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 .

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.

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.

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.

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.

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.

First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis.

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997-2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10-0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and -0.13/-0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

Pulmonary lipiodol embolism after transcatheter arterial chemoembolization for hepatocellular carcinoma: a case report and literature review.

Acute pulmonary lipiodol embolism is a rare but possibly fatal complication of transcatheter arterial chemoembolization (TACE). The authors report a 63-years-old woman with unresectable large (7.4 x 7.9 cm) hepatocellular carcinoma (HCC) who had been diagnosed pulmonary lipiodol embolism after the first TACE. Intraoperative angiography did not show the communication between pulmonary circulation and tumor feeding artery. After lipiodol injection, she developed oxyhemoglobin desaturation immediately and chest computed tomography (CT) angiography showed lipiodol embolism at basal segments of both lower lobes. She also developed fever after TACE without any evidence of infection. Oxyhemoglobin desaturation had improved to baseline spontaneously within 7 days. Fever persisted for 16 days. Two weeks after TACE, follow-up CT of liver revealed the absence of almost lipiodol granule in lungs. The patient did not receive TACE again because of pulmonary metastasis. In this article we reviewed the cases of pulmonary lipiodol embolism that had been reported in the literature including clinical risk factors, possible mechanisms and the pathophysiology of this complication.

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.

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.

Iron overload in the Asian community.

Hereditary hemochromatosis is an iron overload disorder that can lead to the impairment of multiple organs and is caused by mutations in one or more different genes. Type 1 hemochromatosis is the most common form of the disease and results from mutations in the HFE gene. Juvenile hemochromatosis (JH) is the most severe form, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP). The autosomal dominant form of the disease, type 4, is due to mutations in the SLC40A1 gene, which encodes for ferroportin (FPN). Hereditary hemochromatosis is commonly found in populations of European origin. By contrast, hemochromatosis in Asia is rare and less well understood and can be masked by the presence of iron deficiency and secondary iron overload from thalassemia. Here, we provide a comprehensive report of hemochromatosis in a group of patients of Asian origin. We have identified novel mutations in HJV, HAMP, and SLC40A1 in countries not normally associated with hereditary hemochromatosis (Pakistan, Bangladesh, Sri Lanka, and Thailand). Our family studies show a high degree of consanguinity, highlighting the increased risk of iron overload in many countries of the developing world and in countries in which there are large immigrant populations from these regions.

Incidence and risk factors of bone marrow involvement by non-Hodgkin lymphoma.

BACKGROUND: Since trephine bone marrow biopsy is an invasive procedure, the identification of a subgroup of patients with Non-Hodgkin lymphoma (NHL) who have a minimal risk of bone marrow involvement would be helpful. This study is aimed to determine the incidence of bone marrow involvement (BMI) by NHL and the predictors of no BMI to not only avoid this invasive procedure but also decrease the cost of investigation. MATERIAL AND METHOD: Data from 320 patients with NHL at division of hematology between January 2008 and June 2009 were reviewed and analyzed. RESULTS: The cell types of NHL were classified as B-cell in 283 patients (88.4%), T-cell in 37 patients (11.6%) and incidence of BMI is 24.4% and 18.9% in B- and T-cell, respectively. Factors significantly associated with BMI in univariate analysis were the hepatic and splenic involvement (p = 0.03 and < 0.01, respectively), significant weight loss (p = 0.02), presence of lymphadenopathy (LN) below diaphragm (p = 0.02), anemia (p = 0.001), low percent of blood neutrophil (p < 0.001), high percent of blood lymphocyte (p < 0.001), low absolute neutrophil count (p = 0.002), high absolute lymphocyte count (p = 0.045), low platelet count (p < 0.001), high LDH (p = 0.026), and high alkaline phosphatase (p = 0.020). On the multivariate analysis, factors associated with BMI included LN below diaphragm, anemia, low percent of blood neutrophil and low platelet count. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, hemoglobin (Hb) >11 g/dL and platelet > 150,000/uL had BMI in 3/78 (3.8%). CONCLUSION: The incidence of bone marrow involvement in NHL is 23.8%. Excluding Burkitt lymphoma and mantle cell lymphoma, NHL patients with no LN below diaphragm, no hepatic & splenic involvement, no significant weight loss, Hb > 11 g/dL and platelet > 150,000/uL had low risk of BMI.

Inadvertent intrathecal vincristine administration: report of a fatal case despite cerebrospinal fluid lavage and a review of the literature.

