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Bleeding and thrombosis are the common hematological complications found in children who are admitted in the pediatric intensive care units (PICUs). Some of those complications could be mild, however some could be serious or life-threatening for critically-ill children. The etiologies of those conditions could be due to the underlying diseases, i.e., congenital bleeding disorders, complications of the diseases, i.e. coagulopathy due to disseminated intravascular coagulation (DIC), and also the side effects from the treatments themselves, i.e., massive transfusion or extracorporeal membrane oxygenation (ECMO). Early detection and management and prevention of those complications could decrease the morbidity and mortality of the children in PICUs. Although most guidelines of management of those bleeding and thrombosis in adults is well established, the evidences for the management of those conditions in children are limited. In addition, developmental hemostasis during the childhood, which is different from adulthood, could challenge the management of those conditions in children admitted in PICUs.

Inflammatory myofibroblastic tumor (IMT) belongs to mesenchymal neoplasm of intermediate malignancy in WHO classification. Primary CNS disease or CNS metastases (CNS-IMT) occur in minority. We describe a case of relapsed/refractory IMT of lungs with multiple brain metastases in young child who achieved long-term complete response after alectinib. This systematic review also summarizes treatment modalities and outcome of children and adolescent with CNS-IMT.PRISMA 2020 guideline was applied to select an article from PubMed, Scopus, and Cochrane databases without time limits. This review focused on children and adolescent 0-24 years of age with CNS-IMT or inflammatory pseudotumor (CNS-IPT). The clinical characteristics and treatment outcome were explored.A total of 51 patients in 49 publications were identified. Median age of patients with CNS-IMT/IPT was 15-year-old and 60.8% were male. The most common location of tumor was cerebral cortex (54.9%). Complete resection of CNS-IMT/IPT was performed in 27 cases with 100% complete response and 18.5% recurrence. Nearly half of patients who received partial resection without adjuvant therapy experienced progressive disease, while the contrast group totally achieved partial response. Overall responses in 7 patients treating with ALK inhibitors were 57.1% durable complete response and 42.9% transient partial response.First-line treatment of CNS-IMT/IPT is complete resection. Patients who received partial tumor removal might have benefit from adjuvant therapy. ALK inhibitors reveal a promising result in unresectable CNS-IMT/IPT. Our case has shown a success in treating relapsed and refractory CNS-IMT as well as the primary site using 2nd-generation ALK inhibitor.

Mutations in the KLF1 gene, which encodes a transcription factor playing a role in erythropoiesis, have recently been demonstrated to be a rare cause of hereditary haemolytic anaemia. We described the genotypic and phenotypic spectra of four unrelated families with compound heterozygous class 2/class 3 KLF1 mutations. All patients had p.G176RfsX179 on one allele and either p.A298P, p.R301H or p.G335R on the other allele. All presented on the first day of life with severe haemolytic anaemia with abnormal red blood cell morphology, markedly increased nucleated red blood cells and hyperbilirubinaemia. Three patients later became transfusion-dependent. All parents with heterozygous KLF1 mutation without co-inherited thalassaemia had normal to borderline mean corpuscular volume (MCV) and normal to slightly elevated Hb F. Fifteen previously reported cases of biallelic KLF1 mutations were identified from a literature review. All except one presented with severe haemolytic anaemia in the neonatal period. Our finding substantiates that compound heterozygous KLF1 mutations are associated with severe neonatal haemolytic anaemia and expands the haematologic phenotypic spectrum. In carriers, the previously suggested findings of low MCV, high Hb A2 and high Hb F are inconsistent; thus this necessitates molecular studies for the identification of carriers.

Background Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted. Methods A total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1–2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4–5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period. Discussion This trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development. Trial registration This trial was prospectively registered on Thai Clinical Trials Registry (registration number: TCTR20190701001). The posted information will be updated as needed to reflect protocol amendments and study progress.

