Publications by authors named "Lara N Roberts"

65 Publications

Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: Guidance from the SSC of the ISTH.

J Thromb Haemost 2021 Oct 18. Epub 2021 Oct 18.

Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom.

Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall haemostatic rebalance or bleeding risk in the periprocedural setting; however, attempts to correct these parameters remain frequent. We review the literature on periprocedural bleeding risk, bleeding risk factors and the risk and benefits of haemostatic interventions in patients with cirrhosis. We provide guidance recommendations on evaluating bleeding risk in this patient group and management of haemostatic abnormalities in the periprocedural setting.
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http://dx.doi.org/10.1111/jth.15562DOI Listing
October 2021

Prevalence of bleeding and thrombosis in critically ill patients with chronic liver disease.

Thromb Haemost 2021 Oct 12. Epub 2021 Oct 12.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom of Great Britain and Northern Ireland.

Introduction: Haemorrhage and venous thromboembolism (VTE) are recognised complications of chronic liver disease (CLD), but their prevalence and risk factors in critically ill patients is uncertain.

Patients And Methods: We studied a retrospective cohort of patients with CLD non-electively admitted to a specialist intensive care unit determining the prevalence and timing of major bleeding and VTE (early, present on admission/diagnosed within 48h; later diagnosed >48h post ICU admission). Associations with baseline clinical and laboratory characteristics, multi-organ failure (MOF), blood product administration and mortality were explored. Odds ratios (OR) and 95% CIs were calculated using logistic regression.

Results: Of 623 patients with median age 52, bleeding (>48 hours after admission) occurred in 87 (14%) patients. Bleeding was associated with greater illness severity and increased mortality. Gastrointestinal bleeding accounted for 72% of events, secondary to portal hypertension in >90%. Procedure-related bleeding was uncommon. VTE occurred in 125 (20%) patients: Early VTE in 80 (13%) and involving the portal vein (PVT) in 85%. Later VTE affected 45 (7.2%) patients. Hepatocellular Carcinoma (HCC) and non-alcoholic liver disease were independently associated with early VTE (OR 2.79, (95% CI 1.5 -5.2) and 2.32, (1.4 -3.9) respectively), and HCC, sepsis and cryoprecipitate use with late VTE (OR 2.45, (1.11-5.43), 2.26 (1.2-4.3) and 2.60 (1.3-5.1).

Conclusion: VTE was prevalent on admission to critical care and less commonly developed later. Bleeding was associated with MOF and increased mortality. Severe MOF was not associated with an increased rate of VTE which was linked with HCC, and specific etiologies of CLD.
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http://dx.doi.org/10.1055/a-1667-7293DOI Listing
October 2021

Clinical outcomes and the impact of prior oral anticoagulant use in patients with coronavirus disease 2019 admitted to hospitals in the UK - a multicentre observational study.

Br J Haematol 2021 Sep 9. Epub 2021 Sep 9.

Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, UK.

Coagulation dysfunction and thrombosis are major complications in patients with coronavirus disease 2019 (COVID-19). Patients on oral anticoagulants (OAC) prior to diagnosis of COVID-19 may therefore have better outcomes. In this multicentre observational study of 5 883 patients (≥18 years) admitted to 26 UK hospitals between 1 April 2020 and 31 July 2020, overall mortality was 29·2%. Incidences of thrombosis, major bleeding (MB) and multiorgan failure (MOF) were 5·4%, 1·7% and 3·3% respectively. The presence of thrombosis, MB, or MOF was associated with a 1·8, 4·5 or 5·9-fold increased risk of dying, respectively. Of the 5 883 patients studied, 83·6% (n = 4 920) were not on OAC and 16·4% (n = 963) were taking OAC at the time of admission. There was no difference in mortality between patients on OAC vs no OAC prior to admission when compared in an adjusted multivariate analysis [hazard ratio (HR) 1·05, 95% confidence interval (CI) 0·93-1·19; P = 0·15] or in an adjusted propensity score analysis (HR 0·92 95% CI 0·58-1·450; P = 0·18). In multivariate and adjusted propensity score analyses, the only significant association of no anticoagulation prior to diagnosis of COVID-19 was admission to the Intensive-Care Unit (ICU) (HR 1·98, 95% CI 1·37-2·85). Thrombosis, MB, and MOF were associated with higher mortality. Our results indicate that patients may have benefit from prior OAC use, especially reduced admission to ICU, without any increase in bleeding.
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http://dx.doi.org/10.1111/bjh.17787DOI Listing
September 2021

Rivaroxaban for the treatment of superficial vein thrombosis, experience at King's College Hospital.

