Clotting analysis of blood samples from intensive care unit patients.

Introduction: Patients in the intensive care unit have complex haemostatic changes, which may be either procoagulant or anticoagulant. Global assays may reflect a patient’s net haemostatic balance and can contribute to pro- or anti-coagulant assessment. In this project, global assays were used to investigate both coagulation and fibrinolysis in samples taken from intensive care unit patients. Materials and Methods: Comparative clotting analysis was carried out on whole blood and plasma samples from twelve samples from intensive care unit patients. Nine haemophiliac samples and 14 healthy individual samples were used as controls. Several assays were used to assess coagulation in these sample groups. These included coagulation screens, individual factor assays and global assays [calibrated automated thrombography, whole blood and plasma low- dose tissue factor activated rotational thromboelastometry and the clot formation and lysis assay]. Results: Clot initiation in both whole blood and plasma analysis was prolonged in the intensive care unit samples. This was observed in the global assay analysis and was elucidated by the standard laboratory tests such as the clotting screens and the individual factor assays. However, once initiation commenced, the intensive care unit samples showed a clot formation comparable to that seen in healthy volunteers. Conclusion: Clot formation in intensive care unit patients is abnormal compared to that observed in healthy volunteer samples. Several factors such as the fibrinogen and procoagulant factors influence coagulation and the rate of thrombin production. The clot stability in intensive care unit samples was found to be more robust in comparison to that observed in the healthy volunteer sample group. This study showed that the initiation of coagulation is delayed intensive care unit patient samples but, once started, clot formation was comparable to that in healthy volunteer samples

Two Factor XI Concentrates Correct Impaired Thrombin Generation in Major FXI Deficiency but Are Not Equivalent in Their Effect

Abstract Introduction: Factor XI (FXI) deficiency is an autosomally inherited bleeding disorder characterised by an increased risk of excessive bleeding following trauma or surgery. However, considerable phenotypic heterogeneity of the bleeding tendency is observed between individuals with this disorder. Treatment options for patients requiring FXI replacement are fresh frozen plasma (preferably pathogen-inactivated) or FXI concentrate. Two FXI concentrates are available: Hemoleven® ( LFB Biomedicaments, Les Ulis, France) and Factor XI Concentrate (Bio-Products Laboratory (BPL), Elstree, UK). Guidelines previously recommended a maximum replacement dose of 30 U/Kg for both concentrates but more recently a lower dose of 10-15 U/kg has been advised. The two FXI concentrates may reduce bleeding risk in FIX deficiency following surgery but indications for their use are unclear and treatment in some cases has been associated with thrombosis. Aims: To quantify thrombin generation in major FXI deficiency (FXI:C &lt;15 IU/dL) and to compare the in vitro effects of both FXI concentrates on thrombin generation parameters in this population with each other and with reference range values. To assess the clinical relevance of in vitro results through comparison of thrombin generation following in vitro and in vivo FXI replacement in individuals requiring surgery. Methods: Thrombin generation (TG) was measured in controls (n=50), in individuals with FXI deficiency ( FXI &lt; 15 IU/dL) pre and post in vitro spiking with both FXI concentrates (n=10), and in ex vivo samples following treatment with BPL FXI concentrate (n=3). Blood was drawn into S-Monovette® tubes (Sarstedt, Leicester, U.K.) containing 0.106 M trisodium citrate (1:9, V:V) and corn trypsin inhibitor (CTI) (Haematologic Technologies Inc., Essex Junction, VT, U.S.A.), at a concentration of 20 µg/mL whole blood. Thrombin generation was measured in platelet rich plasma using the Calibrated Automated Thrombography method with a tissue factor trigger of 0.5pM. Statistical analysis was performed using GraphPad prism, version 6 software package (GraphPad, san Diego, CA, USA) using student’s t-test, Mann-Whitney U test or a Wilcoxon signed rank test according to data distribution. P value &lt;0.05 was considered significant. Results: Major FXI deficiency (FXI:C &lt;15 IU/dL) was associated with significantly impaired TG compared to controls, demonstrating reduced endogenous thrombin potential (ETP), peak height and velocity (all p&lt;0.0001) and prolonged time to peak (p = 0.021). All TG parameters significantly improved from baseline with FXI replacement with both concentrates in vitro (equivalent in vivo dose 10 U/Kg). Comparison of the two FXI concentrates demonstrated that LFB Hemoleven® had greater effect on TG than BPL FXI in vitro at all doses (equivalent in vivo doses 10, 20 and 30 U/Kg): higher ETP (p &lt; 0.0001), peak height (p &lt; 0.01) velocity (p &lt; 0.0002) and shorter lag time and time to peak (both p &lt; 0.003). However, some measurements with LFB Hemoleven® exceeded the reference range. At lower doses both FXI concentrates normalised TG parameters in vitro (equivalent in vivo dose 2.5 IU/Kg LFB Hemoleven® or 5 U/Kg BPL FXI). Three patients received in vivo treatment with BPL FXI concentrate prior to surgery. TG was compared between baseline, in vitro spiked and post infusion ex vivo samples. Comparable ETP and peak height results were obtained from in vitro spiked and post infusion ex vivo samples. Conclusions: Individuals with FXI:C levels &lt;15 IU/dL show impaired thrombin generation. Both FXI concentrates improve thrombin generation in vitro in patients with FXI deficiency. However, when tested in vitro with the TG assay, the concentrates differ in potency and dose response and for both concentrates, doses lower than present recommendations normalised thrombin generation. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement for the BPL product. Acknowledgments: This work is supported by a Fellowship Project Award from the Bayer Hemophilia Awards Program, an unrestricted grant from LFB Biotechnologies and a Wycherley Fellowship grant. Hemoleven® concentrate was kindly provided by LFB Biotechnologies. Disclosures Pike: Bayer: Honoraria, Research Funding; LFB Biotechnologies: Honoraria, Research Funding. Bolton-Maggs:Bio-Products Laboratory (U.K.): Consultancy; LFB Biotechnologies: Consultancy. </jats:sec

