Correlation of platelet crossmatch results by Solid Phase Red Cell Adherence Assay (SPRCA) with post-transfusion platelet count increment in adult hemato-oncology patients of a tertiary care oncology centre in India.

AIMS: To assess platelet crossmatch result by SPRCA and find its correlation with post-transfusion platelet count increment among adult hemato-oncology patients. METHODS: A prospective observational pilot study of 50 adult hematologic malignancy patients previously transfused, but not already known to be transfusion-refractory and without any nonimmune causes for inadequate response to platelet transfusion were included after obtaining informed consent. They were transfused one unit of ABO identical single donor platelet. Ten minutes to 1 -h post-transfusion CCI was calculated. CCI ≥ 7500 was considered as adequate response. Post-transfusion crossmatching by SPRCA was performed by using preserved platelet samples from donor units with the serum of the respective patient. Statistical analysis of the correlation between platelet crossmatch results and CCI was done. RESULTS: Out of 50 crossmatches, 78% (39/50) showed compatible and 22% (11/50) showed incompatible results. Among 39 compatible results, 87.2% (34/39) showed adequate CCI and 12.8% (5/39) showed inadequate CCI. Among 11 incompatible results, 18.2% had adequate CCI and 81.8% had inadequate CCI. The difference between the response in terms of CCI to compatible and incompatible crossmatches was found to be statistically significant (p < 0.05). Other variables like age, sex, number of previous transfusions and underlying clinical condition of the patient were not found to have any effect on the compatibility of crossmatch. CONCLUSIONS: Transfusion of crossmatched platelets to non-refractory, multiply transfused hematological malignancy patients without serious illness might provide a small benefit over transfusing randomly selected platelets, though these data must be confirmed with a larger sample size.

Detection of bacterial growth in blood components using oxygen consumption as a surrogate marker in a tertiary oncology setup.

Microbiological contamination of blood and blood products is a well-recognised transfusion risk. This study was performed in the blood bank of our oncology centre, with an objective to detect bacterial contamination in our blood products using oxygen consumption as a surrogate marker [Pall Enhanced Bacterial Detection System (eBDS)]. Results revealed that the percentages of failed units were 1.16% for random donor platelets (RDP), 0.81% for single donor platelets (SDP) and 2.94% for packed red blood cells (PRBCs), of which one RDP and one SDP grew coagulase-negative staphylococcus, while one PRBC culture grew Gram-positive bacilli.

Translation and validation of brief patient health questionnaire against DSM IV as a tool to diagnose major depressive disorder in Indian patients.

CONTEXT: Depression is frequently encountered in the primary care setting but is often unrecognized and hence untreated. There is a need for a uniform user-friendly screening instrument for depression for primary healthcare personnel in India. AIMS: Translation and validation of the brief patient health questionnaire (BPHQ) as a screening tool for depression in major Indian languages. MATERIALS AND METHODS: This was a prospective study conducted at 18 sites, in psychiatric and general clinics. The English version of the BPHQ was translated into 11 Indian languages. The translations were reviewed by experts and volunteers and proofread for the final translated BPHQ. The validation exercise included more than 3000 subjects. A psychiatrist and a psychiatry social worker / coordinator conducted the study under the supervision of the principal investigator. For each language, the presence or absence of major depressive disorder (MDD) as diagnosed with the help of a patient-completed BPHQ and the psychiatrist DSM-IV diagnosis was matched. The kappa coefficient was used as a measure of inter-observer agreement between the two diagnostic methods. RESULTS: Seven languages failed the primary validation exercise. These translations were reviewed and the updated versions, after proofreading were re-run for validation. The self-administered BPHQ was successfully translated and validated for diagnosis of MDD against DSM-IV diagnosis made by a psychiatrist, in English, Hindi, Marathi oriya, Malayalam, Assamese, Gujarati, Kannada, Telugu, Bengali and Tamil. CONCLUSIONS: BPHQ is a simple, quick and reliable instrument, which facilitates rapid and accurate diagnosis of depression in the primary care setting in our country.