Accidental intrathecal vincristine administration results in progressive ascending radiculomyeloencephalopathy usually leading to fatal outcome. No specific therapy for intrathecal vincristine toxicity has been reported. We report a 63-year-old man with diffuse large B-cell lymphoma at the right testis who inadvertently received intrathecal vincristine. Direct CSF aspiration and irrigation was done 30 minutes after the incident. Ventriculostomy and lumbar drain was placed. Intrathecal irrigation was started at 6.5 hours using FFP-containing lactate solution and continued for 11 days. In addition, antineurotoxic and neuroprotective agents were given. His neurological symptom deteriorated slowly and he died on day 12. Among 16 reported cases undergoing lumbar drainage and/or irrigation, 56.3% can survive 30 days or more and 37.5% had survive more than 6 months. Immediate CSF drainage and early irrigation is related to good outcome (prolonged survival with no encephalopathy). In our case, his poor outcome might be due to the delayed starting of irrigation. In conclusion, the appropriate and effective management of this complication is unknown. However, emergency cerebrospinal fluid drainage and irrigation remains the principal of management.

The efficacy of 3-mg warfarin initiating dose in adult Thai patients, who required long-term anticoagulant therapy.

BACKGROUND: Warfarin anticoagulation is the standard treatment for patients with thromboembolic diseases. Prior studies recommended commencing warfarin with the initial doses between 5 mg and 10 mg for the first 1 or 2 days. However, lower warfarin loading dose is advised for the elderly and patients with co-morbid diseases. Moreover, warfarin requirement is also affected by several genetic factors, which differ among various ethnic populations. Currently, the optimal initiating dose of warfarin in Thai patients is unknown. However, based on the observation of the clinical practice at Siriraj hospital, a lower starting dose (3 mg/day) of warfarin was commonly given to patients who required long-term anticoagulant therapy. OBJECTIVE: To investigate the efficacy and safety of 3-mg warfarin initiating dose. MATERIAL AND METHOD: A retrospective study of inpatients who received warfarin 3 mg/day for the first two days of oral anticoagulation therapy with the target INR of 2.0-3.0 at Siriraj hospital from January 2004-December 2007 was performed. The efficacy of 3-mg warfarin loading dose was determined by assessing the proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5 of warfarin treatment. RESULTS: Total of 164 patients was included in the study. Eighty-six patients (52.4%) were males. The mean age was 55.1 + 16.8 years (range 16-88 years). The mean body weight and serum albumin were 61.5 +/- 12.2 kg and 3.7 +/- 0.7 g/dl, respectively. Prosthetic heart valve replacement was the most common indication for warfarin anticoagulation therapy (36%), followed by deep vein thrombosis (32.3%). The mean cumulative weekly dose of warfarin was 22.3 +/- 5.8 mg. The median time to therapeutic INR (2.0-3.0) was 6 days. Forty-seven patients (29%) achieved therapeutic INR between day 3 and day 5 of warfarin treatment. Time to therapeutic INR was not affected by age, gender, body weight, serum albumin, or concomitant medication use. Interestingly, patients who received warfarin due to prosthetic heart valve replacement were more likely to achieve therapeutic INR between day 3 and day 5 when compared to those with other indications with adjusted OR 16.25 (95% CI 5.13-51.44, p < 0.001). Bleeding complication was rare (0.6%) and was not associated with excessive anticoagulation. CONCLUSION: 3-mg warfarin initiating dose appeared to be safe in adult Thai patients. However, the efficacy of 3-mg starting dose as determined by the proportion of patients who achieved the target INR between day 3 and day 5 of warfarin treatment was relatively less efficient when compared with that previously reported with a 5-mg loading dose. Further randomized, prospective study is required to examine the efficacy of 3-mg versus higher warfarin starting dose in Thai patients.

Can we predict final outcome of internal medicine residents with in-training evaluation.

OBJECTIVE: To assess the predictive value of in-training evaluation for determining future success in the internal medicine board certifying examination. MATERIAL AND METHOD: Ninety-seven internal medicine residents from Faculty of Medicine Siriraj Hospital who undertake the Thai Board examination during the academic year 2006-2008 were enrolled. Correlation between the scores during internal medicine rotation and final scores in board examination were then examined. RESULTS: Significant positive linear correlation was found between scores from both written and clinical parts of board certifying examination and scores from the first-year summative written and clinical examinations and also the second-year formative written examination (r = 0.43-0.68, p < 0.001). Monthly evaluation by attending staffs was less well correlated (r = 0.29-0.36) and the evaluation by nurses or medical students demonstrated inverse relationship (r = -0.2, p = 0.27 and r = -0.13, p = 0.48). CONCLUSION: Some methods of in-training evaluation can predict successful outcome of board certifying examination. Multisource assessments cannot well extrapolate some aspects of professional competences and qualities.

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.

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.

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.