Praguywan Kadegasem

VENOUS THROMBOEMBOLISM IN THAI CHILDREN

This is a retrospective study of 24 pediatric venous thromboembolism (VTE) patients with or without pulmonary embolism, conducted in Bangkok, Thailand, between 1981 and 2005. The incidence rate of VTE in Thai children was 3.9/10,000 hospital admissions per year. The median age was 11.7 years. Seventy-five percent of the patients had at least one associated medical condition accounting for the VTE; the two most common conditions, however, were infection and malignancy. Pulmonary embolism occurred in 29% of patients. Observed outcomes of VTE in this series included death (13%), postphlebitic syndrome (13%), and recurrence (26%). Genetic risk factors were explored in 19 patients, and no factor V Leiden or prothrombin 20210 mutations were detected. Protein C deficiency was found in 4 patients.

Normalized coagulation markers and anticoagulation proteins in children with severe β-thalassemia disease after stem cell transplantation.

The hypercoagulable state is well recognized in patients with severe β-thalassemia disease. One of the mechanisms of chronic hypercoagulable state is the abnormal expression of phosphatidylserine on red blood cells (RBC). This study aimed to determine the coagulable state in patients with severe β-thalassemia disease following successful stem cell transplantation (SCT). Subjects were classified into three groups: normal controls (NC), β-thalassemia disease receiving regular transfusion (Thal-RT) and β-thalassemia disease post SCT (Thal-SCT). Sixty eight subjects, aged 3-17years, consisting of 21 NC, 28 Thal-RT and 19 Thal-SCT were enrolled. After SCT, the annexin V level in Thal-SCT was normalized. At the median follow-up time of 70.3 (50.9-84.2) months after SCT, the levels of coagulation markers (thrombin antithrombin complex, prothrombin fragment and D-dimer) and anticoagulation proteins (protein C, S and antithrombin activities) returned to the levels similar to controls.

Combined Chelation Therapy with Daily Oral Deferiprone and Twice-Weekly Subcutaneous Infusion of Desferrioxamine in Children with β-Thalassemia: 3-Year Experience

Objective: To study the efficacy of combined treatment with oral and subcutaneous iron chelators. Material and Methods: 50-100 mg/kg/day of oral deferiprone (DFP) combined with 40 mg/kg/dose s.c. desferrioxamine (DFO) twice weekly were given to transfusion-dependent β-thalassemia children. Results: Enrolled patients (9 with β-thalassemia major and 33 with β-thalassemia hemoglobin E), ranging from 3 to 18 years in age, were divided into 3 groups; group 1 ferritin ≥1,000-2,500 ng/ml (n = 10), group 2 ferritin >2,500-4,000 ng/ml (n = 23) and group 3 ferritin >4,000 ng/ml (n = 9). Of the 42 patients, 28 reached the 36-month follow-up. Ten patients whose ferritin declined <15% while receiving 100 mg/kg/day of DFP were considered nonresponders. The median age and previous transfusion duration before enrollment were significantly higher in nonresponders than responders (p = 0.04 and 0.003, respectively). The responders exhibited a significant fall in median ferritin levels from 2,954.6 to 936.6 ng/ml (p < 0.001). Time to a significant decrease in serum ferritin among responders was 6 months. In 13 patients, 16 episodes of adverse events occurred: hemophagocytosis with cytopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 2), elevated alanine aminotransferase (n = 5), elevated serum creatinine (n = 1), proteinuria (n = 1) and gastrointestinal discomfort (n = 4). Conclusion: Combination therapy with daily oral DFP and subcutaneous DFO twice weekly is a safe and effective alternative to chelation monotherapy in β-thalassemia children.

Safety profile of a liquid formulation of deferiprone in young children with transfusion-induced iron overload: a 1-year experience

