Varinder Singh

Thalassemia major - on the verge of bleeding or thrombosis?

Abstract Thrombotic events have been reported in adult thalassemic patients. To investigate this further, we measured hemostatic parameters in thalassemic children to identify possible predisposing factors in early childhood. Objective: To assess hemostatic derangements in polytransfused children with beta-thalassemia major (beta-TM). Methods: Complete blood count, prothrombin time, activated partial thromboplastin time, protein C, protein S, Antithrombin III (AT III), fibrinogen, D-dimer assay, serum iron, serum ferritin and liver function tests were measured in 54 patients and 30 controls using standard lab methods. Results: Sixteen patients exhibited bleeding manifestations. None of the cases had thromboembolic phenomena. The average pretransfusion haemoglobin in the cases studied was 8.45 ± 1.6 g/dl, thrombocytopenia was seen in 33.3%, prolongation of prothrombin time was seen in 40.7% and prolongation of aPTT was seen in 46.3%. None of our patients had laboratory features of DIC. Protein C was low in 26.2%, protein S in 28.6% and AT III levels in 46.8% of cases. Mean fibrinogen levels and D-dimers were similar in cases and controls. Serum ferritin levels in the patients were high with a mean of 3709 ± 1625 ng/ml. Serum ferritin had a significant positive correlation with PT (r = 0.382) and ALT (r = 0.315) and a significant negative correlation with protein S (r = −0.376). Prolonged PT correlated with prolonged aPTT, low protein C, low protein S and serum ferritin levels. Protein C had a significant positive correlation with AT III. Low AT III activity correlated positively with age, aspartate transaminase and alanine transaminase. Average hemoglobin maintained correlated negatively with serum ferritin levels (r = −0.540), and AST (r = −0.417). Bleeding episodes correlated with age, liver size and number of transfusions. Conclusion: Significant alterations in the hemostatic system already exist in polytransfused children with beta-thalassemia that make it a high-risk condition for both hemorrhagic manifestations and future development of thromboembolic events.

Hearing loss in chronic myeloid leukemia.

A 12‐year‐old girl presented with abdominal pain, fever, and hearing impairment of 6 months duration. She had massive hepatosplenomegaly and anemia. On the basis of her peripheral blood and bone marrow findings, she was diagnosed as chronic myeloid leukemia (CML) in chronic phase. Her hearing was assessed by brainstem evoked responses (BERA), which showed objective improvement in hearing with hydroxyurea. The rare occurrence of deafness in CML is reviewed and possible pathogenesis is discussed. Pediatr Blood Cancer 2005; 45: 54–56.

Clinicohematological study of thrombocytosis

ObjectiveTo find out etiology and clinical course of thrombocytosis in Indian pediatric population.MethodsA total of 250 patients having thrombocytosis (defined as platelet count >500 × 109/L) on haematological investigations were studied over one yr period. All patients were evaluated clinically and were subjected to investigations, including complete blood counts (CBC) with peripheral smear examination. To elucidate the possible role of inflammatory cytokines in pathogenesis of RT, levels of Interleukin-6 (IL-6) and C — reactive protein (CRP) were estimated.ResultsInfants and young children (<2 yr age) were most common group, contributing 60% of total cases. Out of total 250 cases, only 3 (1.2%) cases were found to have primary thrombocytosis and remaining 98.8% cases were having RT. Among RT patients, infections (alone or in association with iron deficiency anemia) were most common cause, accounting for 65% cases, while iron deficiency anemia (IDA) was second most common cause accounting for 41.3% cases (12.6% IDA alone and 28.7 % in association with infections). Other causes included nutritional dimorphic anemia and patients on treatment for megaloblastic anemia, acute lymphoblastic leukemia (during treatment) and lymphoma. Among various groups of RT, IL-6 and CRP levels were higher in patients with infection with or without IDA than IDA alone. One child with essential thrombocytosis and one child with RT had thrombotic complications. On follow up, platelet counts normalized in most of the patients with treatment of underlying conditions.ConclusionsResults of this study suggest that essential thrombocytosis is extremely rare in children. Infections and IDA (alone or in association with infections) are common causes of RT. IL-6 and CRP levels are increased in patients with RT, to a higher level in patients with infections than in patients with IDA. Most patients with RT have uneventful recovery of platelet counts to normal range with treatment for underlying condition.

