scholarly journals Rotational Thromboelastometry (ROTEM) for Assessing the Anticoagulant Effect of Rivaroxaban: A Single-Centre Cohort Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5018-5018
Author(s):  
Thomas Andrew Fox ◽  
Andrew Wood ◽  
Anne Riddell ◽  
Pratima Chowdary ◽  
Anja B Drebes
Keyword(s):  
Creatinine Clearance ◽  
Prothrombin Time ◽  
Board Of Directors ◽  
Partial Thromboplastin Time ◽  
Research Funding ◽  
Activated Partial Thromboplastin Time ◽  
Anticoagulant Effect ◽  
Advisory Committees ◽  
Rotational Thromboelastometry ◽  
Coagulation Tests

Abstract Background: The direct, oral, factor Xa inhibitor, rivaroxaban, is increasingly used to provide effective anticoagulation in atrial fibrillation and venous thromboembolism. Whilst rivaroxaban does not require therapeutic monitoring there are situations when it is useful to estimate the anticoagulant effect of the drug such as during bleeding episodes or before emergency surgery. It has previously been shown that conventional coagulation tests can provide a crude estimation of anticoagulant effect of rivaroxaban if a sensitive reagent is used. In this study we explore whether rotational thromboelastometry (ROTEM) would provide a more accurate measure of rivaroxaban effect. Methods: Peak serum rivaroxaban levels were taken 3-5 hours post-dose in 121 consecutive patients established on a once-daily anticoagulation regime with rivaroxaban. Conventional coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (APTT) were performed alongside rivaroxaban level and rotational thromboelastometry (ROTEM, TEM Ltd, Germany) on native citrated whole blood. PT and APTT used HemosIL Recombiplastin 2G and SynthasIL reagents (Instrumentation Laboratory (IL), USA) respectively. Rivaroxaban levels were measured using HemosIL Liquid Anti Xa kit (IL, USA) with rivaroxaban calibrators from Hyphen Biomed, France on an ACL TOP 700 coagulometer (IL, USA)). Demographic and biochemical data was collected on each patient. Results were analysed to determine if ROTEM can be used to assess the anticoagulant effect of rivaroxaban in real-world patients with different demographics and organ function. Results: Significant positive correlation was seen between rivaroxaban level and prothrombin time (PT) (R=0.796, Pearson's correlation coefficient). Weaker correlation was observed between rivaroxaban level and activated partial thromboplastin time (APTT) (R=0.425). There was modest positive correlation between the clotting time (CT) parameter using ROTEM and rivaroxaban level (R=0.328). However, when grouped into low (<200ng/ml), intermediate (200-300ng/ml) and high (>300ng/ml) rivaroxaban levels, the CTs show no meaningful association and therefore cannot be used as a surrogate marker to predict anticoagulant effect. There is no significant difference between the mean rivaroxaban levels for patients on 15mg rivaroxaban, those on 20mg with creatinine clearance <60ml/min and those on 20mg with creatinine clearance >60ml/min (Analysis of Variance, n=121, F=2.009, P=0.159), suggesting that with dose adjustment a similar anticoagulant effect is achieved in patients with different renal function. Conclusion: Our data suggests that the correlation between rivaroxaban levels and ROTEM CT parameter is not sufficiently strong to reliably predict the anticoagulant effect of rivaroxaban and does not confer any advantage over conventional clotting tests. Disclosures Chowdary: Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Honoraria; Bayer: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Drebes:Bayer: Consultancy; Bayer: Other: Educational Grant.

The Population-Based ‘real world’ of Low Risk Myelodysplastic Syndromes; Second Interim Analysis of the European LeukemiaNet MDS Registry at 800 Registered New Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1867-1867
Author(s):  
David Bowen ◽  
Alex Smith ◽  
Jackie Droste ◽  
Pierre Fenaux ◽  
Argyris Symeonidis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Creatinine Clearance ◽  
Board Of Directors ◽  
Neutrophil Count ◽  
Real World ◽  
Research Funding ◽  
Population Based ◽  
Low Risk ◽  
Advisory Committees

