Vol 20, No 3 (2021)

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. This retrospective study was designed to analyze presenting features of ITP cases in Benha, evaluate outcomes in children and determine prognostic factors. This research was accepted by Research Ethics Committee (REC) of Faculty of Medicine, Benha University (chairman: Prof. Nermeen Adly Mahmoud). Ethics comittee refrence number MS 40-3/2019. Records of 308 children with ITP in Benha University Hospitals and Benha Children Hospital haematology clinics between May 2014 and January 2021 were retrospectively analyzed. Socio-demographic, clinical, and laboratory data of the studied children such as age, gender, the type of residence, the date of diagnosis, complaints at presentation, preceding vaccination or infection, the type of bleeding, initial platelet count, LDH (lactate dehydrogenase) level, initial treatment, and outcomes were recorded. A total of 308 children diagnosed with ITP were included, clinical courses were determined as newly diagnosed and chronic in 71.4% and 28.6%, respectively. The median age of patients at diagnosis was 5 ± 3.4 years. The male/female ratio was 1.14. The median age at diagnosis was significantly higher in chronic ITP patients (p < 0.001); patients ≥ 10 years were more likely to develop chronic ITP than younger ones (p = 0.029). Regarding residency, seasonality, type of bleeding and history of preceding infection or vaccination, the difference was not statistically significant. Initial platelet counts > 20 × 10⁹ were significantly more prevalent in chronic ITP (p < 0.001). LDH level at presentation was significantly higher in chronic cases (p = 0.046). Initial lines of treatment were the following: steroids, IVIG, and IVIG with steroids (in 88%, 5.2%, and 2.9% of the cases, respectively). A total of 3.9% of the children did not receive any treatment. There was no significant difference in the outcomes between the initial lines of treatment (p = 0.105). In our study, age > 10 years, female gender, higher platelet count and high LDH level at presentation were found to increase the probability of chronic ITP.

Anemia of prematurity is one of the most common and serious problems of neonatology. The main focus is to prevent of anemia in preterm infants. The aim of the study was to assess effectiveness of umbilical cord milking/delayed cord clamping and erythropoietin therapy in reducing red blood cell transfusions in extremely and very low birth weight infants. This clinical study was approved by the Commission on ethics of biomedical research (Protocol No. 12 November 17, 2016) and approved by the Scientific Council of National Medical Research Center for obstetrics, gynecology and perinatology named academician V.I. Kulakov of the ministry of Healthcare of the Russian Federation (Protocol No. 19 of November 29, 2016). Analysis of 482 extremely and very low birth weight infants was conducted (from 2008 to 2018). Umbilical cord milking or delayed umbilical cord clamping, both, and in combination with recombinant human erythropoietin therapy, decreasing the phlebotomy losses significantly reduces the need for transfusions of red blood cells in extremely and very low birth weight infants. The effectiveness of erythropoietin therapy, time of its start and various treatment schemes remain controversial, therefore further researches are necessary.

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

Infant high grade gliomas (HGG) are the most frequent tumors of the central nervous system in children below 1 year of age. Standard therapy involves surgical resection and chemotherapy. Prognosis in infant HGG is better than in older patients, however, the absence of effective regimens of anti-recurrence therapy and the impossibility of radiation therapy implementation predetermine a negative prognosis in the group of infant gliomas in case of disease progression. In most patients with infant HGG of hemispheric localization, gene rearrangements of receptor tyrosine kinases – NTRK1/2/3 (24%), ALK (41%), ROS1 (28%), MET (7%) are described. The results of tyrosine kinase inhibitor administration show high efficacy and safety in the treatment of patients with NTRK-positive gliomas. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The paper presents two examples of the successful use of targeted therapy in patients with infant HGG lacking the efficacy of the standard chemotherapy. In both cases, a persistent response was obtained: in the first case, a complete response to therapy was achieved, the duration of treatment is currently 1 year, in the second case – there is no progression of the disease during 20 weeks of therapy. Of the adverse events (AE) of targeted therapy in patients, only transitory neutropenia was noted in the first case, in the second case, AEs were not detected. In order to expand therapeutic options and prescribe targeted therapy drugs, a molecular genetic investigation of tumor tissue is mandatory for patients with hemispheric infant gliomas. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

