Whole exome sequencing and rare variant association study to identify genetic modifiers, KLF1 mutations, and a novel double mutation in Thai patients with hemoglobin E/beta-thalassemia.

OBJECTIVES: Clinical manifestations of patients with Hemoglobin E/beta-thalassemia vary from mild to severe phenotypes despite exhibiting the same genotype. Studies have partially identified genetic modifiers. We aimed to study the association between rare variants in protein-coding regions and clinical severity in Thai patients. METHODS: From April to November 2018, a case-control study was conducted based on clinical information and DNA samples collected from Thai patients with hemoglobin E/beta-thalassemia over the age of four years. Cases were patients with severe symptoms, while patients with mild symptoms acted as controls. Whole exome sequencing and rare variant association study were used to analyze the data. RESULTS: All 338 unrelated patients were classified into 165 severe and 173 mild cases. Genotypes comprised 81.4% of hemoglobin E/beta-thalassemia, 2.7% of homozygous or compound heterozygous beta-thalassemia, and 0.3% of (뫧)0 thalassemia Hb E while 15.7% of samples were not classified as beta-thalassemia. A novel cis heterozygotes of IVS I-7 (A > T) and codon 26 (G > A) was identified. Six genes (COL4A3, DLK1, FAM186A, PZP, THPO, and TRIM51) showed the strongest associations with severity (observed p-values of <0.05; significance lost after correction for multiplicity). Among known modifiers, KLF1 variants were found in four mild patients and one severe patient. CONCLUSION: No rare variants were identified as contributors to the clinical heterogeneity of hemoglobin E/beta-thalassemia. KLF1 mutations are potential genetic modifiers. Studies to identify genetic factors are still important and helpful for predicting severity and developing targeted therapy.

Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis.

BACKGROUND: The association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis. METHODS: Two investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel-Haenszel method. RESULTS: A total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84-2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24-2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49-1.04; P = 0.08; I2 = 0%). CONCLUSIONS: The current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs. TRIAL REGISTRATION: INPLASY202180113 .

Human herpesvirus 8-associated multicentric Castleman disease in a patient with advanced HIV infection: A case report.

RATIONAL: Multicentric Castleman disease (MCD) is a nonclonal lymphoproliferative disorder that is rarely reported from Southeast Asian countries. Here, we report a case of human herpesvirus 8 (HHV-8)-associated MCD in a patient with advanced human immunodeficiency virus (HIV) infection who presented with prolonged intermittent fever, urticarial rash, hepatosplenomegaly, and generalized lymphadenopathy. PATIENT CONCERNS: A 34-year-old man with advanced HIV infection who was in good compliance with his antiretroviral treatment regimen presented with intermittent fever, weight loss, marked hepatosplenomegaly, and generalized lymphadenopathy. Recurrent symptoms of high-grade fever, abdominal discomfort, pancytopenia, and high C-reactive protein level occurred for 16 months. DIAGNOSES: Histopathological findings of left inguinal lymph node revealed diffuse effacement of lymph node architecture with coexpression of HHV-8 latency-associated nuclear antigen 1 from immunohistochemical staining. The HHV-8 viral load was 335,391 copies/mL. INTERVENTIONS: The patient was treated initially with one dose of intravenous rituximab (375 mg/m2) followed by subcutaneous rituximab (1400 mg) weekly for 5 weeks. OUTCOMES: The patient's recurrent systemic symptoms subsided dramatically, and he has now been in remission for almost two years. LESSONS: HHV8-associated MCD remains a diagnostic challenge in advanced HIV disease and should be suspected in those with recurrent flares of systemic inflammatory symptoms. Lymph node histopathology is essential for diagnosis and for excluding clonal malignancy. HHV-8 viral load is also useful for diagnosis and for monitoring disease activity.