Orbital involvement is one of the extramedullary manifestations in acute leukemia. It is common in acute myeloid leukemia, but rare in acute lymphoblastic leukemia (ALL). We described a 3-year-old girl who presented with progressive proptosis of the right eye and was later diagnosed with precursor B-cell ALL. Initial blood count showed Hb 6.9 g/dL, WBC 42,000/mm3, lymphoblast 50%, and platelet count 185,000/mm3. Bone marrow aspiration revealed 90% lymphoblasts with positivity for CD10, CD19, CD20, CD22, and HLA-DR markers. Computed tomography (CT) scan of the brain and orbit revealed a homogeneous enhancing mass involving the right orbit with intracranial extension. The cytogenetic study showed 46,XX chromosomes. After 4 weeks of induction chemotherapy for very high-risk ALL, although the bone marrow was in remission, the proptosis was partially resolved. CT scan confirmed a decrease in size of the right orbital mass and degree of intracranial extension. Unfortunately, the patient abandoned the treatment after the induction chemotherapy. The actual incidence of orbital involvement in ALL is unknown. Previous case reports describe diverse manifestations of orbital involvement in ALL. The involvement may be unilateral or bilateral, may occur at first diagnosis or at relapse, and may be seen in isolation or with other systemic symptoms. There is no standard treatment protocol. Chemotherapy with or without radiotherapy is generally suggested. The role of upfront hematopoietic stem cell transplantation remains inconclusive. The previously reported prognosis of ALL with orbital involvement is poor.

Background This study aimed to determine the elements and the extent of information that child participants and their parents would like to read in an informed assent form (IAF)/informed consent form (ICF) of a pediatric drug trial. Methods A descriptive survey was conducted to determine the perceived importance of each element of the ICF content from child participants and their parents who underwent informed assent/consent of a multi-center pediatric drug trial. The respondents were asked to indicate the level of importance of each item in a questionnaire, by giving a rating scale from 1 (not important) to 5 (very important). Results A total of 22 families, 17 child participants with the diagnosis of hematology or oncology diseases and 27 parents, were enrolled. Among 30 items, risk–benefit aspects (i.e., direct health benefit [mean: 4.71 for child respondents, 4.89 for parent respondents], indirect/societal benefit [mean: 4.65, 4.85], major foreseeable risk [mean: 4.47, 4.78], post-trial benefit/provision [mean: 4.59, 4.74], and all adverse effects of the drug including uncommon adverse effects [mean: 4.53, 4.74]) were perceived to be of most concerning items from both child participants’ and parents’ viewpoint. None of the items were considered ‘slightly important’ or lower by more than 20% of the respondents. Conclusions For pediatric drug trials, risk–benefit information (including direct health benefit, indirect/societal benefit, and post-trial benefit/provision, as well as major foreseeable risk and adverse effects of the drug) should be made a salient feature of an IAF/ICF. This empirical data could help related stakeholders arrange essential information in order of importance and tailor an IAF/ICF to better suit child participants’ and parents’ needs, particularly for pediatric drug trials involving children with the diagnosis of hematology or oncology diseases.

A term male newborn born to a mother who had hereditary spherocytosis presented with neonatal jaundice at 20 hours of life. Complete blood count showed hemoglobin 17.1 g/dL, MCV 104.2 fL, MCH 32.9 pg, and MCHC 31.6 g/dL. The patient had indirect hyperbilirubinemia requiring phototherapy. The maximum total bilirubin level was 12.15 mg/dL at 20 hours of life. Peripheral blood smear revealed spherocytes, crenated red cells, and polychromasia. A flow cytometric test with eosin-5-maleimide- (EMA-) labeled RBC was performed in the patient and parents. The fluorescence histograms of EMA-labeled RBC from the patient and mother were shifted to the left, and the fluorescence ratio when compared with normal was 0.69 and 0.84, respectively. The flow cytometric test with EMA is useful in supporting the diagnosis of hereditary spherocytosis during newborn period.

Infantile Cushing’s syndrome is potentially found as part of McCune-Albright syndrome (MAS) which is caused by postzygotic somatic mutations of the GNAS gene. MAS is typically characterized by a triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty or other endocrine hyperfunction. Here, we describe a 2-month-old female infant with features of Cushing’s syndrome without café au lait spots, polyostotic fibrous dysplasia, and clinical evidence of other endocrine hyperfunction. Investigations demonstrated adrenocorticotropic hormone-independent Cushing’s syndrome with bilateral adrenal gland enlargement. Whole-exome sequencing of leukocytes identified a de novo heterozygous novel missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene. The patient experienced clinical improvement of Cushing’s syndrome during ketoconazole treatment. Her clinical course was complicated by Pneumocystis jiroveci pneumonia. She also had shortened activated partial thromboplastin time indicating a hypercoagulable state and resulting in pulmonary embolism. She eventually manifested gonadotropin-independent precocious puberty at the age of 13 months after ketoco­nazole was discontinued. This patient demonstrated that Cushing syndrome can be the presenting sign of MAS in infancy. A high index of suspicion followed by genetic analysis is essential in order to establish a diagnosis.

