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Objective Hemoglobin Constant Spring (HbCS) is often missed by routine hemoglobin analysis. The aim of this research was to study HbCS stability as identified by capillary electrophoresis (CE) to determine the specimen storage time limit. Methods The EDTA blood of 29 HbCS samples were kept at 4°C and analyzed every workday until CE could not detect HbCS or until 7 weeks after blood collection. The genotypes were confirmed by multiplex polymerase chain reaction. Results The median subject age was 27 years and 10 subjects were male. The HbCS levels were stable during the first 7 days but became undetectable in 5 cases (17.2%) after 1 week. All of them were heterozygous HbCS. Longer detection times were correlated with the higher baseline HbCS levels, with a correlation coefficient of 0.582 (P ≤ 0.001) Conclusion Routine hemoglobin typing and quantitation should be performed within 1 week after blood collection to detect low HbCS levels, especially in heterozygous HbCS.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia following adenoviral vector vaccines against severe acute respiratory syndrome coronavirus 2. Platelet-activating anti-platelet factor 4-dependent antibodies (anti-PF4 Abs) have been identified as pathogenic antibodies in almost all patients.We proposed an immunological mechanism of VITT independent of anti-PF4 Abs.Case report.A 68-year-old Thai woman developed pulmonary embolism and deep vein thrombosis with thrombocytopenia one week after the second ChAdOx1 nCoV-19 vaccination with undetectable anti-PF4 Abs. The platelet count responded rapidly to intravenous immunoglobulin and steroids. Therefore, the high clinical suspicion is essential for early recognition and prompt management irrespective of anti-PF4 Ab results.We hypothesize that platelet and endothelial activation following ChAdOx1 nCoV-19 vaccination may lead to generation of pathogenic antibodies which account for VITT independent of anti-PF4 Abs.

Objectives: A sensitive screening for the coexistence of α0-thalassemia and the hemoglobin E (Hb E) trait is important to identify at-risk couples for hydrops fetalis. However, previous cutoff valu...

Background Thromboembolic and bleeding events after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major public concerns leading to vaccine hesitancy. Due to low incidence, an individual randomized controlled trial (RCT) is underpowered to determine whether SARS-CoV-2 vaccines increase the risks of thromboembolism and hemorrhage. Methods We performed a literature search using PubMed, EMBASE, Cochrane, medRxiv databases, and reference lists of relevant articles to identify RCTs that reported thromboembolic, hemorrhagic events, and thromboembolism/hemorrhage-related death after SARS-CoV-2 vaccination. The primary aim of this systematic review and meta-analysis was to estimate the pooled thromboembolic risk related to SARS-CoV-2 vaccines compared to placebo. The secondary outcomes included estimating the risks of arterial thromboembolism (ATE), venous thromboembolisms (VTE), hemorrhage, thrombocytopenia, and thromboembolism/hemorrhage-related death. Results Eight RCTs of 4 vaccine platforms comprised of 195,196 participants were retrieved. SARS-CoV-2 vaccines were not associated with an increased risk of overall thromboembolism (risk ratio [RR], 1.14; 95% CI [confidence interval], 0.61–2.14; I2 = 35%), ATE (RR, 0.97; 95% CI, 0.46–2.06; I2 = 21%), VTE (RR, 1.47; 95% CI, 0.72–2.99; I2 = 0%), hemorrhage (RR, 0.97; 95% CI, 0.35–2.68; I2 = 0), and thromboembolism/hemorrhage-related death (RR, 0.53; 95% CI, 0.16–1.79; I2 = 0). Compared to the baseline estimated risk of these outcomes in participants administered placebos, the risk differences with vaccines were very small and not statistically significant. These findings were consistent in the subgroup analysis across 4 vaccine platforms. Conclusion Vaccines against SARS-CoV-2 are not associated with an increased risk of thromboembolism, hemorrhage, and thromboembolism/hemorrhage-related death.

