Successful Treatment of a Child with Hemoglobin Hammersmith with Hematopoietic Stem Cell Transplantation.

Hemoglobin (Hb) Hammersmith, formed by serine substitution for phenylalanine at residue 42 in the beta-globin chain, is a very rare variant of unstable hemoglobin with low oxygen affinity. For patients with hemoglobinopathies, it is well-established that hematopoietic stem cell transplantation provides a complete cure, but the literature on its role for those with Hb Hammersmith is limited. A seven-month-old girl who was examined for anemia and splenomegaly was followed up for congenital hemolytic anemia. The patient with visible cyanosis of the lips and whose p50 was low in blood gas was diagnosed with Hb Hammersmith through the DNA sequence analysis. During the follow-up, frequent blood transfusions had to be given due to anemia aggravated by infections. Following a successful hematopoietic stem cell transplant from an HLA-matched sibling, the patient completely recovered from Hb Hammersmith. The case is presented because of its rarity.

[Autochthonous Case of Malaria Prediagnosed as Leukemia]. / Lösemi Ön Tanili Yerli Sitma Olgusu.

Malaria is a parasitic disease transmitted by infected female Anopheles mosquitoes. There are five species of Plasmodium species that can infect humans. Of these species, especially P.falciparum and P.vivax pose the greatest threat to human health. In the 2014 report of the World Health Organization, it was reported that there were no locally acquired cases of malaria in 16 countries including Türkiye. Malaria cases originating from outside the country and imported due to migration, travel and working abroad are reported as import cases. In this report, a case of non-imported malaria followed with a preliminary diagnosis of leukemia was presented. A 14-year-old female patient who was admitted to a health institution with complaints of high fever, headache, chills, nausea-vomiting, and diarrhea that had been going on for two weeks, was pre-diagnosed as leukemia and was referred to Manisa Celal Bayar University Faculty of Medicine, Hafsa Sultan Hospital, Department of Pediatric Hematology and after pancytopenia was detected in the complete blood count. The anamnesis of the patient revealed that she had no history of international travel and that she had been prescribed medications such as paracetamol, amoxicillin, and metoclopramide for flu-like complaints while working in the Southeastern Anatolia, Aegean, and Mediterranean Regions of Türkiye. Bone marrow aspiration was performed for the etiological examination of pancytopenia. Giemsa-stained blood smears, rapid diagnostics, and real-time quantative polymerase chain reaction (qRt-PCR) analyses were performed in the medical parasitology laboratory and malaria was suspected in both bone marrow and peripheral blood smears. P.vivax erythrocytic forms and gametocytes were present in abundance in smear preparations stained with Giemsa, and rapid diagnosis kit was positive for P.vivax. The strain was genotyped as P.vivax by qRt-PCR analysis. For the treatment of the patient, airalam (artemether + lumefantrine) tablets were provided with 2 x 4 daily posology for three days after the diagnosis, and primaquine was provided after one week of the diagnosis as 1 x 2 tablets (1 x 15 mg) for 14 days, and the patient was discharged without complications following the treatment regimen. The fight against malaria continues uninterruptedly since the establishment of the Republic of Türkiye. Tropical diseases, especially malaria, is of great importance for Türkiye due to numerous reasons such as its location in the subtropical region where Anopheles mosquitoes are capable of malaria transmission, it is situated at the crossroads on the migration routes between continents where human traffic is busy, there are many people who go abroad for work and most importantly rising temperatures due to climate change. For this reason, this case report is important to emphasize the importance of malaria for the country and to increase the awareness of clinicians and laboratories about malaria and the possibility of autochthonous malaria transmission in Türkiye.

A child with intravascular fasciitis mimicking deep vein thrombosis: a case report.