Background: Febrile neutropenia (FN) is the most common complication in pediatric oncology patients. Appropriate empirical antibiotics treatment is essential for treatment outcome. Methods: This study was a randomized prospective controlled study to demonstrate the efficacy of piperacillin/tazobactam (PIP/TZO) monotherapy compared with ceftazidime/amikacin in children with FN. Pediatric oncology patients at Chiang Mai University Hospital, diagnosed with FN, were randomized to receive either PIP/TZO 320 mg/kg/day divided every 8 hours or ceftazidime 100 mg/kg/ day divided every 8 hours plus amikacin 15 mg/kg/day once daily. Treatment responses were compared between the two groups. Results: One-hundred and eighteen febrile neutropenic episodes in 70 patients (42 males and 28 females) were enrolled. The median age was 7 (3-10) years. The early response and complete response to initial treatment were achieved in 48/59 (81.4%) episodes and 41/59 (69.5%) episodes in PIP/TZO group compared with 40/59 (67.8%) episodes and 33/59 (55.9%) episodes in ceftazidime/amikacin group (p-value 0.091 and 0.128, respectively). Treatment modification in PIP/TZO group was required in 18/59 (30.5%) compared with 26/59 (44.1%) patients in ceftazidime/amikacin group (p-value 0.128). Similarly, the duration of fever, duration of neutropenia and duration of antibiotics treatment were not significantly different between two groups. No serious adverse events were observed. Conclusion: The treatment responses of PIP/TZO monotherapy and ceftazidime/amikacin therapy were not significantly different. Both therapies were effective for FN in pediatric oncology patients.

The diagnosis of MYH9 disorder is guided by recognizing granulocyte Dohle body-like inclusion bodies and large/giant platelets in the peripheral blood smear. Immunofluorescence study of nonmuscle myosin heavy chain IIA is a sensitive screening method for diagnosis of MYH9 disorder. The diagnosis can then be confirmed by genetic analysis. A total of 67 patients with macrothrombocytopenia were included, of which 11 patients (16%), aged 4 months to 22 years, were ultimately diagnosed with MYH9 disorder. One novel mutation in exon 30 at c.4338T>C (p.F1446A) was detected. This mutation was associated with nonhematologic manifestations presenting in late adolescence with cataracts, hearing loss, and hematuria.

Preterm and low birth weight infants are at risk of iron deficiency. Reticulocyte hemoglobin concentration may be useful as a screening test to diagnose iron deficiency in preterm neonates.To evaluate the accuracy and establish the reticulocyte hemoglobin concentration cutoff value for iron deficiency diagnosis in very low birth weight preterm neonates.This study was conducted between May 2018 and March 2019 at Chiang Mai University Hospital. Preterm infants born at gestational age ≤34 weeks and birth weight ≤1500 g were enrolled. Blood samplings were obtained within the first 48 h of life. Iron deficiency was defined by using two or more of these following parameters: mean corpuscular volume100 fL, transferrin saturation16% and serum ferritin30 µg/L. Neonatal anemia was defined as hemoglobin15 g/dL. The optimum reticulocyte hemoglobin concentration cutoff values were performed by using predictive values and receiving operation characteristic analysis.Fifty-seven preterm neonates were enrolled. Nine (15.7%) and three (5.3%) neonates had iron deficiency and iron deficiency anemia, respectively. The reticulocyte hemoglobin concentration cutoff value of29 pg showed the optimum accuracy to diagnose iron deficiency in very low birth weight preterm neonates with sensitivity, specificity, positive and negative predictive values of 89%, 79%, 42% and 97%, respectively.Reticulocyte hemoglobin concentration can be used as a screening parameter to diagnose iron deficiency for VLBW preterm neonates. The optimum cutoff value which provided the acceptable accuracy was29 pg.

