Pravas Mishra

Intracranial haemorrhage in patients with congenital haemostatic defects

Summary.  We investigated 52 of 457 patients with congenital factor deficiencies with 57 episodes of intracranial haemorrhage (ICH) between 1998 and 2007. There were 38 severe haemophiliacs, 6 with factor XIII deficiency, 5 with factor X deficiency, 2 factor V‐deficient patients, and 1 with type 3 von Willebrand disease (VWD). The median age was 8 years (range 1 month–22 years). Most patients were below 15 years of age (86.5%). All patients with factor X deficiency were between 1 and 5 months of age. ICH was the primary bleeding episode leading to detection of factor deficiency in 19.2% (five patients with severe haemophilia and all patients with factor X deficiency). Trauma caused bleeding in 66%. None of the patients with factor X deficiency had history of prior trauma. Surgery was performed in five patients with subdural haematomas, all of whom survived. Conservative factor replacement with 100% correction for 3 days followed by 50–60% correction for 7 days was possible in 60% patients. Seizures requiring prolonged therapy were noted in eight patients. Death was recorded in 15 patients (29%). Inadequate therapy in the form of delay or insufficient replacement was noted in 7/15 deaths. ICH was seen in 11.3% of all patients with coagulation factor deficiencies. Factor X deficiency presented with ICH at an earlier age. Inadequate replacement therapy including delayed treatment caused nearly 50% of all deaths. Most patients can be managed satisfactorily with adequate replacement therapy alone, with surgery being reserved for those with worsening neurological conditions.

Evaluation of eosin-5-maleimide flow cytometric test in diagnosis of hereditary spherocytosis.

A flow cytometry‐based test using eosin‐5‐maleimide (EMA) dye was used for diagnosis of hereditary spherocytosis (HS). The mean fluorescence intensiy (MFI) of EMA tagged erythrocytes is lower in HS than that in other hemolytic and nonhemolytic anemias. We enrolled 114 subjects comprising 20 confirmed HS, 20 suspected HS/hemolytic anemia (HA), 20 normal controls, 20 other hemolytic anemias [13 autoimmune hemolytic anemia, three congenital dyserythropoietic anemia (CDA), one pyruvate kinase deficiency, two microangiopathic hemolytic anemia], 18 microcytic anemia and 16 macrocytic anemia cases. All samples were subjected to flow cytometry as per standard protocol. The mean MFI of normal control subjects was 11 861.5 (SD 883.5) and of confirmed HS was 7949.3 (SD 1304.1). Using this test, of 20 patients suspected to be HS/HA but with no confirmatory diagnosis, eight patients were diagnosed as HS. Using logistic regression analysis, the optimum cut‐off MFI value between HS and normal controls was 10126. The area under the ROC curve was 0.99. The statistical significance of MFI values was obtained by t‐test or Wilcoxon rank sum test as applicable. Compared with normal controls, the MFI values in HS were lower and in megaloblastic anemia were higher which was statistically highly significant (P < 0.01), and the MFI values in CDA were lower which was statistically significant (P < 0.05). False‐positive values were obtained in three cases of AIHA and two cases of CDA. The sensitivity and specificity was 96.4% and 94.2% respectively. The EMA‐based flow cytometry test is a highly sensitive and specific method for the diagnosis of HS.

Fludarabine, cyclophosphamide and horse antithymocyte globulin conditioning regimen for allogeneic peripheral blood stem cell transplantation performed in non-HEPA filter rooms for multiply transfused patients with severe aplastic anemia

Multiply transfused patients of severe aplastic anemia are at increased risk of graft rejection. Five such patients underwent peripheral blood stem cell transplantation from HLA-identical siblings with a fludarabine-based protocol. The conditioning consisted of fludarabine 30 mg/m2/day × 6 days, cyclophosphamide 60 mg/kg/day × 2 days and horse antithymocyte globulin (ATG) × 4 days. Two different ATG preparations were used: ATGAM (dose 30 mg/kg/day × 4 days) or Thymogam (dose 40 mg/kg/day × 4 days). Engraftment: median time to absolute neutrophil count (ANC) >0.5 × 109/l was 11 days (range: 8–17) and median time to platelet count >20 × 109/l was 11 days (range: 9–17). At a median follow-up of 171 days (range: 47–389), there has been no graft rejection and all patients are in complete remission. Acute GVHD (grade 1) occurred in one patient only. Chronic GVHD developed in two patients (extensive in one and limited in another). The transplants were performed in non-HEPA filter rooms. In only one patient, systemic antifungal therapy (voriconazole) was used. The use of Thymogam brand of ATG for conditioning is being reported for the first time. Our experience suggests that this fludarabine-based protocol allows rapid sustained engraftment in high-risk patients without significant immediate toxicity.