In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency

INTRODUCTION: Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis. AIM: To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C &lt;15 IU dL-1 ). METHODS: Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3). RESULTS: Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven(R) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg-1 ): higher endogenous thrombin potential (ETP) (P &lt;0.0001), peak height (P &lt;0.01) velocity (P &lt;0.0002) and shorter lag time and time to peak (both P &lt;0.003). Some measurements with LFB Hemoleven(R) exceeded the reference range. At lower dose (5 U kg-1 ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven(R) normalized the ETP but exceeded the reference range with other parameters. CONCLUSION: Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement

Screen to Save: Results from NCI's Colorectal Cancer Outreach and Screening Initiative to Promote Awareness and Knowledge of Colorectal Cancer in Racial/Ethnic and Rural Populations

Abstract Background: The Center to Reduce Cancer Health Disparities (CRCHD), National Cancer Institute (NCI), launched Screen to Save, NCI's Colorectal Cancer Outreach and Screening Initiative to promote awareness and knowledge of colorectal cancer in racial/ethnic and rural populations. Methods: The initiative was implemented through CRCHD's National Outreach Network (NON) and Comprehensive Partnerships to Advance Cancer Health Equity (CPACHE) programs. NON is a national network of Community Health Educators (CHEs), aligned with NCI-designated Cancer Centers (CCs). CPACHE are partnerships between a CC and a minority-serving institution with, among other components, an Outreach Core and a CHE. In phases I and II, the CHEs disseminated cancer-related information and implemented evidence-based educational outreach. Results: In total, 3,183 pre/post surveys were obtained from participants, ages 50 to 74 years, during 347 educational events held in phase I. Results demonstrated all racial/ethnic groups had an increase in colorectal cancer-related knowledge, and each group agreed that the educational event increased the likelihood they would engage in colorectal cancer-related healthful behaviors. For phase II, Connections to Care, participants were linked to screening. Eighty-two percent of participants who were screened during the follow-up period obtained their results. Conclusions: These results suggest that culturally tailored, standardized educational messaging and data collection tools are key elements that can serve to inform the effectiveness of educational outreach to advance awareness and knowledge of colorectal cancer. Impact: Future initiatives should focus on large-scale national efforts to elucidate effective models of connections to care related to colorectal cancer screening, follow-up, and treatments that are modifiable to meet community needs. </jats:sec