Abstract Abstract 1867 Background: The European LeukemiaNet MDS Registry programme is the largest and most comprehensive prospective population-based registry of ‘low-risk’ MDS patients followed from diagnosis. Objective: The primary objective of this study is to describe the demographics and the disease-management of newly diagnosed MDS patients within IPSS low and intermediate-1 categories. Methods: The project recruits patients from 107 sites in 11 countries, ranging from 2–25 sites per country and including a high proportion of non-University centres in small cities. Consecutive eligible adult patients are registered within 3 months of diagnosis. Local diagnosis is accepted and a large dataset is collected including laboratory data, clinical information (including co-morbidity and concomitant medication) plus health utility (EQ-5D). Data are entered via a web portal and are source verified by study monitoring visits to sites. Results: As of July 2010, 828 patients are registered; data are presented for the first 800 patients. Recruitment is highest from France (n=237) then UK (104), Greece (99), Spain (92), and Sweden (73). Median age is 74.2 yrs (range 18.7–95.3) and from the four largest recruiting countries is 74.6–77.1 yrs. Sixty one percent of patients are male. Twenty patients are non-Caucasian (n=763). Body mass index is overweight (WHO definition) in 43.4% pts and obese in 18.3%, comparable to WHO data for the general adult population (http://apps.who.int/bmi/index.jsp). RCMD is the largest WHO subgroup (34%), followed by RARS (19%), RA (18.4%), RAEB-1 (12.5%), del5q (5.4%), MDS-U (3.5%) and RAEB-2 (0.5%). All WHO subgroups have male predominance except del5q with a striking female excess (79%). IPSS score (n=743) is 0 (52.3%), 0.5 (33.2%), and 1 (14.4%). 84.5% patients have IPSS ‘good’ cytogenetics. 19% patients have 0 cytopenias, 53% 1 cytopenia, 20% 2 cytopenias and 8% 3 cytopenias. WPSS category (with transfusion dependence assessed at time of registration, n=727) is Very Low (35.5%), Low (39.5%), Intermediate (21%), High (4%). Bone marrow features: mean no. of dysplastic lineages = 1.9, bone marrow ring sideroblasts percent = 0 (60% pts), <15 (11.5%), ≥15<50 (19.2%), ≥50 (9.6%). Median haemoglobin (Hb) concentration at presentation is 10.1 g/dl; 36% values were < 10 g/dl and 10% < 8 g/dl. Hb decreased with age (categorical variable Hb. <13>11.5, <11.5>10, <10; Χ2 test, P<.0001). Mean neutrophil count was 2.8 × 109/l with 27% values <1.5 × 109/l, 16% < 1 × 109/l, and 5% < 0.5 × 109/l. Median platelet count was 184 × 109/l; 5% patients had values < 50 × 109/l and 3% < 20 × 109/l. Platelet count and neutrophil count did not change with age. Median serum erythropoietin (EPO) concentration (n=418) was 49 IU/l, 81% values were <200 IU/l and 7% > 500 IU/l. Mean creatinine clearance was 71 mls/min with a marked reduction with age (P<.0001). Baseline serum EPO correlated with Hb. (r=.37, P<.0001), creatinine clearance (r=.22, P<.0001) and age (r=.1, P<.0001). The relationship between creatinine clearance, baseline EPO and response to EPO therapy will be explored. Discussion: This registry records data from the ‘real world’, namely what the hematopathologists in 100 sites diagnose locally as low-risk MDS and will as such be managed as MDS. Median age is consistent with other population-based data (US Medicare, Yorkshire Haematological Malignancy Research Network [www.hmrn.org]). In comparison with registries from specialist MDS centres, median age is higher and a lower proportion have del(5q) WHO subtype. Conclusion: The ELN registry clearly maps the diagnosis and management of low-risk MDS in routine clinical practice in hospitals large and small, specialist and non-specialist and is a unique resource. Acknowledgments: The Steering Committee (SC) acknowledges the commitment and enthusiasm from all 107 sites contributing high quality data to the project. The SC is also grateful for the funding commitment of Novartis Oncology Europe through the University of Nijmegen. Disclosures: Bowen: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AMGEN: Honoraria; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding. Fenaux:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Hellstrom-Lindberg:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Can RoTEM®analysis be applied for haemostatic monitoring in paediatric congenital heart surgery?

2011 ◽  
Vol 21 (6) ◽  
pp. 684-691 ◽  
Author(s):  
Jo Bønding Andreasen ◽  
Anne-Mette Hvas ◽  
Kirsten Christiansen ◽  
Hanne Berg Ravn
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Congenital Heart ◽  
Heart Surgery ◽  
Congenital Heart Surgery ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Coagulation Tests

