Role of Thromboelastogram in monitoring the activation of the coagulation pathway and assessing the associated risk factors for hypercoagulable state in transfusion dependent thalassemia patients.

BACKGROUND: Thromboembolic events are rare but one of the fatal complications in thalassemia. Assessment of the hypercoagulable state is not done regularly, and we have assessed the utility of Thromboelastography (TEG) for monitoring the activation of the coagulation pathway in patients with thalassemia. METHODOLOGY: A prospective single-center cohort study was conducted in a tertiary care set-up. Transfusion Dependent Thalassemia patients registered with the pediatric unit were screened for hypercoagulability using TEG during six months of the study period and followed up for three years for the development of thromboembolic events. Patient demographics, history of splenectomy, Serum ferritin levels and annual red cell transfusion requirement (mL/kg/year) were assessed. TEG parameters used were R time, K time, alpha angle, Maximum amplitude, Clot index, and Lysis 30. The thrombin generation test (V Curve) obtained from the first-degree derivate of the TEG velocity curve was also used for analysis. RESULTS: A total of 34 patients were recruited during the six months study period with an average age of 10.6 years ( ± 5.47). The average pre-transfusion hemoglobin level and the volume of packed red cells received were 7.24 g/dL and 152.82 mL/kg/year respectively. The TEG tracing was suggestive of a hypercoagulable state in 58.82% of patients. The mean values of angle (70.74), MA (64.16), CI (2.65) and TG (774.43) in TDT patients compared to age matched reference range (62.81, 57.99, 0.8, 577.83 respectively) was suggestive of prothrombotic changes. Annual blood transfusion requirement was negatively correlated with hypercoagulable status (-0.344, CI= -0.68 to 0.08). One out of 34 patients developed corona radiata infarct (with annual blood requirement; 112.7 mL/kg/Year). The risk to develop a hypercoagulable state appeared to be higher when the volume of RBCs transfused was less than 154 mL/kg/Year. CONCLUSION: TDT patients are at risk of developing thromboembolism, and screening with TEG may be useful to identify those at high risk.

Age- and gender-related reference ranges for thromboelastography from a healthy Indian population.

INTRODUCTION: Thromboelastography (TEG) is a whole blood clotting assay largely used in major surgeries and trauma to monitor patients' in vivo hemostatic status. Standardization of kaolin-activated citrated whole blood thromboelastography is not done in the Indian population. This study primarily aims to derive reference ranges of kaolin-activated TEG for healthy volunteers in the Indian population. Secondarily, it aims to study the age- and gender-related hemostatic changes in the study population. METHODS: A total of 120 healthy volunteers were enrolled (55 adult males, 32 adult females, and 33 children). The volunteers were interviewed for any bleeding history or drug intake which affects coagulation. Kaolin-activated TEG was performed on citrated whole blood, and parameters including R-time, K-time, angle, MA, LY30, and CI were analyzed. RESULTS: Derived reference range for total volunteers irrespective of age and sex were as follows: R-time: 3.8-10.6, K-time: 1.2-3.1, angle: 44.9-72.0, MA: 41.2-64.5, LY30: 0-9.9, and CI: -3.7 to 3.4. Statistically significant difference was observed in different age and sex groups for R-time, K-time, and angle. About 40% of the volunteers had at least one abnormal parameter according to the manufacturer's reference range which decreased to 12.5% when the derived reference ranges were considered. CONCLUSION: Gender- and age-related variances were observed in reference ranges of our population and which was also differed from the other ethnic population. Many of our healthy volunteers were categorized as coagulopathic when manufacturer's reference range was considered. So, it is important to derive the reference range of the target population before using the TEG into clinical practice.

Clinico-hematological and thromboelastographic profiles in glanzmann's thrombasthenia.