Thrombotic and Hemorrhagic Incidences in Patients After Discharge from COVID-19 Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between coronavirus infection 2019 (COVID-19) and thrombosis has been explicitly shown through numerous reports that demonstrate high rates of thrombotic complications in infected patients. Recently, much evidence has shown that patients who survived COVID-19 might have a high thrombotic risk after hospital discharge. This current systematic review and meta-analysis was conducted to better understand the incidence of thrombosis, bleeding, and mortality rates among patients discharged after COVID-19 hospitalization. METHODS: Using a search strategy that included terms for postdischarge, thrombosis, and COVID-19, 2 investigators independently searched for published articles indexed in the MEDLINE, Embase, and Scopus databases that were published before August 2021. Pooled incidences and 95% confidence intervals were calculated using the DerSimonian-Laird random-effects model with a double arcsine transformation. RESULTS: Twenty articles were included in the meta-analysis. They provided a total of 19 461 patients discharged after COVID-19 hospitalization. The weighted pooled incidence of overall thrombosis among the patients was 1.3% (95 CI, 0. 6-2; I2 90.5), with a pooled incidence of venous thrombosis of 0.7% (95 CI, 0. 4-1; I2 73.9) and a pooled incidence of arterial thrombosis of 0.6% (95 CI, 0. 2-1; I2 88.1). The weighted pooled incidences of bleeding and mortality were 0.9% (95 CI, 0. 1-1.9; I2 95.1) and 2.8% (95 CI, 0. 6-5; I2 98.2), respectively. CONCLUSIONS: The incidences of thrombosis and bleeding in patients discharged after COVID-19 hospitalization are comparable to those of medically ill patients.

Spontaneous heparin-induced thrombocytopaenia with adrenal haemorrhage following orthopaedic surgery: a case report and literature review.

A 68-year-old woman was admitted to the hospital for elective total knee arthroplasty in both knees without preceding heparin exposure. She developed adrenal haemorrhage and thrombocytopaenia on postoperative day 12, followed by right leg arterial occlusion and multiple venous intra-abdominal sites thrombosis. After given unfractionated heparin to treat arterial occlusion, platelet count was gradually declined. Spontaneous heparin-induced thrombocytopaenia was diagnosed by heparin-induced platelet activation test with light transmission aggregometry. The patient was successfully treated with fondaparinux and intravenous immunoglobulin. Apixaban was given after recovery of platelet count. Resolution of both thrombus along aorta and adrenal haemorrhage were shown by CT of whole abdomen after 2 months of treatment. Our case demonstrates that this serious complication is important but seldom recognised early.

Successful Treatment of Factor X Deficiency in a Patient with Lymphoplasmacytic Lymphoma with Bendamustine Plus Rituximab Regimen: A Case Report and Literature Review.

BACKGROUND: Acquired factor X deficiency is an uncommon condition, and affected individuals have severe and spontaneous bleeding. The associated conditions include malignancy, infection, burn, and inflammatory bowel disease. Many previous studies reported association between lymphoproliferative disease and factor X disappearance. Amyloid deposition causing factor X absorption was the most common mechanism. Here, we report a case of stage IV lymphoplasmacytic lymphoma (LPL) with factor X deficiency who was successfully treated with bendamustine plus rituximab (BR) regimen. CASE PRESENTATION: A 52-year-old Thai woman presented with heavy menorrhea, hoarseness, and widespread ecchymosis at her extremities. On physical examination, the patient had bilateral periorbital purpura and vocal cord hematoma. Coagulation testing showed prolonged prothrombin time (PT) and prolonged activated thromboplastin time (aPTT); however, after mixing with 1:1 normal pooled plasma, PT and aPTT were both corrected to normal levels. Factor assays demonstrated markedly decreased factor X levels, but no presence of factor X inhibitor. Bone marrow examination revealed numerous abnormal lymphoplasmacytoid lymphocytes with kappa light chain expression. Serum free light chain assay also showed kappa light chain restriction [kappa 716.16 mg/L, lambda 16.96 mg/L, ratio 42.23 (0.26-1.65)]. The patient was diagnosed as lymphoplasmacytic lymphoma with factor X deficiency. She received chemotherapy with 6 cycles of bendamustine plus rituximab (BR) regimen. The patient responded favorably to treatment, she remains in lymphoma remission at one year after diagnosis, and her factor X level was more than 20%. CONCLUSION: We performed a literature review to identify previous case reports about lymphoma-associated factor X deficiency or inhibitor to determine a possible explanation in our patient. It is important to emphasize that when patients present with acquired factor deficiency, including factor X, lymphoproliferative disease is commonly one of the underlying conditions. Furthermore, the recovery of coagulation factor deficiency is possible if successful remission of lymphoma can be achieved.