AbstractBackgroundSuccessful management of bleeding disorders after congenital heart surgery requires detection of specific coagulation disturbances. Whole-blood rotation thromboelastometry (RoTEM®) provides continuous qualitative haemostatic profiles, and the technique has shown promising results in adult cardiac surgery.SettingTo compare the performance of RoTEM®with that of conventional coagulation tests in children, we conducted a descriptive study in children undergoing congenital cardiac surgery. For that purpose, 60 children were enrolled and had blood samples taken before, immediately after, and 1 day after surgery. Conventional coagulation tests included: activated partial thromboplastin time, prothrombin time, fibrinogen, fibrin D-dimer, thrombin clotting time, factor XIII, and platelet count.ResultsPost-surgical haemostatic impairment was present to some degree in all children, as seen by pronounced changes in activated partial thromboplastin time, prothrombin time, thrombin clotting time, and platelet count, as well as RoTEM®analysis. RoTEM®showed marked changes in clotting time – prolonged by 7–18% – clot formation time – prolonged by 46–71% – maximum clot firmness – reduced by 10–19%, and maximum velocity – reduced by 29–39%. Comparison of the two techniques showed that conventional coagulation tests and RoTEM®performed equally well with regard to negative predictive values for excessive post-operative drain production – more than 20 millilitres per kilogram per 24 hours after surgery – with an area under the curve of approximately 0.65.ConclusionRoTEM®can detect haemostatic impairments in children undergoing cardiac surgery and the method should be considered as a supplement in the perioperative care of the children where targeted transfusion therapy is necessary to avoid volume overload.

scholarly journals Effect of storage time on prothrombin time and activated partial thromboplastin time: study at a tertiary care center in Kashmir valley

2018 ◽  
Vol 4 (7) ◽  
pp. 182
Author(s):  
Sajad Geelani ◽  
Gul Sajad Wani ◽  
Subuh Parvez Khan ◽  
Syed Mudasir Qadri ◽  
Javid Rasool ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Storage Temperature ◽  
Care Center ◽  
Tertiary Care ◽  
Activated Partial Thromboplastin Time ◽  
Time Interval ◽  
Tertiary Care Center ◽  
Kashmir Valley ◽  
Coagulation Tests

<p class="abstract"><strong>Background:</strong> Prothrombin time (PT) and activated partial thromboplastin time (APTT) are tests of haemostasis commonly employed in the evaluation of coagulopathies. Storage temperature and time interval between sample collection and testing can have a significant effect on results of coagulation tests. The aims of the study were investigate whether storage temperature and time influence the results of routine coagulation tests and whether any changes caused by delayed analysis results in a clinically relevant difference, as well as to establish our own acceptable storage temperature and time guidelines.</p><p class="abstract"><strong>Methods:</strong> This study was conducted at Department of Clinical Haematology, in a tertiary care center in Kashmir valley. This study included 50 cases. Individuals with chronic liver diseases or cardiovascular disorders, subjects on anticoagulant therapy were excluded. 25 samples were observed at room temperature (RT) and 25 samples at 2-8°C. PT and APTT was measured at 0, 2, 4, 8, 16 and 24 hours both at RT and 2-8°C. Findings at 0 hr were compared to findings at 2,4, 8,16 and 24 hours in both the groups.  </p><p class="abstract"><strong>Results:</strong> In case of PT, reliable results were obtained up to 24 hrs either kept at RT or at 2 to 8°C and for APTT reliable results were obtained up to 4 hours kept at RT or at 2 to 8°C as there was no significant change during this period.</p><p class="abstract"><strong>Conclusions:</strong> Coagulation test should be performed as soon as possible with PT being performed before 24 hours and APTT before 4 hours of collection of sample irrespective of whether the sample has been preserved at RT or in refrigerator.</p>

scholarly journals Idelalisib Rapidly Improves Platelets Function in Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5566-5566
Author(s):  
Gianluigi Reda ◽  
Ramona Cassin ◽  
Andrea Artoni ◽  
Anna Lecchi ◽  
Bruno Fattizzo ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Pilot Study ◽  
Board Of Directors ◽  
Research Funding ◽  
Bleeding Risk ◽  
Bleeding Tendency ◽  
Advisory Committees ◽  
Coagulation Tests ◽  
Haematological Remission

