Rahul Bhargava

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.

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.

Acquired platelet dysfunction in 109 patients from a tertiary care referral hospital.

Background: Acquired platelet function defects (PFDs) remain poorly characterized, underrecognized, and therefore understudied. Patients/Methods: Clinical and laboratory records of 109 patients with acquired PFDs diagnosed over 5 years were analyzed. Screening studies (platelet count, prothrombin time, activated partial thromboplastin time, and thrombin time), template bleeding time, platelet factor 3 (PF-3) availability test, light-transmission aggregometry, and further testing as indicated were performed. Results: 64 patients had mild and 26 had major bleeding. In all, 15 were referred for preoperative testing, whereas 4 had thrombotic events. Causes and associations of PFDs were drug-induced (34), idiopathic (34), hematopoietic neoplasms (15; myeloma 4, Waldenstrom macroglobulinemia 2, chronic myeloid leukemia 4, essential thrombocythaemia 3, and primary myelofibrosis and chronic lymphocytic leukemia 1 each), chronic liver disease (4), postcardiac surgery (2), uremia (2), and thalassemia major (7). Miscellaneous disorders comprised the rest. Conclusions: Acquired PFDs span a wide range of disease settings. Systematic, sequential laboratory testing identifies patterns of dysfunction, excludes inherited disorders, and streamlines management.

Crystal storing histiocytosis: a rare presentation of plasma cell myeloma

Crystal storing histiocytosis (CSH) is a very rare association with plasma cell dyscrasias. It is presumed to be an intra-lysosomal accumulation of the secreted paraprotein aggregated into crystals and is associated with presence of variable numbers of histiocyte-like cells with phagocytosed crystalline inclusions in the bone marrow and other extramedullary sites Herein we report a case of multiple myeloma associated with CSH with a rapidly downhill clinical course. There was diagnostic confusion at the outset with a histiocytic disorder which was clarified with the use of Immunohistiochemistry along with serum protein electrophoresis and immunofixation.

An unusual presentation of eosinophilic variant of chronic myeloid leukemia (eoCML)

Dear Editor, Eosinophilia, a common sign of chronic myeloid leukemia (CML) and often used as one of the criteria for accelerated phase, but there is paucity of literature with eosinophilia as the only presentation of CML. Whether these patients clinically resemble with other hypereosinophilic syndromes (HESs) is not known. High eosinophil count can cause heart, lung, and central nervous system damage in both the eosiniphilic variant of CML (eoCML) and HES. Superficial venous thrombophlebitis (SVT) is usually a benign disorder but can be the first manifestation of hypercoagulable states. Secondary causes of SVT must be sought, particularly when SVT is recurrent or multifocal or has spontaneous onset. Among the various risk factors of SVT, vasculitis, malignant blood disorders, and solid tumors are the commonest. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, but it has never been described in eoCML, which prompted present communication. A 55-year-old man presented with a history of recurrent subcutaneous swelling of the right upper limb and anterior chest wall for 3 months. Each time, the swelling used to last from a few days to few weeks. There was history of itching and sometimes pain over the swollen area. There was no response to therapy with antihistaminics or analgesics. On examination, there was ill-defined erythematous swelling, with local rise of temperature over the right forearm extending to anterior chest wall. There were palpable, hardened, and painful erythematous veins over the right forearm. Vital signs were stable. Chest and neck examination was remarkable. Therewas no lymphadenopathy or hepatosplenomegaly. Hemogram showed white blood cell count of 12,300/mm with 10% neutrophils, 5% lymphocytes, and 85% eosinophils. The absolute eosinophil count was 10,455/mm. His peripheral blood picture revealed only eosinophilic leukocytosis with normocytic normochromic red blood cells and adequate platelets. Ultrasound color Doppler showed multiple foci of superficial vein thrombosis in the swollen areas without any evidence of deep-vein thrombosis. Magnetic resonance imaging of the right upper limb showed extensive subcutaneous and intramuscular edema with superficial thrombophlebitis. He was further investigated for causes of eosinophilia and recurrent superficial thrombophlebitis. Stool culture for ova and parasites were negative. Chest X-ray and contrast-enhanced computed tomography of the chest and abdomen were normal. Serum carcinoembryonic antigen and prostate-specific antigen levels were also normal. His lipid profile, antinuclear antibodies, anticardiolipin antibodies, lupus anticoagulant, protein S, protein C, and homocysteine levels were also found to be within normal limits. Echocardiography revealed early features of endomyocardial fibrosis, and pulmonary function test was normal. Bone marrow aspirate and biopsy showed a hypercellular marrow with myeloid hyperplasia and increased number of eosinophilic precursors. His peripheral blood and bone marrow aspirate was sent for reverse transcriptase polymerase chain reaction for FIP1L1-PDGFRα and bcr–abl, for detection of any clonal abnormality. The hybrid transcript for FIP1L1-PDGFRα was absent. At presentation, the patient’s BCR–ABL/ABL ratio was 10%. Fluorescent in situ hybridization was performed for BCR/ABL gene fusion, which showed that 60% of cells were positive for this gene rearrangement. On the basis of clonal evidence, a diagnosis of eoCML was made. The patient was started with imatinib mesylate 400 mg/day, and within 4 weeks of therapy, his Ann Hematol (2009) 88:89–90 DOI 10.1007/s00277-008-0545-1