Successful venous thromboprophylaxis in a patient with vaccine-induced immune thrombotic thrombocytopenia (VITT): a case report of the first reported case in Thailand.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication of the Coronavirus Disease 2019 vaccine. The many reports of VITT have mostly been in the Caucasian population. Here, we present the first reported case in an Asian population. CASE PRESENTATION: A 26-year-old female had severe headache and severe thrombocytopenia 8 days after administration of the ChAdOx1 nCoV-19 vaccine developed by AstraZeneca. Although no thrombosis was demonstrated by imaging studies, she had very highly elevated d-dimer levels during hospitalization. Serology for antibodies against platelet factor 4 was positive on several days with very high optical density readings. We found that the antibody could induce spontaneous platelet aggregation without the presence of heparin. We decided to treat her with intravenous immunoglobulin, high-dose dexamethasone, and a prophylactic dose of apixaban. She improved rapidly and was discharged from the hospital 6 days after admission. Neither thrombocytopenia nor thrombosis was subsequently detected at the three-week follow-up. CONCLUSIONS: Despite the lower rate of thrombosis, VITT can occur in the Asian population. Early detection and prompt treatment of VITT can improve the patient's clinical outcome. Thromboprophylaxis with nonheparin anticoagulants also prevents clot formation.

Sensitivity and specificity of 20-minute whole blood clotting test, prothrombin time, activated partial thromboplastin time tests in diagnosis of defibrination following Malayan pit viper envenoming.

Malayan pit vipers (Calloselasma rhodostoma) are major health hazard in Southern Thailand causing systemic bleeding by defibrination and thrombocytopenia. Twenty minute whole blood clotting test (20WBCT) is a useful and informative bedside test recommended by WHO for diagnosis of significant coagulopathy following snakebite envenoming since it to some extent predicts the need for anti-venom therapy. Prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) are standard clotting assays that are widely used for diagnosis of coagulopathy. The purpose of this study is to compare 20WBCT with the standard clotting assays (PT, INR, APTT, fibrinogen) in management of Malayan pit viper bitten-patients. We studied 296 victims prospectively during a 3-year period. In total, 115 (38.9%) cases showed a positive 20WBCT (un-clot) suggesting systemic envenomation. Thrombocytopenia (platelet count less than 100,000/µL), prolonged PT, prolonged APTT, INR ≥ 1.2, and fibrinogen level <100 mg/dl were found in 12.2%, 47.6%, 18.9%, 34.8% and 40.9%, respectively. Significant predictors for thrombocytopenia by multivariate analysis included systemic bleeding (p < 0.001), higher INR (p < 0.001), 20WBCT showing unclotted blood (p = 0.049), and longer bite-to-hospital time (p = 0.031). When a fibrinogen level below 100 mg/dl was determined as hypofibrinogenemic condition, INR had the highest area under ROC curve followed by 20WBCT and APTT, respectively, to identify such as hypofibrinogenemic condition. The diagnostic accuracy of 20WBCT and INR at or more than 1.155 were better than APTT at any cut-off points. INR >1.155 had a sensitivity of 78.5% and specificity of 90.3% while 20WBCT had sensitivity of 81.0% and specificity of 90.3%. CONCLUSIONS: Both 20WBCT and INR are useful to assess coagulation abnormality in Malayan pit viper-bitten patients.

Comparison between optical microscopy and the Sysmex XN-3000 for schistocyte determination in patients suspected of having schistocytosis.