Evaluation of hemoglobin of blood donors deferred by the copper sulphate method for hemoglobin estimation.

INTRODUCTION: The copper sulphate (CuSO4) specific gravity test for Hb screening tends to give inappropriate failures. This prompted us to compare it with alternate screening methods. AIM: To study the impact of inaccuracy of CuSO4 method on donor deferral. METHODS: Capillary and venous blood samples of 400 potential blood donors failing the primary Hb screening using appropriately standardized CuSO4 test (specific gravity 1.053) were tested by Hemocue photometer, the Hb colour scale, Cyanmethemoglobin method as well as the automated hematology analyser, which was considered as the standard reference method. RESULTS: One hundred and sixteen donors (29%) who failed the CuSO4 test had true Hb levels >12.5 g/dl. The Hb levels of 131 (32.8%) deferred donors were between 12 and 12.5 g/dl. The sensitivity of Hemocue, Hb colour scale and Cyanmethemoglobin was 99%, 97% and 96% and their specificity was 45%, 93% and 46%, respectively. The positive predictive values (PPV) of Hemocue and Cyanmethemoglobin methods were low (43% and 44%, respectively) but their negative predictive values (NPV) were high (99%, and 97%, respectively). The Hb colour scale had an overall best performance with a PPV of 96% and NPV of 95%. CONCLUSION: The Hemoglobin colour scale which is inexpensive, convenient for field testing and has the overall best performance, is the most suitable for donor Hb screening. Since its readability is 12 g/dl, lowering the donor Hb threshold to 12 g/dl should be actively considered.

Red cell hemolysis during processing and storage.

INTRODUCTION: Apart from the visual assessment, measurement of plasma hemoglobin in the supernatant from red cell units provides an objective measure of the extent of hemolysis during storage. STUDY DESIGN AND METHODS: Packed red cells (N=50), 25 units each in triple (CPD-A1 and SAGM) and quadruple (CPD-A1 and ADSOL) blood bags were evaluated for plasma hemoglobin by the tetramethylbenzidiene (TMB) method on day 1, 7, 14, 21 and 28 of collection. The hemoglobin, hematocrit, MCV, LDH and potassium levels were also noted. Whole blood units (N=25) were used as controls. RESULTS: Hemolysis increased in all the stored red cell units. Plasma hemoglobin increased significantly in the first week of storage. The hemolysis, LDH and potassium levels were found to be significantly higher in the red cell units harvested from the triple blood bags. However, on day 28 of storage, free hemoglobin in all the red cell units was much below the 0.8% hemolysis. CONCLUSION: Hemolysis of the red cells increases due to processing and during storage and is maximum during the first week. Adequate process control and proper storage facilities should be ensured to minimize the hemolysis of red cells during processing and storage.

Correlation of CD34+ cell yield in peripheral blood progenitor cell product with the pre-leukapheresis cell counts in peripheral blood.

INTRODUCTION: Accurate timing of the leukapheresis procedures is of paramount importance to get the best possible CD34+ cell yield in the minimum number of leukapheresis procedures. AIM: To find if pre-harvest CD34+ cell concentration in peripheral blood correlates with CD34+ cells in the product. MATERIAL AND METHODS: Sixty Leukapheresis procedures were performed for 25 patients (8 autologous and 17 allogeneic transplants) with hematological malignancies. Statistical analysis was performed to correlate the pre-harvest CD34+ cell count and the CD34+ cell yield. Volume processed during PBPC harvests was three times the blood volume. RESULTS: The best correlation was found between the leukapheresis product CD34+ cell count and the pre-harvest PB-CD34+ cell count (PCC=0.674) when compared with the other pre-harvest PB cell counts viz., WBC (PCC=0.229) and MNC (PCC=0.324). This correlation was better in the allogeneic harvest (PCC = 0.645) than the autologous harvest procedures (PCC = 0.348). Correlation analysis based on paired samples from the 60 leukapheresis procedures showed that when the pre-leukapheresis PB-CD34+ cell count was >20x10(3)/ul a yield of >1x10(6) CD34+ cells/Kg could be obtained in 95% of the cases and >2x10(6) CD34+ cells /Kg could be harvested in 68% of cases whereas when the pre-leukapheresis PB-CD34+ cell count was <5x10(3)/microl the yield was <1x10(6) CD34+ cells/Kg in 81% of the procedures. CONCLUSION: The yield of CD34+ cells in PBPC harvests depends on the pre-harvest CD34+ cell concentration and therefore it is more useful than the pre-harvest WBC or MNC counts for predicting the appropriate timing of the harvests and also to achieve the best possible yield of CD34+ cells.