: Glanzmann's thrombasthenia is a rare inherited bleeding disorder characterized by the quantitative or qualitative defect of glycoprotein IIb/IIIa receptor on platelets which leads to ineffective aggregation. Light transmittance aggregometry is considered as the gold standard for diagnosis of Glanzmann's thrombasthenia. Thromboelastography (TEG) is a global hemostatic assay which measures clot formation, clot strengthening and fibrinolysis. This study evaluates the clinical, laboratory and TEG profiles in patients with Glanzmann's thrombasthenia. Bleeding score by (International Society on Thrombosis and Haemostasis) ISTH-bleeding assessment tool (bleeding score), laboratory tests to diagnose Glanzmann's thrombasthenia, and TEG parameters were correlated in 11 Glanzmann's thrombasthenia patients. Seventeen participants with normal bleeding score were included as controls. Bleeding score was increased in all patients. The highest bleeding score was in an adult female (26), whereas the lowest score (4) was in two children of less than 1 year. Majority of TEG parameters (except R-time) showed a statistically significant difference between Glanzmann's thrombasthenia patients and controls (K-time: P < 0.001, angle: P < 0.001, maximum amplitude: P < 0.001). The average time required to record the maximum amplitude was 23 min. Maximum amplitude was markedly reduced in all Glanzmann's thrombasthenia patients with an average of 20.9 mm (reference range 44-68 mm) having 100% sensitivity. The thromboelastographic profile of Glanzmann's thrombasthenia showed a consistently reduced maximum amplitude. Hence reduced maximum amplitude with a normal platelet count, significant bleeding score and prolonged bleeding time could potentially be used as a preliminary algorithm for the diagnosis of Glanzmann's thrombasthenia.

Oral Hygiene and Dentition Status in Patients with Congenital Hemorrhagic Disorders: A Comparative Study

Abstract Objective: To compare the status of oral hygiene and dentition in patients with congenital hemorrhagic disorders with their age-matched healthy counterparts. Also, the prevalence of fear of dentists/ dental treatment among these patients was assessed. Material and Methods: This study was performed on children and adults with von Willebrand disease (vWD), hemophilia (A or B), and healthy subjects. Oral health and dentition status was assessed using the simplified oral hygiene index (OHI-S), plaque index, and the decayed, missing, filled teeth (dmft/DMFT) index. One-way ANOVA test was employed to compare the oral hygiene and dentition status of subjects in the three groups. A p-value of <0.05 was considered statistically significant. Results: The DMFT score did not vary significantly between the groups (p>0.05). Higher OHI-S scores and a poor oral hygiene status was observed more in the hemophilia group than the vWD group and healthy controls. A total of 27.3% of the subjects in the vWD group, 18.2% of subjects in the hemophilia group, and no subjects in the healthy group had a fear of dentists or dental treatment. Conclusion: Subjects with vWD had a higher number of carious teeth when compared to the other groups. Poor oral hygiene status was observed in subjects with hemophilia.

Oral hygiene and dentition status in children and adults with hemophilia: A case-control study.

BACKGROUND & OBJECTIVES: People with hemophilia constitute a significant proportion of the population and an oral health care professional faces a considerable challenge while treating them. This study aimed to assess the oral health and dentition status as well as fear of dental treatment in patients with hemophilia and compare it with age-matched healthy subjects. PATIENTS & METHODS: This single-center, case-control cross-sectional study was performed on 100 subjects with hemophilia and 100 age-matched healthy controls. Oral health and dentition status was recorded for all the subjects and scored using the simplified oral hygiene index (OHI-S), plaque index, and the dmft/DMFT index. RESULTS: There were a total of 41 children and 59 adults in the hemophilia group and 36 children and 64 adults in the healthy group. When compared to healthy subjects it was observed that individuals with hemophilia had higher debris and calculus scores which was indicative of poor orodental status. There was no significant difference observed in the DMFT scores among the study groups. INTERPRETATION & CONCLUSIONS: The oral hygiene of the hemophilics was poorer when compared to the healthy controls. The findings highlight the need for establishing interdisciplinary care for such individuals.

Assessment for learning: a needs analysis study using formative assessment to evaluate the need for curriculum reform in basic sciences.

A needs analysis study for curriculum reform in basic sciences was conducted at Melaka Manipal Medical College, India, by means of a formative assessment method, namely Basic Science Retention Examination (BSRE). Students participated in a BSRE, which comprised recall and clinical multiple-choice questions in six discipline areas. They also rated the clinical relevance of each question and provided responses to three open-text questions about the exam. Pass rates were determined; clinical relevance ratings and performance scores were compared between recall type and clinical questions to test students' level of clinical application of basic science knowledge. Text comments were thematically analyzed to identify recurring themes. Only one-third of students passed the BSRE (32.2%). Students performed better in recall questions compared with clinical questions in anatomy (51.0 vs. 40.2%), pathology (45.1 vs. 38.1%), pharmacology (41.8 vs. 31.7%), and biochemistry (43.5 vs. 26.9%). In physiology, students performed better in clinical questions compared with the recall type (56.2 vs. 45.8%). Students' response to BSRE was positive. The findings imply that transfer of basic science knowledge was poor, and that assessment methods should emphasize clinical application of basic science knowledge.