BACKGROUND AND AIMS: Diagnosis of thrombotic microangiopathy (TMA) relies on microscopic schistocyte determination by an experienced microscopist. In addition, schistocytes can be found in non-TMA-related disorders such as thalassaemia. We aimed to compare the accuracy of the automated haematology analyser Sysmex XN-3000 for schistocyte detection, to that of the microscopy approach, in patients suspected of having schistocytosis. METHODS: Consecutive blood samples were collected between April 2016 and March 2017 at Siriraj Hospital, Mahidol University, Bangkok, Thailand. Specimens were collected from adults with suspected TMA or with thalassaemia trait and/or disease. All blood samples were examined by both microscopy and the analyser. Samples were considered to be positive for schistocytes (ie, schistocytosis) if they had a schistocyte count ≥1% by microscopy. The analyser's ability to determine schistocytosis was assessed by receiver operating characteristic (ROC) curve. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of an appropriate cut-off point were calculated, with manual microscopy as the standard. Quantitative agreement in schistocyte counts between the two approaches was assessed using 95% limits of agreement, Bland-Altman plots, intraclass correlation coefficient, and concordance correlation coefficient. RESULTS: Ninety-seven blood samples (62 suspected TMA and 35 thalassaemia) were collected. ROC curve analysis of the analyser for determining schistocytosis showed an area under the curve of 0.803 (95% confidence interval, 0.689-0.917, P < 0.001). A cut-off point of 0.6% yielded 86.1% sensitivity, 77.8% specificity, 94.4% PPV, and 56.0% NPV. The automated schistocyte count did not quantitatively agree with schistocyte counts by microscopy, neither in all blood specimens (mean of difference: -1.09; 95% limits of agreement, -11.9 to 9.7) nor in the subgroups (TMA, -0.88; 95% limits of agreement, -6.60 to 4.84; thalassaemia, -2.4; 95% limits of agreement, -14.10 to 9.30). The differences in the estimation of fragmented red blood cells between the methods tended to increase at higher schistocyte counts. CONCLUSION: Sysmex XN-3000 can be used for qualitative measurement of schistocytosis, but should not be used as a quantitative tool for schistocyte counting. Improvements are needed before this analyser's schistocyte detection feature can be recommended for use in clinical practice.

Efficacy and Safety of Metronomic Chemotherapy Versus Palliative Hydroxyurea in Unfit Acute Myeloid Leukemia Patients: A Multicenter, Open-Label Randomized Controlled Trial.

BACKGROUND: Management of unfit AML patients is a therapeutic challenge. Most hematologists tend to avoid aggressive treatment leaving patients with a choice of best supportive care. We hypothesized that metronomic chemotherapy could be an alternative treatment for unfit AML patients. METHODS: A multi-center randomized controlled trial was conducted in seven university-affiliated hospitals in Thailand. Unfit AML patients were recruited and followed up from December 2014 to December 2017. Patients were randomly assigned to receive either metronomic chemotherapy or palliative hydroxyurea. Overall survival rates were compared using Cox's proportional hazard survival analysis. RESULTS: A total of 81 eligible patients were randomly allocated and included for ITT analysis. The OS rate was higher in group receiving metronomic chemotherapy than in group receiving palliative treatment at 6 and 12 months with borderline significance (6 months HR 0.60; 95%CI 0.36, 1.02; p-value 0.060; 12 months: HR 0.66; 95%CI 0.41, 1.08; p-value 0.097). CONCLUSION: Metronomic chemotherapy could prolong survival time of unfit AML patients, especially in the first 12 months after diagnosis without increasing treatment-associated adverse events.

Determination of Normal HbA1C Levels in Non-Diabetic Patients with Hemoglobin E.

OBJECTIVE: Hemoglobin E (Hb E) possesses an influence on HbA1c levels. Careful interpretation of HbA1c is needed in areas with a high prevalence of Hb E, including Thailand. Therefore, the normal levels of HbA1c in non-diabetic Hb E subjects were collected and assessed. METHODS: A cross-sectional study was conducted in Hb E subjects aged 18 years and above (N=70). An oral glucose tolerance test was performed. HbA1c levels were measured with 3 assays: ion exchange HPLC, immunoassay (ImmA), and enzymatic assay (EnzA). Individuals who received regular blood transfusions and diabetic patients were excluded. RESULTS: Among 34 subjects with heterozygous Hb E (EA), the mean (±SD) HbA1c levels by HPLC, ImmA, and EnzA were 5.63±0.55%, 4.73±0.62%, and 5.29±0.37%, respectively. Among 29 subjects with homozygous Hb E (EE), the mean (±SD) HbA1c levels by HPLC, ImmA, and EnzA were 3.37±0.69%, 4.37±0.76, and 4.91±0.28%, respectively. Immunoassay and enzymatic methods seem preferable over HPLC for this population. The HbA1c level of 5.7 (99th percentile) from immunoassay is a proposed cut-off point for detecting individuals who are at an increased risk of diabetes. CONCLUSION: There are subjects with hemoglobin E whose HbA1c levels are deemed inaccurate due to the techniques used. Within this study normal HbA1c levels were determined by 3 different assays. The HbA1c level of 5.7 by immunoassay (Advia, 1600) is proposed as the cut-off point for diagnosing subjects at risk of diabetes.

