Thrombo-hemorrhagic liability in children with congenital heart diseases.

BACKGROUND: The precise mechanisms of the increased incidence of hemostatic abnormalities in congenital heart disease (CHD) have not been determined. The aim of the study was to evaluate some indicators of activation of platelets and vascular endothelial cells in patients with CHD, evaluation of bleeding liability of these patients, and correlation with the clinical presentation of these patients. METHODS: This work was carried out on 20 patients with cyanotic congenital heart diseases (CCHD), 20 patients with acyanotic congenital heart diseases (ACHD), and 20 healthy children who served as the control group, aged between 1 and 10years. All were subjected to full clinical examination, complete blood count, oxygen saturation, echocardiography, bleeding and coagulation times, PT, PTT, FDPs, plasma soluble P-selectin, E-selectin, and platelet factor 4 (PF4). RESULTS: There was significant prolongation of PT and PTT, and there was a significant lowering of platelet counts. These results were obtained in CCHD and ACHD, but were more significant in CCHD patients. There was a significant elevation in PF4 (55.0±25.5ng/mL), P-selectin (128.9±42.44ng/dL), and E-selectin (9461.5±1701.24pg/mL) levels in children with CCHD as compared to those with ACHD (PF4, 21±7.94ng/mL; P-selectin, 80.1±13.2ng/mL; E-selectin, 7969.6±2127.5pg/mL), and significant increase in both groups when compared to the control group (PF4, 8.1±4.7ng/mL; P-selectin, 27.83±9.73ng/mL; E-selectin, 6750.00±3204.00pg/mL). There was a significant negative correlation between oxygen saturation, plasma P-selectin (r=-0.865), E-selectin (r=-0.401), and PF4 (r=-0.792) in patients with CCHD. CONCLUSION: Patients with CHD-both cyanotic and acyanotic-have variable degrees of increased liability for both thrombosis and hemorrhage that represents some sort of adaptation to preserve hemostasis and to protect these patients against the clinical presentation of both thrombosis and bleeding. This is to say that CHD patients have their own point of balance between thrombogenicity and bleeding liability. Wide-scale studies are needed to detect the normal levels of different thrombohemorrhagic parameters of these patients.

Frequency of 11q23/MLL gene rearrangement in Egyptian childhood acute myeloblastic leukemia: Biologic and clinical significance.

BACKGROUND: Molecular cytogenetic abnormalities involving 11q23 are among the most common cytogenetic abnormalities in acute myeloid leukemia (AML) patients. AIM OF THE WORK: we aimed to evaluate the frequency of MLL/AF9 fusion gene in de novo AML patients, its impact on clinical features, and its prognostic significance. PATIENTS AND METHODS: Twenty-eight children patients with AML and 20 healthy controls were subjected to complete clinical examination and laboratory investigations including, complete hemogram and bone marrow (BM) examination. Diagnosis was based on FAB morphologic and immunophenotypic criteria. Detection of (MLL/AF9) fusion gene was assessed by dual color fluorescent in situ hybridization (FISH). Follow-up were carried out clinically and by blast count in BM, and response to therapy to detect the outcome of the disease. RESULTS: The incidence of MLL-fusion gene MLL/AF9 in AML cases was about (6/28) (21%). Four patients with MLL/AF9 fusion gene were newly diagnosed, two cases were at relapse and no patient at remission showed positivity. As regard the clinical outcome, five out of six MLL positive cases died, three of them during induction and two during relapse. The FAB AML subtypes with MLL/AF9 fusion were one M2, three M4, and two M5. CONCLUSION: MLL-fusion gene MLL/AF9 was found in about 21% of studied AML patients when assessed by FISH technique and this is of high clinical relevance as most of these abnormalities have been associated with poor prognosis.

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis.

BACKGROUND: A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 10(9)/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real-life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis. PROCEDURE: This non-interventional surveillance program assessed the monitoring of deferiprone therapy in clinical practice. A total of 294 patients with transfusion-dependent anemias received deferiprone, as monotherapy or with another chelator, for up to 1 year. The participating physicians were not given any instructions about treatment and monitoring beyond being referred to the information in the package insert. RESULTS: ANC monitoring was conducted at an average interval of 5 ± 4 weeks, and deferiprone was not always interrupted upon detection of neutropenia. One patient (0.3%) experienced agranulocytosis, and nine others (3%) experienced a total of 11 episodes of neutropenia. All neutropenia episodes resolved; median time to resolution was similar whether or not treatment was interrupted; and no case of neutropenia progressed to agranulocytosis. CONCLUSIONS: These data indicate that less frequent ANC monitoring and continuation of deferiprone therapy during neutropenia are not associated with prolonged neutropenia or with progression to agranulocytosis.