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).     

Vitamin K deficiency bleeding in Thailand: a 32-year history.

Vitamin K deficiency bleeding cases in Thailand from 1963 to 1995 were extensively studied. From 1963 to 1987 there were 499 reported cases from 10 papers including 102 cases of the authors' series. From March 1994 to April 1996, two subsequent nationwide surveys were conducted where questionnaires were sent to 714 and 732 hospitals located throughout Thailand. The responding rate was 58.2% and 67% respectively. 331 cases were found during 1988 to 1995. The total number was 830 cases of which 799 were idiopathic vitamin K deficiency in infancy (IVKDI) and 31 were secondary types. IVKDI was found exclusively breast-fed infants (92%) who did not receive vitamin K prophylaxis at birth (90%). Bleeding and pallor were the common features. The occurrence of intracranial hemorrhage was strikingly high (82%); the fatality rates was 24%. However, the fatality rate among patients receiving either 1 mg of vitamin K, intramuscularly, (17%) or 2 mg, orally, (18%) were lower than those not receiving vitamin K prophylaxis (36%). The incidence of IVKDI significantly declined to 4.2-7.8 per 100,000 births between 1988 to 1995 which was in reverse proportion to the coverage of vitamin K prophylaxis (r = -0.94, p < 0.05).     

Home therapy for hemophilia in Thailand

The home therapy for hemophilia in Thailand was initiated in 1979. The therapeutic material first used was frozen cryoprecipitate or fresh frozen plasma and later fresh dry plasma (FDP). During 1979-1982, ten patients attended regular home therapy. All of them lived in the rural area which were far from the provincial hospitals. The age ranged from 7 to 15 years with a mean age of 10 years. The duration of follow up ranged from 7 months to 7 years with a mean duration of 3 years. The utilized blood products as FDP varied from 3 to 30 bottles per year with a mean of 16 bottles per year or 0.5-2.9 bottles per kilogram body weight per year which increased gradually as the patients grow up. A total of 252 episodes of bleeding was recorded; mostly hemarthrosis 70% and muscular bleeding 19%. There was no any further disability detected in 6 cases (60%). The significant advantages were the reduction in admission rate from 6-8 admission per year to 0-1 admission per year; economic savings; psychological independence of well being and having a normal life. The disadvantage were inadequate dosage of infused material, delayed consultation and transfer which were preventable. Home therapy for hemophilia by using FDP is recommended for any developing country. It is safe, practical, efficient enough to preserve normal joint status and prevent disability.     

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.     

Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.     

The use of rituximab as an adjuvant for immune tolerance therapy in a hemophilia B boy with inhibitor and anaphylaxis to factor IX concentrate.

We describe a 10-year-old severe hemophilia B boy with a stop codon mutation of exon 2 in the factor IX gene who developed high inhibitor of 70 Bethesda units (BU) from 12 months of age after exposure to prothrombin complex concentrate for 14 days. The inhibitor spontaneously disappeared within 3 months. The patient, however, exhibited anaphylactic reaction to the administration of prothrombin complex concentrate and factor IX concentrate at ages 15 and 23 months, respectively. Although recombinant activated factor VII was alternatively given, he suffered from progressive hemophilic arthropathy. At the age of 10 years, the boy underwent desensitization to factor IX concentrate and could tolerate factor IX concentrate of 40 U/kg administered on day 9 of desensitization. Unfortunately, the inhibitor of 16 BU was detected on day 6 and rapidly increased to 180 BU on day 9 of desensitization. Rituximab 375 mg/m2 per week was therefore immediately initiated on day 10 and a total of four doses were given. The inhibitor gradually decreased to 21.5 BU after the fourth dose of rituximab. The daily factor IX concentrate administration of 40 U/kg was continued for 1 month and decreased to three times per week for another month, and then to once to twice per week for the remaining 14 months of desensitization. The patient was able to attend regular school and the most recent inhibitor ranged from 4.4 to 10 BU. No proteinuria or alteration of renal function was found. In conclusion, rituximab is a helpful adjuvant to immune tolerance therapy in a hemophilia B boy with inhibitor and anaphylaxis to factor IX concentrate.     

Comparison between the Conventional Tube Technique and the Gel Technique in Direct Antiglobulin Tests

Objectives: The direct antiglobulin test (DAT) is a diagnostic procedure demonstrating in-vivo antibody or complement coating on red cells. The gel technique (GT) for this test is sensitive and easier to do than the conventional tube technique (CTT). Methods: We tested 52 newborns with hyperbilirubinemia and 6 children and 17 adults with autoimmune hemolytic anemia (AIHA) using the (DAT) in the form of the conventional tube technique (CTT) and the gel technique (GT) simultaneously. The gradings of the agglutination reactions of both techniques were scored as 12, 10, 8, 5, 3, 0 for 4+, 3+, 2+, 1+ and w+ and negative, respectively. Results: The GT yielded higher scores than the CTT (p < 0.01). The overall sensitivity and specificity of the GT were 93.5 and 88.6%, respectively. The specificity of the DAT-positive results in newborns was determined by IgG only, while in AIHA, it was determined by IgG and/or C3d and, in only one sample, by IgM. Conclusion: The GT is equal to or better than the CTT. Since the GT is simple, the exposure of blood bank personnel to the blood sample is low. We highly recommend the GT, especially in areas where HIV infection is prevalent.     

The use of dengue nonstructural protein 1 antigen for the early diagnosis during the febrile stage in patients with dengue infection

BACKGROUND: To evaluate the use of dengue nonstructural protein 1 (NS1) antigen for the early diagnosis during the febrile stage in patients with dengue infection. METHODS: A total of 445 sera obtained from 165 patients [dengue fever (DF): 42, dengue hemorrhagic fever (DHF) grade I: 50, II: 63, III and IV: 10] and 8 other febrile illnesses 5-15 years of age, were assayed for the NS1 antigen, dengue-specific Ig M and Ig G antibodies. RESULTS: The positive rates of NS1 antigen among patients with either DF or DHF was 100% (7 of 7) on day 2, 92.3% (12 of 13) on day 3, 76.9% (40 of 52) on day 4, 56.5% (61 of 108) on day 5 of fever; and declined to 43.1% (59 of 137) on day 6 with defervescence and 29.8% (25 of 84) on day 7 (1 day after defervescence). The positive rates of patients with DF were higher than those with DHF but no statistically significant difference was found. However, patients with primary DHF infection had significantly higher positive rates than those with secondary DHF infection. The positive rates of Ig M antibodies were in reverse proportion to those of NS1 antigen. The additional Ig M antibody determination increased the positive rates to 90.4% (47 of 52) on day 4, 83.3% (90 of 108) on day 5 of fever; 95.6% (131 of 137) on day 6 with defervescence, and 88.1% (74 of 84) on day 7. CONCLUSIONS: Dengue NS1 antigen testing is suggested as a helpful tool for the early diagnosis of dengue infection after the onset of fever. The additional Ig M antibody determination increased the diagnostic rates.