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Biomedical subjects

A Chuansumrit

Publications and source records attributed to A Chuansumrit.

At least 19 recordsLinked to original sources
PubMed2007

Rituximab as an adjuvant therapy to immune tolerance in a haemophilia A boy with high inhibitor titre.

We report a haemophilia A boy with high inhibitor titre (170 BU) who experienced five life-threatening bleeding episodes during a one-year period from 9 to 21 months. At the age of 22 months, he received rituximab (375 mg m(-2) per dose) at one- and three-week intervals, three courses each and alternative daily treatment with factor VIII concentrate at doses of 100 units kg(-1) for 24 weeks and 50 units kg(-1) for the following 28 weeks. Although the pretreatment inhibitor level of 4.5 BU showed an anamnestic response reaching the maximum level of 200 BU at the 9th week of treatment, it gradually declined to 30 BU at the 22nd week and was constantly maintained at 25-30 BU for the following 30 weeks. Only three bleeding episodes of two haematomas and one haemarthrosis were found during the one-year treatment period. No opportunistic infection occured during this period.

Adjuvants, Immunologic↗
PubMed2006

Ethical issues in haemophilia.

Ethical issues surrounding both the lack of global access to care as well as the implementation of advancing technologies, continue to challenge the international haemophilia community. Haemophilia is not given the priority it deserves in most developing countries. Given the heavy burdens of sickness and disease and severe resource constraints, it may not be possible to provide effective treatment to all who suffer from the various 'orphan' diseases. Nevertheless, through joint efforts, some package of effective interventions can be deployed for a significant number of those who are afflicted with 'orphan' diseases. With cost-effective utilization of limited resources, a national standard of care is possible and affordable. Gene-based diagnosis carries attendant ethical concerns whether for clinical testing or for research purposes, even as the list of its potential benefits to the haemophilia community grows rapidly. As large-scale genetic sequencing becomes quicker and cheaper, moving from the research to the clinic, we will face decisions about the implementation of prenatal, neonatal and other screening programs. Such debates will require input from not just the health care professionals but from all stakeholders in the haemophilia community. Finally, long-term therapeutic success gene transfer in small and large animal models raises the question of when and in which patient population the novel therapeutic approach should first be studied in humans with haemophilia. Although gene therapy represents a worthy goal, the central question for the haemophilia community should be whether it wishes to volunteer itself as a model for a much broader set of innovations.

Adult↗
PubMed2006

Intracellular readthrough of nonsense mutations by aminoglycosides in coagulation factor VII.

BACKGROUND: Nonsense mutations in coagulation factor (F) VII potentially cause a lethal hemorrhagic diathesis. Readthrough of nonsense mutations by aminoglycosides has been studied in a few human disease models with variable results. OBJECTIVES: We investigated the K316X and W364X FVII mutations, associated with intracranial hemorrhage, and their correction by aminoglycosides. The rare nonsense mutations in FVII represent favorite models to test this strategy, because even tiny increases in the amount of functional full-length protein in patients could ameliorate hemorrhagic phenotypes. RESULTS: A FVII-green fluorescent protein (GFP) chimaera provided us with a fluorescent model of FVII expression in living cells. Appreciable fluorescence in cells transfected with nonsense FVII-GFP mutants was detected upon geneticin treatment, thus demonstrating suppression of premature translation termination. To investigate the rescue of FVII function, nonsense variants of the native FVII without GFP (p316X-FVII and p364X-FVII) were transfected and found to secrete low amounts of FVII (approximately 1% of Wt-FVII activity), thus suggesting a spontaneous stop codon readthrough. Geneticin treatment of cells resulted in a significant and dose-dependent increase of secreted FVII molecules (p316X-FVII, 24 +/- 12 ng mL(-1), 3.6 +/- 0.8% of Wt-FVII activity; p364X-FVII, 26 +/- 10 ng mL(-1), 3.7+/-0.6%) characterized by reduced specific activity, thus indicating the synthesis of dysfunctional proteins. Similar results were observed with gentamicin, a commonly used aminoglycoside of potential interest for patient treatment. CONCLUSIONS: Our approach, extendable to other coagulation factors, represents an effective tool for a systematic study of the effects of aminoglycosides and neighboring sequences on nonsense codon readthrough. These results provide the rationale for a mutation-specific therapeutic approach in FVII deficiency.

Adolescent↗
PubMed2005

Combined factor V and factor VIII deficiency in a Thai patient: a case report of genotype and phenotype characteristics.