Effectiveness of a training program for bleeding disorders among accredited social health activists in Udupi District, Karnataka, India.

INTRODUCTION: Hemophilia and other bleeding disorders are underreported and cause significant morbidity and mortality in resource-constrained countries. Training and the creation of awareness among accredited social heath activists (ASHAs) will aid in the early detection of bleeding disorders at the community level. OBJECTIVE: To develop awareness and skills for the screening and identification of cases with bleeding symptoms among ASHAs in Udupi District, Karnataka, India. METHODS: An interventional study was undertaken in Udupi District, which has three taluks and approximately 233 villages. All ASHAs with a current role (586) from rural Udupi were provided a competency-based training program at the community health center using a specifically designed training manual for the identification of cases with bleeding disorders. A pre-test/post-test evaluation was performed to discover the training outcomes. RESULTS: Sixteen (2.7%) participants had average knowledge in the first post-test, and 570 (92.2%) participants had good knowledge. Thirty-nine (6.6%) participants had average knowledge in second post-test, and 547 (94.3%) participants had good knowledge. The effectiveness of the training program was assessed using Friedman's two-way test. A significant difference in knowledge scores (χ2 = 955.1) was found at baseline evaluation and end of the training test 1 and at 30 days of training test 2 among the ASHAs. CONCLUSION: Accredited social heath activists health care workers, who are the most important link between the community and health services, successfully created public awareness concerning the early detection of bleeding disorders.

Continuing episodes of pain in recurrent acute pancreatitis: Prospective follow up on a standardised protocol with drugs and pancreatic endotherapy.

AIM: To assess the outcomes of drug therapy (DT) followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis. METHODS: DT comprised of pancreatic enzymes and anti-oxidants failing which, endotherapy (ET; pancreatic sphincterotomy and stent placement) was done. The frequency of pain, its visual analogue score (VAS), quality of life (QoL), serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET. Response was defined as at least 50% reduction in the severity of pain to below a score of 5. RESULTS: Of the thirty nine patients analysed, 21 (53.9%) responded to DT and 18 (46.1%) underwent ET. The VAS for pain (7.0 ± 2.0 vs 1.3 ± 2.5, P < 0.001) and the number of days with pain per month decreased [1.0 (1.0, 2.0) vs 1.0 (0.0, 1.0), P < 0.001], and the QoL scores [55.0 (44.0, 66.0) vs 38.0 (32.00, 51.00), P < 0.01] improved significantly during follow up. Similar significant improvements were seen in patients in the subgroups of DT and ET except for QoL in ET. The serum C-peptide (P = 0.001) and FE (P < 0.001) levels improved significantly in the entire group and in the two subgroups of patients except for the C peptide levels in patients on DT. CONCLUSION: A standardised protocol of DT, followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis, enhanced QoL and improved pancreatic function.

Comparing acid steatocrit and faecal elastase estimations for use in M-ANNHEIM staging for pancreatitis.

AIM: To compare two tests for exocrine pancreatic function (EPF) for use in M-ANNHEIM staging for pancreatitis. METHODS: One hundred and ninety four consecutive patients with acute pancreatitis (AP; n = 13), recurrent acute pancreatitis (RAP; n = 65) and chronic pancreatitis (CP; n = 116) were enrolled. EPF was assessed by faecal elastase-1 (FE-1) estimation and stool fat excretion by the acid steatocrit method. Patients were classified as per M-ANNHEIM stages separately based on the results of the two tests for comparison. Independent Student's t-test, χ2 test, Kruskal-Wallis test, Mann-Whitney U test and McNemar's test were used as appropriate. RESULTS: Sixty-one (52.5%) patients with CP had steatorrhoea when assessed by the acid steatocrit method; 79 (68.1%) with CP had exocrine insufficiency by the FE-1 test (χ2 test, P < 0.001). The results of acid steatocrit and FE-1 showed a significant negative correlation (Spearman's rho = -0.376, P < 0.001). A statistically significant difference was seen between the M-ANNHEIM stages as classified separately by acid steatocrit and the FE-1. Thirteen (6.7%), 87 (44.8%), 89 (45.8%) and 5 (2.5%) patients were placed in M-ANNHEIM stages 0, I, II, and III respectively, with the use of acid steatocrit as against 13 (6.7%), 85 (43.8%), 75 (38.6%), and 21 (10.8%) respectively by FE-1 in stages 0, I, II, and III thereby altering the stage in 28 (14.4%) patients (P < 0.001, McNemar's test). CONCLUSION: FE-1 estimation performed better than the acid steatocrit test for use in the staging of pancreatitis by the M-ANNHEIM classification since it diagnosed a higher proportion of patients with exocrine insufficiency.

