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BACKGROUND: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. MATERIALS AND METHODS: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. RESULTS: The average body weight of patients was 26.4 ± 14.8 (n=22), 32.9 ± 19.4 (n=23) and 37.9 ± 20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2 ± 13.4, 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8, 16.2 ± 8.3, and 14.7 ± 10.7 days, respectively. The time to resolve fever was 13.3 ± 10.2, 10.9 ± 7.1, 10.1 ± 6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4 ± 9.6, 10.6 ± 7.6 and 7.3 ± 3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS: This small randomized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

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The t(8;21)(q22;q22) is one of the most frequent chromosomal abnormality associated with acute myeloid leukemia (AML) M2 sub type. The additional chromosomal abnormalities including structural and numerical are frequently reported with the translocation, t (8;21)(q22;q22). We report a case of AML-M2 with t(X;8;21)(p22;q22;q22) associated with loss of Y chromosome. Using a dual color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative chromosome 8 and one ETO signal on derivative Chromosome Xp22. The patient did not respond to therapy and follow-up of cytogenetics revealed same chromosome abnormality. Hence, this three way translocation involving X chromosome might be associated with poor prognosis.

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Intracranial haemorrhage (ICH) is a common cause of morbidity and mortality in haemophilic patients all over the world. From 1995 to 2004, we have investigated 37 patients with 43 episodes of ICH at our Comprehensive Haemophilia Care Center from a total of 600 registered patients. Diagnosis of ICH in the patients was confirmed by clinical, haematological and computed tomographic imaging data. Three patients died despite replacement therapy while one child who had a ventriculo-atrial shunt for acute hydrocephalus also died before further intervention. One of the four patients who died also had severe aplastic anaemia for 6 years in addition to severe haemophilia. Detailed history obtained from 143 families with haemophilia attending the Genetic Diagnosis Clinic at our Center showed a positive history of cerebral bleed in 39 episodes in 37 patients. Sixteen families gave a history of death in the family of haemophilic patients due to ICH, while in the remaining 21 families, the patients had survived the episode after treatment elsewhere. However, the ICH was not confirmed by image data in these cases. The treatment protocols were also not available in these cases. Conservative factor replacement therapy 100% correction for 3 days followed by 50-60% correction for 7 days) coupled with the epsilon amino caproic acid, the antifibrinolytic agent at least for 30 days led to a mortality (10.8%) similar to that of the western countries and almost no morbidity. Surgery was not required in any of these patients except in one elderly patient with HIV infection on antiretroviral therapy.

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We managed bleeding crisis in 10 consecutive severe haemophilic patients with inhibitors (eight had an inhibitor level of >5 BU mL(-1)) mainly with the antifibrinolytic agent, i.e. epsilon amino caproic acid (EACA). EACA was used by local, oral or intravenous routes either in combination or separately. Five patients developed inhibitors postoperatively and among the remaining five, four had recurrent haemarthrosis or soft tissue bleeds and one patient presented with severe gastrointestinal bleeding without demonstrable lesion. In all the patients, addition of EACA to their management protocol resulted in stoppage and/or reduced frequency of bleeding. In six of 10 patients, the results were excellent; of these six patients, five developed inhibitors postoperatively. Although a reduction in the frequency of bleeding was observed in patients with haemarthrosis and soft tissue bleed, it was not spectacular and the patients required additional therapy. Hence the results could be described as poor. No patient needed to stop the medicine because of the side-effect of EACA. Symptoms like mild nausea and vertigo were seen as the side-effects of this medicine when high intravenous dosage was administered. EACA thus appears to be an excellent adjuvant therapy for haemophilic patients with inhibitors. Besides its well-recognized antifibrinolytic activity, EACA may have additional mechanisms of action in haemophilic patients with inhibitors. More extensive use of this cheap and safe product is warranted in haemophilic patients with inhibitors. If larger studies confirm this observation, then using antifibrinolytics will allow substantial reduction of FEIBA or activated prothrombin complex (APCC) usage in such patients without necessarily increasing the thrombotic complications or reduction of the clinical efficacy, when compared with higher dosage of FEIBA or APCC alone. This will lead to substantial financial savings in countries where up to 35% of severe haemophilia A patients develop inhibitors.