Due to rebalanced haemostasis in cirrhosis, viscoelastometric testing (VET) is more accurate than standard coagulation tests (SCTs) in preprocedural haemostatic evaluation, resulting in decreased unnecessary transfusion. We aimed to determine the impact of VET-guided strategy on postprocedural bleeding, periprocedural transfusion rates and quantities, transfusion-related adverse events (TRAEs), lengths of stay (LOS) and mortality from randomized controlled trials (RCTs) of cirrhotic patients.PubMed and EMBASE were searched for RCTs comparing VET-guided with SCT-guided transfusion in cirrhotic adults undergoing esophagogastroduodenoscopy, liver transplantation or other invasive interventions. Using random-effects models, the pooled risk ratios (RRs) and/or mean differences (MDs) of postprocedural bleeding-free events and the other outcomes were estimated alongside 95% confidence intervals (CIs).Of seven included RCTs (n = 421; 72.2% men; mean age 49.1 years), VET-guided transfusion did not change postprocedural bleeding-free statuses (RR 1.05; 95% CI 0.94-1.17). However, VET-based algorithms decreased the rates of fresh frozen plasma (FFP; RR 0.52; 95% CI 0.35-0.77) and platelet transfusions (RR 0.34; 95% CI 0.16-0.73), the quantities of transfused FFP (MD -1.39 units; 95% CI -2.18 to -0.60), platelets (MD -1.06 units; 95% CI -2.01 to -0.12) and cryoprecipitate (MD -7.13 units; 95% CI -14.20 to -0.07) and the risk of TRAEs (RR 0.42; 95% CI 0.27-0.65). The overall mortality rates and LOS were not significantly different between two groups.Compared with conventional SCT-guided, VET-guided strategy decreases periprocedural plasma and platelet transfusions and TRAEs, without increasing haemorrhagic complications, LOS or mortality in cirrhosis.

We reported three cases of immune thrombocytopenia (ITP) that developed within 6 weeks after ChAdOx1 nCoV-19 vaccination. Antiplatelet factor 4 antibodies were undetectable in all three cases. Therefore, vaccine-induced immune thrombotic thrombocytopenia was very unlikely. Other potential causes of thrombocytopenia were excluded. Their clinical presentations, severity of thrombocytopenia and outcomes were varied. Only one ITP case, an 80-year-old man, received ITP treatments and achieved complete response after 2 weeks of eltrombopag. An 84-year-old man had spontaneous complete remission, and a 55-year-old woman had partial platelet recovery without ITP treatments. Among 107 720 Thais administered the ChAdOx1 vaccine between 16 March and 10 May 2021, these three ITP cases resulted in an estimated risk of ITP of at least one per 36 000 doses, which was approximately similar to the risk of ITP after measles-mumps-rubella immunization. This raises the concern of an increased risk of ITP after ChAdOx1 vaccination.

Pulmonary hypertension (PH) is the commonest cardiac complication in β-thalassemia intermedia, including β-thalassemia/hemoglobin E (β-thal/HbE), and is strongly associated with splenectomy. We aimed to define the prevalence and comprehensively explore mechanisms of PH in β-thal/HbE patients receiving regular transfusion and iron chelation, which were reported to alleviate PH.β-Thal/HbE patients receiving regular transfusion and iron chelation over one year were enrolled. Patients at risk for PH were defined by tricuspid-regurgitant-jet-velocity (TRV) ≥ 2.5 m/s. Laboratory and echocardiographic variables were compared with healthy controls.There were 68 β-thal/HbE, including 31 (45.6%) splenectomized patients, and 38 controls included for analysis. PH was detected in 29 β-thal/HbE (42.6%). β-Thal/HbE with PH had a significant reduction in nitric oxide metabolites (NOx) but elevations in thrombin-antithrombin (TAT) complex, soluble thrombomodulin (sTM), endothelin-1 (ET-1) and flow-mediated dilation (FMD) values compared to those without PH (all, p 0.05). TRV was significantly correlated with NOx, TAT, sTM, ET-1 and FMD values (r = -0.514, r = 0.281, r = 0.313, r = 0.245 and r = -0.474; all p 0.05). Erythropoietic activity, serum ferritin, circulating total tissue factor (TF) antigen, microparticle-associated TF activity, microparticle's procoagulant activity and soluble p-selectin levels were not different between PH and non-PH subgroups. Notably, there were no significant associations between splenectomy and PH.PH remains prevalent in β-thal/HbE patients receiving long-term transfusion and iron chelation. PH is not associated with splenectomy status but correlated with NO depletion, TF-independent hypercoagulability and endothelial perturbation.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed. ispartof: EUROPEAN CARDIOLOGY REVIEW vol:16 ispartof: location:England status: published