Imatinib-induced Stevens–Johnson syndrome: recurrence after re-challenge with a lower dose

Dear Editor, Imatinib mesylate (STI-571), a selective BCR–ABL (BCR, breakpoint cluster region) tyrosine kinase inhibitor, has been found to be effective in the treatment of different phases of chronic myeloid leukemia (CML). Cutaneous reactions to imatinib therapy are known, with 5% of these reactions being severe [1]. Although a variety of skin manifestations have been described, the occurrence of Stevens–Johnson syndrome (SJS) is rare. A 60-year-old woman was diagnosed as Philadelphiapositive CML in the chronic phase. She had a splenomegaly of 20 cm below costal margin. Her initial hemogram revealed the following: hemoglobin, 12.6 gm/dl; white blood cell count, 196×10/l; and platelet count, 420×10/l with 8% myeloblasts. She was started on imatinib at a dose of 400 mg daily. On the 12th day of therapy, she developed pruritic maculopapular erythematous rash together with mild periorbital edema. The following day, these lesions had progressed into a disseminated rash with confluent areas over the neck, chest, and upper abdomen. In addition, there were oral and vaginal mucosal erosions. The hemogram showed hemoglobin at 12.1 gm/dl, total leukocyte count of 4,300/mm, and platelet count of 470× 10/l with no blasts. The skin biopsy from lesions on the upper abdomen showed parakeratosis, mild irregular acanthosis of the epidermis along with perivascular and periappendigeal lymphohistiocytic infiltration in the dermis. A diagnosis of SJS was made, and imatinib was stopped immediately. She was not on any other medication; therefore, imatinib was the most probable cause for the reaction. Healing started within few days of stoppage of the drug, and in 10 days, the lesions were completely cleared. Her baseline variables put her in the Sokal highrisk group. Therefore, 2 weeks after complete clearance of the rash, imatinib was restarted at a lower dose of 200 mg daily. The following day, she again developed a perioral pruritic erythematous eruption that suggested an early recurrence of the similar adverse drug reaction. The drug was stopped again, and the patient was given fexofenadine and oral prednisolone (40 mg/day). The rash quickly resolved. The patient was started on hydroxyurea, and imatinib was stopped for 1 month. Imatinib was again restarted at 100 mg together with prednisolone 40 mg/day (1 mg/kg). There was no further recurrence of the rash. In the next 6 weeks, the prednisolone was slowly reduced and stopped while dose of imatinib was increased to 300 mg. The patient has now been on treatment for 6 months with no further recurrence of the rash. Imatinib is the most active agent for the treatment of CML, and skin rashes are quite common with this agent [2]. Imatinib is associated with a variety of adverse cutaneous reactions, including urticaria, maculopapular exanthem, generalized exanthematous pustulosis, exfoliative dermatitis, and SJS [1–4]. In our patient, the lesions reappeared on re-challenge with imatinib, which was also reported earlier [5, 6]. Brouard and Saurat [2] have shown that the incidence of cutaneous reactions with imatinib increases with escalating doses of the drug. Valeyrie et al. [1] have reported female sex and imatinib dosage as being independent risk factors for the development of rashes in a multivariate analysis. Most cutaneous eruptions caused by imatinib do not necessitate discontinuance of imatinib and are usually self-limited despite continued treatment. Administration of oral or topical corticosteroids can ameliorate Ann Hematol (2007) 86:537–538 DOI 10.1007/s00277-007-0265-y

Intracranial hemorrhage in childhood immune thrombocytopenic purpura

We retrospectively analyzed 750 patients with ITP for development of intracranial hemorrhage (ICH). Seventeen cases with age range of 10 months to 18 years were studied. Ten patients were of acute ITP and seven had chronic ITP. Nine patients developed ICH one month after the onset of ITP and five patients had ICH on presentation. ICH was precipitated by trauma in four patients and possibly the use of NSAIDs in one patient. Median platelets counts at the time of ICH were 12 × 109/L (range 2–50 × 109/L). Most patients were treated with corticosteroids. Four patients (24%) died due to ICH. Pediatr Blood Cancer 2009;52:529–531.

