Gülersu Irken

Assessment of clinical impact and predisposing factors for neonatal thrombocytopenia

Thrombocytopenia is a common hemostatic abnormality in the newborn infant. The early diagnosis of thrombocytopenia and the underlying primary pathology process play an important role in reducing the risk of severe complications and mortality. We performed a 2-year prospective study of 643 neonates admitted to our neonatology unit to determine the frequency, predisposing factors, and clinical impact of thrombocytopenia. Thrombocytopenia developed in 18.2% of the preterm neonates and 0.8% of the term neonates. Prematurity, sepsis, hypoxia, intrauterine growth retardation, and disseminated intravascular coagulation were identified as predisposing factors for thrombocytopenia. The incidence of complications and mortality were higher in thrombocytopenic infants. Especially the prognosis was worse in cases who had mucosal hemorrhage, without a relation with the degree of thrombocytopenia. The thrombocytopenia occurred by day 2 in 43% of the infants, and resolved by day 8 in 61%. The platelet count nadir occurred by day 2. Since thrombocytopenic infants are at greater risk for bleeding, and the thrombocytopenia itself may have contributed to the high mortality, predisposing factors such as prematurity, infections, hypoxia must be eliminated by prividing better care, giving adequate hygiene of both mother and the baby during the prenatal, natal, and neonatal period.

Disseminated intravascular coagulation in pediatric patients: clinical and laboratory features and prognostic factors influencing the survival.

Although disseminated intravascular coagulation (DIC) has been a well-known disorder for many years, there is lack of sufficient number of clinical trials about incidence, frequency of underlying disorders, and prognosis of DIC in children. The aim of this study was to evaluate the frequency, etiologic factors, and clinical and laboratory findings of DIC and to determine the prognostic factors influencing the mortality in hospitalized pediatric patients. Medical records of 5535 children who were hospitalized were investigated. Sixty-two patients who were diagnosed as acute DIC were enrolled. The frequency of DIC was 1.12%. The underlying etiologic factors were infection in 59 patients (95.2%) and major trauma in 3 patients (4.8%). The frequency of bleeding and thrombosis was 48.8 and 4.8%. Respiratory, cardiovascular, hepatic, renal, neurologic, and gastrointestinal dysfunction was present in 71, 67.7, 35.5, 16.1, 16.1 and 11.3% of patients, respectively. Respiratory and cardiovascular dysfunctions were significantly associated with mortality. Multiorgan dysfunction syndrome (MODS) was present in 85.5% of the patients, and 54.8% of the patients had developed acute respiratory distress syndrome (ARDS). Mortality rate was significantly high in patients with MODS and ARDS. In multivariete logistic regression analysis, only ARDS and cardiovascular dysfunction had predictive and prognostic value on mortality. None of the diagnostic laboratory tests had predictive or prognostic value and the degree of abnormality of these tests did not show any correlation with mortality. In conclusion, DIC is not a rare disorder in hospitalized children, especially in patients with sepsis, and MODS, ARDS, and respiratory and cardiovascular system dysfunctions are poor prognostic factors.

Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.

Parvovirus B19: A cause for aplastic crisis and hemophagocytic lymphohistiocytosis†

A 17-year-old female patient with hereditary spherocytosis (HS) presented with fatigue, nausea, headache, and fever for 2 days. On physical examination, she had high fever, pallor, icterus, and mild splenomegaly. Peripheral blood examination demonstrated a Hb level of 8.2 g/dL, WBC 1.9 10/L, platelets 74 10/L,MCV88.9 fL,MCH33.9 pg, MCHC 38.1 g/dL, and reticulocyte 0.7%. The peripheral blood smear revealed 70% neutrophils, 18% lymphocytes, 10% monocytes and 2% band neutrophils, vacuolization in neutrophils andmonocytes;many spherocytes. Bonemarrow aspirate showed hypocellularity with many hemophagocytic histiocytes, giant proerythroblasts, and absence of mature erythroblasts, suggesting a parvovirus infection (Fig. 1). On the second day of hospitalization, her Hb level decreased to 5.6 g/dL. Hepatomegaly developed and splenomegaly progressed. Serum ferritin level was 7,478 ng/mL, triglyceride 1.17 nmol/L and fibrinogen 2.31 g/L. Prothrombin and partial thromboplastin time were within normal limits, but the D-dimer level was very high (3,004 mg/L). The serum folic acid levelwas normal. Parvovirus B19 IgMand IgGwas found to be positive by indirect immunofluoroscent assay. Secondary hemophagocytic lymphohistiocytosis (HLH) and aplastic crisis due to Parvovirus B19 infection was diagnosed. She received red blood cell transfusions and intravenous immunoglobulin was given for the HLH. Shewas discharged from the hospital after a marked clinical and hematological improvement on day 6 with a Hb level of 9.9 g/dL, WBC 4.8 10/L and platelets 198 10/L. Ten days later, her 13-year-old brother, who also had HS, presented with similar clinical features and Parvovirus B19 infection. He improved with red blood cell transfusions and supportive treatment. In patients with hemolytic anemia, with shortened red cell survival time and expanded marrow erythropoiesis, Parvovirus B19 infection can lead to a transient aplastic crisis. Giant proerythroblasts and absence of mature erythroblasts are characteristic findings of parvovirus infection [1–3].