Heparin thromboprophylaxis is routinely administered during hospitalization for COVID-19. Because of the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane, and medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in patients with COVID-19. The primary aim was to systematically review the clinical features and outcomes of patients with COVID-19 with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized patients with COVID-19. A meta-analysis of 7 studies including 5849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2%-3.2%; I2 = 89%). The estimated incidences were 1.2% (95% CI, 0.3%-3.9%; I2 = 65%) vs 0.1% (95% CI, 0.0%-0.4%; I2 = 0%) in therapeutic vs prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill patients with COVID-19 (2.2%; 95% CI, 0.6%-8.3%; I2 = 72.5%) compared with noncritically ill patients (0.1%; 95% CI, 0.0%-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and 1 with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 days (interquartile range, 10.75-16.25 days). Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in patients with COVID-19 was comparable to patients without COVID-19, with higher incidences with therapeutic anticoagulation and in critically ill patients.

Hypercoagulability in coronavirus disease 2019 (COVID-19) may aggravate disease severity during hospitalization but the reported survival benefits from anticoagulation (AC) vary among studies. We performed a literature research to estimate pooled odds ratios (ORs) of in-hospital mortality and major bleeding comparing among intermediate-to-therapeutic dose AC, prophylactic dose AC, and no AC. Until October 22, 2020, PubMed, EMBASE, and Cochrane Library Database were searched for studies reporting AC utilization and mortality in COVID-19. Studies with suspected risk of bias were excluded before the synthesis of pooled ORs with 95% confidence intervals (CIs) using random-effects models. Of 37 identified studies (N = 19,510), 17 (N = 17,833) were aggregated in the meta-analysis. The overall mortality rate was 23.1% (95% CI 18.7-28.2). The pooled odds of mortality comparing anticoagulated to non-anticoagulated patients were similar, but lower in prophylactic dose AC group (OR 0.83; 95% CI 0.73-0.95). Notably, intermediate-to-therapeutic dose AC increased mortality (OR 1.60; 95% CI 1.11-2.31) and major bleeding compared to prophylactic dose AC (OR 3.33; 95% CI 2.34-4.72). Our findings support the optimal efficacy and safety profiles of prophylactic dose AC in hospitalized COVID-19 patients.

Coagulation activation has been reported in several cohorts of patients Coronavirus Disease 2019 (COVID-19). However, the true burden of systemic coagulopathy in COVID-19 remains unknown. In this systematic review and meta-analysis, we performed a literature search using PubMed, EMBASE, and Cochrane Database to identify studies that reported the prevalence of systemic coagulopathy using established criteria in patients with COVID-19. The primary outcome was the prevalence of systemic coagulopathy (disseminated intravascular coagulation [DIC] and/or sepsis-induced coagulopathy [SIC]). Pooled prevalences and 95% confidence intervals [CIs] were calculated using random-effects model. A total of 5 studies including 1210 patients with confirmed COVID-19 were included. The pooled prevalence of systemic coagulopathy was 7.1% (95%CI: 3.2%,15.3%, I2 = 93%). The pooled prevalence of DIC (N = 721) and SIC (N = 639) were 4.3% (95%CI 1.7%, 10.4%, I2 = 84%) and 16.2% (95%CI: 9.3%, 26.8%, I2 = 74%), respectively. Only 2 studies reported the prevalence of elevated D-dimer levels with the pooled prevalence of 84.6% (95%CI: 52.0%,96.5%, I2 = 94%). Average D-dimer and fibrinogen levels were remarkably increased, while platelet counts, PT, and aPTT ratios were minimally affected in COVID-19. The estimated prevalence of systemic coagulopathy in patients with COVID-19 was low despite D-dimer elevation in most patients. Relatively low systemic coagulopathy in COVID-19 may contribute to the high incidence of thrombosis rather than bleeding in patients with COVID-19.