Screening for iron deficiency anemia (IDA) in infants is usually carried out by hemoglobin (Hb) level and mean corpuscular volume (MCV). A coinherited thalassemia carrier may confound the diagnosis of IDA. This study aimed to characterize the hematologic parameters in infants with IDA and in thalassemia carriers, and to study the use of red cell parameters in IDA screening in a thalassemia-endemic area. Healthy infants, 6 to 12 months of age were enrolled. Blood samples were taken for complete blood count, ferritin level, Hb analysis, and polymerase chain reaction for alpha-thalassemia. IDA was defined as Hb

Objective This study aimed to explore real-world evidence on health resource use (HRU) spending on patients with haemophilia and inhibitor. Materials and methods Medical records from 1990 to 2019 of patients with haemophilia and inhibitor from three comprehensive haemophilia treatment centres were retrospectively retrieved. Results In all, 31 patients with haemophilia (A = 30, B = 1) and inhibitor ≥5 BU were included. The mean initial inhibitor of 95.4 BU was detected at the mean age of 6.7 years. The mean number of annual hospitalisations was 3.9. A total of 795 bleeding episodes (major =125, minor =670) were evaluated. The treatment included bypassing agents or plasma exchange before administering high-dose factor VIII concentrate and intervention or surgery. Six patients succumbed to bleeding at the mean age of 17.2 years. Nineteen surviving patients experienced multiple morbidity except six patients with successful and partially successful immune tolerance induction (ITI). The mean (SD) annual total medical consumption for episodic treatment and successful ITI per patient with haemophilia A were 30,804 (81,332) USD and 55,531 (100,566) USD, respectively. Only episodic treatment was paid by the government budget for limited amounts of bypassing agents. Conclusion Management for patients with haemophilia and inhibitor exhibiting severe bleeding is challenging for medical personnel in countries having limited resources over decades. The real-world data will be used to negotiate with the government to increase budget for adequate bypassing agents or nonreplacement therapy and to include ITI in the national haemophilia treatment.

INTRODUCTION Disseminated intravascular coagulation (DIC) is a systemic activation of hemostatic system caused by several causes. Biomarkers including antithrombin (AT), protein C (PC), and thrombomodulin (TM) were reported as the additional markers for DIC in adults. This study aimed to determine the association between biomarkers among patients with overt DIC (ODIC) and nonovert DIC (NDIC) in children in PICU. METHODS We enrolled 103 subjects, aged 1 month-18 years, who were admitted to PICU at Chiang Mai University (CMU) Hospital >24 hours with underlying conditions predisposing to DIC were enrolled. Biomarkers were tested after 24 hours of admission. Subject who had NDIC on the 1st investigations would have other tests on days 3-5 of admission. RESULTS The incidence of ODIC by the International Society on Thrombosis and Hemostasis (ISTH) DIC score was found 24%. The bleeding, thrombosis, and death were significantly higher in ODIC group (P

Background Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor and approved for indefinite treatment of pediatric CML. Potential side effects regarding growth failure and bone metabolism were reported, however, the data is still scattered in pediatric CML. Methods 6 chronic-phase CML children with the IM treatment with a median age of 9.87 years (range 5.33-12.67) were enrolled onto study. Growth, bone mineral density (BMD), bone parameters, 25(OH)-vitamin D3 (25-OHD3) and blood tests including parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGF-BP3), thyroid function test and sex hormones were assessed. Results The median duration of IM treatment was 78.5 months. Height velocity was suppressed during the first 30 months of treatment and improved gradually afterwards. Two patients (33.3%) had decreased lumbar spine BMD z-scores with

Renal disorders can impact the balance of hemostasis and can result in predispositions to either bleeding or thrombosis. This delicate balance is influenced by normal physiologic changes in childhood that need to be taken into consideration when assessing and treating children with kidney diseases. This chapter reviews normal physiologic conditions and changes that occur during childhood. The two spectrums of hemostasis are then described in detail including conditions associated with bleeding (uremic coagulalopathy) and thromboses (nephrotic syndrome, antiphospholipid antibody syndrome, renal vascular thromboses and hemolytic uremic syndrome). Treatment recommendations are provided based on best evidence and standards. Hemostasis, the balance between bleeding and clotting in the body, differs in normal children compared to adults. In children with renal disease, disturbances in the balance of hemostasis can occur resulting in either bleeding or thrombosis. This chapter will describe normal developmental hemostasis in children in addition to hematologic disturbances in those with renal diseases.