Platelet activation in congenital heart diseases

The research presented here investigated platelet activation in cyanotic and acyanotic congenital heart diseases (CHD). Children with cyanotic CHD are prone to both thrombosis and hemorrhage. However, patients with acyanotic CHD may also have a mild bleeding disorder. The platelet activation in CHD was investigated in support of a hypothesis that platelet activation may play a role in the hemostatic abnormalities reported in these patients. Platelet activation was determined by using flow cytometry with anti‐CD62 monoclonal antibody (mAb), which has been shown to be a specific marker of platelet activation. Thirteen children with cyanotic CHD, 33 children with acyanotic CHD and 17 healthy children serving as controls were studied. Platelet activation was significantly higher in the cyanotic group and also in the acyanotic group compared with the healthy children (P = 0.0000 and P = 0.019, respectively). In the cyanotic group, platelet activation showed a direct correlation with arterial O2 saturation (SaO2) (P = 0.014). There was no correlation between platelet activation and erythrocyte related parameters in either group. Platelet activation occurs in CHD, particularly in patients with cyanotic CHD (even in patients with no evidence of clinical thrombosis) and it may play a role in the pathogenesis of thrombotic disorders seen in these patients.

FACTOR VIII INHIBITORS IN PATIENTS WITH HEMOPHILIA A

In 58 hemophilia A patients aged 1–18 years (mean 9.5 ± 4.7 years), the prevalence of inhibitors was found to be 27% by the Bethesda method in November 1995. Inhibitor activity was not detected in any of 14 patients with mild hemophilia while it was present in 9 of 27 (33%) patients with moderate, and 7 of 17 (41%) with severe disease. During follow-up, the inhibitors were transient in 10 of 16 patients (17%) and the prevalence of inhibitors was 10% at the end of the study. Our study has demonstrated that the patients’ age, factor VIII (F VIII) coagulant activity levels, type of F VIII replacement therapy, and frequency of F VIII administration affect inhibitor development, and these factors should be considered in the follow-up of hemophiliacs.

Platelet Activation during the Early Neonatal Period

The first week of life is a time when hereditary or more frequently acquired factors lead to some important differences in the hemostatic mechanism of the newborn. It has been well known that ill neonates are prone to both hemorrhage and thrombosis. The aim of this study was to answer the question of whether there is a difference in platelet activation in healthy neonates during the first days of life that may contribute to both hemorrhage and thrombosis in the presence of additional pathologic insults. Platelet activation was determined with flow cytometry using monoclonal antibodies in 63 healthy children (29 neonates, 17 infants, and 17 older children). There was no significant difference in platelet activation among these three age groups (p > 0.05). In addition, platelet activation did not show any significant relationship to age, sex, mode of delivery, or blood bilirubin concentration (p > 0.05). It has been previously reported that platelet activation occurs at the time of birth. We could not find any evidence that healthy newborns during the first 3 days of life exhibit increased platelet activation. Further studies on platelet activation in ill neonates will help to clarify whether platelet activation plays a role in the pathogenesis of thrombotic and/or hemorrhagic disorders.

CLINICAL FEATURES, TREATMENT RESPONSES, AND OUTCOME OF CHILDREN WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA

The authors investigated demographics, clinical and laboratory features, treatment responses, and outcomes of 93 children (median age 5 years) admitted for idiopathic thrombocytopenic purpura (ITP). The therapy responses of high-dose methylprednisolone (HDMP) (n = 77) and intravenous immunoglobulin (IVIG) (n = 10) treatments were similar. None of the patients with hemorrhage died. Fifteen patients (16.1%) had progressed into chronic ITP. Seven infants had a probable relationship with vaccination; none of these infants progressed into chronic ITP. In conclusion, the overall prognosis in childhood ITP is good. The therapy responses of HDMP and IVIG treatments are similar. Also, ITP cases who havw vaccination history have a benign course.

Autoimmune lymphoproliferative syndrome: report of two cases and review of the literature

Abstract. Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease occurring in childhood. Recently, it has been shown that heritable mutations in Fas or Fas ligand genes, which regulate lymphocyte survival by triggering apoptosis of lymphocytes, are the most frequent cause of ALPS. Patients with ALPS frequently have lymphadenopathy, splenomegaly and hepatomegaly, especially at young ages. A positive result of the Direct Coombs test, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura are the most common features of autoimmunity in patients with ALPS. Elevated numbers and percentages (>1%) of double-negative (CD4–CD8–) T cells, and characteristic pathologic findings in lymph nodes or spleen are other important diagnostic features. In this report, we present the clinical, immunologic, and pathologic features of two children who were diagnosed with ALPS. The early recognition of ALPS in children with enlarged lymph nodes, hepatosplenomegaly, and autoimmune hematologic features has important diagnostic and prognostic value in avoiding expensive and time-consuming studies and unnecessary treatments. The ratio of CD4–CD8– T cells, immunoglobulin levels and the histopathologic features of lymph nodes should be rapidly determined in these patients in order to establish an early diagnosis and treatment.

Mutational analysis of beta-thalassemia cases from the Aegean region of Turkey using an allele-specific oligonucleotide hybridization technique.

The aim of the present study was to evaluate the point mutations of beta-thalassemia patients from the Aegean region of Turkey by using an allele-specific oligonucleotide hybridization technique. DNA isolated from peripheral blood samples of 75 children with beta-thalassemia major or intermedia was analyzed using a Bio-Rad mDxTM-Be Tha Gene 1 kit. We determined mutations in 56 (74.6%) patients. The allelic frequency of mutations in 150 chromosomes was as follows: IVS-I-110 (G–A) 44.1%, IVS-I-1 (G–A) 28.2%, IVS-I-6 (T–C) 13.3%, IVS-II-745 (C–G) 9.3%, IVS-II-1 (G–A) 2.7%, Cd 39 (C–T) 2.4%, –87 (C–G) 0% and Cd 6 (–A) 0%. The distribution of the mutation types was consistent with the findings of other research groups.