Multi-organ failure due to Mycobacterium tuberculosis and Aspergillus flavus infection after allogeneic bone marrow transplantation.

Mycobacterium tuberculosis (MT) is a serious, but rare infectious complication after allogeneic bone marrow transplantation (BMT). We describe a case of fatal sepsis due to MT and Aspergillus flavus after allogeneic BMT for Aplastic Anemia. The diagnosis was made on bone marrow biopsy and asitic fluid culture. Broadspectrum antituberculous and Amphotericin B therapy was started immediately after diagnosis. The patient developed severe hypoxia and finally died of multi-organ failure. Rapid progression of mycobacterial infection as well as fungal infection should be considered in patients post BMT with unexplained fever, particularly in patients from endemic areas.

Acute lymphoblastic leukaemia with unusual chromosomal abnormality: t(3;9) (p21;p13), del(10p12) [13]

We report a case of pre-B acute lymphoblastic leukaemia with an unusual translocation between chromosome 3 and 9, with del(10p12) [13]. The diagnosis at presentation was made by the morphology, cytochemistry and immunophenotyping. Cytogenetic analysis was also done at presentation. To the best of our knowledge and after literature search this appears to be a rare cytogenetic abnormality in ALL.

Efficacy of immunization against hepatitis B virus infection in acute leukemia

OBJECTIVE The aim of this study was to assess the antibody response to combined passive-active immunization versus active immunization against hepatitis B in 71 patients with acute leukemia with negative hepatitis B virus serology at presentation. METHODS The first group (n=28) received a double dose of hepatitis B vaccine at 0, 1, 2 and 6 months and immunoglobin (HBIG) at 0 and 1 month concurrently with vaccine but at a different intramuscular site. The second group (n=43) received double dose of hepatitis B vaccine at 0, 1, 2, and 6 months. HBsAg and anti-HBs titers were determined one month after the 1st, 2nd, 3rd and 4th doses of vaccine. ESULTS In the vaccine-only group, 2.56%, 8.33%, 14.28% and 34.29% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. In the HBIG group, 91.30%, 91.30%, 69.56% and 73.91% of patients developed anti-HBs titer ≥10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. Those in the vaccine-HBIG group maintained their anti-HBs titer ≥10 IU/L from the 1st to the 4th doses. In the vaccine-only group, 34.29% of patients gained protective antibody titer after receiving the 4th dose of vaccine. Subgroup analysis of age (pediatric vs adult) and disease (acute lymphoblastic leukemia vs acute myeloid leukemia) groups showed no effect of either on the development of protective antibody titer. The incidence of HBsAg positivity one month after the 4th dose of vaccine was 8.62%. No patient became positive for anti-HCV or HIV antibody before or after chemo therapy. CONCLUSION Combined HBIG and vaccine may protect acute leukemia patients during the intensive chemotherapy period.