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Development of inhibitor to FVIII in haemophilia patients is well-known and is not uncommon. However, their development for the first time during the postoperative period has hardly been reported. In a developing country such as India, where resources are limited, development of such an eventuality may prove disastrous. However, as many of our patients are sparingly treated, therefore, even if they test negative for the inhibitor preoperatively, they may get the requisite FVIII antigenic stimulation during the preoperative and immediate postoperative period, leading to the development of inhibitors during this critical time of wound healing. We describe here six patients who developed such an inhibitor, from a group of 35 patients with haemophilia A who underwent various surgical procedures (19%). We stress that such an eventuality may not remain rare in developing countries as more patients of severe haemophilia undergo surgery and are therefore challenged for the first time in their life with large amounts of FVIII concentrate during their preoperative period.

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A 9-year-old-boy with severe haemophilia A (factor VIII < 1%) developed colicky abdominal pain with swelling in the left iliac fossa for 4 weeks. His LDH level was 1423 IU/l (normal range < 220 IU/l) and his uric acid, 6.8 mg/dl. A computerised tomography (CT) scan of the abdomen demonstrated a tumour of the terminal ileum and mild hepatosplenomegaly. Pre-operative screening for factor VIII inhibitor was negative. Post-operatively, the patient needed high doses of factor VIII to maintain haemostasis. The tumour was found to be a high-grade lymphoma of Burkitt's type. He recovered from his operation and chemotherapy was commenced. Investigations demonstrated an anti-von Willebrand factor (VWF) antibody. He subsequently relapsed and died of progressive disease. Development of anti-VWF antibody in lymphoma is well known, but development of this antibody in a haemophilia A patient developing lymphoma has not been reported. The present case shows that antibody to VWF should be considered as a possible reason for an increased factor VIII requirement in such patients.

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We report a patient with plasma cell leukaemia with systemic capillary leak syndrome, a rare disorder often associated with monoclonal gammopathy. In this patient, the manifestation of capillary leak syndrome antedated the diagnosis of plasma cell leukaemia by 5-6 months. During that time, he was repeatedly admitted to the hospital with weight gain, congestive cardiac failure, cough and anasarca in the presence of normal renal function, liver function and normal echocardiography. On presentation, a serum protein electrophoresis showed monoclonal IgG; the blood smear showed 60% plasma cells with a total count of 4.4 x 10(9)/l. A bone marrow aspirate showed replacement of the normal marrow by sheets of immature plasma cells. His systemic capillary leak syndrome initially responded to decongestive therapy with terbutaline and aminophylline but later on he became refractory to them and responded to vincristine, doxorubicin and dexamethasone (VAD) combination therapy only transiently. Danocrine and pentoxifylline, added during VAD chemotherapy, did not produce a durable response in capillary leak syndrome, which finally responded to autologous peripheral blood stem cell transplantation (PBSCT). After PBSCT, he remained free of capillary leak for 10 months without terbutaline, pentoxifylline corticosteroids, aminophylline or danocrine. His disease relapsed without recurrence of the capillary leak. He died 15 months after PBSCT and 20 months after the diagnosis of plasma cell leukaemia.

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A wide range of ophthalmic surgical procedures were conducted in five patients with haemophilia of varying severity (one severe and four mild) aged between 8 and 75 years. The operations included intraocular lens implantation, trabeculectomy and vitrectomy. Successful postoperative outcome with haemostasis was achieved in all patients with moderate use of clotting factor concentrates (3000-7000 IU), simultaneous use of oral epsilon amino caproic acid therapy and intravenous deamino-8-D-arginine vasopressin (desmopressin; DDAVP) wherever feasible. None of the patients had circulating inhibitor. One of the patients with milder disease (FVIII 32%) was referred to us after he was operated on for hyphaema elsewhere, without prior knowledge of his diagnosis of haemophilia. Thus, satisfactory eye surgery in patients with haemophilia is possible with a restricted amount of factor concentrates with gratifying results.