Supplemental Material, sj-doc-1-cat-10.1177_10760296211008999 for Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis by Chatphatai Moonla, Darintr Sosothikul, Thita Chiasakul, Ponlapat Rojnuckarin and Noppacharn Uaprasert in Clinical and Applied Thrombosis/Hemostasis

Supplemental Material, sj-pdf-1-cat-10.1177_1076029620987629 for Systemic Coagulopathy in Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis by Noppacharn Uaprasert, Chatphatai Moonla, Darintr Sosothikul, Ponlapat Rojnuckarin and Thita Chiasakul in Clinical and Applied Thrombosis/Hemostasis

Supplemental Material, sj-pdf-1-cat-10.1177_10760296211008999 for Anticoagulation and In-Hospital Mortality From Coronavirus Disease 2019: A Systematic Review and Meta-Analysis by Chatphatai Moonla, Darintr Sosothikul, Thita Chiasakul, Ponlapat Rojnuckarin and Noppacharn Uaprasert in Clinical and Applied Thrombosis/Hemostasis

Background Hypereosinophilia (HE), defined by blood eosinophils > 1.5 ? 109/L persisting over one month, is commonly found in clinical practice. Objective This study aimed to explore etiologies, clinical characteristics, and outcome of HE. Methods The HE patients from a single center in Thailand during 2014-2019 were retrospectively reviewed. Results Among 166 HE patients, 102 (61.5%) cases had reactive HE (HER) of which 52% was due to parasitic infestations. Two-thirds of these patients were diagnosed based on the patients' response to empirical anti-parasite therapy. Without secondary causes, eosinophil-related symptoms were found in 20 (12.0%) patients (Hypereosinophilic syndrome: HES) of which three of them had myeloid neoplasms (HESN) and one case had lymphocytic variant HES (L-HES). Among 11 of 16 idiopathic HES (HESI) patients who were treated with systemic steroid, nine (81.8%) patients responded well, and two cases obtained symptom improvement with stable eosinophilia. There was 44 (26.5%) asymptomatic HE of undetermined significance (HEUS) and 37 (84.1%) of them had HE for more than 6 months before diagnosis. Marked eosinophilia (> 10 ? 109/L) was more common in HES (37.5%), but it was also found in HER (16.7%) and HEUS (11.4%). During the median follow-up period of 16 months, 82.9% (34/41) of HEUS cases remained asymptomatic while seven (17.1%) patients spontaneously recovered. Conclusions A therapeutic trial of anti-parasite is reasonable for asymptomatic HE in tropical countries. Most HESI responded to systemic corticosteroids and HEUS showed benign courses without therapy.