BACKGROUND: Intravascular fasciitis (IF) is a benign, reactive, myofibroblastic proliferation that originates from the superficial or deep fascia of small / medium-sized arteries and veins. CASE REPORT: An 8-year-old male patient was admitted to a health center with the complaint of swelling in the inguinal region. Lower extremity venous Doppler ultrasonography showed deep vein thrombosis (DVT) of the femoral vein and anticoagulation with low-molecular weight heparin (LMWH) was initiated. The patient was referred to our center for follow-up. The D-dimer level was detected within normal limits. Doppler ultrasonography was repeated and showed an intraluminal expanding mass lesion with increasing vascularity, without distinct borders and LMWH was discontinued. This lesion at the sapheno-femoral junction was excised surgically and the histopathological examination revealed intravascular fasciitis. CONCLUSION: Clinicians should be aware that the clinical findings of IF may mimic sarcoma and thrombosis.

α-Thalassemia frequency and mutations in children with hypochromic microcytic anemias and relation with ß-thalassemia, iron deficiency anemia.

The majority of the anemias during childhood are hypochromic and microcytic. The aim of the present study was to determine the status of α-thalassemia mutations and its association with other etiologies, such as iron deficiency anemia (IDA) and ß-thalassemia trait, that are frequently seen hypochromic microcytic anemias in children. Children with hypochromic microcytic anemias were included in the study. Serum iron (SI), total iron-binding capacity (TIBC), ferritin levels, and hemoglobin electrophoresis with high-performance liquid chromatography (HPLC) method were analyzed. Reverse hybridization of biotinylated polymerase chain reaction (PCR) product method was used for detection of α-globin gene mutations. Of the 46 patients involved in the study, 54.3% (n = 25) were boys, and 45.7% (n = 21) were girls. Iron deficiency anemia and ß-thalassemia trait were diagnosed in 67.4% (n = 31) and 19.5% (n = 9), respectively. In 17.4% there were α-thalassemia mutations (in 10.9% 3.7 single-gene heterozygote mutation, in 4.3% 20.5-kb double-gene deletion mutation, and in 2.2% α-2 poly-A-1 heterozygote mutation was detected). In 2 patients (4.3%) no etiology was determined. In 2 patients (4.3%) association between iron deficiency anemia and α-thalassemia, in 1 patient (2.2%) association between ß and α-thalassemia was detected. In conclusion, α-thalassemia carrier status and its association with other etiologies are frequently seen in Manisa. So, α-thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemias, especially in cases without iron deficiency (ID) and ß-thalassemia carrier state.

Diagnostic yield of upper gastrointestinal endoscopy in the evaluation of iron deficiency anemia in older children and adolescents.

Iron deficiency anemia (IDA) is frequent in childhood. Inadequate nutrition and gastrointestinal malabsorption are the frequent causes of IDA in children. But reduced iron absorption and insidious blood loss from the gastrointestinal tract has been identified as the most frequent causes of IDA in older children and adolescents. Therefore the authors evaluated the frequency and etiologies of the upper gastrointestinal system pathologies causing IDA in older pediatric population. Patients with known hematological or chronic diseases, heavy menstrual flow, and obvious blood loss were excluded from the study. Forty-four children between the ages of 9.5 and 17.5 years and diagnosed with IDA were enrolled. They underwent upper gastrointestinal endoscopy and biopsy from esophagus, stomach, and duodenum. Mean age and hemoglobin (Hb) levels of study group (32 boys, and 12 girls) were 14.6 ± 2.0 years and 7.9 ± 1.8 g/dL, respectively. Only 1 patient had a positive serology testing with anti-tissue transglutaminase and small bowel biopsy correlating with celiac disease. Endoscopy revealed abnormal findings in 25 (56.8%) patients (21 endoscopic antral gastritis, 2 active duodenal ulcers, and 2 duodenal polyps). Helicobacter pylori (HP) infection was identified by using antral histopathological evaluation in 19 of 44 children (43.2%). In 2 of duodenal samples, one patient had celiac disease, and the other one was diagnosed as giardiasis. In conclusion, there are different etiologies resulting in IDA in older children and adolescents. When older children and adolescents are found to have iron deficiency, HP infection and other gastrointestinal pathologies should be ruled out before iron deficiency treatment.

Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: A report of two cases.