Abstract INTRODUCTION Platelet function has never been studied systematically in patients with CLL. Novel drugs are now available for CLL treatment that may impact on platelet functions. Fifty per cent of patients treated with Ibrutinib suffered from minor bleedings and only 5% from major bleedings, partly caused by the drug driven inhibition of platelet glycoprotein VI signaling. No data on bleeding tendency has yet emerged on patient treated with Idelalisib, the first specific inhibitor of PI3K δ p110 approved for the treatment of relapsed/refractory CLL or for patients with del17p or TP53 as first line therapy. In animal models a reduction of p110δ on platelets (PLT) does not increase bleeding, causing only a slight reduction of platelet aggregation and activation. Knowledge about potential bleeding complications associated with the use of small molecules may be relevant in older patients and those at increased bleeding risk due to concomitant therapies. PATIENTS AND METHODS Ten patients with CLL (M/F: 6/4; median age: 71 years, range 47-82) who started therapy with Idelalisib were enrolled in a prospective observational pilot study. The Bleeding Severity Score (BSS), a validated questionnaire, was administrated to patients to estimate bleeding before and during idelalisib therapy. All patients underwent coagulation tests and platelet aggregation/secretion studies with different aggregating agents before starting therapy with Idelalisib, after 28 + 7 days and after 3 months. Patients with a platelet count less than 80.000/mm3, in antiplatelet or anticoagulant therapy, with recent use (within 7 days) of NSAIDs and a diagnosis of hereditary thrombocytopenia/pathy were excluded. We defined complete haematological remission (CHR) as Hb more than 11g/dl, PLT more than 100.000/mm3, lymphocyte less than 5.000/mm3 and partial haematological remission (PHR) as a response not fulfilling criteria for CHR. RESULTS No cases of hemorrhagic complications or increased bleeding tendency were observed in patients with CLL and no patients had a pathologic BSS (>5) at enrolment. All patients had coagulation tests within normal limits at baseline and after 28 days. Platelet count was below 100.000/mm3 in 5 patients. In 9 out of 10 patients platelet aggregation was pathological with at least 2 of the 4 aggregating agents tested. Platelet secretion before initiation of treatment with Idelalisib was particularly impaired with ADP (8/10 patients), while was pathological with collagen, a strong agonist, in only 2 patients. In 8 patients intraplatelet ATP/ADP ratio was pathological, as observed in delta storage pool disease. After 28 days of treatment 4 of 10 patients were in CHR and 3 in PHR. Platelets count was still below 100.000/mm3 in 2 subjects. At 28 days in 5 out of the 9 patients with pathological baseline test, platelet aggregation improved, while 3 remained unchanged and in one worsened. Even ADP secretion normalized in 4 patients. ATP/ADP ratio did not significantly change. At three months 7 patients reached CR and 2 reached PR. At three months platelets count was still below 100000/mm3 in 2 patients. In 3 patients platelet aggregation further ameliorated. CONCLUSIONS In this pilot study, treatment with idelalisib improved platelet aggregation tests in most of the CLL patients who presented a pathological test before starting therapy. It's unlikely that the drug has a direct effect on platelets, given their low expression of PI3Kδ; therefore our results are probably due to the rapid idealisib effect on CLL clone. Based on these preliminary data, Idelalisib seems to be safe in patients with an increased bleeding risk. Disclosures Reda: Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding. Peyvandi:Alexion: Other: research funding paid to Luigi Villa Foundation, Research Funding; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: research funding paid to Luigi Villa Foundation, Research Funding; CSL Behring: Speakers Bureau; Biotest: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; Octapharma: Consultancy; Kedrion Biopharma: Consultancy, Other: research funding paid to Luigi Villa Foundation, Research Funding; LFB: Consultancy; Grifols: Speakers Bureau; Novo Nordisk: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; SOBI: Speakers Bureau; Bayer: Speakers Bureau.

Interferences in coagulation tests – evaluation of the 570-nm method on the Dade Behring BCS analyser

2005 ◽  
Vol 43 (2) ◽  
Author(s):  
Ralf Junker ◽  
Margit Käse ◽  
Helmut Schulte ◽  
Ruth Bäumer ◽  
Claus Langer ◽  
...  
Keyword(s):  
Optical Properties ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Plasma Samples ◽  
Comparison Methods ◽  
Coagulation Tests ◽  
Elisa Technique ◽  
Roche Diagnostics ◽  
D Dimer

AbstractThe Dade Behring BCS is a coagulation analyser with optical reaction detection (standard 405nm). The present study was conducted to evaluate measurement at 570nm for analyses in interfering plasma samples. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer in normal (n=50), lipaemic (n=60), icteric (n=113), and haemolytic (n=58) samples were measured at 405 and 570nm. As they are unaffected by the optical properties of the sample, the mechanical STAcompact analyser (Roche Diagnostics) and an ELISA technique were defined as the “comparison” methods. The percentage of valid PT results using the 570-nm method varied from 54% (lipaemic samples) to 97% (haemolytic samples). Valid aPTT measurements were found in 67% (lipaemic samples) up to 93% (icteric samples) of samples. Fibrinogen measurement revealed valid results in 58% (lipaemic samples) to 100% (haemolytic samples) of samples. The number of valid D-dimer results varied from 28% (lipaemic material) up to 100% (haemolytic material). Significant inter-method differences were found: aPTT in lipaemic (BCS 405 vs. 570nm) and icteric samples (STAcompact vs. BCS 405 and 570nm); fibrinogen in lipaemic (BCS 405 vs. 570nm), icteric (BCS 405 vs. 570nm; STAcompact vs. BCS 570nm) and haemolytic samples (STAcompact vs. BCS 405 and 570nm). Differences between the BCS 570-nm and the STAcompact methods were in most cases low and less pronounced than between the BCS 570- and 405-nm methods, making the BCS 570-nm method an alternative to measurement at 405nm. Limitations have to be taken into account regarding lipaemic plasma.