G-protein coupled receptors (GPCRs) are the most abundant superfamily of cell surface receptors. Approximately 35% of approved drugs target GPCRs and class A GPCRs account for ~85% of this superfamily. Class A GPCRs are characterized in part by two highly conserved disulfides in their extracellular domains that are thought to stabilize protein structure. Whether these disulfides can be enzymatically modified to influence G-protein signaling is not known. We and others have previously shown that disulfide bond modification by thiol isomerases such as protein disulfide isomerase (PDI) represent a previously unrecognized level of control of thrombus formation. We therefore evaluated the ability of recombinant PDI (rPDI) to modulate signaling through modification of the canonical disulfides within platelet GPCRs. Exposure of platelets to rPDI had no effect on stimulation through PAR1, PAR4, or the α 2A-adrenergic receptor. In contrast, rPDI exposure dramatically decreased platelet activation induced by the TP receptor agonists U46619 or arachidonic acid, implicating rPDI-mediated modulation of TP receptor signaling. Consistent with this finding, rPDI blocked U46619-mediated activation of α IIbβ 3, α-granule release, and dense granule release. Conversely, inhibition of endogenous PDI using either inhibitory antibodies or PDI-targeted small molecules enhanced TP receptor-mediated platelet aggregation and granule release, indicating that endogenous platelet PDI influences TP receptor signaling. Inhibition of TP receptor-mediated signaling required PDI active site cysteines since rPDI mutants lacking these cysteines lost inhibitory activity. Evaluation of the inhibitory activity of different PDI fragments showed that the PDI substrate binding domain is also critical for inhibitory activity. The ability to inhibit signaling through the TP receptor was specific for rPDI since incubation with other recombinant thiol isomerases including ERp57, ERp5, and ERp72 had no effect. To determine the specific modifications to TP receptor canonical disulfides induced by PDI, HEK cells were transfected with TP receptor and exposed to rPDI. TP receptor was subsequently immunopreciptated and disulfide-linked peptide analysis was performed using mass spectrometry. Compared to untreated controls, TP receptor exposed to rPDI demonstrated cleavage of Cys11-Cys102 and Cys105-Cys183 bonds and the generation of a new Cys102-Cys183 bond. To determine how modification of the disulfide bonding pattern affected signaling through the TP receptor, we evaluated signaling through specific Gα subunits in platelets. The platelet TP receptor signals through Gα q (which couples to phospholipase and increases calcium flux) and Gα 13 (which couples to RhoA and myosin light chain kinase). PDI-mediated cleavage of the platelet TP receptor resulted in biased signaling, with substantial inhibition of G α13-mediated RhoA-GTP activation and myosin light chain phosphorylation and little effect on Gα q-mediated calcium flux. These results show how PDI can modify platelet signaling and represent the first demonstration that a thiol isomerase can modulate the function of a GPCR via rearrangement of canonical disulfide bonds. Disclosures No relevant conflicts of interest to declare.

Background Vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare distinctive syndrome characterized by unusual site thrombosis accompanied by thrombocytopenia after ChAdOx1 nCoV‐19 vaccination. Platelet‐activating anti–platelet factor 4–dependent antibodies (anti‐PF4 Abs) were detected in most cases of VITT. To date, data from Asian countries are lacking. Objectives To determine the prevalence of thrombocytopenia, anti‐PF4 Abs, and D‐dimer elevation in Thai people administered the ChAdOx1 vaccine. Patients/Methods A total of 521 vaccinated and 146 nonvaccinated subjects were enrolled. Blood samples were collected to determine platelet counts, anti‐PF4 Abs using ELISA and D‐dimer levels 5 to 30 days after the first vaccination. Results None of the participants developed thrombocytopenia or had significantly decreased platelet counts from baseline after ChAdOx1 vaccination. The frequencies of anti‐PF4 Abs between vaccinated (16/521; 3.1%; 95% confidence interval [CI], 1.8‐4.9) and nonvaccinated Thai people (6/146; 4.1%; 95% CI, 1.5‐8.7) were similar. None of the detectable anti‐PF4 Abs activated platelets in vitro. The average D‐dimer levels between vaccinated and control groups were similar (282.2 ± 286.3 vs 267.8 ± 219.3 ng/mL; P = 0.58). Four vaccinated and one nonvaccinated participants had markedly elevated D‐dimer levels >2000 ng/mL without detectable anti‐PF4 Abs. Imaging studies of these asymptomatic subjects revealed incidental pulmonary embolism in a vaccinated elderly woman. Conclusions This study demonstrated a low prevalence of thrombocytopenia and pathogenic anti‐PF4 Abs after ChAdOx1 vaccination. D‐dimer testing revealed no significant coagulation activation. Routine tests for platelet counts, anti‐PF4 Abs, and D‐dimer levels are not recommended for VITT screening without clinical suspicion.

