National survey of patients with hemophilia and other congenital bleeding disorders in Thailand.

A national survey of patients with hemophilia and other congenital bleeding disorders in Thailand was conducted in the years 2000 to 2002. Questionnaires were sent to physicians working at hospitals throughout the country. Although the overall response rate to the questionnaires was 19%, the two highest rates of 80% and 73.7% were found at university and regional hospitals, respectively, where most of the patients received their diagnosis and treatment. A total of 1,450 patients comprised of hemophilia 1,325 cases, von Willebrand disease, 69 cases, congenital factor VII deficiency, 15 cases, hereditary platelet dysfunction, 22 cases, and undefined causes of congenital bleeding disorders, 19 cases. Most were pediatric patients <15 years of age. Treatment was mainly given on demand for a bleeding episode, while only 8.6% received additional home treatment for early bleeding episodes. Replacement therapy primarily relied on fresh frozen plasma, cryoprecipitate and cryo-removed plasma. Factor concentrate was seldom used because of the high price. As a result, hemophilia care services in Thailand should be strengthened by providing comprehensive education for medical personnel, making available simple laboratory kits to determine hemophilia A and B, ensuring an adequate supply of blood components and affordable factor concentrate, and establishing home care treatment.

Thrombotic complications during induction chemotherapy of acute childhood lymphoblastic leukemia.

The incidence of thrombosis during induction chemotherapy of acute childhood lymphoblastic leukemia (ALL) patients was 6 found to be in 105 (5.7%). There were 4 cerebral infarctions, 1 superior vena cava (SVC) obstruction and 1 deep vein thrombosis. Among these, 2 of them died. A prospective study was further conducted of the change in coagulation and anticoagulation factors during 6 weeks of induction chemotherapy. It was found that the activated partial thromboplastin time (aPTT) was within normal range in all cases throughout 6 weeks, while prothrombin time (PT) and thrombin time (TT) were slightly prolonged, especially during the first 3 weeks of this phase. The natural anticoagulant panels which included protein C (PC), protein S (PS) and antithrombin III (AT III) and also fibrinogen level, were lower during the first 3 weeks and reached its nadir during the second and third week. The lower level of natural anticoagulants might be an important predisposing factor for the occurrence of thrombosis in these patients.

Carrier detection by DNA linkage analysis in eighty Thai hemophilia A families.

DNA linkage analysis was performed in Thai hemophilia A families to evaluate its value for carrier detection. Both intragenic and extragenic polymorphic DNA regions of the factor VIII gene, including Bcl I-RFLP in intron 18, microsatellites (CA repeats) in introns 13 and 22, and extragenic Stl4 (DXS 52) VNTR, were amplified by polymerase chain reaction (PCR) before analyses by appropriate electrophoretic procedures. A total of 80 Thai hemophilia A families (48 with a family history and 32 with a sporadic case), containing 349 DNA samples from 90 hemophilia A patients, 143 parents, and 116 relatives, were analyzed. Heterozygosities in the patients' mothers from both families with a family history and with a sporadic case were observed in 71 out of 80 families (88.75%) for all polymorphic DNA markers analyzed. The carrier status could be identified in 36 females and excluded in 44 females. This result indicates that the DNA linkage analysis can be used for carrier detection or exclusion in the majority of Thai hemophilia A families. It should also be useful for prenatal diagnosis in families at risk of hemophilia A, which is part of the prevention and control of this disease.

Secondary hemophagocytic lymphohistiocytosis in children: an analysis of etiology and outcome.

Fifty-two pediatric patients were diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH) at the Department of Pediatrics, Siriraj Hospital between 1989 and 1998. Of these, 15 were infection-associated (IAHS), 25 were malignancy-associated (MAHS) and 12 were idiopathic HLH. Causative organisms for IAHS were Salmonella (3), Staphylococcus (2), enterobactor (2), dengue virus (3), malaria (2) and one each of Ebstein Barr virus (EBV), Serratia marcesens and Penicillium maneffei. Unlike those reported in adults and in the Western literature, 47 of 52 children in the present series were immunocompetent hosts. In addition, the proportion of MAHS was higher than expected (48.1%). Twenty-two of 25 MAHS presented with hemophagocytic syndrome and were subsequently found to have malignant diseases. Sixty per cent of MAHS (15 cases) were associated with non-Hodgkin's lymphoma (NHL), mainly T-cell. Other malignancies included acute leukemias (7) MDS (1), Langerhans cell histiocytosis (1) and histiocytic sarcoma (1). Treatment approaches were specific therapy for individuals with known causes. Supportive treatment with blood components transfusions, steroid, intravenous immunoglobulins (IVIG), and chemotherapeutic agents, mainly vinblastine and etoposides, were used in indicated cases. Of the 52 cases, 15 (28.8%) had a fatal outcome during the acute phase, and other 4 died of their subsequent malignant diseases. There was a statistically significant association between poorer prognosis and patients' age < 3 years (p= 0.004) or MAHS (p=0.005). Conclusion: Secondary HLH is not uncommon in Thai children who are immunocompetent. Malignancies, particulary NHL, are highly suspicious especially for cases not responsive to conventional therapy. Poor prognostic factors are age less than 3 years and MAHS.