Tuberculosis in acute leukemia: A clinico-hematological profile

Abstract We studied 130 consecutive cases of acute leukemia over a 2-year period and identified 9 cases (6.9%) with active tuberculosis (TB). Eight patients with TB had acute myeloid leukemia (AML). Patients with AML were more likely to develop TB as compared to patients with acute lymphoblastic leukemia (ALL) despite the wider use of steroids and radiotherapy in ALL protocols {OR 4.41 (CI 0.53–36.44)}. Only 1 patient died of disseminated TB during post induction neutropenia. All other patients were successfully managed using current anti-tuberculous therapy (ATT). On the whole, TB did not cause any undue delay in chemotherapy and did not flare up during subsequent chemotherapy cycles. However it is not a commonly described infection in acute leukemia and a high index of suspicion is warranted especially in areas endemic for TB.

Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: initial experience from a single center in India

In developing countries, it is important to ascertain the safety of performing allogeneic hematopoietic SCT (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters. We present our experience of performing 40 such transplants from July 2004 to November 2007. Source of stem cells was peripheral blood in 33, bone marrow in six and combined in one. G-CSF started from day +1. The indications were SAA-18, CML-7, AML-7, ALL-2, myelodysplastic syndrome-2 and thalassemia major-4. The median age was 19 years (range 2.2–46) with 29 male and 11 female participants. Antibacterial and antifungal prophylaxis was administered along with conditioning, and at the onset of fever, systemic antibiotics were started. Antifungal agents were added if fever persisted for 3 days. Median time for neutrophil engraftment was 10 days (range 8–17). Fever occurred in 38 (95%) for a median of 5 days (range 1–38), and blood cultures were positive in seven (17.5%). Systemic antibiotics were used in 95% and antifungals in 57.5% cases. The 30-day mortality was nil, and 100-day mortality was 1 (2.5%). After day 100, there were eight fatalities (20%) due to chronic GVHD-3, relapse-2, graft rejection-2, disseminated tuberculosis and aspergillosis-1. Our experience suggests that allogeneic HSCT can be safely performed in non-HEPA filter rooms in India.

Clinical, haematological and histomorphological profile of adult myelodysplastic syndrome. Study of 96 cases in a single institute

Abstract:  Myelodysplastic syndromes (MDS) are clonal haematopoietic stem cell disorders characterised by ineffective and dyspoietic haematopoiesis. The natural history of these disorders is variable and ranges from a chronic to a rapid course towards leukaemic progression. Certain shortcomings have been encountered in the French–American–British (FAB) classification over the years, and therefore there is a need for an alternative method of classification. In 1999, the WHO published a revised classification of MDS. In the present study, we have analysed the clinical, haematological and histomorphological features in 96 cases of primary MDS seen in the department of haematology at the All India Institute of Medical Sciences (AIIMS) over a 6‐yr period (1996–2001). Both FAB and WHO classifications have been incorporated and the Bournemouth scoring system applied in each case at presentation. The Bournemouth scoring system, in the absence of a cytogenetic study, offers a good prognostication and long‐term survival estimate.

Excitation dependent photoluminescence study of Si-rich a-SiNx:H thin films

We report photoluminescence (PL) investigations on Si-rich amorphous hydrogenated silicon nitride (a-SiNx:H) thin films of different compositions, using three different excitation lasers, viz., 325 nm, 410 nm, and 532 nm. The as-deposited films contain amorphous Si quantum dots (QDs) as evidenced in high resolution transmission electron microscopy images. The PL spectral shape is in general seen to change with the excitation used, thus emphasizing the presence of multiple luminescence centres in these films. It is found that all the spectra so obtained can be deconvoluted assuming Gaussian contributions from defects and quantum confinement effect. Further strength to this assignment is provided by low temperature (300 °C) hydrogen plasma annealing of these samples, wherein a preferential enhancement of the QD luminescence over defect luminescence is observed.

Disseminated Intravascular Coagulation in Acute Leukemia at Presentation and During Induction Therapy

Between January 2001 and December 2003, 67 patients with acute leukemia were evaluated prospectively for hemostatic abnormality at presentation, of which 43 (64.2%) had acute lymphoblastic leukemia and 24 (35.8%) had acute myelogenous leukemia. At presentation, 27 patients (40.3%) had bleeding manifestations. Thrombocytopenia was present in 57 patients (85%), and 33(49.3%) had some abnormality of global coagulation markers. Disseminated intravascular coagulation was defined by International Society of Thrombosis and Hemostasis criteria. Disseminated intravascular coagulation was more often associated with bleeding manifestations in acute myelogenous leukemia cases than in acute lymphoblastic leukemia cases. Two patients presented disseminated intravascular coagulation on day 7 of chemotherapy, without any bleeding manifestations. Four of 15 evaluated cases who had a bleeding or infection complication after day 7 of induction therapy also had disseminated intravascular coagulation. It is recommended that all patients with leukemia be investigated for disseminated intravascular coagulation at presentation.