Purpose To report a case of daratumumab-induced bilateral angle closure glaucoma and myopia that showed no recurrence after repeated drug administration with prophylactic cycloplegia. Observations A 63-year-old man with relapsing multiple myeloma presented with acute bilateral eye pain and blurred vision 14 hours after first daratumumab infusion. Eye examination revealed raised intraocular pressure and shallow anterior chamber. Anterior segment ocular coherence tomography and ultrasound biomicroscopy showed ciliochoroidal effusions in both eyes. The diagnosis of bilateral acute angle closure glaucoma and induced myopia was made. Cycloplegia- and intraocular-pressure-lowering medications were given, which gradually deepened the anterior chambers and normalized intraocular pressure and refraction. The ciliochoroidal effusions completely resolved on day 14. The cycloplegic was given as a premedication for subsequent infusions. There was no recurrence of effusion throughout his 6-month daratumumab treatment course. Conclusions and importance Daratumumab can induce ciliochoroidal effusion, which results in acute secondary angle closure and myopia. The potential prophylactic effect of the cycloplegic drug may enable continuation of daratumumab infusion under close monitoring.

Mechanisms of vascular disorders in β-thalassemia/HbE patients remain poorly understood. In the present study, we aimed to determine the presence of endothelial dysfunction and its association with altered vascular mediators in this population. Forty-three β-thalassemia/HbE patients without clinically documented vascular symptoms and 43 age–sex-matched healthy controls were enrolled. Endothelial function was assessed using flow-mediated dilatation (FMD) before and after administration of nitroglycerine (NTG). β-Thalassemia/HbE patients showed a significant endothelial dysfunction using FMD. The percentage change in the brachial artery diameter before NTG was significantly lower in the thalassemia group compared to the control (5.0 ± 5.9 vs. 9.0 ± 4.0%, p

Correlations between bleeding symptoms and von Willebrand factor (VWF) levels may help to predict hemorrhagic severity in the Westerners with von Willebrand disease (VWD), but data in Asians are lacking. In this study, Thai patients with VWF levels

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger patients and associated with hemophagocytic lymphohistiocytosis. To clarify the molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole-exome sequencing. All cases were Asians and were phenotypically sporadic with no family history of SPTCL. Consistent with a recent report, germline mutations in HAVCR2, encoding T-cell immunoglobulin mucin 3 (TIM3), were identified in 11 of 13 (85%) cases. All mutated cases were primary SPTCL, whereas the 2 cases without mutation were secondary SPTCL associated with underlying diseases, including viral infection and autoimmune disease. Ten patients harbored homozygous p.Y82C mutations, and 1 showed compound heterozygous mutations (p.Y82C and p.T101I). Both missense mutations altered highly conserved residues located in the extracellular immunoglobulin variable–like domain. According to the Genome Aggregation Database of >138 500 general individuals, both mutations were documented with minor allele frequencies < 0.007, indicating remarkable enrichment of these HAVCR2 alleles in SPTCL. SPTCL cells also harbored somatic mutations (6.2 per patient) that are frequently identified in genes associated with epigenetic regulation and signal transduction. In conclusion, individuals harboring biallelic HAVCR2 (TIM3) germline mutations were highly susceptible to sporadic SPTCL, which was also associated with clonal somatic mutations.