Background: Data on the use of deferiprone in young children with iron overload are limited. Objective: To study the safety profile of a liquid formulation of deferiprone in chelating young children with transfusion-induced iron overload. Patients and methods: A daily dose of 50–100 mg/kg BW in three divided doses of oral deferiprone was given to young patients who had received at least ten packed red cell transfusions and achieved a serum ferritin level >1000 μg/L during a 12-month period from 2011 to 2012. Results: Nine children (four males) diagnosed with various types of thalassaemia (n = 8) and hereditary spherocytosis (n = 1) were enrolled. Their mean (SD) age was 4.5 (1.9) years. The patients received 15–20 ml/kg BW of packed red cell transfusions every 4–8 weeks from a mean (SD) age of 2.1 (1.7) years to maintain a pre-transfusion haematocrit at 27%. A mean (SD) total of packed red cells of 5132 (2725) ml were given within a mean (SD) duration of 2.4 (1.1) years before the study. During the 1-year study period, they received a mean (SD) total of packed red cells of 2194 (680) ml or 138 (50) ml/kg BW with a mean (SD) daily iron load of 0.29 (0.12) mg/kg BW. The pre-treatment geometric mean of serum ferritin of 1863.8 μg/L decreased to 1279.7 μg/L after 1 year of treatment (P = 0.05). All patients tolerated the liquid formulation well and did not experience any gastro-intestinal discomfort, nausea or vomiting. Conclusion: The liquid formulation of deferiprone is safe in young children with transfusion-induced iron overload.BACKGROUND Data on the use of deferiprone in young children with iron overload are limited. OBJECTIVE To study the safety profile of a liquid formulation of deferiprone in chelating young children with transfusion-induced iron overload. PATIENTS AND METHODS A daily dose of 50-100 mg/kg BW in three divided doses of oral deferiprone was given to young patients who had received at least ten packed red cell transfusions and achieved a serum ferritin level >1000 μg/L during a 12-month period from 2011 to 2012. RESULTS Nine children (four males) diagnosed with various types of thalassaemia (n = 8) and hereditary spherocytosis (n = 1) were enrolled. Their mean (SD) age was 4.5 (1.9) years. The patients received 15-20 ml/kg BW of packed red cell transfusions every 4-8 weeks from a mean (SD) age of 2.1 (1.7) years to maintain a pre-transfusion haematocrit at 27%. A mean (SD) total of packed red cells of 5132 (2725) ml were given within a mean (SD) duration of 2.4 (1.1) years before the study. During the 1-year study period, they received a mean (SD) total of packed red cells of 2194 (680) ml or 138 (50) ml/kg BW with a mean (SD) daily iron load of 0.29 (0.12) mg/kg BW. The pre-treatment geometric mean of serum ferritin of 1863.8 μg/L decreased to 1279.7 μg/L after 1 year of treatment (P = 0.05). All patients tolerated the liquid formulation well and did not experience any gastro-intestinal discomfort, nausea or vomiting. CONCLUSION The liquid formulation of deferiprone is safe in young children with transfusion-induced iron overload.

Aspirin resistance in children and young adults with splenectomized thalassemia diseases

Aspirin is now recommended for splenectomized thalassemia patients with high platelet counts. However, aspirin resistance defined by arachinodic acid (ACA) induced platelet aggregation ≥20%, has never been reported in this group of patients. In this study, twenty-four splenectomized thalassemia patients (15.7±4.1years), with platelet counts ≥800x10(9)/L, and 21 non-splenectomized severe thalassemia patients (14.3±3.2years), were enrolled. After taking aspirin (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum thromboxane B2 (TXB2) levels in the aspirin responsive group decreased significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, p<0.001], while no change was demonstrated in the aspirin resistant group. Having increased aspirin to 4mg/kg/day, three of the seven aspirin resistant patients responded, while one developed upper GI bleeding from esophageal varices and was withdrawn from the study. For the three remaining patients, their doses were increased to the maximum of 300mg/day, and two of the three responded. Thrombin antithrombin complex and D-dimer levels were significantly decreased after taking aspirin (2mg/kg/day), although D-dimer level was still significantly higher than that in non-splenectomized group. Therefore, aspirin dosage can be adjusted individually to reach maximum effect of platelet inhibition. In addition, aspirin can reduce the levels of coagulation markers.

Lipoprotein(a) and the risk of thromboembolism in Thai children

High lipoprotein(a) [Lp(a)] level was identified as a risk factor of both venous and arterial thromboembolism (TE), especially in Caucasian children. The Lp(a) level is affected by apo(a) gene. The genetic polymorphisms that associated with Lp(a) level are the size of apo(a) gene, pentanucleotide repeat (TTTTA)(n) and +93C/T at promoter region. The increasing size of apo(a) gene, more than 8 pentanucleotide repeats and +93C>T polymorphisms are associated with low level of Lp(a) in African and Caucasian populations. This cross - sectional, case control study, aims to identify the association of Lp(a) level and the risk for TE in Thai children. Forty-nine patients and 116 healthy children were enrolled. Mean ± SD for age of patients and controls were 7.6 ± 4.7 and 11.2 ± 1.7 years, with female:male ratios of 1:1.2 and 1.8:1, respectively. The median Lp(a) levels in patients was 8.2 (0-87.3) mg/dL and 7.9 (0-74.9) mg/dL in controls, which were not statistically different, P=0.65. The frequencies of 8 pentanucleotide repeats and +93C/T were different compared to Caucasian and African populations but similar to Chinese population. However, both polymorphisms did not affect the level of Lp(a).