Abdominal compartment syndrome (ACS) is a life-threatening condition which can occur in patients with hemophilia although they have trivial traumas. Hemostatic control for bleeding episodes in hemophilia patients with inhibitors is difficult particularly when the availability of bypassing agents, recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC), is constrained. Plasma exchange with continuous infusion of factor concentrate has been reported as a life-saving intervention in these patients. We reported a teenager with severe hemophilia A and a high-titer inhibitor who underwent two surgeries for ACS which developed after a minor trauma. Computerized tomography angiogram (CTA) of abdomen revealed a large pelvic hematoma and a bleeding from the sigmoidal artery. He underwent an abdominal angiography followed by the first surgery to relieve the ACS, and the second surgery for abdominal closure. The patients received plasma exchange with cryo-removed plasma peri-operatively. High-dose factor VIII (FVIII) concentrate (100 U/kg) was started after plasma exchange followed by continuous infusion at the rate 14 units/kg/hour for 7 days. rFVIIa and APCC concomitant with tranexamic acid were used for breakthrough bleeding. He received six times of plasma exchange, three doses of rFVIIa and five doses of APCC. Bleeding was successfully stopped and the titers of inhibitor decreased from the maximum of 4,400 BU to 3,680 BU. Plasma exchange and continuous FVIII infusion can be considered as an option for life-threatening hemorrhage in hemophilia patients with high-titer inhibitors in the countries where an access to bypassing agents is limited.

Hereditary elliptocytosis is an inherited red blood cell membrane disorder characterized by typical peripheral blood smear findings of elliptocytes or rod-like red blood cells. Hemoglobin H disease is a form of α-thalassemia disease resulting in mild to moderate hemolytic anemia. The authors report 1 case of a girl who was diagnosed with oculo-auriculo-vertebral spectrum and a coinheritance of hereditary elliptocytosis and deletional hemoglobin H disease. She had moderate, non-transfusion-dependent anemia. The red blood cells showed marked poikilocytosis and fragmentation. The parents were α-thalassemia carriers and the father had the typical red blood cell morphology of common hereditary elliptocytosis.

We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended.

Introduction Patients with hemoglobin E/beta-thalassemia disease (E/β) are at risk of thromboembolism. Rotational thromboelastometry (ROTEM®) can be used to determine a hypercoagulable state. The objective was to describe the hemostatic and thromboelastometric changes in pediatric patients with E/β with different clinical severity, in comparison with healthy children as controls. Materials and methods Fifty-three pediatric patients with E/β and 21 healthy children were enrolled. The clinical severity of E/β was categorized by using the clinical severity scores. All subjects were tested for complete blood count, protein C activity (PC), total protein S (PS), antithrombin (AT), D-dimer and fibrinogen (Fib) levels and thromboelastometry, measured by ROTEM®. Results The levels of PC (65.7 vs 118.5%), PS (46.8 vs 78.4%), AT (95.7 vs 105.7%) and Fib (217 vs 294 mg/dL) were significantly lower, and the platelet count (PLT) was significantly higher in the patient group than the controls. The maximum clot firmness (MCF) of patients with moderate disease who were previously splenectomized (seven patients) and patients with severe disease (nine patients) were higher than patients who had intact spleen with moderate disease, patients with mild disease and controls ( P P Conclusions Hypercoagulable state was demonstrated by ROTEM® in patients with E/β with severe disease and who were previously splenectomized. The hypercoagulable state was associated with the higher numbers of PLT rather than the decrease of PC, PS, and AT.

Pulmonary hypertension is a major cardiac complication in non-transfusion-dependent thalassemia (NTDT). Several clinical and laboratory parameters, including iron overload, have been shown to have a positive correlation with the incidence of pulmonary hypertension. Non-transferrin-bound iron (NTBI) is a form of free-plasma iron that is a good indicator of iron overload.The aim of this study was to determine the prevalence of pulmonary hypertension in patients with NTDT and to investigate its correlation with the clinical parameters, liver iron concentration (LIC) and NTBI.Patients with NTDT were evaluated using echocardiography, and magnetic resonance imaging for cardiac T2* and LIC. Pulmonary hypertension was defined as peak tricuspid regurgitation velocity ≥2.9 m/s measured using trans-thoracic echocardiography. Clinical parameters and the status of iron overload as determined by LIC, serum ferritin, and NTBI level were evaluated for their association with pulmonary hypertension.Of 76 NTDT patients, mean age 23.7 ± 8.5 years, seven patients (9.2%) had pulmonary hypertension. Previous splenectomy (71.4 vs. 24.6%, P-value 0.019), higher cumulative red blood cell (RBC) transfusions (received ≥10 RBC transfusions 85.7 vs. 33.3%, P-value 0.011), higher nucleated RBCs (353 ± 287 vs. 63 ± 160/100 white blood cells, P-value0.001), and a high NTBI level (5.7 ± 3.0 vs. 3.3 ± 2.8 µmol/l, P-value 0.034) were associated with pulmonary hypertension. There was no significant correlation between LIC or serum ferritin and pulmonary hypertension.Pulmonary hypertension in NTDT is common, and is associated with splenectomy and its related factors. NTBI level shows a significant correlation with pulmonary hypertension.

