Assessment of aPTT-based clot waveform analysis for the detection of haemostatic changes in different types of infections.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.

Incidence and Management of Toxicity Associated with LAsparaginase in the Treatment of ALL and NK/TCell Lymphoma: an Observational Study.

BACKGROUND: Lasparaginase (ASNase) is commonly used in the treatment of acute lymphoblastic leukemia (ALL) and natural killer (NK)/Tcell lymphoma. This study was designed to describe the incidence of toxicity associated with ASNase in Asian adults. Secondary objectives were to investigate the management and impact of toxicity on subsequent ASNase use, and to compare the actual management against current recommendations. MATERIALS AND METHODS: In this retrospective, multicenter, observational study, Asian patients ≥ 18 years old who received ≥ 1 dose of the native E. coli ASNase from 2008 to 2013 were included. Patients were excluded if they did not receive ASNase. Endpoints of this study were development of specific toxicities, whether ASNase was discontinued or rechallenged, and developmentg of recurrent toxicity. All data analyses were performed using SPSS version 20.0. RESULTS: A total of 56 patients were analyzed. Mean (±SD) age was 36.2 (±15.2) years old, with 62.5% being males, 55.4% with ALL and 28.6% with NK/Tcell lymphoma. Hypersensitivity (12.5%) was associated with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4 toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for nonCNS thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis. Hypersensitivity recurred in the 3 patients who were rechallenged with E. coli ASNase. CONCLUSIONS: ASNase is associated with a wide range of toxicities, with hypersensitivity being the most commonly observed among Asian adult patients.

Cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for stroke prevention in patients with atrial fibrillation.

PURPOSE: This study aimed to evaluate the cost-effectiveness of dabigatran and rivaroxaban compared with warfarin for the prevention of stroke in patients with atrial fibrillation (AF) in Singapore. METHODS: A Markov model was constructed to compare the lifetime costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) of dabigatran 110 and 150 mg, rivaroxaban 20 mg and adjusted-dose warfarin from the perspective of the Singapore healthcare system, using clinical data from published studies, utilities from a patient-reported survey and costs from hospital databases. The target population was a hypothetical cohort of 65-year-old AF patients with no contraindications to anticoagulation. RESULTS: In the base-case analysis, the QALYs were 8.75 with warfarin, 8.73 with dabigatran 110 mg, 8.82 with dabigatran 150 mg, and 9.33 with rivaroxaban. The costs were Singapore dollar (SG$) 34,648 for warfarin, SG$54,919 for dabigatran 110 mg, SG$50,484 for dabigatran 150 mg and SG$51,975 for rivaroxaban. The ICER of rivaroxaban versus warfarin was SG$29,697 (US$26,727) per QALY. Rivaroxaban and warfarin had extended dominance over the high-dose dabigatran. The low-dose dabigatran was dominated by warfarin. Deterministic sensitivity analyses showed that the ICER of rivaroxaban versus warfarin was sensitive to cost of rivaroxaban and utilities for rivaroxaban and warfarin. Probability sensitivity analysis demonstrated that the probability of rivaroxaban being the optimal choice was 97.8% and 99.5% at a willingness-to-pay threshold of SG$65,000 (US$58,500) and SG$130,000 (US$117,000) per QALY, respectively. CONCLUSION: Rivaroxaban may be a cost-effective alternative to warfarin for the prevention of stroke in patients with AF in Singapore.

Feasibility, cost-effectiveness and patients' acceptance of point-of-care INR testing in a hospital-based anticoagulation clinic.

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.