Monocyte chemoattractant protein-1, transforming growth factor-beta1, nerve growth factor, resistin and hyaluronic acid as serum markers: comparison between recurrent acute and chronic pancreatitis.

BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta1 (TGF-beta1), nerve growth factor (NGF), resistin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differentiate the two conditions. METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively compared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP. RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were significantly higher in CP patients than in the controls (P<0.001); MCP-1, NGF and HA were significantly higher in RAP patients than in the controls (P<0.001). Stepwise discriminant analysis showed significant difference (P=0.002) between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP. CONCLUSION: Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

Niemann-Pick disease type C or Gaucher's disease type 3? A clinical conundrum.

We describe a patient who presented with a neurovisceral syndrome characterised by ataxia, bulbar dysfunction, supranuclear gaze palsy, splenomegaly and foamy histiocytes in the bone marrow. This presentation was suggestive of a lysosomal storage disorder such as Niemann-Pick disease type C or Gaucher's disease type 3. We review the presentation of these disorders, with a focus on the neurological features. In addition, we briefly discuss the disease-modifying therapeutic options which have recently become available.

Spontaneous tumour lysis syndrome in a case of multiple myeloma - A rare occurrence.

We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS), following a compression fracture of the L-2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M-band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL), hyperkalaemia (> 7.0 mEq/L), hyperphosphatemia (16.2 mg of phosphorus/dL), normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS.

Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia.

INTRODUCTION: The classification of acute leukemias has revolutionized over the years. Immunophenotyping of acute leukemia has gained popularity because of its influence on treatment and prognosis of the disease. The various antigens expressed by the leukemic cells can be assessed by flowcytometry (FCA) and can be used in rendering specific treatment and predicting the outcome of the different types of acute leukemia. AIMS: The main aim of this study was to compare the morphologic and cytochemical diagnoses with flowcytometric diagnoses in acute leukemia and to analyze the usefulness of FCA over morphology. RESULTS: In this study we analyzed 50 cases of acute leukemia and found concordance rate as high as 86% between morphologic/cytochemical diagnosis and flowcytometric diagnosis. Of these, complete concordance was seen in 58% of the cases and partial concordance was seen in 22% of the cases. Non-concordance was seen in only 4% of our cases. In remaining 16% of our cases FCA helped in sub classifying the acute leukemia where morphology and cytochemistry had failed to do so. CD19 and 20 were found to be consistent B-cell markers and CD3 was a very specific marker for T-cell leukemia. CD13 and 33 were important myeloid markers and were aided by other secondary panel of markers like CD14, CD117 and CD41. CONCLUSION: FCA not only helps in confirming morphologic diagnosis in acute leukemia but also helps in assigning specific lineage to the blasts, particularly in acute lymphoid leukemia. Immunophenotyping is of utmost importance in classifying acute leukemia as it greatly influences the treatment and the prognosis.

Chronic myeloid leukemia with hyperdiploidy: a case report with review of literature.

Chronic myeloid leukemia (CML) is a common marrow stem cell neoplasm characterized by the presence of the Philadelphia (Ph) chromosome in more than 90% of patients. Studies have shown that CML can be associated with various other cytogenetic abnormalities. 5-10% of these cases can show complex translocations involving other chromosomes in addition to Ph chromosome. Here, we report a Ph-positive CML patient with a hyperdiploid karyotype who presented clinically in chronic phase but progressed to blast crisis in spite of treatment with Imatinib. This case highlights the significance of cytogenetic abnormalities on the prognosis in CML.

Anthropometric measurements of nutritional status in chronic pancreatitis in India: comparison of tropical and alcoholic pancreatitis.