Plasma exchange for thrombotic thrombocytopenic purpura following hematopoietic stem cell transplantation.

A 17 years old female diagnosed with acute myeloid leukemia (AML)-M2 received an allogeneic haematopoietic stem cell transplant (HSCT) and was given graft versus host disease (GVHD) prophylaxis with methotrexate, cyclosporin-A (CsA) and methyl prednisolone. On day +42 post-transplant, she was diagnosed to have thrombotic thrombocytopenic purpura (TTP). Therapeutic plasma exchange (TPE) (40 ml/kg body mass) using fresh frozen plasma was performed on 8 consecutive days. The renal function, LDH levels, platelet count and peripheral smear findings improved but the neurological symptoms persisted even after TPE. Few reports are available in literature on the effectiveness of therapeutic plasma exchange (TPE) in post-bone marrow transplant (BMT) TTP. The good hematologic response achieved in this patient suggests that TPE could be life-saving and should be tried in every patient with post-BMT TTP.

Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic phase following conditioning with busulphan and cyclophosphamide: a follow up report.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation remains the only modality of treatment that can eradicate a leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML). However, the advent of the targeted molecule imatinib mesylate (formerly STI-571) against the bcr-abl chimeric protein in the disease has brought the issue of managing newly diagnosed CML patients, especially those with available donors, to the crossroads. Although the curative potential of this agent remains unknown, it can produce complete cytogenetic response in > 60% of newly diagnosed patients. METHODS: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as a conditioning regimen. All patients received human leucocyte antigen (HLA)-identical sibling donor haematopoletic stem cells--bone marrow in 41 patients (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant prophylaxis for graft-versus-host disease included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients (69.1%), while a combination of cyclosporin and methylprednisolone was used in the remaining 17 (29%). RESULTS: At a median follow up of 48 months (10-144 months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17 patients (30.9%). Acute graft-versus-host disease developed in 37 patients (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till date. The leukaemia-free survival is 64.3% in the peripheral stem cell group, whereas it is 41.5% in the bone marrow recipient group. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease-free survival in about half the patients. However, efforts should be made to prevent graft-versus-host disease and minimize early mortality.

A longitudinal study of serum creatinine levels in patients of rheumatoid arthritis on long term NSAID therapy.

AIM: Primary: To study the effect of long term NSAID therapy on serum creatinine in patients of rheumatoid arthritis. Secondary: To study the effect of discontinuation, reduction in the dose or continuation of NSAID and of rechallenge. MATERIAL AND METHODS: Case records of RA patients with a minimum two years of follow up were analysed. Age, sex, duration of RA, type, dose and duration of NSAID and DMARD therapy, co-morbid conditions and serial serum creatinine levels were charted. RESULTS: Ninety nine case records were studied. Incidence of abnormal creatinine level (renal insufficiency) defined as rise in creatinine equal to or above the upper limit of normal was 27.7%. This rise was asymptomatic in all patients. No NSAID was particularly associated with an increased risk in renal insufficiency. The rise of serum creatinine was reversible in most patients irrespective of discontinuation or continuation of NSAID but settled at a higher level. Rechallenge resulted in rise of serum creatinine in 50% patients. Hypertension, DM, IHD and diuretics carried a higher but not statistically significant risk of renal insufficiency. CONCLUSION: NSAID-induced asymptomatic rise of creatinine in patients of RA on long term NSAIDs is common. It is mostly reversible. Regular monitoring of serum creatinine is essential.