A Thai woman, with no family history of bleeding disorders, presented with excessive bleeding after minor trauma and tooth extraction. The screening coagulogram revealed prolonged activated partial thromboplastin time and prothrombin time. The specific-factor assay confirmed the diagnosis of combined factor V and factor VIII deficiency (F5F8D). Her plasma levels of factor V and factor VIII were 10% and 12.5% respectively. The medications and blood product treatment to prevent bleeding from invasive procedure included 1-deamino-8-d-arginine vasopressin, cryoprecipitate, factor VIII concentrate, fresh frozen plasma and antifibrinolytic agent. Gene analysis of the proband identified two LMAN1 gene mutations; one of which is 823-1 G --> C, a novel splice acceptor site mutation that is inherited from her father, the other is 1366 C --> T, a nonsense mutation that is inherited from her mother. Thus, the compound heterozygote of these two mutations in LMAN1 cause combined F5F8D.

Adult↗
PubMed2004

Outcome of transplantation with unrelated donor bone marrow in children with severe thalassaemia.

SUMMARY: We conducted a study of unrelated donor bone marrow transplantation (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 x 10(8) /kg (range; 3.5-8.0 x 10(8) /kg). Median time of granulocyte recovery was 16 days (range; 13-21 days), and of platelet recovery was 39 days (range; 14-196). Grade 2-4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and grade 3-4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic GVHD (limited stage). All 11 patients are alive without thalassaemia after a median follow-up time of 397 days (range; 171-814 days). This study lends support to consideration of unrelated donor BMT as an acceptable therapy to cure severe thalassaemia especially in patients who are young and do not yet show irreversible severe complications of iron overload.

Age Factors↗
PubMed2004

Survival analysis of patients with haemophilia at the International Haemophilia Training Centre, Bangkok, Thailand.

Haemophiliac treatment in less developed countries is limited to locally prepared fresh frozen plasma, cryoprecipitate, cryo-removed plasma and lyophilized products as replacement therapy. Factor concentrate is seldom used because of the high price. The present study reports the survival analysis of 164 patients comprising 138 haemophilia A and 26 haemophilia B cases from 134 families registered at the International Haemophilia Training Centre-Bangkok, Faculty of Medicine, Ramathibodi Hospital, Mahidol University from 1971 to 2000. The duration of follow-up ranged from 1 to 27 years and 8 months with a median of 9 years and 1 month. They received treatment on demand of bleedings, and 85 patients received additional home treatment for early bleedings. The proportion of death was 15.2%. The Kaplan-Meier survival curves revealed the median (95% CI) survival time of patients with severe and moderate degrees of 35 years and 6 months (21.4-49.7), and 38 years and 1 month (28.8-47.3), respectively. To compare the progressive achievement of haemophilia care services, the treatment period was divided into three decades: 1971-1980, 1981-1990 and 1991-2000. The patients with unaided proper walking increased from 62.8% in the first decade to 84.5% in the third decade. However, one-third of the patients developed one to four chronic haemarthrosis determined by clinical evaluation, especially patients with severe degree. Moreover, the estimated probability of a survival time beyond 13 years of age among patients with severe degree increased from 0.85 in the first decade to 0.94 and 1 in the second and third decades, respectively. Thus, established haemophilia care, even with limited resources, has significantly decreased the risk of death and increased the survival time among patients with haemophilia.

Adolescent↗
PubMed2004

Essential issues of laboratory investigation for patients with haemophilia and bleeding disorders.

Apart from history-taking and physical examination, laboratory investigation is one of the essential issues for the definite diagnosis of haemophilia and bleeding disorders. The limited resources of medical personnel, equipment and reagents should be shared among several departments in the hospital, especially for serving patients with common genetic diseases such as thalassemia and haemoglobinopathies. Medical personnel require appropriate training to expand their skills in laboratory techniques. Laboratory procedures can be created, modified and simplified using locally produced and shared equipment. Molecular genetic studies can also be set up at different levels of hospital service using simple, rapid and low-cost methods. Finally, a system of periodic external quality control will guarantee the accuracy of laboratory results.

Blood Coagulation Disorders↗
PubMed2003

Treatment of haemophilia in the developing countries.

In developing countries, most of the patients with haemophilia are in the paediatric age group as they seldom reach adulthood because of inadequate treatment. Haemophilia is not given the priority it deserves as there are high numbers of other serious health problem. Haemophilia care should be integrated into the existing healthcare system of a primary care centre, a treatment centre, a comprehensive care centre and a reference centre. It is considered important to educate the personnel through the curriculum of medical students and all healthcare personnel. Diagnosis should be started at the antenatal stage and subsequently confirmed by laboratory testings. Qualified therapeutic products should be produced locally in combination with imported affordable factor concentrate. In-house preparation of fibrin glue is helpful for dental procedures without the need for any blood component. Home care treatment is essential and can be adopted even by parents with low literacy. Lastly, research for laboratory diagnosis, treatment and prevention should be continuously conducted to serve people with haemophilia specifically in developing countries.