Br J Haematol 2021 Aug 5. Epub 2021 Aug 5.

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/bjh.17757DOI Listing
August 2021

Treatment of bleeding in patients with liver disease.

J Thromb Haemost 2021 07 6;19(7):1644-1652. Epub 2021 Jun 6.

Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital National Health Service (NHS) Foundation Trust, London, UK.

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure-related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post-procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.
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http://dx.doi.org/10.1111/jth.15364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362012PMC
July 2021

Heparins have adequate ex vivo anticoagulant effects in hospitalized patients with cirrhosis.

J Thromb Haemost 2021 06 9;19(6):1472-1482. Epub 2021 Apr 9.

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

Background: Patients with cirrhosis are at risk of venous thromboembolism (VTE), but strategies for thromboprophylaxis have not been defined. Previous in vitro studies suggest an altered anticoagulant effect of heparins in patients with cirrhosis.

Objectives: To assess the anticoagulant effects of prophylactic low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) doses in patients with cirrhosis in a real-life clinical setting.

Methods: We studied patients with cirrhosis (n = 16) and acute-on-chronic liver failure (ACLF) (n = 14), and compared these with patients without underlying liver disease admitted to non-liver general medical wards (n = 18) and non-liver intensive care units (n = 14), respectively. Blood samples were taken before and 4 h after administration of the first dose of LMWH or UFH. We assessed hemostatic status using thrombin generation assays, thrombin-antithrombin complexes (TAT), and conventional coagulation assays, and included healthy controls (n = 20) to establish reference values. Anti-Xa activity was determined to estimate peak heparin levels.

Results: Baseline thrombin generation was similar among all cohorts and healthy controls despite alterations in conventional coagulation assays. On heparin, both absolute and proportional changes of thrombin generation were comparable between all four cohorts (-62% to -85%). TAT levels decreased in all cohorts apart from the ACLF cohort, but did not correlate with the proportional change in thrombin generation. Anti-Xa activity correlated with the proportional change in thrombin generation in patients receiving LMWH, but not in patients receiving UFH.

Conclusions: These data suggest that current prophylactic heparin doses have comparable anticoagulant effects in patients with cirrhosis compared with patients without underlying liver disease.
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http://dx.doi.org/10.1111/jth.15296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252552PMC
June 2021

The effect of microgravity on the human venous system and blood coagulation: a systematic review.

Exp Physiol 2021 May 25;106(5):1149-1158. Epub 2021 Mar 25.

Space Medicine Team, European Astronaut Centre, European Space Agency (ESA), Cologne, Germany.

New Findings: What is the central question of this study? Recently, an internal jugular venous thrombus was identified during spaceflight: does microgravity induce venous and/or coagulation pathophysiology, and thus an increased risk of venous thromboembolism (VTE)? What is the main finding and its importance? Whilst data are limited, this systematic review suggests that microgravity and its analogues may induce an enhanced coagulation state due to venous changes most prominent in the cephalad venous system, as a consequence of changes in venous flow, distension, pressures, endothelial damage and possibly hypercoagulability in microgravity and its analogues. However, whether such changes precipitate an increased VTE risk in spaceflight remains to be determined.

Abstract: Recently, an internal jugular venous thrombus was identified during spaceflight, but whether microgravity induces venous and/or coagulation pathophysiology, and thus, an increased risk of venous thromboembolism (VTE) is unclear. Therefore, a systematic (Cochrane compliant) review was performed of venous system or coagulation parameters in actual spaceflight (microgravity) or ground-based analogues in PubMed, MEDLINE, Ovid EMBASE, Cochrane Library, European Space Agency, National Aeronautics and Space Administration, and Deutsches Zentrum für Luft-und Raumfahrt databases. Seven-hundred and eight articles were retrieved, of which 26 were included for evaluation with 21 evaluating venous, and five coagulation parameters. Nine articles contained spaceflight data, whereas the rest reported ground-based analogue data. There is substantial variability in study design, objectives and outcomes. Yet, data suggested cephalad venous system dilatation, increased venous pressures and decreased/reversed flow in microgravity. Increased fibrinogen levels, presence of thrombin generation markers and endothelial damage were also reported. Limited human venous and coagulation system data exist in spaceflight, or its analogues. Nevertheless, data suggest spaceflight may induce an enhanced coagulation state in the cephalad venous system, as a consequence of changes in venous flow, distension, pressures, endothelial damage and possibly hypercoagulability. Whether such changes precipitate an increased VTE risk in spaceflight remains to be determined.
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http://dx.doi.org/10.1113/EP089409DOI Listing
May 2021

Three-month follow-up of pulmonary embolism in patients with COVID-19.