Efficacy and safety of second-line treatment in Thai patients with primary warm-type autoimmune hemolytic anemia.

Objectives:: To investigate the efficacy and safety of second-line treatment in Thai patients with primary warm-type autoimmune hemolytic anemia (AIHA) that failed corticosteroid treatment. Methods:: This descriptive retrospective study included patients aged >14 years who were diagnosed with and treated for primary warm-type AIHA at the Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, during January 2007 to December 2016. All 54 included patients failed first-line corticosteroid treatment after which second-line treatment was prescribed. Baseline clinical characteristics, laboratory results at diagnosis and at start of second-line treatment, type of second-line treatment, treatment outcome, and complications of treatment including death were collected. Results:: Included patients had a mean age at onset of 55.8 years (14.5-87.4) and 83.3% of patients were female. Most patients (63%) were refractory to steroids, and the rest of them relapsed while on steroids. The second-line medications were azathioprine (61.1%), cyclophosphamide (31.5%), chlorambucil (1.9%), danazol (3.7%), and rituximab (1.9%), with respective response rates of 78.8%, 58.8%, 1/1 patient, 2/2 patients, and 0/1 patient. Strong positive direct Coombs' test (3+-4+) was the only predictive factor of treatment response (p = 0.008). Males had better relapse-free survival than females (not reached vs. 20.6 months) (p = 0.023). Approximately 40% of the patients who responded to second-line treatment relapsed at a median of 7.4 months. Conclusion:: Immunosuppressive drugs are the most common second-line treatment for primary warm-type AIHA in Thailand; however, relapse was common. Additional therapies are needed to reduce the relapse rate and prolong remission.

Random skin biopsy in the diagnosis of intravascular lymphoma.

BACKGROUND: Random skin biopsy (RSB) is a method for diagnosis of intravascular lymphoma (IVL). However, the indications for RSB to diagnose IVL have not yet been established. The aim of this study was to determine the appropriate indications for RSB to diagnose IVL. METHODS: Thirty-two patients with fever of unknown origin (FUO) and without skin lesion underwent RSB for diagnosis of IVL. Clinical data, including fever, neurological symptoms, hematologic disorders, organomegaly, bone marrow (BM) study, hypoxemia and serum level of lactate dehydrogenase (LDH), were evaluated. RESULTS: Seven of 32 patients were definitively diagnosed with IVL. In addition to FUO, 2 IVL patients also suffered from dyspnea and neurological disorders. Patients who had FUO with accompanying hematologic disorders, high LDH, negative BM study and no lymphadenopathy or hepatosplenomegaly had a significant tendency to have IVL by RSB (P = .03). FUO with hypoxemia was also identified as a significant indication for RSB (P = .02). CONCLUSIONS: RSB is a reliable method for diagnosis of IVL, especially in patients with FUO and any 1 or more of the 4 following abnormalities: (1) hematologic abnormalities; (2) high serum LDH; (3) hypoxemia; and/or, (4) unusual neurological symptoms with co-existing hematologic abnormalities and without lymphadenopathy, hepatosplenomegaly or BM abnormality.

Clinical Significance of Bone Marrow Involvement as Confirmed by Bone Marrow Aspiration vs. Bone Marrow Biopsy in Diffuse Large B-cell Lymphoma.

BACKGROUND: In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement confirmed by BM biopsy confers a poor prognosis. However, in clinical practice, there may be disagreement in results between BM biopsy and BM aspiration in determination of BM involvement. It is unknown which of BM biopsy or BM aspiration better correlates with clinical outcome. OBJECTIVE: To evaluate clinical outcome of BM involvement as confirmed by BM aspiration vs. confirmation by BM biopsy in patients with DLBCL. MATERIAL AND METHOD: Clinical data, treatment, and outcome of 126 DLBCL patients with available BM aspirate slides who attended the Hematology Clinic at Siriraj Hospital between January 1, 2007 and December 31, 2009 were reviewed. BM aspirate slides were revised and interpreted by hematologists. RESULTS: BM involvement was found in 12.7% (16/126) by BM biopsy and 24.6% (31/126) by BM aspiration. Regarding BM biopsy results, rates of complete remission (CR) among patients with unequivocal involvement, equivocal involvement, and without involvement were 75.0%, 57.1%, and 77.7%, respectively (p = 0.464). Two-year overall survival (OS) rates among the three groups were not significantly different (p = 0.663). Regarding BM aspiration results, CR rates among patients with unequivocal involvement, equivocal involvement, and without involvement were 80.6%, 75.8%, and 72.7% (p = 0.755). Two-year OS rates among the three groups were not significantly different (p = 0.118). In multivariate analysis, BM involvement as determined by either BM biopsy or BM aspiration was not associated with CR rate or 2-year OS rates. However, the International Prognostic Index (PI) and use of rituximab were found to be signifcantly associated with CR rate and OS. CONCLUSION: In patients with DLBCL, BM involvement confirmed by either BM biopsy or BM aspiration appears not to influence the rate of complete remission or 2-year overall survival.