Incidences, risk factors and outcomes of neonatal thromboembolism

Abstract Background: The incidences of thromboembolism (TE) in neonates were reported to be around 0.51 per 10,000 live births per year for overall TE and 24 per 10,000 NICU admissions per year. As the incidences of TE in children and adults are lower in Asian populations, the incidences, risk factors, and outcomes of neonatal TE may be different to those reports from other countries. Objectives: To determine the incidences, risk factors, and outcomes of neonatal TE in a tertiary care hospital in Thailand. Materials and methods: A retrospective study between the years 1998 and 2015. Results: From a total of 2463 neonatal admissions, 28 patients were diagnosed with TE. The female/male ratio was 1:1.2. The breakdown of diagnoses of neonatal TE were arterial ischemic stroke (AIS; 36%), arterial TE (ATE; 29%), deep vein thrombosis (DVT; 14%), cerebral venous sinus thrombosis (CVST; 11%), renal vein thrombosis (RVT; 3%), and purpura fulminans (2%). Underlying diseases were identified 57.1% of patients. The most common thrombophilic risk factor was protein C (PC) deficiency (14.3%). The overall mortality rate was 14.3%. Conclusion: The most common TE was AIS. PC deficiency was the most prevalent inherited risk factor, especially in neonates without precipitating factors.

Low plasma FVII:C and activated FVII as predictive markers for overt disseminated intravascular coagulation

In sepsis, binding of factor VII (FVII:C) and activated factor VII (FVIIa) with tissue factor is the key step of coagulation resulting in disseminated intravascular coagulation (DIC). We conducted a prospective cohort study among 47 septic patients, aged 8 months to 18.8 years. They were initially divided into three groups of no DIC (n=27), non-overt DIC (n=14) and overt DIC (n=6). Blood samples were collected at 0, 24 and 48 hours (h) after the onset of sepsis. At the onset of sepsis, FVII:C tended to be lower in the non-overt DIC [median 57 % (interquartile range [IQR] 41-80)] and overt DIC groups [33 % (23-52)] than that in the no DIC group [65 % (44-87)]. Whereas FVIIa tended to be lower in the overt DIC group [1.29 % (0.50-4.19)] than those in the non-overt DIC [3.01 % (1.01-5.24)] and no DIC groups [2.49 % (1.14-3.13)]. At 24 h, FVII:C was significantly lower in the non-overt DIC [57 % (41-101)] and overt DIC groups [31 % (28-49)] than that in the no DIC group [83 % (70-102)]. While FVIIa was significantly lower in the overt DIC group [2.15 % (0.86-3.96)] than that in the no DIC group [3.83 % (2.90-5.46)]. Using FVII:C <65 % or FVIIa <3 % at 24 h among patients without hepatic dysfunction to determine overt DIC at 24 h, the sensitivity was 83.9 % and 77.4 %, respectively, and the specificity was both 83.3 %. Patients with low FVII:C and low FVIIa at 24 h after the onset of sepsis had a 20.8-fold (95 % confidence interval [CI], 2.0-213.0, p=0.010) and 14.4-fold (95 %CI, 1.5-142.4, p=0.023) chance of overt DIC.

Blood Coagulation and Asthma Exacerbation in Children

Background: Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. Methods: Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. Results: A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p < 0.001), 41.9 ng/ml (IQR: 21.91-48.61) versus 26.17 ng/ml (IQR: 15.89-34.44, p < 0.03), and 4.46 mg/l (IQR: 2.15-16.23) versus 0.87 mg/l (IQR: 0.20-3.89, p < 0.015), respectively. However, the median protein C during asthma exacerbation was significantly lower than that of the stable state: 99.5% (IQR: 86.75-117) versus 113% (IQR: 94-115.25), p = 0.01. No significant difference was found between the levels of D-dimer, F1 + 2, and TAT during asthma exacerbation and stable state. Ultimately, D-dimer was positively correlated with asthma exacerbation score (R = 0.466, p = 0.027). A significant correlation was observed between vWF and CRP (R = 0.527, p = 0.012). Conclusion: Evidence was found of increased endothelial activation and increased PAI-1 during asthma exacerbation. This may emphasize the potential role of blood coagulation in asthma exacerbation.

Prenatal diagnosis for haemophilia: the Thai experience

Haemophilia is a lifelong X‐linked recessive inherited bleeding disorder. Since the haemophilia management in economically less‐developed countries is inadequately provided, prevention of new cases of haemophilia is essentially required.