Rare inherited coagulation disorders in young children in Oman.

Background: Rare coagulation disorders represent 3-5% of all inherited coagulation deficiencies and are usually inherited as autosomal recessive. Oman has high rate of consanguineous marriages; we aimed to study the prevalence, presentation and management in affected Omani children. Materials and Methods: Retrospective study in pediatric patients with rare coagulation disorders in a tertiary hospital in Oman from 2009 to 2020. Results: Rare coagulation disorders were diagnosed in 79 patients (39 males/40 females), aged 1 day to 13 years, accounting for 24.7% (79/319) of all children with inherited coagulation disorders; remainder included patients with hemophilia and von Willebrand disease. FXI deficiency was most common with prevalence of 39.2%, followed by fibrinogen disorders 32.9%, FVII 18.9%, FV 5%, FXIII 2.5%, and FX deficiencies 1.2%. Manifestations ranged from mild to serious to rare/atypical; presentation at birth, ruptured-hemorrhagic ovarian cyst, splenic laceration-rupture, and sight-threatening retrobulbar-intraocular hemorrhage. Intracranial hemorrhage (ICH) occurred in 9/79 patients, it was initial mode of presentation in seven of them. Global developmental delay as a complication occurred in three. Standardized treatment strategies were used with prophylaxis initiation early in life in severely affected children. Conclusions: This ethnic group demonstrated unique features in terms of: heterogenous/atypical presentations; severe manifestations in moderate phenotype hypofibrinogenemia; clinical severity and laboratory phenotype correlation in FV deficiency; poor association between factor activity level and bleeding severity in FVII deficiency and severe bleeding tendency despite moderate laboratory phenotype in FXIII deficiency. We recommend multicenter collaboration to identify the genotype-phenotype correlation and therapeutic options of such rare, yet serious disorders.

Anthracycline-related acute cardiotoxicity in a very young Omani patient with acute myeloid leukaemia.

Anthracycline-related cardiomyopathy is of concern in children treated for acute myeloid leukemia (AML). Risk is dose-dependent, increasing with higher doses. We aim to highlight the risk of early-onset cardiotoxicity with low-cumulative anthracycline dose in a young Omani boy with AML. We conclude in the presence of other known risk factors for cardiac dysfunction, there is probably no risk-free anthracycline dose.

Selected highlights of the VIII International Symposium of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) on Growth, Puberty and Endocrine Complications in Thalassaemia. Auditorium of the Sultan Qaboos University (SQU) Muscat (Sultanate of Oman), 20th of December 2014.

The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on the 20th of December, 2014. The symposium included four sessions on a wide range of topics covering growth disorders and endocrine complications in thalassaemia. Despite the fact that endocrine complications are very common in multi-transfused thalassaemia patients a recent survey conducted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported by hematologists or pediatricians experienced in thalassaemias or thalassaemia syndromes in following endocrine complications included: Lack of familiarity with medical treatment of endocrine complications, interpretation of endocrine tests, lack of collaboration and on-time consultation between thalassaemic centres supervised by haematologists and endocrinologists. Endocrine monitoring of growth, pubertal development, reproductive ability and endocrine function in general are essential to achieve a good quality of life as well as controlling the pain which results from the defects of bone structure, all of which increase with the age of patients. Such comprehensive care is best provided by coordinated, multidisciplinary teams working in expert centres. The multidisciplinary team must include an endocrinologist, preferably someone experienced in the management of hormonal deficiencies caused early in life by transfusion-induced iron overload.

Single dose darbepoetin alfa is useful in reducing red cell transfusions in leukemic children receiving chemotherapy.

The role of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia (CIA) is becoming increasingly recognized in the field of medical oncology, with paucity of data in pediatrics. We evaluated the efficacy and tolerability of a single-dose darbepoetin alfa, a long-acting ESA, given to 35 pediatric acute lymphoblastic leukemia (ALL) children during induction chemotherapy. Compared to a retrospective control group, the studied patients have required significantly less units of packed red blood cells (0.88 units/patient in the studied group versus 2.04 units in controls), with no major side effects. We recommend further prospective double-blinded studies with more tailored dosing regimens in pediatric ALL cases and solid tumors.

Comparative assessment of deferiprone and deferasirox in thalassemia major patients in the first two decades-single centre experience.

Iron overload is mainly responsible for the morbidity and mortality in patients with beta thalassemia major (TM). Our aim was to compare treatment outcomes with oral iron chelators, deferiprone (DFP), and deferasirox (DFX) in the first two decades on therapy. Seventy patients with TM (mean age ± SD, 7.9 ± 4.2; range 1.5-17 years) attending the pediatric day care unit for regular transfusional support were enrolled in this cross-sectional cohort study. The patients were treated either with DFP at the dose of 75-100 mg/kg/d in three divided doses after food or DFX at the dose of 25-40 mg/kg/d as single dose before food. Mean serum ferritin (±SD) was lower in patients below 10 years (n = 44) at 1283 (±600) ng/mL when compared with patients ≥10 years (n = 19) at 1546 (±589) ng/mL. There was no significant difference in mean serum ferritin (±SD) level in patients receiving DFP (1360 ± 589) versus DFX (1260 ± 641) in this cohort, P > 0.05. 67% of the patients had Vitamin D deficiency (<50 umol/L). Our results show comparable efficacy of DFP and DFX with regards to iron chelation as estimated by serial serum ferritin levels; however, MRI T2* values were higher in the DFP-treated patients compared to DFX treatment.

T2* MRI in regularly transfused children with thalassemia intermedia: serum ferritin does not reflect liver iron stores.

Nontransfused patients with thalassemia intermedia (TI) accumulate iron due to increased gastrointestinal absorption of iron. Recent studies using T2* MRI revealed that serum ferritin does not reflect the severity of iron overload in nontransfused TI patients. We evaluated the iron overload status in TI children on monthly transfusion. Based on serum ferritin levels, 11 such patients (mean age 13.18 ± 4.09 years), were classified into two groups, group 1 (six patients) and group 2 (five patients) with serum ferritin levels below and above 1000 ng/mL, respectively. T2* MRI assessments were done for evaluation of hepatic and cardiac iron status. Group 1 and group 2 had mean serum ferritin levels of 817.300 ± 244.690 ng/mL and 1983.80 ± 662.862 ng/mL, respectively (P = .003). T2* MRI showed comparable moderate to severe hepatic iron overload status in both. None of the patients had myocardial iron deposition. We conclude that serum ferritin does not reflect the hepatic iron overload status in our patients with TI on regular transfusion.

Prepubertal Hypertransfusion in Thalassemia Intermedia: A Case Report of Sustained Positive Effects on Growth, Splenic Function and Endocrine Parameters.

We report a known case of thalassemia intermedia (Hb Dhofar) who in spite of mild thalassemic facies, attained his normal genetic height, pubertal maturity and improved self-image with minimal splenomegaly through a hypertransfusion/chelation regimen that was started just before puberty and maintained for 5 years. As there are no clear guidelines in the management of patients with thalassemia intermedia, the option of hypertransfusion/chelation during the pubertal growth spurt may alleviate some of the complications associated with thalassemia intermedia.