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The goal of this article is to study the association of known markers of thrombophilia with venous thrombosis in young patients (< 45 years) from the Western part of India. A prospective study of 432 patients (252 males and 180 females, age 1-45 years) was conducted between 1994 and 2000 (6 years). The diagnosis was confirmed in all the patients by ultrasound with Doppler or by a computed tomograph (CT) scan of the brain with or without contrast depending on the case. Detailed clinical examination, and family history was taken to establish recurrent thrombosis and familial occurrence of thrombosis. The markers studied were protein C, protein S, antithrombin (AT) III, factor V Leiden mutation, prothrombin gene G20210A polymorphism, and the thermolabile MTHFR variant C677T polymorphism, using appropriate techniques. Lupus inhibitor was tested in the first 72 patients using Dilute Russel Viper Venom Time (DRVVT) test, and anticardiolipin antibodies were tested by enzyme-linked immunosorbent assay. Protein C, protein S, and AT III deficiency was detected in 9.5%, 6.5%, and 2.6%, respectively, among the patients. Anticardiolipin antibody was present in 9.9% of the patients, whereas lupus anticoagulant was present in 8.3% of patients; factor V Leiden mutation was detected in 3% of patients; thermolabile variant of MTHFR C677T polymorphism was present in 14.9% of patients with 1.2% homozygotes. Prothrombin G20210A polymorphism was not detected in any sample in this population. One hundred and four patients of 432 (24.9%) had recurrent attacks of thrombosis without any proximate precipitating cause, whereas 7.5 % of the patients had another close member of the family with a history of deep venous thrombosis. Eighty-six members from 28 families (out of 32 families giving family history of thrombosis) were investigated and found to have protein C and protein S deficiency in seven each; factor V Leiden was present in 6, and MTHFR C677T polymorphism was present in 5 cases. Hence, 25 of 86 members (28%) from the family of patients with familial history deep venous thrombosis had positive markers for thrombophilia. Thus, we could show that in young patients presenting with thrombosis, at least 34% of them had a demonstrable cause for thrombophilia. Prothrombin gene polymorphism G20210A seems to be nonexistent in our population and AT III deficiency also appears to be low compared to other markers of thrombophilia. There is a high prevalence of variant MTHFR C677T in our series, but the incidence of MTHFR C677T in our general population is also high. Hence, the significance of this finding in our cases of deep venous thrombosis remains to be seen, but we did not see any homozygotes when we tested 70 randomly selected asymptomatic persons, whereas in the present series, 1.8% of the patients had homozygosity for the MTHFR C677T polymorphism.

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BACKGROUND & OBJECTIVES: Transfusion related human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have been a major cause for morbidity and mortality in the haemophilic population in the west. The prevalence of these markers of transfusion transmitted viral diseases in severe and moderate haemophilia patients was studied. METHODS: The seropositivity for these viral markers was evaluated in 400 haemophilics (323 severe and 77 moderate) in a 5-year survey starting from 1995. First 188 of these patients were also tested for HCV. Serological tests for HIV, HBsAg and HCV were done by third generation ELISA; positive samples were also confirmed by Western blot. RESULTS: Fifteen of the 400 patients were found to be HIV positive (3.8%), 24/400 were HBsAg positive (6%) and 45/188 (23.9%) were positive for HCV (28 for both non-structural and core antigen, 13 for core only and 4 for non-structural antigen only). The lowest age of HIV positivity was 12 yr and that of HCV positivity was 8 yr. INTERPRETATION & CONCLUSION: The above study shows a reduction in blood product related HIV transmission in severe and moderately affected haemophilics but more stringent policy for blood product usage, universal hepatitis C screening, hepatitis B vaccination and continuous awareness programmes for medical staff, general public and patients is needed to reduce the incidence of these diseases in haemophilics.

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In this study, the use of the dual force system to correct recent or relatively longstanding knee deformities in ten patients is described. (Nine of the patients had severe haemophilia and one had severe von Willebrand's disease.) The mean duration of deformity in these patients was 10 months. The mean range of movement at the affected knee joints increased from 50 degrees at pre-intervention to 110 degrees following 6 weeks of application of the dual force system. In nine of ten patients (90%) the residual flexion deformity ranged from 0 degrees to 10 degrees. The dual force system offers an easily affordable and effective means of correcting a flexion deformity of the knee joint in severely affected haemophilia and allied disorders. More extensive use of this technique in different centres is required to determine its place in the day-to-day management of such patients.

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The haemophilia patient tends to live a more protected life than his normal counterpart, this is particularly so in underdeveloped and developing countries where due to poor health infrastructure, financial constraints and nonavailability of factor concentrates, patients quickly learn that they need to live a protected life. Under such circumstances, gas gangrene seems to be a very unusual infection for this group of patients. We report here a 25-year-old male with severe haemophilia who developed gas gangrene due to inadequate medical management following a road traffic accident. Subsequently, his affected limb was salvaged by conservative therapy. A literature search failed to reveal any reports of similar patients in the English literature.

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A 28 year old female patients presented with refractory anaemia since childhood and recurrent still-births at 28-30 weeks of gestation. One still-born child was hydropic at birth. Bone marrow showed characteristic morphological changes of congenital dyserythropoietic anaemia (CDA)-Type III. Electron microscopy showed disruption of the nuclear membrane, spongy appearance of nuclei, stacks of microtubules in intermediate normoblasts and myelin figures in erythroid cells. In vitro culture and karyotype data from the bone marrow of the patient is presented. Recurrent still-births in association with congenital dyserythropoietic anaemia has rarely been reported in the literature.

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