Anemia and Neutropenia in Copper-Deficient Patients: A Report of Two Cases and Literature Review.

Copper deficiency is an uncommon, but treatable cause of hematologic abnormalities. We present and describe two interesting cases in this report. The first case was a 37-year-old man with history of short bowel syndrome and long-term total parenteral nutrition (TPN) presenting with pancytopenia and chronic symmetrical polyarthritis that resembled rheumatoid arthritis. The second case was a 64-year-old man with malabsorption from Cronkhite-Canada Syndrome (CCS) and history of subtotal gastrectomy presenting with macrocytic anemia and neutropenia. Bone marrow examination in both cases revealed cytoplasmic vacuolization of myeloid and erythroid precursors. After copper supplementation was initiated, hematological abnormalities and arthritis were significantly improved. We encourage clinicians to recognize early and identify copper deficiency in patients who have unexplained cytopenia, especially if there is history of upper gastrointestinal tract surgery, malabsorption, or long-term TPN.

Expression of S100 Protein in CD4-positive T-cell Lymphomas Is Often Associated With T-cell Prolymphocytic Leukemia.

S100 T-cell lymphomas are infrequent, and except 1 all have been CD4 negative. On the basis of an index case of CD4 S100 T-cell prolymphocytic leukemia (T-PLL), we studied S100 protein expression in 19 additional T-PLLs and 56 other T-cell lymphomas that are usually CD4, including 15 angioimmunoblastic T-cell lymphomas, 24 anaplastic large cell lymphomas (16 ALK and 8 ALK), 7 mycosis fungoides/Sézary syndrome, and 10 peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Two additional S100 CD4 PTCL, NOS cases were also reviewed. Thirty percent (6/20) of T-PLLs were S100 compared with 0/56 other T-cell lymphomas with previously unstudied S100 reactivity (40 CD4, 2 CD8, 11 CD4/CD8, 3 unknown) (P=0.0007). There were no significant differences between the S100 and S100 T-PLLs with regard to the male:female ratio (2:1 vs. 1:1), age (71.6±7.7 vs. 65.4±9.3), peripheral blood lymphocyte count (67.2±116.6 vs. 101.1±159.7×10/L), or median survival (463 vs. 578 d, where known). The 2 S100 PTCL, NOS cases occurred in a 7-year-old boy and a 45-year-old woman. Both had involvement of the bone marrow and peripheral blood but were morphologically unlike T-PLL and lacked TCL1 gene rearrangement. These results demonstrate that S100 T-cell lymphomas include a subset that are CD4 and most often, but not exclusively, are T-PLL. Although having diagnostic implications, there were no documented clinical differences between the S100 and S100 T-PLLs.

Learning environment and resident achievement.

OBJECTIVE: To evaluate the effect of program training atmosphere on the academic performance among internal medicine residents. MATERIAL AND METHOD: Data of satisfaction survey among internal medicine residents in academic year 2012, conducted by the Royal College of Physicians of Thailand, were retrieved. Association between training environment rating scores in three major aspects (program training structure, faculty nurturance, and support system) and board certifying examination scores, were then assessed. RESULTS: There were 12 training centers with 535 residents in that academic year. The mean satisfaction score for second-year residents was 77.1 ± 6.1, and the mean written examination score was 56.4 ± 4.6, with the modest correlation (r = 0.515, p = 0.087). For the third-year residents, the mean satisfaction score was 78.5 ± 6.5 and the mean clinical examination score was 71.1 ± 1.6, with no correlation (r = -0.004, p = 0.991). In the subgroup analysis in second-year residents, program training structure had strongest influence (r = 0.569, p = 0.053), as compared to faculty nurturance (r = 0.425, p = 0.169), andsupport system (r = 0.492, p = 0.104). CONCLUSION: Perception of positive training environment, especially the program training structure, may influence the performance of internal medicine residents in term of knowledge achievement as determined by written examination score. However, it has no effect in terms of clinical skill accomplishments, as determined by clinical examination scores.