Treatment of AA amyloidosis in rheumatoid arthritis.

Four patients of rheumatoid arthritis (RA) with biopsy confirmed AA amyloidosis were treated with chlorambucil. All had established but uncontrolled RA with a persistently raised ESR. Moderate (> 1 gm, < 3.5 gm/d) to nephrotic range (> 3.5 gm/d) proteinuria and a relatively well preserved renal function was noted in three patients. One patient had deranged renal function and required dialysis. On chlorambucil, there was complete recovery, partial improvement and no improvement in one patient each. The fourth patient required haemodialysis, did not tolerate chlorambucil and succumbed to the illness. Therapy with chlorambucil can benefit some patients of RA with AA amyloidosis. Leucopenia is the most important dose limiting side effect.

Plasmapheresis: an adjunct therapy in severe progressive neuropsychiatric lupus.

OBJECTIVE: We report our experience with use of plasmapheresis (PP) as an adjunct therapy in severe progressive neuropsychiatric systemic lupus erythematosus (NPSLE). METHOD: Three patients of NPSLE (including 2 with status epilepticus) who were progressively worsening on steroids or combination of pulse cyclophosphamide (CPM) and steroids were treated with PP followed by synchronized CPM. Pre and post treatment SLE Disease Activity Index (SLEDAI) and laboratory tests were carried out. RESULTS: Significant clinical improvement with decrease in SLEDAI occurred immediately following PP. Mean SLEDAI before and after PP were 33 and 11. Mean erythrocyte sedimentation rate decreased from 121 to 31. Rebound flare of disease activity noted in two patients between 7th-10th day requiring additional immunosuppressants or steroids. CONCLUSIONS: PP used as an adjunct therapy in severe, progressive NPSLE is well tolerated and can turn the patient around. PP should be followed by synchronized pulse CPM to prevent disease flare.

Controversies in febrile seizures.

Febrile seizures are benign, self limiting, common neurological problems encountered in children between 3 months and 5 years. Controversies exist regarding its definition and it is important to distinguish between the terms febrile seizures and convulsions with fever. In the vast majority, febrile seizures occur within the first 24 hours of illness, and an encephalitic process should be considered if it occurs later, especially with exanthema. The temperature threshold varies in the same child and from one child to another. Febrile seizures are classified as simple and complex and debate continues regarding the usage of these terms and their prognostic value. Practice parameters are suggested regarding the performance of lumbar puncture in a child with first febrile seizure, but they should be used as guidelines and the decision depends on the experience and judgement of the physician. EEG is of limited value and not a guide to treatment or prognosis and neuroimaging not recommended. The predictors of recurrent febrile seizures include younger age, lower threshold of temperature, onset within one hour of fever and positive family history. Whether the syndrome of mesial temporal sclerosis beginning with prolonged febrile seizure has a causal relationship with pre existing brain disease is a matter of debate. There are effective therapies to prevent febrile seizures but the potential side effects of drugs outweigh their benefit. Intermittent prophylaxis during fever may be effective but long term prognosis is not influenced by the treatment applied in early childhood. A practical approach to a child with febrile seizure is suggested.

Does treatment change the outcome of seizures and computerized tomographic lesions in intracranial granulomas?