The major complication of Kawasaki disease is coronary aneurysm which can cause acute coronary disease in early adulthood. There are some reports of coronary artery thrombosis during the period of active Kawasaki disease in infants with giant coronary aneurysm. This report demonstrated a 5-month-old male infant who presented high-grade fever for 7 days. He was treated as urinary tract infection for 6 days before referral. At admission, he had fever, red lips and swelling of both feet, then was diagnosed Kawasaki disease. His EKG showed ST elevation at lead II, III and AVF. His initial echocardiogram revealed coronary dilatation with perivascular brightness; RCA 2.7 mm (Z-score 4.38), LMCA 2.88 mm (Z-score 2.83) and LAD 2.7 mm (Z-score 5.79). There was a clot 2.5 X 2.5 mm in LAD. However, his LV systolic function was normal (EF 76%). His blood test showed low hemoglobin as 8.9 g/dL and MCV as 61.9 fL, high white cell count 20,400/mm3 and platelet count as 606,000/mm3. His initial ESR and CRP elevated at 91 mm/hr and 52 mg/L, respectively. The cardiac enzymes were normal; CKMBmass 2.9 ng/mL (0-3) and troponin-T 0.004 ng/mL (< 0.4). He received IVIG 2.3 g/kg and aspirin 79 mg/kg/day and was closely monitored the vital signs and cardiac enzymes. His fever completely disappeared within 24 hours after treatment, then aspirin was decreased to 6 mg/kg/day. Also, he received intravenous heparin for 4 days, and then was switched to Enoxaparin. He was discharged uneventfully on day 22 of admission. Further blood test confirmed the diagnosis of iron deficiency anemia as follow; serum iron 30 [[Unable to Display Character: ɥ]]g/dL, transferrin-iron binding capacity 446 [[Unable to Display Character: ɥ]]g/dL and transferrin saturation 6.7% (< 16). He received iron supplement for 4 months. The clot in coronary artery gradually decreased in size and finally disappeared in seven months after diagnosis. So, the Enoxaparin was discontinued. He received low-dose aspirin for total course 15 months. His thrombophilia work up was unremarkable. Anemia which is one of the supplementary criteria for atypical Kawasaki disease should be properly evaluated for the cause. The study to find the association between iron deficiency anemia, which was reported as a risk for thromboembolic events, and severity of Kawasaki disease should be further investigated.

3, 54, Chiang Mai Medical Journal

Venomous snakes with hematotoxin—Russell’s viper (Daboia spp), Malayan pit viper (Calloselasma rhodostoma), and green pit viper (Cryptelytrops albolabris and C macrops, previously named Trimeresurus spp) are commonly found in Thailand. Coagulation factor activation, thrombocytopenia, hyperfibrinolysis, and disseminated intravascular coagulation are the main mechanisms of hemorrhaging from these snake bites. The neurological involvement and hepatocellular injury after Russell’s viper bites were reported in Sri Lanka, but there is no report from Southeast Asia. This case was a 12-year-old hill tribe boy who had ptosis and exotropia of the left eye, respiratory distress, and prolonged venous clotting time, prothrombin time, and activated partial thromboplastin time; low fibrinogen and platelet count; and transaminitis after being bitten by a darkish-colored snake. He did not respond to antivenom for cobra, Malayan pit viper, or Russell’s viper. However, his neurological abnormalities, respiratory failure, and hepatocellular injury improved, and coagulopathy was finally corrected after receiving antivenom for green pit viper. The unidentified snake with hematotoxin was alleged for all manifestations in this patient.

High factor VIII levels and a risk factor of arterial ischemic stroke is controversial. Levels of factor VIII depend on ethnicity, age, and sex. This report included 24 Thai children with cryptogenic arterial ischemic stroke and 41 controls, with a mean (standard deviation) age of 11.5 (6.3) and 9.0 (4.7), respectively. The study was performed during the post–arterial ischemic stroke events to avoid acute phase reaction of factor VIII and von Willebrand factor. The levels of factor VIII activity and von Willebrand factor antigen in patients were not significantly different compared to controls (119.8 ± 41.3% vs 138.0 ± 48.7%, P = .29 and 92.8 ± 29.8% vs 103.7 ± 39.1%, P = .4, respectively). Therefore, high factor VIII and von Willebrand factor antigen levels were not risk factors of cryptogenic arterial ischemic stroke in Thai children.

