Phospholipid-dependent clotting time is able to identify cancer patients with high levels of circulating microparticles

Introduction: Circulating procoagulant microparticles (MP) have been associated with a prothrombotic state in many diseases, including cancer. MP can enhance thrombin formation by exposing tissue factor (TF), the initiator of coagulation in vivo. Whether procoagulant TF is really exposed on circulating MP in cancer, however, is still debated. In addition, MP can also expose procoagulant phospholipids, which are essential for propagation of coagulation. In this study, we determined the contribution of circulating MP to phospholipid (PPL)-dependent coagulation in plasma samples from a heterogeneous group of cancer patients and compared them to healthy subjects. Methods: Citrate-anticoagulated blood was collected from healthy subjects (n = 85) and cancer patients (n = 50). The procoagulant activity of circulating MP was measured in fresh plasma using the STA procoag PPL assay (Diagnostica Stago). Results: The mean age of healthy subjects was 54 ± 12 years and 62% was female. The PPL-dependent clotting time (CTPPL) was 77.8 s ± 8.7 (mean ± SD, normal distribution), gender independent (P = 0.97) and not associated with age (r = 0.24, P = 0.83). Both removal of MP by high speed centrifugation or addition of annexin V strongly prolonged the CTPPL, indicating that MP are indeed the main source of PPL under these conditions. With regard to plasma samples from cancer patients, seven patients (14%) showed a faster CTPPL than controls (below 2.5 percentile). Five of these patients had metastatic disease (four gastrointestinal, one pancreatic cancer). The other two had local disease (one breast and one gastrointestinal cancer). Conclusions: The CTPPL is useful in identifying cancer patients with high levels of circulating procoagulant MP

Measurement of procoagulant activity of microparticles by the fibrin generation test as a predictor for venous thrombosis in cancer patients

Background: Although in patients with cancer the risk of venous thromboembolism (VTE) is increased, the incidence is too low to routinely give prophylactic treatment. Procoagulant microparticles (MPs), especially tissue factor (TF)-bearing MPs, contribute to the risk of VTE in cancer patients. In the present study, we assessed the MP-associated procoagulant activity using a functional assay, the fibrin generation test (FGT), to identify cancer patients who will develop VTE. Methods: As an ongoing study, plasma was collected from cancer patients, mainly with stage III or IV pancreatic, gastro-intestinal, breast or lung cancer. The MP-associated procoagulant activity was determined via the FGT with the addition of an inhibitory antibody to factor VII. The prolongation of the clotting time in the presence of anti-factor VII is a measure for the contribution of TF-bearing MPs to the clotting time. Patients were followed up for 6 months. Preliminary results: 100 patients were included, of which 77 had complete follow-up. The first 43 patients were used to establish a cut-off value of the FGT. Receiver operating characteristics showed that a prolongation of the clotting time of 13% after addition of anti-factor VII, was the optimal cut-off value. In the entire group, 8 of 77 patients (10%) developed VTE, of which 7 could have been predicted by the FGT. Using this cut-off value, 23 patients (30%) had a FGT-result above the cut-off (positive test) and 54 patients had a FGT-result below the cut-off (negative test). The prevalence of VTE was 30% in the FGT-positive patients and 2% in the FGT-negative patients (sensitivity 88%, specificity 77%). Conclusion: The FGT seems an excellent predictor for VTE in cancer patients. The next step will be to test the efficacy of prophylactic anticoagulants in patients with cancer and a high thrombosis risk based on the FGT

Prediction of venous thrombosis in cancer patients using a microparticle based clotting test

Background: Although in patients with cancer the risk of venous thromboembolism (VTE) is increased, the incidence is too low to routinely give prophylactic treatment. Procoagulant microparticles (MPs), especially tissue factor (TF)-bearing MPs, contribute to the risk of VTE in cancer patients. In the present study, we assessed the MP-associated procoagulant activity using a functional assay, the fibrin generation test (FGT), to identify cancer patients prone to develop VTE. Methods: As an ongoing study, plasma was collected from cancer patients, mainly with stage III or IV pancreatic, gastro-intestinal, breast or lung cancer. The MPassociated procoagulant activity was determined via the FGT with the addition of an inhibitory antibody to factor VII. The prolongation of the clotting time in the presence of anti-factor VII is a measure for the contribution of TF-bearing MPs to the clotting time. Patients were followed up for 6 months. Results: 100 patients were included, of which 77 have completed follow-up until now. The first 43 patients were used to establish a cut-off value of the FGT. Receiver operating characteristics showed that a prolongation of the clotting time of 13% after addition of anti-factor VII, was the optimal cut-off value. In the entire group, 8 of 77 patients (10%) developed VTE, of which 7 could have been predicted by the FGT. Using this cut-off value, 23 patients (30%) had a FGT-result above the cut-off (positive test) and 54 patients had a FGT-result below the cut-off (negative test). The prevalence of VTE was 30% in the FGT-positive patients and 2% in the FGTnegative patients (sensitivity 88%, specificity 77%). Conclusions: The FGT seems an excellent predictor for VTE in cancer patients. The next step will be to test the efficacy of prophylactic anticoagulants in patients with cancer and a high thrombosis risk based on the FGT

