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The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials. Development of specific antidotes in management of bleeding complications and development of coagulation assays for their plasma levels will further boost the confidence in the DOACs. Nonetheless, there are still limitations associated with the DOACs. Many patients in need of anticoagulant therapy for indications not studied in the clinical trials will not be eligible for treatment with a DOAC. Conditions where more data is required include DOACs use in the paediatric age group, patients with atrial fibrillation and valvular heart disease, thrombosis associated with the anti-phospholipid syndrome and cancer associated thrombosis. The affordability and access to these drugs may pose an issue for many patients under healthcare systems not providing for these medications. With four new anticoagulants coming onboard very quickly, the focus has shifted to the practical approach and management in real life as many clinicians are not yet familiar with the DOACs. Clinicians need to be educated on how to manage this new class for drugs, from choosing the appropriate drug to prevention and managing bleeding complications as a lack of knowledge and understanding in these drugs will lead to inappropriate use and compromise on patient safety. [ABSTRACT FROM AUTHOR]

With increasing usage of thrombolysis in the treatment of acute ischemic strokes within 4.5- hour window, it is becoming more important to recognize stroke mimics. Though the incidence of stroke mimics being thrombolysed is less than 3%, it is essential to diagnose them so as to avoid wrong thrombolytic treatment which carries potential complications of bleeding. We describe the case of a 17 year old girl with acute lymphoblastic leukemia, who developed stroke like episodes on two consecutive challenges with a chemotherapeutic regime which included intravenous and intrathecal methotrexate. She had MRI changes consistent with acute ischemic stroke on both occasions. Her deficits recovered completely and spontaneously, as did the MRI changes. She did not have any further episodes when methotrexate was excluded from the chemotherapeutic regime. [ABSTRACT FROM AUTHOR]

Introduction: A hypercoagulable state is a predisposition for venous thromboembolism (VTE). The activated partial thromboplastin time (aPTT)- based clot waveform analysis (CWA) is a global haemostatic measure but its role in assessment of hypercoagulability and thrombotic disorders is uncertain. We aimed to study the changes of CWA parameters in acute VTE. We hypothesized that patients with acute VTE would demonstrate higher CWA values than control patients without VTE and having elevated CWA parameters is associated with acute VTE. Materials and methods: Clot waveform analysis data from patients (N = 45) with objectively proven acute VTE who had an aPTT performed prior to initiation of anticoagulation were compared with controls (N = 111). The CWA parameters measured were min1, min2, max2 and delta change. Results: While the mean aPTT between VTE patients and controls did not differ (P = 0.830), the mean CWA parameters were significantly higher among VTE patients than controls (min1, P < 0.001; min2, P = 0.001; max2, P = 0.002; delta change, P < 0.001). There were significantly more cases within the VTE group exhibiting CWA values above their reference intervals than the control group (all P < 0.001), with the odds ratios for VTE of 8.0, 5.2, 4.8 and 18.6 for min1, min2, max2 and delta change, respectively (all P < 0.001). Conclusions: Patients with acute VTE had elevated aPTT-based CWA parameters than controls. Higher CWA parameters were significantly associated with acute VTE. [ABSTRACT FROM AUTHOR]

Background: Chronic liver disease (CLD) has been suggested to be associated with venous thromboembolism (VTE) in western populations. However, little is known about the risk effects of CLD on VTE among Asians. Objective: To compute the prevalence of VTE among hospitalised Asian patients, and to evaluate the pattern and scale of risk effects of CLD on VTE occurrence. Method: Retrospective study of hospital discharge database from 2004 to 2011 to identify patients with VTE and CLD using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. Results: Of 199904 medically managed inpatients during the 8 years, 1744 (0.9%) patients had VTE. Patients with CLD had significant higher prevalence of VTE (non-cirrhosis CLD 1.5%, cirrhosis 2.0%) than patients without CLD (0.8%, p < 0.001). In the logistic regression analyses, non-cirrhosis CLD (odds ratio, OR 1.4, 95% CI 1.2-1.7, p < 0.001) and cirrhosis (OR 1.5, 95% CI 1.2-2.0, p = 0.002) were significant predictors of VTE after adjustment for age, gender, ethnicity, hospital long stayer, cancer, infectious disease, and other comorbid conditions such as diabetic mellitus, anaemia, and cardiovascular, cerebrovascular, renal and pulmonary diseases. Conclusion: CLD, particular liver cirrhosis, increases the risks of VTE in hospitalised Asian patients. As CLD patients are perceived to be at risks of bleeding due to the prolonged clotting times and thrombocytopenia, the results of this study brings attention to opposite end of the haemostatic pendulum in patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) coagulometers are increasingly used by patients for self-monitoring of oral vitamin K antagonists therapy. We studied the feasibility of introducing POC international normalised ratio (INR) testing in place of standard laboratory assays in a hospital-based anticoagulation clinic with 250 active patients. The CoaguChek® XS system was first validated in 253 INR samples and found to have a correlation of r = 0.945 with standard assays. Variations increased with INR readings above 3.5 and this was chosen as the cutoff for acceptance of POC INR results. POC testing was done for 1,332 clinic visits during the subsequent 6-month study. Rate of rejections of INR over 3.5 was 4.3% (95% CI 3.3–5.5%). POC testing reduced clinic visit duration by 35 min ( p < 0.001, 95% CI 25–45) without cost increments to patients or the laboratory. Among 232 respondents surveyed, 87.5% (95% CI 82.5–91.5%) preferred POC INR monitoring. Rates of thrombosis and major bleeding complications were 1.2% (95% CI 0.2–3.5%) and 0.4% (95% CI 0.01–2.2%), respectively. In conclusion, provided mechanisms are in place to address increased variations of INR at higher ranges, POC testing can be successfully implemented in busy hospital-based anticoagulation clinics. [ABSTRACT FROM AUTHOR]

