Immune tolerance in a haemophilia A patient with high inhibitor using locally prepared lyophilized cryoprecipitate

The immune tolerance in a 12-year-old haemophilia A patient was carried out at the Faculty of Medicine, Ramathibodi Hospital, Bangkok in 1998. His inhibitor titres ranged from 10 to 3450 Bethesda units (BU). He suffered from serious bleeding episodes requiring prolonged hospitalization and the disarticulation of the left knee joint. After obtaining informed consent, locally prepared lyophilized cryoprecipitate (LC), heat treated at 60 degrees C for 25 h, was given in a dose of 13 units kg-1 body weight of factor VIII three times per week. His inhibitor was increased from 15 to 580 BU within the first 4 weeks of immune tolerance. Finally, it was decreased to 40 BU in the 36th week. The only adverse effect was seroconversion of anti-hepatitis C virus after receiving 108 bottles of LC for 36 weeks. In conclusion, the locally prepared LC was able to control the bleeding episodes in a haemophilia A patient with high inhibitor. To our knowledge, this is the first reported case in Thailand.     

Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia

Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.     

Bone mineral density,biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease

OBJECTIVE: Thalassaemia/haemoglobinopathy is a hereditary disease causing increased erythropoiesis and expansion of the bone marrow cavity. As a consequence, there is a reduction in trabecular bone tissue resulting in osteopenia/osteoporosis. The present study was performed to assess bone mineral density (BMD) in children and adolescents with beta-thalassaemia disease and to determine biochemical and hormonal changes that may affect BMD. METHODS: Forty-eight children and adolescents with beta-thalassaemia were divided into two groups, transfusion-dependent (TD) (n = 16) and transfusion-independent (TI) (n = 32). All patients were treated suboptimally. BMD was determined by dual-energy X-ray absorptiometry. Bone maturation was assessed by radiographic bone age (BA). Blood and urine samples were obtained for the determination of biochemical and hormonal profiles, which included PTH, 25-hydroxyvitamin D (25-OHD), osteocalcin, bone-specific alkaline phosphatase, IGF-1, fT4, TSH and urine deoxypyridinoline. RESULTS: Most of the patients were short and underweight, and they had delayed BA with mean Z-scores of -2.77 in the TD and -2.04 in TI groups. The mean Z-scores of BMD in the TD vs. TI groups of total body, radius, femoral neck and lumbar spine were -2.09 vs.-1.49, -0.73 vs. -0.54, -1.93 vs.-1.17 and -3.45 vs.-2.43, respectively. Although the means BMD values in the TD group were lower than those in the TI group, they were not significantly different. Mean serum IGF-1 levels were lower in the TD than the TI groups, 11.6 and 24.9 nmol/l, respectively (P < 0.05). Other biochemical and hormonal profiles did not differ between these two groups. CONCLUSIONS: Patients with undertransfused severe beta-thalassaemia had more bone marrow expansion, lower serum IGF-1 levels and more delayed bone age than did patients with untransfused moderately severe beta-thalassaemia. Therefore, the severity of the disease appeared to be a primary factor for low bone mineral density in undertransfused patients in association with bone age delay and low serum IGF-1.     

Acquired bleeding disorders: the impact of health problems in the developing world

Summary.  Several acquired bleeding disorders in the developing world have impacts on health, including late vitamin K deficiency bleeding (VKDB) in infants, dengue haemorrhagic fever (DHF), and malaria. This paper describes their clinical manifestations, mechanisms involved, and treatment.     

Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature

The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis.     

Outcomes of transplantation with related- and unrelated-donor stem cells in children with severe thalassemia.

Recently published reports indicate that the outcome of unrelated donor transplantations in patients with leukemia is currently comparable to that of transplantation from identical family donors. We investigated the possibly favorable outcomes of related and unrelated transplantation in children with severe thalassemia. We reviewed transplantation outcome in 49 consecutive children with severe thalassemia who underwent allogeneic stem cell transplantation with related-donor (n=28) and unrelated-donor (n=21) stem cells between September 1992 and May 2005 at the Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Bangkok, Thailand). Analysis of engraftment, frequency of procedure-related complications, and thalassemia-free survival showed no advantage from use of related-donor stem cells. The 2-year thalassemia-free survival estimate for recipients of related-donor stem cells was 82% compared with 71% in the unrelated-donor stem cell group (P=.42). The present study provides evidence to support the view that it is quite reasonable to consider unrelated-donor stem cell transplantation an acceptable therapeutic approach in severe thalassemia, at least for patients who are not fully compliant with conventional treatment and do not yet show irreversible severe complications of iron overload.