2-Hour Cryotherapy Effectively Reduces Severe Mucositis Associated with High-Dose Melphalan Followed By Stem Cell Rescue: Results from a Randomized Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3960-3960 ◽  
Author(s):  
Douglas W. Sborov ◽  
Misty Lamprecht ◽  
Don Benson ◽  
Karen Tackett ◽  
Yvonne A Efebera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Creatinine Clearance ◽  
Board Of Directors ◽  
Research Funding ◽  
High Dose ◽  
Advisory Committees ◽  
Stem Cell Rescue ◽  
Grade 3 ◽  
High Dose Melphalan ◽  
Severe Mucositis

Abstract Introduction: Severe mucositis in the autologous transplant setting has been correlated with adverse outcomes; longer febrile neutropenia duration, doubling of infectious risk, 2.7 additional days of total parenteral nutrition, 2.6 additional days of IV narcotics, increased length of stay (LOS), 3.9-fold increase in 100-day mortality, and US$25,405 increase in hospital charges (Sonis, JCO, 2001 19(8)). In a 40 patient randomized trial investigating cryotherapy (6 hours versus none) following high dose melphalan, grade 3/4 mucositis occurred in only 14% of patients using cryotherapy compared to 74% of patients using saline rinses (Lilleby, BMT, 2006 37). Prolonged cryotherapy is a significant hardship for patients and has resulted in nausea, vomiting, headache, toothache, and chills. We performed a randomized study investigating 2 versus 6 hours of cryotherapy in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) with melphalan conditioning. Hypothesis: We hypothesized that a 2-hour cryotherapy regimen would be non-inferior to 6-hours in severity of mucositis, LOS, and incidence of bacteremia. Methods: We conducted a non-inferiority investigation of 146 sequential MM patients undergoing high dose melphalan with autologous stem cell rescue. Patients were consented and randomized to either 2 (n = 73) or 6 hours (n = 73) of cryotherapy via block randomization based on hemoglobin (less or greater than 11 g/dL), fat free mass (30-50, 50-70, >70 kg), or measured 24hr creatinine clearance (<30, 30-60, >60 mL/min). The cryotherapy process consisted of patients’ melting shaved ice inside their mouth for the designated period of time; flavoring with snow cone syrup was permitted. Inpatient nurse practitioners graded mucositis via WHO criteria. Patients received antifungal (fluconazole) and antiviral (acyclovir or valacyclovir) prophylaxis. Subset analyses investigated the incidence of bacteremia in all patients. Results: Median age was 59 years (range 35 - 72) and 60 (range 38 – 71), and the median measured creatinine clearance was 90.6 mL/min (range 0.2 – 168.7) and 85.4 mL/min (range 21.5 – 196.5) for the 2 hour and 6 hour groups respectively. Length of hospitalization (mean of 15 days) did not differ significantly between the 2 cohorts (p = 0.54). Mucositis was graded daily after melphalan infusion. In the 2-hour cohort, 59% of the patients had mucositis (31 patients with grade 1, 10 with grade 2, and 2 patients with grade 3). In the 6-hour cohort, 64% had mucositis (35 patients with grade 1, 9 with grade 2, and 3 patients with grade 3). These results suggest that 2-hour cryotherapy was not inferior to 6-hour therapy in decreasing mucositis grade. In the entire 146 patient group, approximately 30% developed a positive blood culture after transplant, including 25 (34%) and 20 (27%) in the 6-hour and 2-hour groups respectively. The three most common infectious organisms included gram negatives (n = 12 patients), polymicrobial (n = 7), and non-group A streptococcus (n = 7). In the cohort treated with 2-hour cryotherapy, positive blood cultures did not correlate with grade of mucositis (r = 0.05, p = 0.65). Conclusions: In MM patients undergoing ASCT, 2-hour cryotherapy did not increase mucositis compared to 6-hours. The incidence of blood stream infection was not different between groups. In addition, having an infection did not correlate with grade of mucositis.These results suggest that a 2-hour cryotherapy regimen is not inferior to a 6-hour regimen, and may be considered a standard supportive care measure in patients receiving high dose melphalan. Disclosures Hofmeister: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Honoraria, Research Funding; ARNO Therapeutics: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Rivaroxaban Reduces the Levels of Extracellular Vesicles in Patients with Venous Thromboembolism and Non-Valvular Atrial Fibrillation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2437-2437
Author(s):  
Sarah Kelliher ◽  
Luisa Weiss ◽  
Paulina Szklanna ◽  
Karl Egan ◽  
Tadhg Prendiville ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Flow Cytometry ◽  
Platelet Count ◽  
Venous Thromboembolism ◽  
Creatinine Clearance ◽  
Board Of Directors ◽  
Research Funding ◽  
Vitamin K Antagonists ◽  
Advisory Committees ◽  
Particle Counts