Objectives: The outcomes of primary central nervous system lymphoma (PCNSL) are much improved with multi-modality regimens. Unfortunately, in limited-resource countries, chemo-radiotherapy is the only option of curative-intent treatment. This study aimed to evaluate the effects of low-dose whole brain radiotherapy (WBRT) as a consolidation on disease control and long-term neurocognitive functions. Methods: We conducted a retrospective single-center study enrolling PCNSL patients from 2011 to May 2016 to evaluate the real-life treatment outcome and neurotoxicity from treatment especially radiotherapy. Results: Thirty-seven newly diagnosed immunocompetent PCNSL patients were treated with a high-dose methotrexate-based regimen with or without WBRT. The median age was 56 (range 16–78) years old. After chemotherapy, the overall response and complete response (CR) rates were 59.5% and 43.2%, respectively. All 6 partial response (PR) patients and 6 of 16 CR patients underwent radiotherapy. In 22 patients who achieved CR, the progression-free survival (PFS) of patients without WBRT was significantly inferior to the WBRT group with the hazard ratio of 4.7 (95% confidence interval 1.14–19.82, p = 0.03). The 3-year PFS were 35% and 78.75%, respectively, but there was no difference in overall survival. The serial Montreal Cognitive Assessment evaluations (20–72 months post chemotherapy) of 10 long-term CR patients revealed one dementia among three patients without WBRT and five mild cognitive impairments in seven patients with WBRT. Except for the dementia case, all the other patients can perform daily activities without assistance. Conclusion: The low-dose WBRT consolidation is associated with lower PCNSL relapses with only mild neurocognitive toxicity.

Thalassemia is the most common monogenetic disorder worldwide, with 60 000 infants with thalassemia major born annually.1 Survival often depends on regular blood transfusions to correct anemia and to reduce ineffective erythropoiesis, but these transfusions can result in iron overload and organ failure unless chelation therapy is undertaken. Serum ferritin levels continue to be used as a guide to chelation but are unreliable, and the availability of cardiovascular magnetic resonance (CMR) T2* imaging has transformed patient management by allowing organ-specific quantification of iron content. Countries with a high prevalence of thalassemia major have CMR, but magnet time is expensive and analytic expertise lacking. The aim of TIC-TOC (Thailand and UK International Collaboration in Thalassaemia Optimising Ultrafast CMR) was to investigate whether ultrafast CMR mapping could provide reliable immediate diagnoses of heart and liver iron content, eliminating the need for complex analysis, thus reducing costs to a level within local resources. The research received approval by the Institutional Review Board of the Faculty of Medicine at Chulalongkorn University. All participants provided written informed consent.

Mechanisms of vascular disorders in β-thalassemia/HbE patients remain poorly understood. In the present study, we aimed to determine the presence of endothelial dysfunction and its association with altered vascular mediators in this population. Forty-three β-thalassemia/HbE patients without clinically documented vascular symptoms and 43 age-sex-matched healthy controls were enrolled. Endothelial function was assessed using flow-mediated dilatation (FMD) before and after administration of nitroglycerine (NTG). β-Thalassemia/HbE patients showed a significant endothelial dysfunction using FMD. The percentage change in the brachial artery diameter before NTG was significantly lower in the thalassemia group compared to the control (5.0 ± 5.9 vs. 9.0 ± 4.0%, p 0.01) while no significant differences after NTG (18.4 ± 8.3 vs. 17.8 ± 6.3%, p = 0.71). Plasma nitric oxide metabolites (NO

Case 1-2013: a 30-year-old man with chronic rhino-sino-orbital infiltration and nephritic/nephrotic syndrome

No well-defined phenotypes that distinguish between unknown α- and β-globin mutations have been reported to date. Direct DNA sequencing of α-globin genes can be technically challenging, as α1- and α2-globin genes are nearly indistinguishable. To detect hemoglobin variants (HbXs) on Hb analysis, the entire β- and α-globin genes were directly sequenced using a newly developed sequencing protocol for α-globin genes. An algorithm to distinguish between α- and β-HbXs was constructed and subsequently validated in the independent validation group. Distinctive characteristics that can distinguish 39 α-HbXs from 24 β-HbXs were the presence of unidentifiable variants of HbA2 and/or HbX of