Malignancies in HIV-infected children at Siriraj Hospital.

BACKGROUND: Some malignancies such as Kaposi's sarcoma, non-Hodgkin's lymphoma (NHL) are one of the acquired immunodeficiency syndrome (AIDS)-defining illnesses. With the improving survival of patients with AIDS due to better prevention and treatment of infectious complications, there may well be an increase in AIDS-related malignancies. OBJECTIVE: To study malignancies in human immunodeficiency virus (HIV)-infected children in view of demographic data, HIV disease status, characters of malignancies, and treatment outcome. METHOD: Retrospective study was performed in HIV-infected children with malignancies at Siriraj Hospital from January 1995 to October 2001. RESULTS: During the 6 year and 10 month period, there were 7 HIV-infected children (2 boys, 5 girls) with malignancies. Mean age at diagnosis of malignancies was 3 years 7 months (2 years 6 months-5 years). Hepatomegaly and lymphadenopathy were the most common presenting symptoms. All patients had NHL stage III or IV. Burkitt's lymphoma was the predominant type. Six patients were treated with appropriate chemotherapy and one patient also received antiretroviral therapy. Only one patient with large cell lymphoma stage IV who received both antiretroviral and chemotherapy has survived to date. Five patients died during chemotherapy treatment and one patient died before receiving chemotherapy. Causes of death of these patients were infections. One of them with Burkitt's lymphoma stage III also had central nervous system (CNS) relapse at the time of death. Mean survival time after diagnosis with malignancies was 11 months (15 days-3 years 1 month). CONCLUSION: NHL is the most common malignancy in HIV-infected children at Siriraj Hospital. Age at presentation of NHL in these children is younger than their non-HIV counterpart. Outcome of treatment is poor. Adjustment protocol for treatment of malignancy in HIV-infected children combined with antiretroviral therapy for controlling HIV infection should be studied further.

Treatments of severe aplastic anemia in children.

We carried out a retrospective analysis of the outcome of treatment in patients with severe aplastic anemia who attended the Department of Pediatrics, Siriraj Hospital, during 1972- 1998. There were 31 patients, 17 boys and 14 girls, by Camitta’s criteria for severe aplastic anemia. All of them were idiopathic. Twenty patients were treated conventionally with steroid and androgen compounds, 5 with immunosuppressive therapy and 6 with bone marrow transplantation. In the conventional treatment group, after 1 year to 19 years of follow up, 64.7% achieved complete response, 11.8% achieved partial response and 23.5% died. The response rate in the immunosuppressive therapy group was only 40% after 3 months to 2 years of follow up. In the bone marrow transplantation group, bone marrow engraftment was achieved in all cases (means 29.8, range 19 - 42 days), and the patients yielded the highest complete response rate (100%). However, 1 case relapsed after complete response for 1 year, but he was successfully cured after second transplantation. The overall survival rate and cure rate were also 100% after 1 year and a half to 10 years of follow up. Bone marrow transplantation, when compared to other treatments, resulted in the highest response or cure rate with the shortest treatment duration. The only disadvantages of bone marrow transplantation are the high cost and the limited availability of HLA compatible donors.

Nutritional support for children underwent bone marrow transplantation.

Nutritional support for children underwent bone marrow transplantation was studied by comparing parenteral nutritional support and oral intakes. During 1988-1991 a total of 15 recipients, 10 boys and 5 girls, ages ranging 1-12 years from the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital were studied. The patients were classified according to underlying diseases into 3 groups; Group I (thalassemia), Group II (aplastic anemia) and Group III (malignancy). The results indicate that Group I required less parenteral support than the other groups. Group III required the most parenteral support. Complications from bone marrow transplantation support among the 3 groups were similar. Therefore the requirement for nutritional support depend on the type of hematologic disease from which the patient is suffering.