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ABSTRACTObjectives 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 (δβ)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

Abstract 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 .

Abstract 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.

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; I 2 90.5), with a pooled incidence of venous thrombosis of 0.7% (95 CI, 0. 4-1; I 2 73.9) and a pooled incidence of arterial thrombosis of 0.6% (95 CI, 0. 2-1; I 2 88.1). The weighted pooled incidences of bleeding and mortality were 0.9% (95 CI, 0. 1-1.9; I 2 95.1) and 2.8% (95 CI, 0. 6-5; I 2 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.

Rectus sheath hematoma is a rare complication of anticoagulant therapy. We have described the case of a 78-yearold woman with unstable angina who developed a life-threatening rectus sheath hematoma during treatment with antiplatelet drugs and enoxaparin. The patient had underlying diseases of hypertension and triple vessels disease status post coronary artery bypass graft. She was admitted initially with an asthmatic attack. Three days later, she developed unstable angina and thus received aspirin, clopidogrel, and enoxaparin. After the fifth dose of enoxaparin, she developed progressive suprapubic pain with a newly palpable mass, anemia, hypotension, and oliguria. Abdominal computed tomography revealed a rectus sheath hematoma sized 15 cm., (about 2,000 mL by volume). Her coagulogram was normal. Despite rapid fluid resuscitation, packed red cell transfusion (1,300 mL), platelet transfusion, and protamine sulfate injection, the patient’s hemodynamic status remained unstable. Finally recombinant activated factor VII (rFVIIa) injection improved her hemodynamic status and stabilized her hemoglobin level without a thrombotic complication. This case report provides evidence of the benefit of rFVIIa use as a part of the treatment of refractory bleeding from enoxaparin.

Abstract 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.