Cost-effectiveness in establishing hemophilia carrier detection and prenatal diagnosis services in a developing country with limited health resources

The cost-effectiveness of carrier detection and prenatal diagnosis for hemophilia at the International Hemophilia Training Center, Bangkok, Thailand was studied. From 1991 to 2002, 209 females from 124 families with hemophilia A and B were included. There were 180 hemophilia A carriers and 29 hemophilia B carriers which could be classified into 78 obligate and 131 possible carriers. The phenotypic analysis for possible carriers involved the determination of levels of factor VIII or IX clotting activity (FVIII:C, FIX:C) and the ratio of FVIII:C and von Willebrand factor antigen. The result revealed that 49 females (37.4%) were diagnosed as carriers, 65 females (49.6%) were normal and 17 females (13%) were undetermined. Additional genotypic analysis was provided to 46 families with 74 females with obligate, proven or undetermined carriers within the reproductive life. The polymorphisms associated with factor VIII and IX genes were used including Bcl I for the factor VIII gene and combined use of Mse I, Sal I, Nru I, Hha I and Dde I for the factor IX gene. The informative rate was 59.4% (44/74). Consequently, 12 prenatal diagnoses for fetus at risk were performed. Sex determination was initially determined and followed by the diagnosis of hemophilia through informative gene tracking and/or the measurement of fetal levels of FVIII:C or FIX:C. The result revealed that 3 male fetuses were affected. The total cost of carrier detection and prenatal diagnosis that the families had to pay in the government hospital was 238,600 Baht (US dollars 5,965). It was compared to the estimated cost of minimal replacement therapy using lyophilized cryoprecipitate for the survival time of 30 years in one patient with hemophilia of 1,012,500 Baht (US dollars 25,312.5). The cost of prevention was much less than the replacement therapy. In conclusion, it is cost-effective to establish the service for carrier detection and prenatal diagnosis for hemophilia especially in developing countries with limited health resources.     

Preventable Severe Thalassemia among Children

Abstract

This retrospective study analyzed 27 children with preventable severe thalassemia born to 24 at-risk couples between 1997 and 2017. The couples were categorized into two groups: the prenatal diagnosis (PND) group (n?=?8) and the non PND group (n?=?16). In the PND group, following comprehensive counseling on having a fetus with thalassemia, six couples decided to continue the pregnancy (n?=?6). Termination of the two remaining fetuses was excluded as the thalassemia status was reported at a gestational age of 24?weeks. In the non PND group, medical errors were found in the misdiagnosis of couples as non thalassemia carriers (n?=?4) and not offering PND to couples with known thalassemia carrier status when attending the antenatal clinic (ANC) (n?=?2). Additionally, parental ignorance was found in parents experiencing their own thalassemia, or that of their spouse or child (n?=?6). The remaining couples (n?=?4) with known carrier status either directly refused PND or were ineligible for it. A total of five divorces (5/24?=?20.8%) occurred in the PND (n?=?2) and the non PND (n?=?3) groups. Knowledge, beliefs, religion, experience of thalassemia, as well as the sex of the at-risk fetus all influenced parental decisions. Therefore, both medical personnel and parents are key in preventing new cases of thalassemia. Parents should be aware of the consequences of having children with severe thalassemia, while medical personnel should provide accurate carrier detection and PND.     

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 3-17 years, 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.     

Polymorphisms of drug-metabolizing enzymes and risk of childhood acute lymphoblastic leukemia

The involvement of phase I and II enzymes is well documented in the metabolism of a wide range of drugs and xenobiotics. Single-nucleotide polymorphisms (SNPs) of these enzymes are also known to alter their protein expression and function. Moreover, genetic susceptibility and environmental exposure have been proposed to be an etiology of cancer. We hypothesized that polymorphisms of these enzymes might affect the risk of childhood acute lymphoblastic leukemia (ALL). CYP 1A1, CYP 3A4*1B, CYP 3A5*3, CYP 3A5*6, GSTM1, and GSTT1 polymorphisms were genotyped by using PCR-RFLP in 107 children with ALL and 320 healthy controls. Allele and genotype frequencies of each of the SNPs were compared between two groups. It was found that the allele frequencies of CYP 1A1*1, *2A, *2B, and *4 were not different between cases and controls. CYP 3A4*1B allele frequency was only 0.8% and 0.9% in ALL and controls, respectively. CYP 3A5*1/*1, *1/*3, and *3/*3 genotype frequencies showed no statistically significant difference between patients and controls. CYP 3A5*6 was not detected in our population. The GSTM1 null genotype was significantly increased in children with ALL (OR 1.7; 95% CI, 1.0, 2.7). In contrast, the GSTT1 null genotype did not show this effect. Our data thus demonstrate that the GSTM1 null genotype might increase the risk of childhood ALL in a Thai population.     

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 + 93 C/T at promoter region. The increasing size of apo(a) gene, more than 8 pentanucleotide repeats and + 93 C > 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 + 93 C/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).     

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.