Hb Lepore, as the result of fusion of the b- and d-globin genes, leads to decreased amount of non-a-globin chains availability for hemoglobin formation. Hb Lepore, up to now, was not identified among Russian patients. We provide clinical and laboratory information on Hb Lepore Boston–Washington in two cases, one of them familial. A small amount of abnormal Hb was detected by capillary electrophoresis, an abnormal globin chain was shown by HPLC, and the final diagnosis of Hb Lepore Boston– Washington was made by molecular biological analysis of globin genes. Peripheral blood for all affected people revealed RBC’s hypochromia microcytosis and normal Hb concentration. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.

Performance of surgical interventions in patients with severe hemophilia A on emicizumab requires the development of a protocol for the perioperative period management. Objective. To present the first experience of laparoscopic hernioplasty, hemostatic therapy and laboratory monitoring in a patient with severe hemophilia A on emicizumab. A transperitoneal hernioplasty was performed in a 31-year-old patient with severe hemophilia A on emicizumab. The patient received hemostatic therapy with recombinant FVIII for 5 days. Laboratory parameters (detection of FVIII via chromogenic and clotting methods, thromboelastography, determination of aPTT and FVII inhibitor titer) were monitored for 8 days. For a complete postoperative hemostasis, a significantly smaller amount of FVIII concentrate was required due to the lower frequency of administrations compared to similar surgical interventions in patients with severe hemophilia A who did not receive prophylactic therapy with emicizumab. According to thromboelastrography data, not a single episode of hypercoagulation was recorded. Emicizumab monotherapy can maintain adequate hemostasis during surgical procedures associated with a potentially low risk of perioperative bleeding in patients with hemophilia A. In other situations, the use of standard doses of FVIII concentrate concomitantly with emicizumab makes it possible to control hemostasis during postoperative period without the risk of thrombotic complications. The patient has signed a consent to the use of information, including photos, for research purposes and in publications.

The new coronavirus infection (currently classified as COVID-19), first identified in December 2019 in Wuhan, China, has contributed to a significant increase in global mortality. Coagulopathy is a common disorder in COVID-19 patients, which develops in parallel with respiratory failure. Currently, COVID-19 continues to be a life-threatening disease and requires new developments and solutions to define preventive and curative strategies. Studies often report an abnormality in the balance of coagulation and fibrinolytic systems in COVID-19, but there is still no adequate set of laboratory tests that could provide a diagnosis of coagulopathy in COVID-19. This review analyzes current studies on the clinical manifestations of COVID-19 coagulopathy, and also analyzes the informativeness of laboratory hemostasis tests in relation to the severity of the disease and clinical outcomes.

The high mortality rate in COVID-19 can be explained by the development of a hyperinflammatory syndrome, characterized by a cytokine storm and extensive thrombus formation. The main direction for preventing the development of hyperinflammatory syndrome and reducing mortality from COVID-19 is immune therapy, however, the data on the efficacy and criteria for prescribing immune drugs is very heterogeneous. The purpose of this review is to analyze the results of clinical trials on the use of various types of immune therapy and possible criteria for its prescription. Analysis of literature data showed that the most effective among the existing variants of immune therapy were monoclonal antibodies to IL-6, the use of donor plasma in the early stages of treatment. Janus kinase inhibitors, intravenous immunoglobulin improved the clinical characteristics of patients, but did not affect the mortality rate. An analysis of possible predictor-markers of the development of a cytokine storm revealed an increase in the number of neutrophils > 11 × 10³/ml, a decrease in the number of lymphocytes > 1000 × 10³/ml, an increase in the level of IL-6 > 24 pg/ml, LDH > 300 IU/L, D-dimer > 1000 ng/ml, and CRP > 10 mg/dL as the most informative and accessible in clinical practice at the moment.