Background: Rivaroxaban is a direct oral anticoagulant (DOAC) with similar efficacy to vitamin K antagonists in the management of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) but with a more favourable bleeding profile. Recent studies including the landmark COMPASS trial have demonstrated that rivaroxaban possesses cardioprotective and anti-inflammatory properties beyond its well-established anticoagulant effects however, these remain poorly characterized. The effects of FXa inhibition on the generation of circulating extracellular vesicles (EV) are currently unknown. We hypothesize that circulating proinflammatory EV profiles differ in patients treated with rivaroxaban compared to those treated with warfarin and that these changes may represent a novel biomarker for cardioprotective effects mediated by FXa inhibition. Methods: Patients stably anticoagulated with 20 mg Rivaroxaban (n=15) once daily or warfarin (n=15) (at a target INR of 2.0 - 3.0) who had commenced therapy no sooner than 3 months previously for VTE treatment or NVAF were recruited following informed consent at the Mater Misericordiae University Hospital, Dublin. Demographic and clinical data were collected including patient age, body mass index, smoking and alcohol history, medical comorbidities, white cell and platelet count, creatinine clearance, liver profile, medications, detailed indication for anticoagulation and time since last dose of medication. Patients receiving warfarin had a time in therapeutic range of > 55% and had an INR within target range at the time of sampling. Exclusion criteria included severe renal impairment (creatinine clearance < 30 ml/min), significant liver impairment, known proinflammatory conditions (including systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis), recurrent VTE, active malignancy, previous stroke or systemic inflammation, antiphospholipid syndrome, strong thrombophilia (eg antithrombin deficiency), individuals aged < 18, patients receiving inhibitory CYP3A4 and P-glycoprotein medications or platelet inhibitors, bleeding or platelet function disorders, and thrombocytopenia (platelet count < 150 x 109/ml) Total particle counts in platelet poor plasma were measured by Nanoparticle Tracking Analysis (NTA) and flow cytometry. NTA was carried out using a NanoSight NS300 (Malvern) with a camera level of 13 and a detection threshold of 10. 15 x 60 second videos were captured per sample. Flow Cytometry analysis was performed using a CytoFlex LX (Beckman Coulter). Gigamix beads (Biocytex) were used to establish size gates for 100, 300, 500 and 900 nm particles. Samples were analysed in triplicate. Statistical analysis was performed in RStudio (version 1.2.1335) using a two-tailed t-test with a significance level of 5%. Results and Conclusion: Overall, we observed lower circulating EV levels in patients anticoagulated with FXa inhibitors versus vitamin K antagonists (Figure 1). Within our groups, patients with NVAF exhibited overall lower EV particle counts than VTE patients. Interestingly, EV levels were observed to be further diminished in patients treated with rivaroxaban versus warfarin. In this group, we detected a 2.5-fold decrease in the level of circulating EVs in patients with NVAF (1.18x1011±5.03x1010 particles/mL vs 2.92x1011±2.08x1011 particles/mL, p=0.039) and a 1.7-fold decrease in patients with VTE (3.37x1011±2.46x1011 particles/mL vs 5.71x1011±1.471011 particles/mL, p=0.164), in contrast to warfarin treatment. Collectively, these data suggest that FXa inhibition reduces the generation of circulating EVs, independent of the disease. These findings are of translational relevance towards characterizing cardioprotective mechanisms associated with rivaroxaban therapy. Disclosures Ni Ainle: Leo Pharma: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Actelion: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Maguire:Bayer: Research Funding; Leo Pharma: Research Funding; Actelion: Research Funding.

scholarly journals Development of a Predictive Pharmacokinetic and Pharmacodynamic Model to Personalize Melphalan Dosing in Autologous Transplant for Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1086-1086
Author(s):  
Yu Kyoung Cho ◽  
Junan Li ◽  
Douglas W. Sborov ◽  
Jiang Wang ◽  
Yue Gao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Creatinine Clearance ◽  
Board Of Directors ◽  
Research Funding ◽  
Mononuclear Cells ◽  
Prospective Trial ◽  
Fat Free Mass ◽  
Interpatient Variability ◽  
Advisory Committees ◽  
P53 Mrna