We report two male cases (4- and 5-years-old) of intrathecal methotrexate overdose. The two boys with acute lymphoblastic leukemia were to receive intrathecal injection of methotrexate. Instead of the prescribed 12 mg, they both received a dose of 120 mg. The initial cerebrospinal fluid samples showed methotrexate concentration of 2.24x10-2M in case 1 and 1.32x10-2M in case 2. The cases were successfully treated with cerebrospinal fluid (CSF) exchange and intravenous folinic acid rescue. The favorable outcome in our cases suggests that CSF exchange is safe and that folinic acid rescue may be adequate to prevent sequelae in patients subjected to intrathecal MTX overdoses up to 120 mg. We propose CSF exchange and intravenous folinic acid as the mainstay of treatment. In addition to the staff's failure to check the drug label carefully, the marked resemblance of the two dose preparations of MTX may have been contributory.

Genetic basis and hematologic manifestations of sitosterolemia in a group of Turkish patients.

BACKGROUND: Sitosterolemia is a rare lipid disorder caused by mutations in adenosine triphosphate-binding cassette genes (ABCG) 5 and 8. OBJECTIVE: To evaluate the phenotypic/genotypic features of sitosterolemia in a group of Turkish patients. METHODS: Seven probands with unexplained hematologic abnormalities and their 13 relatives were enrolled. Sterol levels were measured by gas chromatography and genetic studies were performed using Sanger sequencing. Individuals were diagnosed with sitosterolemia if they were found to have frankly elevated sitosterol level >15 µg/mL and/or pathogenic variants of the ABCG5/ABCG8. RESULTS: The seven probands and their six relatives  were diagnosed with frank sitosterolemia, and all these patients had hematologic abnormalities. The remaining seven relatives were asymptomatic heterozygous carriers. Three novel variants in the ABCG5 gene (c.161G>A, c.1375C>T, IVS10-1G>T), one novel variant in the ABCG8 gene (c.1762G>C) and one known variant in the ABCG5 gene (c.1336 C>T) were identified. No variant was identified in one case. The mean sitosterol level was significantly higher and mean platelet count was significantly lower in patients with homozygous variants compared to heterozygous variants (p<0.05, for all). Diets low in plant sterols were recommended for 13 symptomatic cases. Four homozygotes received ezetimibe, and their splenomegaly, anemia, and thrombocytopenia completely resolved except one. CONCLUSION: The five pathogenic variants identified in this study indicate the genetic heterogeneity of sitosterolemia in Turkish population. Patients with unexplained hematologic abnormalities (specifically macrothrombocytopenia) should have their sterol level measured as initial testing. Ezetimibe can be a good choice for sitosterolemia.

Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

Coexistence of symptomatic iron-deficiency anemia and duodenal nodular lymphoid hyperplasia due to giardiasis: case report.

Iron-deficiency anemia due to iron malabsorption and duodenal nodular lymphoid hyperplasia (NLH) has been described in children with Giardia intestinalis infection. Also, symptomatic iron-deficiency anemia is rarely encountered in male adolescents. A 14-year-old boy underwent esophagogastroduodenoscopy for investigation of symptomatic iron-deficiency anemia (hemoglobin 5.8 g/dL, mean corpuscular volume 65.3 fL, serum ferritin < 1.5 ng/mL). He had a sufficient diet for iron and recurrent bouts of diarrhea without melena. At upper endoscopy, duodenal mucosa was diffusely nodular. Histopathologic evaluation of biopsy samples from the duodenum revealed infection with Giardia intestinalis. His anemia improved with metronidazole and iron treatment.

The evaluation of blood donor deferral causes.

Safety of blood and blood products is a major problem all over the world. Screening for the markers of infectious diseases is an incomplete solution. One of the most important steps in improving the safety of blood and blood products is donor selection. In this study, causes of donor deferral were evaluated retrospectively in the blood center of a children's hospital. Analysis of the deferrals showed that the most commonly defined causes were recent sexual exposure in high-risk activity, recent ingestion of medication, low hemoglobin level, abnormal blood pressure, being underweight, tattoos, piercing or acupuncture in the preceding 6 months, recent history of infection and presenting for a subsequent donation too soon, elevation of transaminases, presence of the markers of the infectious diseases.

A rare familial thrombocytopenia: May-Hegglin anomaly report of two cases and review of the literature.