AIM: Undernutrition is considered to be a cause of tropical pancreatitis (TP) since this disease is commonly seen in the underprivileged populations of the world. This study was done to compare the nutritional status in patients with TP and alcoholic chronic pancreatitis (ACP) using anthropometric measurements. METHODS: Anthropometric measurements were done in patients with TP and ACP aged >18 years and matched healthy controls. Presence of pain, recent dietary restriction, diabetes mellitus (DM), calcification, serum prealbumin (PAB), and quantitative fecal elastase (FE) was assessed. Premorbid body mass index (BMI) was determined from weight before the onset of illness as reported by the patients. RESULTS: Of 54 patients (47 male), 39 (72.2%) had TP and the rest had ACP. Patients with TP were younger than those with ACP; the frequency of pain, DM, calcification, and exocrine insufficiency was similar in the two groups. Compared to control subjects, patients had lower BMI, triceps skin fold thickness (TSFT) and mid-arm circumference (MAC) (p < 0.01), but waist-to-hip ratio (W/H) was similar. Undernutrition was equally common in TP and ACP (15 [38.5%] vs. 6 [40%]). The BMI, TSFT, MAC, and W/H were similar in TP and ACP. The premorbid BMI was higher than that at presentation (20.2 [3.8] kg/m² vs. 19.1 [3.3] kg/m², p < 0.01). There was no association between BMI and features contributing to undernutrition (DM, pain, recent dietary restriction, FE level, and calcification) on univariate analysis. CONCLUSIONS: Energy undernutrition occurs equally commonly in TP and ACP and this appears to develop after the onset of illness.

Lupus anticoagulant and anticardiolipin antibodies in SLE with secondary Antiphospholipid Antibody Syndrome.

Thirty patients with systemic lupus erythematosus (SLE) and suspected secondary antiphospholipid antibody syndrome (APLAS) were evaluated in the study based on their clinical manifestations. The aim was to study the prevalence of various antiphospholipid antibodies, compare the tests used for their detection and to find a correlation between clinical and laboratory parameters. Coagulation tests used were activated partial thromboplastin time, dilute Russell viper venom time and kaolin clotting time and the results were analyzed statistically. In our study, arteriovenous thrombosis was more common than recurrent abortions and other clinical manifestations. Twelve percent of patients had positive lupus anticoagulant and 78% had elevated anticardiolipin antibody titers. We concluded that the prevalence of lupus anticoagulant and anticardiolipin antibodies in SLE patients with secondary APLAS was 12% and 17%, respectively. We also proved that dilute Russell viper venom time and kaolin clotting time proved to be much more specific tests and the anticardiolipin antibody a much more sensitive test.

Role of slit skin smear examination in cutaneous T-cell lymphomas and other chronic dermatoses.

The purpose of this study was to evaluate the utility of slit-skin smear examination in the diagnosis of various chronic dermatoses. The study included 24 patients with chronic dermatoses who presented to the skin outpatient department. Ten patients had idiopathic erythroderma, seven were diagnosed with airborne contact dermatitis, four had cutaneous T-cell lymphoma, two had chronic actinic dermatoses, and a single patient had panniculitis. Slit skin smears were obtained from all patients, stained with Leishman stain, and examined under microscope. Out of 24 patients, all four cases of cutaneous T-cell lymphoma showed abnormal cells suggestive of lymphomatous infiltration, two patients with airborne contact dermatitis showed reactive lymphocytes, and two idiopathic erythroderma cases showed numerous eosinophils in the smear. Slit skin smear examination is a simple rapid, decisive test in the diagnosis of cutaneous T-cell lymphoma. It is a useful screening test, especially in Sezary syndrome and diseases with specific skin infiltrate.

Rosette formation in non Hodgkin's lymphoma in the bone marrow--a case report.

This is a case report of rosette formation in non-Hodgkin's lymphoma in the bone marrow. A 66 year old female on treatment for metastatic papillary carcinoma thyroid and non-Hodgkin's lymphoma of the nodular small cleaved cell type was found to have bone marrow infiltration by a low grade B cell lymphoma. Bone marrow aspirate, imprint and trephine biopsy showed rosettes of the abnormal lymphoid cells. The associations of papillary carcinoma thyroid, hyperglobulinemia and retroperitoneal fibrosis in this case which explain the histogenesis of rosette formation are discussed.