Abstract Introduction: Melphalan is an interstrand cross-link (ICL)-inducing agent and, in the setting of autologous stem cell transplantation for multiple myeloma, is one of the most effective treatments, providing 30 months of disease stability on average, but with a dramatic progression free survival (PFS) range of 6 months to 12 years. While 200 mg/m2 is the standard dose, there is extensive interpatient variability, and individual melphalan sensitivity with the ability to repair double-stand breaks in primary myeloma cells mirrored by a similar efficiency in peripheral blood mononuclear cells (PBMCs) (Gkotzamanidou M et al, Leukemia and BJC, 2013 and 2014). Our hypothesis is that our PK model will predict > 85% of interpatient variability, AUC achieved as well as measurements of DNA damage ex vivo will correlate with mucositis and duration of neutropenia, and we will be able to create an integrated model to personalize melphalan dosing to maximize myeloma cell killing while minimizing toxicities. Methods: We enrolled 146 patients on a prospective trial using a block randomization scheme based on fat-free mass, calculated creatinine clearance, and hemoglobin as known factors affecting melphalan disposition. Plasma was collected from all patients to assess melphalan pharmacokinetics, and PBMCs were collected to assess ex vivosensitivity to melphalan therapy, including p53 gene expression and WST-1-based cytotoxicity. DNA from PBMCs was collected to assess the presence of SLC7A5 polymorphisms associated with melphalan-induced enteritis (Giglia JL et al, BBMT, 2014). PK/PD modeling and identification of covariates contributing to observed variability in melphalan disposition and outcomes is being achieved using a nonlinear mixed effects approach Results: Melphalan has been quantified in samples from 119 patients, and this data was used in population modeling. Estimated PK parameters (CV%) for the model were ӨCL=0.445 L/min (33.6%), ӨV1=19.4 L (36.6%), ӨQ=0.392 L/min (34.5%) and ӨV2=17.4 L (36.9%). Creatinine clearance (normalized to 70 kg), hematocrit, fat free mass on CL, sex on V1, and body surface area on Q were chosen for the final covariate model. IC50value (CV%=31.2%), and the baseline of p53 mRNA level (47.3%) and viability (20.1%) in donor’s PBMCs were variable. Response of p53 mRNA expression and viability in donor’s PBMCs were dose-dependent. PD modeling, and covariate and SCLA5 polymorphism analyses are underway. Conclusions: This study represents the largest and most comprehensive for identifying variables associated with melphalan pharmacokinetics and pharmacologic activity. An integrated PK/PD model that incorporates PK/PD and other predictive factors form the basis of a prospective randomized clinical trial to validate that the model reduces toxicities while prolonging PFS. Disclosures Hofmeister: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Honoraria, Research Funding; ARNO therapeutics: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees.

scholarly journals In vitro Anticoagulant Effect of Grape Seed Extract (Vitis vinifera) on Human Normal Blood Sample

2020 ◽  
pp. 40-45
Author(s):  
Somia Attaelseed Hassan ◽  
Zeinab Sayed Abdelaziz ◽  
Mohammed Mobarak Elbasheir ◽  
Wala Eldin Osma Elradi ◽  
Elharam Ibrahim Abd Allah ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Seed Extract ◽  
Activated Partial Thromboplastin Time ◽  
Anticoagulant Effect ◽  
Normal Blood ◽  
Grape Seeds ◽  
Blood Samples

Background: Scientists have used herbs nowadays for curing many diseases because they are safer and to overcome the side effect of the chemical drugs. Grape is one of the ancient herbs that used for diseases of the heart and blood vessels, high blood pressure, high cholesterol, skin care and many other conditions. Grape seeds have significantly higher concentrations of polyphenols which has anticoagulant and antithrombotic effect. Materials and Methods: In this study 20 normal blood samples from healthy individuals with age range (19-38) years were enrolled in this study]. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were performed before adding grape seed extraction (GSE) (as control) and after adding GSE with different concentrations (25%, 50% and 75%). Results: The results revealed that grape seed extract has an anticoagulant effect as proven by the increase of Prothrombin time and Activated partial thromboplastin time results of the blood samples in different concentrations of the extract. The GSE showed a high statistical significant (P= 0.000) in all concentrations of both PT and APTT tests. Conclusion: This study suggests that GSE has a strong anticoagulant effect; so it can potentially be used as a supplementary anticoagulant agent to prevent thrombosis and cardiovascular diseases.

