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Introduction: Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting., Method: This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited., Results: A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications., Conclusion: Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.

Management of adult patients with immune thrombocytopenia (ITP) is often unsatisfactory, due to variable efficacy of treatment, risk of life-threatening bleeding if disease control is poor, and side effects associated with treatment. Lack of data on the platelet count threshold associated with bleeding and infection risk associated with ITP treatment limits risk/benefit clinical decision making. We reviewed medical records of all ITP patients who were admitted to our hospital between 2012 and 2017 to evaluate the platelet count threshold for bleeding, infection burden associated with treatment, and real-world efficacy of second-line treatment. We demonstrated fair discrimination between platelet count and occurrence of bleeding, with 15 × 10 9 /L being the optimal cut-off for predicting any bleeding while 20 × 10 9 /L had the highest negative predictive value for severe bleeding. In multivariable analyses, patients who were treated with corticosteroids for at least 2 months were 5.3 times as likely to have an infection. In addition, rituximab response was strongly associated with response to frontline corticosteroids and infection was associated with older age ≥ 65 years and corticosteroid dependence. If corticosteroids are initiated, physicians should aim for the shortest duration of treatment before switching to effective second-line agents for hemostatic platelet counts.

Although the estimated incidence of acquired haemophilia A (AHA) in Singapore is similar to those reported in the literature, we have observed differences in the frequency of their associated diseases, particularly bullous pemphigoid (BP). We investigated the actual incidence of BP among our AHA cohort, their clinical characteristics and treatment outcomes. 6 out of 37 (16%) patients with AHA had BP, making it the most common underlying disorder in our cohort. The median age at diagnosis of AHA was 76 years old with a female preponderance. Most patients had their AHA diagnosed after BP with the median time between BP to AHA diagnosis being 107.5 days. Initial haemostasis was achieved, and factor VIII inhibitor was eliminated in all patients with a median time of disappearance being 52 days. Two patients had recurrence of their factor VIII inhibitor during the tapering of their immunosuppression. There was no relationship between the relapse of BP and AHA. This study suggests that BP is a common association with AHA. These patients respond well to bypassing agent and immunosuppression. However, they have a higher recurrence of factor VIII inhibitor and should be monitored closely for relapse during the tapering period of their immunosuppression.

Race is touted as an independent risk factor for venous thromboembolism (VTE), although the basis for this is varied and contentious. Comparison of plasma thrombin generation (TG) using calibrated automated thrombogram (CAT) across races offers a modality that objectively measures global hemostatic function to evaluate this influence. Direct comparative data across races are currently not available. Aim is to establish the influence of race on plasma TG. Sixty normal participants, matched for age and gender, equally representing 4 races-Caucasian, Chinese, Indian, and Malay-were recruited. Thrombin generation parameters (lag time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet-poor plasma were measured using CAT. The mean ETP (standard deviation) for the different races were Caucasians: 1338.18 (194.19) nM·min; Chinese, 1318.91 (108.90) nM·min; Indians, 1389.81 (182.61) nM·min; and Malays, 1436.21 (184.24) nM·min. Caucasians had the longest mean lag time of 2.59 ± 0.37 seconds; Indians had the highest mean peak of 284.22 ± 30.74 nM, and Malays had the longest mean time to peak of 5.47 ± 0.59 seconds. Analysis based on race did not demonstrate any significant difference for all TG parameters. The greatest mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM·min (95% confidence interval: -45.86 to 280.46 nM·min) which was within the predefined limit of equivalence. In a cohort of healthy participants, TG mediated by plasma factors is not influenced by race and does not explain the reported racial differences in VTE incidence. For the 4 racial groups studied, the use of separate normal ranges for plasma TG might not be essential.

Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires treatment. We retrospectively analyzed the impact of time from diagnosis-to-treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in 581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01) and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern Cooperative Oncology Group ≥2 (p = .02), stage 3-4 disease (p < .001), and longer TDT (HR 1.12, p = .028) predicted shorter PFS. The significant interactions between TDT with lactate dehydrogenase (LDH) and with disease stage prompted separate analyses in high versus normal LDH, and stage 3-4 versus 1-2 disease. Longer TDT was associated with shortened PFS and OS only with advanced stage, and, if high LDH was present. Treatment should be started as early as possible for high-tumor burden disease. Delaying treatment in patients with early stage or low LDH does not seem harmful.

Aim: Hereditary thrombophilic markers are commonly screened among patients diagnosed as having venous thromboembolism, but optimal patient selection and the goals of screening may differ between populations. Determining the patterns of hereditary thrombophilia may improve screening strategies., Method: An unselected cohort of venous thromboembolism patients in three tertiary institutions in Singapore was prospectively tested for the prevalence of deficiencies of protein C, protein S, antithrombin III, factor V Leiden and prothrombin 20210 gene mutations., Results: Among 384 patients screened, the prevalences of protein S, protein C and antithrombin III were 9.20%, 1.18% and 4.19% respectively. Only one patient was positive for the factor V Leiden mutation and none tested positive for the prothrombin 20210 gene mutation. At least 1 in 9 patients (11.52%, 95% CI 8.20 to 15.93) will test positive for one of the above markers in an unselected group of 269 patients who completed all tests. The exclusion of patients with clinical risk factors did not improve the detection rates, in comparison with those with obvious provoking clinical risk factors (11.72%, 95% CI 7.36 to 18.06 vs 11.29%, 95% CI 6.73 to 18.18). When upper age limits were set for thrombophilia screening by decades, a statistical difference in the likelihood of a positive thrombophilia screen between younger and older patient was seen for patients below 40 (p<0.001)., Conclusion: In Singapore and countries with similar demographics, hereditary thrombophilia screening should be confined to testing for protein C, protein S and antithrombin III.

Objectives: To compare the clinical presentation, response to therapy and outcome of thrombotic thrombocytopenic purpura (TTP) in an inception cohort of patients with and without SLE., Methods: Medical records of patients diagnosed with TTP at Singapore General Hospital between January 2003 and December 2007 were reviewed., Results: Ten idiopathic TTP (iTTP) and eight SLE-associated TTP (sTTP) patients were identified, with iTTP patients being older (mean 50.4 vs 34.5 yrs). Five iTTP patients were ANA positive but did not have any features of SLE. All sTTP patients had active SLE at TTP diagnosis and had more renal involvement than iTTP (87.5% vs 50%). The mean duration from the first symptom suggestive of TTP to diagnosis was 7.7 days and 19.5 days in iTTP and sTTP patients. All patients received high-dose corticosteroids. Cytotoxic and immunosuppressive drugs were used more commonly (87.5% vs 50%) and earlier (Day 2/3 vs after Day 7) in sTTP patients. Vincristine was the drug of choice in iTTP and cyclophosphamide in sTTP. Three SLE patients received rituximab. Mortality for iTTP and sTTP was 50% (95% CI 19%, 81%) and 62.5% (95% CI 29%, 96%), respectively. The mean (s.d.) time to complete remission was 31.3 (+/- 26.4) days in sTTP (n = 3) and 16.8 (+/- 6.1) days in iTTP (n = 5)., Conclusion: Despite early and more aggressive therapy in sTTP, mortality was higher and the time to complete remission were longer, suggesting that sTTP is more severe. The tempo of development of TTP in SLE patients was slower.