Background Prolonged euglobulin clot lysis time (ECLT) and increased level of plasminogen activator inhibitor-1 (PAI-1) were reported to be risk factors of arterial ischemic stroke (AIS) by some studies; however, these findings were not supported by other studies. The objective of this study was to determine the association of ECLT, PAI-1 level, and polymorphisms of 4G and 5G of PAI-1 gene to the development of AIS in Thai children. Methods This study included patients aged 1-18 years old. Diagnosis of AIS was confirmed by imaging study. The control group was age- and sex-matched healthy subjects. Demographic data were recorded, and blood was tested for ECLT, PAI-1 level, lipid profiles, fasting blood sugar (FBS), and 4G and 5G polymorphisms of PAI-1 gene. Results There were 70 subjects participating in this study, consisting of 30 patients and 40 controls. Demographic data, lipid profiles, and FBS were similar between the 2 groups. Furthermore, ECLT and PAI-1 level did not differ between patient and control groups; however, both showed significant correlation ( r = .352, P = .006). The 4G/5G polymorphism was the most common genotype in both patient and control groups (69.0% vs. 80.0%). However, 4G and 5G polymorphisms of PAI-1 gene did not correlate with PAI-1 level in this study ( P = .797). Conclusions The PAI-1 level and 4G/5G polymorphism may not be a risk factor of AIS in this population. It was also found that the 4G/5G polymorphism was the most common PAI-1 genotype in this study.

Kasabach-Merritt phenomenon (KMP) is relatively rare in childhood and adolescents with high mortality rate because of its hemorrhagic complications and unresponsiveness to treatments such as corticosteroids, vincristine, intravascular embolization, and/or surgery. Propranolol, aβ-adrenergic receptor blocker, has a promising efficacy against vascular tumors such as infantile hemangiomas. But limited and variable data has been reported regarding the role of propranolol in treatment of KMP. We herein reported the successful treatment of mild pediatric KMP with propranolol monotherapy in a case of a five-week-old child with kaposiform hemangioendothelioma with successful treatment of both clinical and hematologic responses. After eight months of follow-up, patient still had stable cutaneous lesion while receiving propranolol monotherapy. Regular hematologic monitoring was done in order to detect any late relapse of the disease. Six months after discontinuation of propranolol, patient has still remained free of hematologic relapse, and primary cutaneous lesion has become a pale pink, 1 cm sized skin lesion.

Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5% respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and

Dengue and thalassaemia are prevalent in tropical regions. Thalassaemia patients with dengue present with atypical clinical manifestations and may experience more severe disease and complications.To investigate the clinical manifestations and outcome in thalassaemia patients with dengue.Medical records of thalassaemia patients aged from birth to 18 years with serologically-confirmed dengue who were admitted to Chiang Mai University Hospital, Thailand from January 2005 to December 2010 were reviewed retrospectively. Clinical presentation, laboratory results and outcome were analysed.Twenty patients were included and their mean (SD) age was 13·6 (3·1) years. Patients were as follows: haemoglobin H (HbH)/Hb Constant Spring disease 7, HbH disease 3, HbH disease/HbE trait one, beta-thalassaemia/HbE disease 7, beta-thalassaemia/HbS disease one and unspecified thalassaemia one. Four patients had primary and the others secondary dengue. Five patients (25%) had severe dengue, three with severe liver involvement, one with a massive upper gastro-intestinal haemorrhage and one with acute interstitial nephritis, raised creatinine and seizures. Nineteen patients required red cells transfusions. All made a full recovery. Almost all patients presented with haemoglobin lower than baseline. While mean (SD) haemoglobin at baseline was 8·2 (1·6) g/dl, mean (SD) haemoglobin on admission was 6·4 (1·6) g/dl. Median maximum AST and ALT levels were 359 (range 42-5344) and 81 (12-1846) units/L, respectively.Thalassaemia patients with dengue present with anaemia rather than haemoconcentration. Most patients have markedly increased AST levels in relation to ALT, and severe dengue, especially severe liver involvement, is common. In patients with thalassaemia, awareness of the atypical manifestations should aid early recognition of dengue.