EFFECTS OF NICKEL CHLORIDE ON INDICES OF HEMOCOAGULATION AND LIPID PEROXIDATION IN RATS

2019 ◽  
pp. 83-90
Author(s):  
Э.М. Гаглоева ◽  
В.Б. Брин ◽  
С.В. Скупневский ◽  
Н.В. Боциева ◽  
Т.В. Молдован
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Nickel Chloride ◽  
Activated Partial Thromboplastin Time ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Hemostasis System

Цель исследования - изучить состояние системы гемостаза при хронической интоксикации хлоридом никеля, исследовать взаимосвязь показателей гемокоагуляции с процессами липопероксидации у крыс в эксперименте. Методика. Опыты проводили на крысах-самцах Вистар (n=50, 230-250 г). Раствор NiCl2 (5 мг/кг) вводили внутрижелудочно ежедневно в течение 2 нед, 1 и 2 мес. По завершении эксперимента исследовали состояние тромбоцитарного и коагуляционного звеньев гемостаза, антикоагулянтную и фибринолитическую активность крови, а также определяли активность процессов перекисного окисления липидов и антиоксидантных ферментов. Результаты. Установлено, что через 2 нед и 1 мес интоксикации у крыс отмечались гиперкоагуляционные изменения показателей свертывающей системы крови: повышение агрегационной активности тромбоцитов, увеличение концентрации фибриногена, снижение активированного частичного тромбопластинового времени (АЧТВ) и протромбинового времени. В этот период регистрировалось увеличение антитромбиновой и фибринолитической активности крови. Через 2 мес наблюдалось подавление активности клеточного звена гемостаза - тромбоцитопения, ослабление степени АДФ-индуцируемой агрегации тромбоцитов. Выявлялась тенденция к уменьшению концентрации фибриногена. На фоне снижения АЧТВ и тромбинового времени отмечалось увеличение протромбинового времени. В то же время регистрировалось угнетение противосвертывающего звена системы гемостаза (снижалась активность антитромбина III), наблюдалось истощение резервных возможностей фибринолитического звена (замедление фXIIа-зависимого эуглобулинового лизиса) и увеличение содержания растворимых фибрин мономерных комплексов, что свидетельствует о наличии тромбинемии. Через 2 нед, один и два месяца интоксикации у животных выявлялись корреляционные связи между основными показателями системы гемостаза и активностью процессов перекисного окисления липидов и антиоксидантных ферментов. Заключение. Полученные данные подтверждают наличие взаимосвязи активности процессов липопероксидации и системы гемостаза, в том числе при хронической никелевой интоксикации. Результаты исследования позволяют рекомендовать применение антиоксидантов для разработки способов коррекции гемостатических сдвигов при воздействии на организм тяжелых металлов. The aim. To study the state of the hemostasis system in chronic nickel intoxication and to investigate the relationship between hemocoagulation indices and lipoperoxidation processes in rats. Methods. Experiments were carried out on male Wistar rats (n=50, 230-250 g). A solution of nickel chloride (5 mg/kg) was administered daily intragastrically for two weeks, one and two months. At the end of the experiments, indices of platelet and coagulation hemostasis systems, anticoagulant and fibrinolytic activity of blood plasma, and activities of lipid peroxidation and antioxidant enzymes were studied. Results. Hypercoagulative changes in indices of the coagulation system were observed in rats after two weeks and one month of intoxication, including increased platelet aggregation and fibrinogen concentration and shortened activated partial thromboplastin time and prothrombin time. During the same period, increased antithrombin and fibrinolytic activities were observed. The depressed activity of the cellular component of hemostasis evident as thrombocytopenia and impaired ADP-induced platelet aggregation was detected after two months of intoxication. A tendency to decrease in fibrinogen concentration was observed. The shortened activated partial thromboplastin time and thrombin time were associated with prolonged prothrombin time. At the same time, inhibition of the anticoagulant component of hemostasis (decreased antithrombin III activity), exhaustion of the fibrinolysis system reserve (delayed fXIIa-dependent euglobulin lysis), and a significant increase in soluble fibrin monomeric complexes indicative of thrombinemia were observed. After two weeks, one and two months of nickel intoxication, a correlation was found between the major indices of the hemostasis system and the activities of lipid peroxidation and antioxidant enzymes. Conclusion. The study confirmed a relationship between the lipid peroxidation activity and the hemostasis system, specifically in chronic nickel intoxication. This result allows to recommend the use of antioxidants in developing methods for correction of hemostatic induced affected by heavy metals.

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