May-Hegglin anomaly is a hereditary thrombocytopenia associated with giant platelets and large basophilic, cytoplasmic inclusion bodies (resembling Döhle bodies) in the granulocytes. Patients may experience easy bruising, recurrent epistaxis, gingival bleeding, menorrhagia and sometimes excessive bleeding associated with surgical procedures. Failure to appropriately diagnose May-Hegglin anomaly could result in inappropriate treatment. In states of chronic thrombocytopenia associated with large platelets, including chronic idiopathic thrombocytopenic purpura, May-Hegglin anomaly should be considered in the differential diagnosis. In this case report, we present a five-year-old girl previously followed as idiopathic thrombocytopenic purpura without bleeding symptoms and a 14-year-old boy who were diagnosed with May-Hegglin anomaly.

Hyperleukocytosis in childhood acute lymphoblastic leukemia: complications and treatment outcome.

Hyperleukocytosis, defined as a peripheral leukocyte count ≥ 100x109/L, is seen in 5-20% of newly diagnosed cases of childhood leukemia and is a poor prognostic factor. In this study, we aimed to examine the presenting clinical and laboratory features, complications, and treatment outcome of 47 children with acute lymphoblastic leukemia (ALL) and hyperleukocytosis who were diagnosed and treated in four medical centers of Izmir between January 1990 and January 2001. The median age was 5.0 years (range: 0.1-16.3 years). Median white blood cell count was 495x109/L (range: 107x109/L- 794x109/L). Forty-two of 47 patients (90%) had hepatosplenomegaly, 5 (11%) had respiratory distress, 3 (6%) had neurologic symptoms, 3 (6%) had diffuse cervical lymphadenopathy, and 3 (6%) had acute renal failure at admission. Ten of 47 patients (21%) had central nervous system involvement, and 17 (36%) had mediastinal mass. Ten patients (21%) had coagulopathy and 15 patients (32%) had metabolic complications (8 patients had hyperuricemia, 4 had hyperphosphatemia, 2 had hyperuricemia, hyperphosphatemia and hypercalcemia, and 1 had hypocalcemia) before the initiation of therapy. Forty of 47 patients (85%) with hyperleukocytosis were effectively managed with intravenous hydration, alkalinization, and allopurinol therapy. Early death during remission induction therapy occurred in 5 patients (11%) with respiratory distress and sepsis. Kaplan-Meier estimates of event free survival and overall survival were 37.0% and 40.5%, respectively.

Premature labor and leukoerythroblastosis in a newborn with parvovirus B19 infection.

Leukoerythroblastosis is a rarely observed disease characterized by the presence of leukocytosis, erythroid and myeloid blast cells in peripheral blood. To our knowledge, it had not been diagnosed in a premature newborn before the case we report have.A female baby weighing 1164 grams, who was born prematurely at the 29th week of gestation by Cesarean section was referred to our newborn intensive care unit due to prematurity and respiratory distress with no prenatal pathological findings. Physical examination revealed tachypnea and hepatosplenomegaly. Routine laboratory measurements showed significant leukocytosis (85,000/mm3) and anemia (Hb: 9.6 g/dL and Hct: 27.6%). The platelet count was normal. The peripheral blood smear suggested leukoerythroblastosis with the presence of nucleated erythrocytes, monocytosis, and 4% blasts. Bone marrow cytogenetic examination was normal. Parvovirus B19 Ig G and M serology were detected to be positive. The etiological factors observed in leukoerythroblastosis occurring during neonatal and early childhood period are congenital-postnatal viral infections, juvenile myelomonocytic leukemia and osteopetrosis. To our knowledge, no case of leukoerythroblastosis in such an early phase has been reported in the in literature. As a result, premature delivery and leukoerythroblastosis were thought to have developed secondary to intrauterine parvovirus B19 infection. Leukoerythroblastosis is a rarely observed disease characterized by the presence of leukocytosis, erythroid and myeloid blast cells in peripheral blood. It is reported that it can be observed following hematologic malignancies especially juvenile myelomonocytic leukemia, acute infections, hemolytic anemia, osteopetrosis, myelofibrosis, neuroblastoma and taking certain medicines. To our knowledge, it has not been diagnosed in a premature newborn before. Here we the case of a newborn who was referred to our intensive care unit due to being born prematurely at the 29th week of gestation and diagnosed with leukoerythroblastosis.