Blood Component Transfusion↗
PubMed2002

Full chimerism in nonmyeloablative stem cell transplantation in a beta-thalassemia major patient (class 3 Lucarelli).

Bone marrow transplantation is the only therapeutic option that can eliminate thalassemic disease. Early results indicated that children in class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. We therefore tried to investigate a nonmyeloablative stem cell transplantation (NST) approach for such a disease in order to reduce mortality and rejection. We report here the case of successful NST in a 10-year-old girl who had class 3 Lucarelli beta-thalassemia major. The conditioning regimen consisted of busulfan, fludarabine, antilymphocyte globulin and total lymphoid irradiation. Her GVHD prophylaxis included mycophenolate mofetil and cyclosporin. The patient had full donor engraftment without acute and chronic GVHD. She is now alive and well and remains disease-free 1 year after transplant.

Bone Marrow Transplantation↗
PubMed2001

The usefulness of X-linked polymorphic loci as gene markers to track X allele and chimerism in a post-allogeneic peripheral blood stem cell transplant patient with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by progressive T-cell immunodeficiency. Laboratory findings generally demonstrate reduced response to T-cell mitogens, markedly decreased serum concentration of IgM, and thrombocytopenia with small platelet volume. Allogeneic HLA-matched sibling bone marrow transplantation (BMT) can correct this disorder. We report the usefulness of X-linked polymorphic loci to detect X-allele gene tracking among WAS siblings and chimerism between a pre- and post-allogeneic matched sibling peripheral blood stem cell transplantation (PBSCT). A 3 1/2 year old boy with clinical and laboratory findings consistent with WAS underwent allogeneic matched sibling PBSCT. We used BclI restriction fragment length polymorphism (RFLP) of intron 18 of factor VII gene and MseI RFLP of the 5' flanking region of factor IX gene to detect X-allele gene tracking among siblings and family members and chimerism in patients between pre-and post-allogeneic matched sibling PBSCT. We were able to demonstrate that determination of BclI and MseI RFLP can be employed to recognize the difference in X-allele genes between the recipient and donor for allogeneic matched sibling PBSCT. The authors also were able to demonstrate that these polymorphic loci can detect full chimerism of donor hematopoietic cells in recipient blood after allogeneic PBSCT. This finding was correlated with improvement of post-PBSCT clinical and laboratory findings. BclI and MseI RFLP associated with X-chromosome can effectively track X-allele, detect carrier state, and demonstrate the different X-allele among male siblings, and chimerism of hematopoietic cells between donors and recipients in a setting of allogeneic matched sibling BMT or PBSCT for X-linked hereditary diseases such as Wiskott-Aldrich syndrome.

Child, Preschool↗
PubMed2001

Prevalence of factor V Leiden in Thai blood donors.

Factor V Leiden was recently found to be the most common cause of familial venous thrombosis in the European population. We have studied the prevalence of factor V Leiden by DNA analysis among 500 Thai blood donors (male 285, female 215). Their ages ranged from 18 to 60 years with a mean of 33 years and 2 months. All of them were healthy voluntary blood-donors who met the standard criteria of the American Association of Blood Banks. No history of thrombosis was found. The results revealed that factor V Leiden was not present among 1,000 chromosomes from Thai blood donors. This suggests that factor V Leiden is not the common genetic predisposing factor of venous thrombosis in the Thai population as compared to the European population.

Adolescent↗
PubMed2001

HLA alloimmunization in patients receiving multitransfusions of red blood cells.

HLA antibodies were studied in 88 patients with chronic hemolytic anemia who received multitransfusions of red blood cells prepared by conventional (PRC-C), inverted centrifugation (LR-I) and leukocyte filter (LR-F) techniques. Their mean age was 8 years and 4 months with a duration of transfusion of 8 years. The patients were divided into five groups: group 1, receiving PRC-C (n=20); group 2, receiving LR-I (n=33); group 3, receiving LR-F (n=11); group 4, subsequently receiving LR-I and LR-F (n=10); and group 5, receiving PRC-C followed by LR-I and LR-F (n=14). The HLA class I antibodies were found in 30 out of 88 patients (34%). All were against HLA antigens commonly found in the Thai population. The patients receiving PRC-C exhibited HLA antibodies of 65%, which was significantly higher than those of patients receiving LR-I (24%) and LR-F (0%). Consequently, the transfusion reactions of fever, chill, rash and urticaria were also commonly found in patients receiving PRC-C (13.4%), which was significantly higher than patients receiving LR-I (0.4%) and LR-F (0%). The leukocyte filter technique has been shown to be effective in preventing HLA alloimmunization and transfusion reactions but the price is rather high. For the inverted centrifugation technique, only transfusion reactions were effectively prevented and the HLA alloimmunization continued to develop. A more effective and low-cost method for the removal of leukocytes should be investigated for these multitransfusion patients.

Adolescent↗