Thromb Res 2021 05 26;201:113-115. Epub 2021 Feb 26.

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2021.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908844PMC
May 2021

Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis - Reply to Jacobs & Ryan comment.

J Thromb Haemost 2021 03;19(3):872-873

Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/jth.15196DOI Listing
March 2021

More on enoxaparin thromboprophylaxis in pregnancy: A review of 10 years' experience from King's College Hospital.

J Thromb Haemost 2021 01;19(1):304-308

Department of Haematological Medicine, King's College Hospital, London, UK.

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http://dx.doi.org/10.1111/jth.15128DOI Listing
January 2021

Prophylactic fresh frozen plasma and platelet transfusion have a prothrombotic effect in patients with liver disease.

J Thromb Haemost 2021 03 25;19(3):664-676. Epub 2020 Dec 25.

Liver Intensive Care Unit, Institute of Liver Studies, King College Hospital, London, UK.

Background And Aims: Patients with liver disease acquire complex changes in their hemostatic system, resulting in prolongation of the international normalized ratio and thrombocytopenia. Abnormalities in these tests are commonly corrected with fresh frozen plasma (FFP) or platelet transfusions before invasive procedures. Whether these prophylactic transfusions are beneficial and truly indicated is increasingly debated. In this study, we studied ex vivo effects of FFP and platelet transfusions in patients with liver disease-associated hemostatic changes in a real-life clinical setting.

Methods: We included 19 patients who were deemed to require prophylactic FFP transfusion by their treating physician and 13 that were prescribed platelet transfusion before a procedure. Hemostatic status was assessed in blood samples taken before and after transfusion and compared with healthy controls (n = 20).

Results: Ex vivo thrombin generation was preserved in patients with liver disease before FFP transfusion. Following FFP transfusion, both in and ex vivo thrombin generation significantly increased, as evidenced by a 92% and 38% increase in thrombin-antithrombin and prothrombin fragment 1 + 2 levels, respectively, and a 20% increase in endogenous thrombin potential. Platelet counts increased from 28 [21-41] × 10 /L before to 43 [39-64] × 10 /L after platelet transfusion (P < .01), and was accompanied by increases in in vivo markers of hemostatic activation.

Conclusions: FFP and platelet transfusion resulted in increased thrombin generation and platelet counts in patients with liver disease, indicating a prothrombotic effect. However, whether all transfusions were truly indicated and had a clinically relevant effect is questionable.
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http://dx.doi.org/10.1111/jth.15185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986736PMC
March 2021

Effect of type 1 diabetes and type 2 diabetes on the risk of venous thromboembolism.

Diabet Med 2021 May 27;38(5):e14452. Epub 2020 Nov 27.

Faculty of Health & Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Aims: Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk.

Methods: Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE.

Results: There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14).

Conclusions: Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.
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http://dx.doi.org/10.1111/dme.14452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247424PMC
May 2021

Tranexamic acid in acute gastrointestinal bleeding - A cautionary tale.

Authors:
Lara N Roberts

J Thromb Haemost 2020 10 28;18(10):2440-2443. Epub 2020 Aug 28.

Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/jth.15046DOI Listing
October 2020

Hypercoagulability and Anticoagulation in Patients With COVID-19 Requiring Renal Replacement Therapy.

Kidney Int Rep 2020 Sep 25;5(9):1377-1380. Epub 2020 Jul 25.

King's Thrombosis Centre, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1016/j.ekir.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381908PMC
September 2020

Incidence of Bleeding and Thrombosis in Patients with Liver Disease.

Semin Thromb Hemost 2020 Sep 5;46(6):656-664. Epub 2020 Aug 5.

Liver Intensive Therapy Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.

Historically, liver disease has been associated with a bleeding tendency. Global hemostatic assays have demonstrated that hemostasis is overall rebalanced, in both acute liver failure and chronic liver disease. It is now recognized that many bleeding events in chronic liver disease are mediated by portal hypertension rather than an underlying hemostatic defect. This is acknowledged in recent guidelines, which recommend against coagulation testing prior to low risk procedures in this patient group, with avoidance also of attempts at correction of prolonged coagulation times. Over time, the incidence of bleeding events has decreased in both chronic liver disease and acute liver failure, with improved supportive care, targeted treatments for underlying cause of liver disease, and the advent of liver transplantation. Concurrently, there has been increased recognition of the risk of thrombosis in chronic liver disease, with a predilection for the splanchnic vasculature. This review describes the incidence of bleeding and thrombosis in chronic liver disease and acute liver failure, including the periprocedural and liver transplantation setting.
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http://dx.doi.org/10.1055/s-0040-1714205DOI Listing
September 2020

Postdischarge venous thromboembolism following hospital admission with COVID-19.