High on-clopidogrel treatment platelet reactivity in Thai patients with chronic stable angina scheduled for percutaneous coronary intervention.

OBJECTIVE: To determine the prevalence, clinical profile, and risk factors of high on-clopidogrel treatment platelet reactivity in Thai patients with chronic stable angina scheduled for percutaneous coronary intervention. MATERIAL AND METHOD: The patients were prospectively recruited from the consecutive patients undergoing coronary angiography and planned for elective percutaneous coronary intervention (PCI). Ten ml of blood samples were cautiously drawn from the antecubital vein of the patients to determine the hemoglobin and platelet count. Platelet aggregation test was performed by light transmittance aggregometry using platelet-rich plasma. Platelets were stimulated with 5 microM adenosine diphosphate (ADP). Platelet aggregation was expressed as the maximal percent change in light transmittance from baseline. High on-clopidogrel treatment platelet reactivity was defined as post treatment maximal platelet aggregation > 46% with 5 micromol/l ADP used as agonist. RESULTS: The present study consecutively enrolled two hundred four patients diagnosed with chronic stable angina planned for PCI. Seventy-nine patients demonstrated the high on-clopidogrel treatment platelet reactivity (38.7%). Among these patients, 48% were men with a mean age of 66 years. Diabetes mellitus and chronic kidney disease were detected in 34.2%. Original clopidogrel (Plavix) was prescribed in 72% of the patients and 28% received generic clopidogrel (Apolets). The prevalence of high on-clopidogrel treatment platelet reactivity increased in the older patients, patients with CKD and patients receiving angiotensin receptor blockers (ARB). However from multivariate analysis, none of the risk factors, including age, BMl, diabetes mellitus, smoking, CKD, ARB use, and type of clopidogrel (Plavix versus Apolets) had a statistically significant association with the high on-clopidogrel treatment platelet reactivity. CONCLUSION: The prevalence of high on-clopidogrel treatment platelet reactivity in the present study was 38.7%. No significant association was demonstrated between age, BMI, diabetes mellitus, smoking, CKD, ARB use, type of clopidogrel, and high on-clopidogrel treatment platelet reactivity.

Aspirin resistance in Thai patients with chronic stable angina.

OBJECTIVE: To determine the prevalence, clinical profile and risk factors of aspirin resistance in Thai patients with chronic stable angina. MATERIAL AND METHOD: The patients were prospectively recruited from the consecutive patients diagnosed chronic stable angina at Siriraj Hospital during March 2011 to February 2012. Ten milliliter of blood samples were cautiously drawn from the antecubital vein of the patients to determine the hemoglobin, platelet count and platelet aggregation test performed by light transmittance aggregometry using platelet-rich plasma. Platelets were stimulated with 0.5 mg/ml of arachidonic acid and 10 mM adenosine diphosphate. Platelet aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as the mean platelet aggregation of > or = 70% with 10 mM ADP and the mean platelet aggregation of > or = 20% with 0.5 mg/ml of arachidonic acid. RESULTS: One-hundred and fifty seven patients diagnosed chronic stable angina were enrolled in the present study. There were 34 patients (21.6%) demonstrating aspirin resistance. The clinical characteristic of these patients included male 58.8% with mean age of 66 years, body mass index 27.5 kg/m2, diabetes mellitus 52.9%, smoking 8.8%, hypercholesterolemia 70.6% and proton pump inhibitor use 23.5%. Multivariate analysis demonstrated none of the risk factors including age, female, body mass index, diabetes mellitus, hypercholesterolemia, smoking and proton pump inhibitor (PPI) use had a statistically significant association with aspirin resistance. CONCLUSION: Our study demonstrated that the prevalence of aspirin resistance in Thai patients with chronic stable angina was 21.6%. No significant association was demonstrated between age, female, body mass index, diabetes mellitus, hypercholesterolemia, smoking, proton pump inhibitor (PPI) use and aspirin resistance.