What is already known about this subject • Recent studies on pharmacogenetics of warfarin have implicated apolipoproteinE ( APOE) polymorphisms to influence the vitamin K dependent coagulation cascade and hence the efficacy of warfarin. • Studies among Caucasian and African Americans showed a significant but conflicting role of apolipoproteinE (APOE) isoforms in warfarin pharmacogenetics. • The contribution of APOE isoforms in influencing variations in warfarin requirements in Asian subjects remains to be investigated. What this study adds • This is the first report of a population study in Asians exploring the role of isoforms encoded by three APOE alleles ( ε2, ε3, ε4) in influencing warfarin dose requirements. • The present study showed that the APOE ε3/ ε3 isoform is the predominant genotype in the Asian population. • The study also showed that APOE isoforms may not be important in affecting warfarin pharmacodynamics in Asian patients. It also suggested that the impact of different APOE isoforms depended on the frequency of APOE genotypes in the population, in particular the ε4 allele containing genotypes. Aims To investigate the influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients. Methods A total of 174 Asian patients (Chinese, n = 96; Malays, n = 50; Indians, n = 28) who had stable daily warfarin doses for at least 1 month were recruited. Following genomic DNA extraction from venous blood, pharmacogenetic analysis of APOE and VKORC1 genes was done by DNA sequencing. Results The majority of the Asian patients (78%) harboured the APOE ε3/ε3 genotype. Different APOE genotypes were found not to have any significant influence on mean daily warfarin dose requirements. Warfarin dose requirements in the pooled Asian patients homozygous for the VKORC1 H1 haplotype were significantly lower compared with patients homozygous for the H7 haplotype (H1-H1 vs. H7-H7: 2.79 ± 1.06 mg day−1 vs. 5.45 ± 2.3 mg day−1, P < 0.001). Conclusions The present study suggests that APOE variants have minimal impact on warfarin dose requirements in Asian patients, probably due to the low frequency of ε4 allele containing genotypes. [ABSTRACT FROM AUTHOR]

Aim of the study: This study aims to evaluate the association between hepatitis B virus (HBV) and lymphoma and to characterize HBV-related lymphomas. The efficacy of prophylactic lamivudine on HBV reactivation was also evaluated. Methods: We compared the prevalence rate of HBV infection in 556 patients with lymphoma seen over a 4-yr period with that in a group of 4698 Singapore residents aged 18–69 who participated in the National Health Survey. Next, we compared the clinic-pathologic characteristics of HBV-positive and HBV-negative lymphoma cases. Results: The prevalence rate of HBV infection in our study was 10.3% (57/556), higher than the prevalence rate of 4.1% (192/4698) in the general population ( P ≤ 0.001). The higher prevalence was observed in both sexes and across different age groups. An association was observed for non-Hodgkin’s lymphoma (NHL) but not Hodgkin’s lymphoma. The characteristics of HBV-infected patients with lymphoma were similar to those who were HBV-uninfected in terms of age, ECOG, extra-nodal involvement, LDH level, stage, complete remission rate and overall survival. Use of prophylactic lamivudine significantly decreased the incidence of HBV reactivation (13% vs. 38%, P = 0.02) and disruption to chemotherapy (43% vs. 4%, P = 0.02), with a trend towards improved overall survival. Conclusions: Our findings suggest that an association exists between HBV infection and NHL. However, HBV infection does not appear to have a significant impact on the clinical characteristics and prognosis of NHL. Prophylactic lamivudine should be considered in all HBV-infected patients receiving antracycline and/or steroid containing chemotherapy. [ABSTRACT FROM AUTHOR]