Neutropenia in Patients with Thalassemia Major.

Monitoring of the neutrophil count has become an important issue in the management of thalassemia patients after the introduction of the new oral chelator deferiprone, as this chelator has been associated with agranulocytosis and milder neutropenias. Although a clear relation between deferiprone and agranulocytosis has been demonstrated, it is unclear whether milder neutropenias are due to deferiprone use or to other factors such as hypersplenism, infections, autoantibodies, or other drugs. In this study we evaluated 7,708 consecutively blood counts and leukocyte differential obtained between August 2003 to June 2004 from 344 patients with thalassemia major, aged 2 to 40 years, treated with deferiprone (N=39), desferrioxamine (N=179), ICL670 (N=45), or a combination of deferiprone and desferrioxamine (N=81). Complete blood count and differential were performed with Coulter LH 750 automated haematology analyzer (Beckman Coulter, Miami, FL), which can detect nucleated red blood cells (NRBC) and correct the white blood cell (WBC) count in the presence of NRBC, platelets clumps, unlysed or fragmented RBC. The capability to correct the WBC count is particularly relevant in the monitoring of the neutrophil counts of patients with excessive NRBC, which could lead to potential errors in the differrential count. Neutropenia was defined as a neutrophils count below 1500 cells/μL, whereas agranulocytosis was defined as a neutrophil count below 500 cells/μL. No episodes of agranulocytosis were observed. Episodes of neutropenia (range 850 – 1490 neutrophils/μL) were observed in 29 (8,4%) patients. Repeated episodes of neutropenia were observed in 7 of the 29 patients. At the time of neutropenia, 23 (79%) of the patients were being chelated with desferrioxamine, 2 (7%) with deferiprone, 3 (10%) with a combination of both chelators, and 1 (3%) with ICL670. Considering the type of chelation, neutropenia was observed in 12,8% of patients being treated with desferrioxamine, 5% in patients treated with deferiprone, 3,7% in patients treated with combination therapy, and 2.2% in patients treated with ICL670. The severity of neutropenia, assessed as absolute neutrophil count, was not different on the basis of the type of chelation (p=0,26). Neutropenia was more frequent in children than in adults (31% vs 7.8%, respectively, p=0.0001). No statistically significant difference in the incidence of neutropenia was found between males and females (10.2% vs 6.5% respectively, p=0.2), anti-HCV positive and negative (7.7% vs 10.3% respectively p=0.43), or splenectomized and non-splenectomized patients (11.1% vs 8.1% respectively, p=0.5). Neutropenia appears to be a common event in patients with thalassemia major, irrespectively of the chelation therapy used. The higher incidence in children may be secondary to a greater frequency of viral infections at this age, which may produce neutropenia with several mechanisms including redistribution, sequestration and destruction of neutrophils.