Safety and efficacy of deferasirox in multitransfused Indian children with β‐thalassaemia major

Abstract Background: Iron chelation is an important component of management of transfusion‐dependent patients with thalassaemia major. Deferasirox is a relatively new oral iron chelator and experience of its use in children is limited. Aim: To report experience with deferasirox in north Indian children with β‐thalassaemia major. Methods: This prospective study included 40 patients with transfusion‐dependent β‐thalassaemia major. The patients were receiving deferiprone alone (37 patients) or deferiprone and desferrioxamine combination (three patients) before commencing deferasirox. Patients were clinically monitored every month. Information on side‐effects including gastro‐intestinal symptoms, skin rash or discoloration, jaundice and complaints regarding vision and hearing were obtained from patient records. Laboratory investigations included complete blood count and renal and liver function tests estimated at baseline and then every month. Serum ferritin level was estimated at baseline and then every 3 months. The initial dose of deferasirox was 20 mg/kg/body weight and was increased to 25 mg/kg if serum ferritin remained unchanged or increased 3 months after deferasirox therapy. Results: Therapy with deferasirox in 40 children was well tolerated. Gastro‐intestinal symptoms were the most common side‐effects. Nausea, vomiting and abdominal pain were observed in 25%, 20% and 15% patients, respectively. Skin rashes were seen in 5% cases. We observed greyish‐brown pigmentation of the skin in four (10%) children which has not been described before. A non‐progressive rise in serum creatinine was observed in 16 (40%) patients. In the majority, however, serum creatinine remained within the normal range. Leucopenia, neutropenia and thrombocytopenia were not observed. None of the side‐effects necessitated cessation of the drug therapy. Serum ferritin levels fell in 24 of 32 patients (75%) who received deferasirox for over 1 year from a mean (SD) 6323·37 (2756·5) μg/L to 5458·91 (2301·2) μg/L (p<0·05). Conclusions: Therapy with deferasirox is safe in paediatric patients with thalassaemia major. However, they should be carefully monitored for side‐effects.

Giant thymolipoma in an infant

Abstract Thymolipomas are benign neoplasms that usually occur in adults and are rarely described in children. They are usually detected incidentally but can be of massive size and lead to respiratory compromise. A 6-month-old boy presented with respiratory distress and an anterior mediastinal mass which proved to be a thymolipoma. He underwent surgical resection and remains well on follow-up. Although rare, thymolipomas should be considered in the differential diagnosis even in infants presenting with an anterior mediastinum mass.

Distal ulnar changes in children with thalassemia and deferiprone related arthropathy.

Regular blood transfusion and iron chelation are the standard of care for children with thalassemia. Deferiprone is an effective oral iron chelator but is known to cause significant arthropathy. Though clinical and radiographic features of deferiprone related arthropathy have been described, the long‐term effects are not known.

Short-course High-dose Dexamethasone Therapy for Chronic Idiopathic Thrombocytopenic Purpura in Children

First-line therapies of acute and chronic idiopathic thrombocytopenic purpura (ITP) include intravenous immunoglobulin, IV anti-D and corticosteroids. A short-course high-dose dexamethasone (HDD-SC) therapy has recently been reported to be efficacious in acute ITP. The present study was conducted to assess the efficacy of HDD-SC in children with chronic ITP. Over a period of 10 months, 13 patients with chronic ITP were given HDD-SC (20 mg m(-2) IV daily for 4 days, four cycles repeated every 15 days). Of the 12 patients who could be evaluated, complete response was observed in 8 (66.6%) and moderate response in 2 (17%) patients, whereas 2 (17%) patients had no response. HDD-SC appears to be a safe and effective therapy in childhood ITP.

Kimura’s disease: An unusual glandular involvement with blood and tissue esinophilia

Kimura’s disease is a rare cause of a progressive neck swelling associated with blood and tissue esinophilia. Though it is a benign disease, however, its unrelating course and unpredictable response to the therapeutic interventions, poses a great challenge to the treating physician, the patients and the caregiver. Here is one such case of Kimura’s disease.

Serious and life-threatening bleeding in late vitamin K deficiency

We read with interest the article on late vitamin K deficiency bleeding (L-VKDB) by Zengin et al. and present our experience with 12 cases seen over a 4-month period. Children were diagnosed with L-VKDB if they were more than 1 week old had bleeding manifestations and prolonged prothrombin time (PT) and partial thromboplastin time (aPTT) which normalised after vitamin K therapy. Cases with thrombocytopenia septicaemia or disseminated intravascular coagulation were excluded. Children were treated with 5 mg vitamin K intravenously. PT and aPTT were repeated after 24 hours of vitamin K administration. Fresh frozen plasma transfusion was given as and when required. The clinical profile of the infants is shown in Table 1. All were term deliveries and none had received vitamin K prophylaxis. Liver function tests were normal. Three cases had a history of diarrhoea and had received oral antibiotics. One child had nutritional rickets and another megaloblastic anaemia. One child had developed a muscle haematoma following DPT vaccine. Skin bleeds in the form of bruises with a central nodule were present in all cases. Skin bleeds preceded the more serious bleeds by a period of 4-15 days. (excerpt)