Calcinosis cutis in a pediatric patient with Burkitt's lymphoma.

Calcinosis cutis, an uncommon disorder characterized by hydroxyapatite crystals of calcium phosphate deposited in the skin, has been described infrequently in childhood. Cutaneous calcification may be divided into four major categories: dystrophic, metastatic, idiopathic, and iatrogenic. Here, we report an example of iatrogenic type with a 4-year-old boy who diagnosed with Burkitt's lymphoma, and developed calcinosis cutis secondary to a tumour lysis syndrome with induction chemotherapy.

Evaluation of telomerase mRNA (hTERT) in childhood acute leukemia.

Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children.

Analysis of thalassemia syndromes and abnormal hemoglobins in patients from the Aegean region of Turkey.

Turkey is located in a geographic area of the world where thalassemia syndromes and abnormal hemoglobins are common. In this study we aimed to evaluate the thalassemia syndromes and abnormal hemoglobins in patients from the Aegean region of Turkey. Among the patients admitted to our Pediatric Hematology or Hematology Clinic between January 1997-September 1999, hemoglobin electrophoresis of 3,228 cases investigated for anemia was done using high performance liquid chromatography. Beta thalassemia trait was diagnosed in 21.1%, beta thalassemia major in 0.2%, S-beta thalassemia in 0.37%, Hb D in 0.37%, Hb S trait in 0.32%, Hb E in 0.18%, Hb O-Arab in 0.12%, Hb G-Copenhagen in 0.09%, Hb D-Iran in 0.06%, Hb Lepore in 0.06%, Hb Hasharon in 0.03%. Our results demonstrate that people in the Aegean region of Turkey have a wide spectrum of thalassemia syndromes and abnormal hemoglobins.

Successful Treatment of Infection- Associated Hemophagocytic Syndrome with Intravenous Immunoglobulin.

Hemophagocytic syndrome is a rare disorder characterized by a group of clinical, laboratory and histopathological findings such as fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and hemophagocytosis in the bone marrow, spleen, and lymph nodes. Hemophagocytic syndrome may occur as a primary or secondary disease. Primary type of hemophagocytic syndrome is also known as familial erythrophagocytic lymphohistiocytosis and secondary type is mostly associated with an viral infection and known as infection-associated hemophagocytic syndrome (IAHS). Rapid diagnosis is very important in these patients since suggested treatment strategies for the two types have been different and mortality rate is very high. In this report we present the clinical and laboratory findings and the outcome of two children with IAHS to emphasize the importance of early diagnosis and the effectiveness of intravenous immunoglobulin therapy in these patients.

Hypohidrotic ectodermal dysplasia associated with glucose-6-phosphate dehydrogenase deficiency.

Hypohidrotic ectodermal dysplasia (HED) is a syndrome characterized by hypodontia, hypotrichosis, and partial or total ecrine sweat gland deficiency. The most prevalent form of HED is inherited as an X linked pattern. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is an X-linked recessive disease, which leads to hemolytic anemia and jaundice. It is expressed in males, while heterozygous females are usually clinically normal. A 12-year-old boy with the complaints of hair and eyebrow disturbances, teeth disfigurement, decreased sweating, and xerosis presented to the outpatient clinic. Dermatological examination revealed sparse hair and eyebrows, conical-shaped teeth, xerosis, syndactylia, transverse grooves, and discoloration of nails. Laboratory findings indicated anemia. His 3-year-old sister also had sparse hair and eyebrows, xerosis, and syndactylia. We learned that the patient had a previous history of neonatal jaundice and a diagnosis of G-6-PD deficiency. Although it has been shown that loci of ectodermal dysplasia and G-6-PD deficiency genes are near to one another, we did not find any case study reporting on occurrence of these two genetic diseases together. With the aspect of this rare and interesting case, the relationship between HED and G-6-PD deficiency was defined.