doses based on LIC at end-of-core and prior chelation response). The deferasirox safety profile was assessed between baseline and 6 months before reaching LIC<3 (Period 1), and the 6 months immediately before achieving LIC<3 (Period 2). Results: Mean ± SD deferasirox treatment duration up to reaching LIC<3 was 476 ± 207 d, and deferasirox dose was 9.7 ± 3.0 mg/kg/d. The exposure-adjusted AE incidence regardless of causality was similar in periods 1 (1.026) and 2 (1.012). There were no clinically relevant differences in renal and hepatic laboratory parameters measured close to the time of LIC<3 compared with measurements near the previous LIC assessment. Conclusions: The deferasirox safety profile remained consistent as patients approached the chelation interruption target, indicating that, with appropriate monitoring and dose adjustments in relation to iron load, low iron burdens may be reached with deferasirox with minimal risk of over-chelation. © 2014 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd