A correlation of thrombin generation assay and clot waveform analysis in patients on warfarin.

OBJECTIVES: Thrombin generation assays and activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA), are some examples of global coagulation assays. Each modality evaluates different aspects of the clot forming process to globally define haemostasis with exclusive measurement parameters. Data on CWA are emerging, but its performance against other haemostatic assays is yet to be ascertained. This study evaluates the correlation between aPTT-based CWA and CAT parameters across a range of INR in warfarin-treated patients. PATIENTS/METHODS: A prospective study consisting of patients on warfarin anticoagulation with varying INR levels. CWA and CAT were performed for the study subjects. RESULTS: 54 samples were included covering an INR range from 1.33-6.89, with a mean of 4.31 +/- 1.13. For CAT parameters, endogenous thrombin potential (ETP) and peak thrombin were assessed. Both unadjusted and adjusted (adjusted for final plateau transmittance) aPTT-based CWA were evaluated for parameters min1 (maximum velocity), min2 (maximum acceleration) and max2 (maximum deceleration). Peak thrombin showed significant correlation with all CWA parameters (min1: r = 0.435, P<0.001; min2: r = 0.485, P<0.001; max2: r = 0.578, P<0.001; adjusted min1: r = 0.734, P<0.001, adjusted min2: r = 0.693, P<0.001; adjusted max2: r = 0.751, P<0.001). ETP correlated significantly with all CWA parameters except unadjusted min1 (min1: r = 0.235, P = 0.087; min2: r = 0.326, P = 0.016; max2: r = 0.437, P<0.001; adjusted min1: r = 0.610, P<0.001, adjusted min2: r = 0.563, P<0.001; adjusted max2: r = 0.642, P<0.001). CONCLUSION: We demonstrated a modest correlation between CAT and CWA parameters. Adjusted CWA improved this correlation. These findings provide additional understanding of CWA and it's role in the evaluation of global haemostatic function.

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.

Screening frequency, incidence and pattern of heparin-induced thrombocytopenia syndrome at a large tertiary institution.

Increasing awareness and availability of tests for anti-PF4/heparin complex antibodies has raised concerns about indiscriminate testing and inappropriate diagnosis of heparin-induced thrombocytopenia. A retrospective review of HITS testing at a large tertiary centre was performed to determine test patterns and incidence of HITS. Records of anti-PF4 tests over 4 years were reviewed. Positive results were matched against patient medical records and records of heparin utilisation for the diagnosis of HITS. Total of 33,308 patients (9.89 % of admissions) were exposed to at least 1 day of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Of 346 anti-PF4 antibody assays performed, 52 (15 %) were positive. Seventeen patients (4.9 % of total) were determined to have HITS. Of these, 13 cases (76 %) were patients who were initiated on haemodialysis via central venous catheters. Five patients (29 %) subsequently experienced thrombosis. The rate of HITS in patients given UFH was 0.33 %. HITS occurred in only one patient given LMWH. Of 1337 patients with chronic renal failure initiated on long term haemodialysis, the incidence of HITS was 0.97 %. Despite increased awareness of HITS, testing frequency remains conservative. An overwhelming majority of HITS cases were diagnosed among patients initiated on haemodialysis.