Microparticle tissue factor activity is increased in cancer patients prior to the development of venous thromboembolism

Introduction: Cancer greatly increases the risk of venous thromboem-bolism (VTE). Here, we investigated the contribution of microparti-cle-dependent procoagulant activity to the prothrombotic state in these patients. Methods: In 43 cancer patients without VTE at entry and 22 healthy volunteers, markers of in vivo and microparticle-dependent coagulation were measured and patients were prospectively followed for 6 months for the development of VTE. Procoagulant activity of microparticles (MPs) was measured using a phospholipid dependent test (STA Procoag PLL), a factor Xa-generation assay (Xa-assay) with and without anti-tissue factor (TF), and a fibrin generation test (FGT) with and without anti-factor VII(a). Results: Markers of in vivo coagulation activation and total number of circulating MPs were elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/L, D-dimer 0.76 vs. 0.22 mg/L and 5.53 x 106 vs. 3.37 x 106 microparticles per mL; all P <0.001). Five cancer patients (12%) developed VTE during follow-up. Patients with VTE had comparable levels of coagulation activation markers and phos-pholipid dependent MP procoagulant activity. However, TF-mediated Xa-generation (0.82 vs. 0.21 pg/mL, P = 0.016) and the VIIa-dependent FGT (13% vs. 0%, P = 0.036) were higher in the VTE group compared with the non-VTE group

Quality and Quantity of Sleep and Factors Associated With Sleep Disturbance in Hospitalized Patients

Item does not contain fulltextImportance: Although inadequate sleep has a proven negative association with health care outcomes, to date, no large-scale studies have examined sleep in general hospital wards. Objectives: To assess the subjective quantity and quality of sleep and to identify the hospital-related factors associated with sleep disturbances in hospitalized patients. Design: For this nationwide, single-day, multicenter, cross-sectional, observational study, which took place on February 22, 2017, all hospitals in the Netherlands were encouraged by word of mouth and conventional and social media to participate in this study. A total of 39 hospitals participated. Included patients were at least 18 years of age, were able to give informed consent, and had spent at least 1 night in a regular-care hospital ward. Exposures: Hospitalization in a regular-care ward. Main Outcomes and Measures: Quantity and quality of last night's sleep in the hospital compared with habitual sleep at home the month before hospitalization. The Consensus Sleep Diary and the Dutch-Flemish Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance item bank were used. Complementary questions assessed sleep-disturbing factors. Results: A total of 2005 patients were included (median age, 68 years; interquartile range, 57-77 years; 994 of 1935 [51.4%] were male [70 patients did not identify their sex]). Compared with habitual sleep at home, the total sleep time in the hospital was 83 minutes (95% CI, 75-92 minutes; P < .001) shorter. The mean number of nocturnal awakenings was 2.0 (95% CI, 1.9-2.1) times at home vs 3.3 (95% CI, 3.2-3.5) times during hospitalization (P < .001). Patients woke up 44 minutes (95% CI, 44-45 minutes; P < .001) earlier than their habitual wake-up time at home. A total of 1344 patients (70.4%) reported having been awakened by external causes, which in 718 (35.8%) concerned hospital staff. All aspects of sleep quality measured using PROMIS questions were rated worse during hospitalization than at home. The most reported sleep-disturbing factors were noise of other patients, medical devices, pain, and toilet visits. Conclusions and Relevance: This study demonstrated that the duration and quality of sleep in hospitalized patients were significantly affected and revealed many potentially modifiable hospital-related factors negatively associated with sleep. Raising awareness about the importance of adequate sleep in the vulnerable hospital population and introducing interventions to target sleep-disturbing factors may improve healing