Serial rotational thromboelastometry measurements show worsening hypocoagulability in acute-on-chronic liver failure and are associated with the severity of liver disease.

Background: Viscoelastic tests are used to better understand the complex picture of hemostasis in cirrhosis. Limited data exist regarding the clinical relevance of rotational thromboelastometry (ROTEM) in acute-on-chronic liver failure (ACLF) or acute decompensation (AD). We examined the pattern and role of sequential observations of 9 ROTEM components in both ACLF and AD groups. Method: ROTEM measurements were compared within and between groups at 3 time points: on admission (T1), at 24 h (T2) and 48 h post-admission (T3). Results: Forty-two consecutive patients (22 ACLF, 20 AD) were included. ROTEM determinants exhibited significant hypocoagulable deterioration in ACLF but not in AD over the 3 time points in clot formation time (CFT)EXTEM (P=0.01), maximum clot firmnessEXTEM (P=0.014), CFTINTEM (P<0.001), and alphaINTEM (P=0.028). The sum of hypocoagulable determinants increased from T1 to T3 in ACLF (P=0.029), but remained stable in AD. Five ROTEM variables showed significant differences towards hypocoagulability in ACLF compared to AD at T3. A "hypocoagulable" profile was associated with more severe liver disease (P<0.001 for model for end-stage liver disease [MELD] or Child-Pugh scores) and higher 30- and 90-day mortality (log-rank P=0.001 and P=0.013, respectively) but no more bleeding episodes or transfusions. Two ROTEM variables displayed strong correlations with MELD at T1 and 7 at T3 (|r coefficient|>0.5). Conclusions: ROTEM measurements indicated worsening hypocoagulability shortly post-admission compared to baseline in ACLF, but remained stable in AD. The hypocoagulable derangement was mostly correlated with the severity of liver disease and higher short-term mortality, but not more bleeding episodes.

A combination of clot formation abnormalities in thromboelastometry has a high prognostic value in patients with acute-on-chronic liver failure.

BACKGROUND: Global coagulation tests offer a better tool to assess procoagulant and anticoagulant pathways, fibrinolysis and clot firmness and evaluate more accurately coagulation defects compared to conventional coagulation tests. Their prognostic role in acute-on-chronic liver disease (ACLF) or acute decompensation (AD) has not been well established. AIMS: To assess the properties and prognostic value of the coagulation profile measured by rotational thromboelastometry (ROTEM) in ACLF and AD. METHODS: 84 consecutive patients (35 ACLF and 49 AD) were prospectively studied. Twenty healthy persons matched for age and gender were used as controls. 'Hypocoagulable' or 'hypercoagulable' profiles on admission were assessed based on nine ROTEM parameters and mortality was recorded at 30 and 90 days. RESULTS: Individual ROTEM parameters denoted significantly more hypocoagulability in patients compared to controls. 'Hypocoagulable' profile (defined as a composite of 4 or more ROTEM parameters outside the range) was associated with more severe liver disease assessed either as MELD or Child-Pugh scores ( P  < 0.001 for both) and higher 30-day mortality (Log-rank P  = 0.012). 'Hypocoagulable' profile (HR 3.160, 95% CI 1.003-9.957, P  = 0.049) and ACLF status (HR 23.786, 95% CI 3.115-181.614, P  = 0.002) were independent predictors of 30-day mortality, in multivariate model. A higher early mortality rate was shown in ACLF patients with 'hypocoagulable' phenotype compared to those without (Log-rank P  = 0.017). 'Hypocoagulable' profile was not associated with mortality in AD. CONCLUSION: 'Hypocoagulable' profile was associated with more advanced liver disease and higher short-term mortality in patients with ACLF.

Real-World Data on Health-Related Quality of Life Assessment in Patients With Breast Cancer Receiving Subcutaneous Trastuzumab.

PURPOSE: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (anti-HER2) antibody delivered intravenously, has revolutionized the treatment of patients with breast cancer overexpressing HER2 protein. Recently, a newer subcutaneous formulation was shown to have comparable efficacy to the initial intravenous trastuzumab. In this study, we aimed to evaluate the impact of subcutaneous trastuzumab on the health-related quality of life (HRQoL) of patients diagnosed with early or metastatic HER2-overexpressing breast cancer. METHODS: Patients were provided with the EORTC QLQ-C30 (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and the BR-23 questionnaires. The scoring of questionnaires and patient's sociodemographic and clinicopathologic characteristics were recorded and analyzed by descriptive and correlation statistics employing t test and 2-way analysis of variance. RESULTS: A total of 163 patients agreed to participate in the study. About 90 of 163 patients (55.21%) received subcutaneous trastuzumab and 21 patients intravenous trastuzumab (12.88%). A control group of 52 HER2+ patients received chemotherapy without trastuzumab (31.90%). Patients receiving subcutaneous trastuzumab were older and of more advanced disease stage compared with those receiving chemotherapy (58.5 vs 51 years, 39.8% vs 28.8% advanced disease). In univariate analysis, subcutaneous trastuzumab was associated with less nausea and vomiting (P = .002) but worse cognitive function (P = .013) and dyspnea (P = .042). Patients who have received >8 cycles of subcutaneous trastuzumab reported less diarrhea (P = .049) and systemic therapy side effects (P = .015). Multivariate analysis showed that patients without comorbidity receiving subcutaneous trastuzumab had less treatment side effects, less upset by hair loss, and higher emotional functioning. Of note, mastectomy and subcutaneous trastuzumab were associated with improved role functioning (P = .021). In metastatic disease, no negative impact of subcutaneous trastuzumab on HRQoL was found. CONCLUSIONS: The administration of subcutaneous trastuzumab improved certain symptoms and did not adversely affect most of the assessed functional scales. Particularly, in the metastatic setting, subcutaneous trastuzumab had no negative impact on HRQoL.