Although natural anticoagulant deficiencies are the established causes of thrombosis, their roles in bleeding are not fully studied. The objective is to correlate haemostatic factors with haemorrhagic symptoms quantified by a standardized questionnaire. Adult subjects were recruited from Bangkok and nearby provinces as part of routine health surveys/checkups. The validated MCMDM-1VWD form was used to assess their bleeding symptoms. At the same time, von Willebrand factor (VWF) activity, free protein S levels and protein C activity were measured. There were 5196 individuals. The mean age was 44.3 years (range 15-99) and 41% were male subjects. The mean bleeding score was -0.28 and 95% of subjects had scores between -2 and +2. The scores were lower in female subjects than in male subjects (-0.35 vs. -0.16, P < 0.001). Bleeding scores correlated negatively with age, VWF and protein C activities (Spearman's ρ-0.258, -0.091 and -0.098, respectively, all P < 0.001), but did not significantly correlate with protein S levels. Using multivariate analysis, female gender, VWF below 100 IU dL(-1), protein C below 100 IU dL(-1) and protein S over 150 IU dL(-1) significantly related to high (≥3) bleeding scores (adjusted odds ratio 1.95, 1.83, 1.56 and 2.84, P = 0.001, 0.001, 0.039 and 0.017, respectively). These findings may suggest interacting roles of VWF and natural anticoagulants in modifying bleeding symptoms.

SummaryThromboprophylaxis for venous thromboembolism (VTE) failed to reduce overall mortality in hospitalised medical patients. As a VTE prediction model for Asians is still lacking, this study aimed to identify very high risk patients who would be the main target for prevention. In 2009, medical patients admitted to King Chulalongkorn Memorial hospital, a tertiary care centre, were prospectively evaluated for risk factors. The high-risk cohort was monitored for symptomatic VTE until six weeks after discharge. No heparin prophylaxis was given. Of 1,290 high-risk patients, 27 (2.1%, 95% confidence interval [CI] 1.3–2.9) developed proven VTE, 25.9% of which were diagnosed after discharge. Cases with VTE stayed longer in the hospital (median 18 vs. 11 days, p < 0.001). The significant risk factors in a multivariate analysis were autoimmune disease, solid tumours, family history of VTE, varicose vein and oestrogen with the relative risks of 11.8, 4.7, 120.3, 40.1 and 17.1 (p < 0.001, 0.001, 0.001, 0.002 and 0.038), respectively. Either autoimmune disease or solid tumours were found in 63% of VTE with the relative risk of 4.5 (95% CI 2.1–9.7, p < 0.001). In contrast, previously reported VTE scores in western patients could not stratify the VTE risks, but all the scores predicted higher mortality. In conclusion, VTE is common in Asian hospitalised medical patients. Patients with autoimmune disease and those with solid tumours are highly susceptible to VTE. A prophylactic strategy in these groups is required.

Summary Chrysosporium species, saprobic soil fungi, comprise more than 60 species. There is some confusion regarding the taxonomy and nomenclature between Chrysosporium and Emmonsia since the causative agents of adiaspiromycosis, the development of big thick-walled spores (adiaspores) in humans or animals, were previously thought to be Chrysosporium. Chrysosporium articulatum has never been reported to cause invasive infection in humans. We report herein the first case of invasive pulmonary infection caused by Chrysosporium articulatum in a 16-year-old man with acute T-cell lymphoblastic leukaemia. He was successfully treated with voriconazole.

Hemoglobin (Hb) E is the commonest beta-globin variant in Thailand. Other uncommon variants have been rarely reported. We performed direct DNA sequencing of the entire beta-globin gene in cases showing unidentified bands by isolectric focusing electrophoresis or high-performance liquid chromatography. Six different beta-globin mutations were found in 24: 9 Hb Hope, 6 Hb New York, 4 Hb Tak, 3 Hb D Punjab, 1 Hb Pyrgos, and 1 Hb Rambam. Hb New York was misidentified as HbA on HPLC. All Hb Tak carriers had hemoglobin over 15.0 g/dL and a Hb Tak/beta(0)-thalassemia compound heterozygote presented with symptomatic polycythemia.