In children, intracranial granuloma diagnosed on computerized tomography (CT) scan and presenting with seizures as the sole manifestation has traditionally been treated with antitubercular (ATB) therapy or albendazole (Alb) in addition to antiepileptic drugs (AED). This study was conducted to determine whether AED therapy alone or specific treatment (ATB + Alb) influences the outcome of seizures and the CT lesion. Sixty-eight children presenting with seizures along with intracranial granuloma on CT scan were selected for the study. They were randomly divided into two groups. Group A (n = 34) was treated with AED alone and group B (n = 34) received antitubercular therapy and albendazole in addition to AED. Seizure type was noted and electroencephalogram (EEG) and CT scan were done in all. They were followed up for a period of 2 to 9 years, during which a record of seizure count and type was maintained. CT scans were repeated at 3 monthly intervals and EEGs were repeated whenever indicated. Four patients in each group were lost to follow-up. Seizures persisted in four out of 30 in group A and six out of 30 in group B. There was no statistically significant difference (p > 0.05) in the outcome of seizures in the two groups. Taking the whole group together (n = 60), of the 13 who had presented with multiple seizures at onset, epilepsy was a sequela in five (p < 0.05); and of the 17 in whom the lesion had calcified, seizures persisted in seven (p < 0.05), irrespective of treatment modality. In conclusion, though specific treatment did not alter the outcome of seizures, children with multiple seizures at presentation and calcification of CT lesion had epilepsy as a sequela.

T lymphocytes in pulmonary tuberculosis.

T cells and their sub-populations were evaluated with respect to reactive, intermediate and unreactive forms of tuberculosis as classified by Lenzini. Significant CD4 lymphopenia and a reduction of CD4/CD8 ratios were found in patients with reactive tuberculosis. It was observed that there was a B lymphocytosis, CD8 lymphocytosis and a reduction of CD4/CD8 ratio in patients with intermediate and unreactive forms of tuberculosis. The T lymphocytes and CD4 subset were unchanged. There was no significant difference in the lymphocytes and sub-populations among the intermediate and unreactive groups.

Juvenile Huntington's disease.

A rare case of juvenile Huntington's disease manifesting since the age of seven years is reported. The inheritance was typically autosomal dominant as three other members on the paternal side died of similar disease. A definite family history can becrucial in the diagnosis of juvenile Huntington's disease.

Experience with the International League Against Epilepsy classifications of epileptic seizures (1981) and epilepsies and epileptic syndrome (1989) in epileptic children in a developing country.

Four hundred eighty-three epileptic children attending the Pediatric Epilepsy Clinic at Bai Jerbai Wadia Hospital for Children, Bombay, India were classified according to the International League Against Epilepsy (ILAE) classification of epileptic seizures (1981) and epilepsies and epileptic syndromes (1989). The predominant seizures were partial (53.6), generalized (40.3%), and unclassifiable (6%). In epilepsies and epileptic syndromes, 55.3% were partial, 27% were generalized, 13.5% were undetermined, and 4.1% were special syndromes. Although our results were similar in many respects to those of other reported series, some differences were observed in the incidence of partial and generalized seizures, and partial and generalized epileptic syndromes and their subgroups, such as idiopathic, symptomatic, and cryptogenic partial syndromes, idiopathic generalized syndromes, and symptomatic specific syndromes. These differences are probably due to different age limits, methods of case ascertainment and inclusion criteria, different genetic and environmental factors, variable interpretation of clinical and EEG features, and lack of facilities for investigation in developing countries. Despite various limitations, we were able to classify most cases; the ILAE classification can be used in developing countries so that comparison can be made with other studies.

Exchange transfusions via peripheral vessels.

During a 15 month period, partial exchange transfusions (ET) were done in 40 neonates with polycythemia, and double volume ET attempted in 7 neonates with hyperbilirubinemia via peripheral vessels. The procedure was effective and not associated with any complications for partial ET. During double volume ET minor complications were noted in 2 cases, both of whom recovered and subsequently successfully underwent supraumbilical ET. Of the 5 cases who had uneventful double volume exchanges, there was a significant drop in indirect serum bilirubin following the procedure. The mean pre-ET serum indirect bilirubin in these 5 cases was 334 mumol/L and mean post-ET level was 179 mumol/L with a mean drop of 155 mumol/L (46% drop). Technical difficulties in catheterization may be overcome with greater expertise and use of heparin to flush arterial catheters.