Blood 2020 09;136(11):1347-1350

King's Thrombosis Centre, Department of Haematological Medicine, and.

The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE). Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges. Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1). COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness. Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.
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http://dx.doi.org/10.1182/blood.2020008086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483432PMC
September 2020

Pulmonary embolism in hospitalised patients with COVID-19.

Thromb Res 2020 11 10;195:95-99. Epub 2020 Jul 10.

King's Thrombosis Centre, Department of Haematological Medicine, King's College NHS Foundation Trust, London, UK. Electronic address:

Background: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19.

Objectives: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19.

Patients/methods: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR).

Results: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 ('PE likely') was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001). In the 'low probability' group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE.

Conclusions: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed.
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http://dx.doi.org/10.1016/j.thromres.2020.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351054PMC
November 2020

Fixed dose rivaroxaban can be used in extremes of bodyweight: A population pharmacokinetic analysis.

J Thromb Haemost 2020 09;18(9):2296-2307

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.

Background: Emerging safety and efficacy data for rivaroxaban suggest traditional therapy and rivaroxaban are comparable in the morbidly obese. However, real-world data that indicate pharmacokinetic (PK) parameters are comparable at the extremes of body size are lacking. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee (ISTH SSC) suggests avoiding the use of direct oral anticoagulants (DOACs) in patients weighing >120 kg or with a body mass index >40 kg/m and gives no recommendation on the use of DOACs in those <50 kg.

Objectives: To generate a population PK model to understand the influence of bodyweight on rivaroxaban exposure from clinical practice data.

Method: Rivaroxaban plasma concentrations and patient characteristics were collated between 2013 and 2018 at King's College Hospital anticoagulation clinic. A population PK model was developed using a nonlinear mixed effects approach and then used to simulate rivaroxaban concentrations at the extremes of bodyweight.

Results: A robust population PK model derived from 913 patients weighing between 39 kg and 172 kg was developed. The model included data from n = 86 >120 kg, n = 74 BMI >40 kg/m , and n = 30 <50 kg. A one-compartment model with between-subject variability on clearance and a proportional error model best described the data. Creatinine clearance calculated by Cockcroft-Gault, with lean bodyweight as the weight descriptor in this equation, was the most significant covariate influencing rivaroxaban exposure.

Conclusions: Our work demonstrates rivaroxaban can be used at extremes of bodyweight provided renal function is satisfactory. We recommend that the ISTH SSC revises the current guidance with respect to rivaroxaban at extremes of body size.
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http://dx.doi.org/10.1111/jth.14948DOI Listing
September 2020

Comment on Comparison of three transfusion protocols prior to central venous catheterisation in patients with cirrhosis; a randomised controlled trial.

J Thromb Haemost 2020 03;18(3):753-754

Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/jth.14732DOI Listing
March 2020

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay.

J Thromb Haemost 2020 04 18;18(4):834-843. Epub 2020 Feb 18.

Institute of Liver Studies, King's College Hospital, London, UK.

Background And Aims: Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin-generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma.

Methods: Thrombin-generating capacity in WB and plasma were assessed with a near-patient WB-TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed.

Results: Thirty-four patients with cirrhosis and twenty-two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB-TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB-TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma.

Conclusions: The WB-TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma-TG. The clinical value of this assay needs further validation.
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http://dx.doi.org/10.1111/jth.14751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186949PMC
April 2020

Mode of Delivery Does Not Influence Postpartum Hypercoagulability Measured by Thrombin Generation or Thromboelastometry.

TH Open 2020 Jan 7;4(1):e1-e11. Epub 2020 Jan 7.

Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital NHS Foundation Trust, London, United Kingdom.

 Venous thromboembolism (VTE) is a significant cause of maternal mortality with the greatest risk postpartum. Mode of delivery influences VTE risk, with emergency caesarean section (CS) associated with the highest risk (CS). Thromboprophylaxis is recommended for selected women to reduce the risk of VTE. We aimed to investigate the impact of mode of delivery and thromboprophylaxis on hypercoagulability as measured by thromboelastometry (TEM) and thrombin generation (TG) in women at high VTE risk.  Blood was collected from 99 pregnant women with VTE risk factors at up to five time points from pre- (T1) and post (T2)-delivery to 6 weeks postpartum (T5). Multiple linear regression was utilised to compare TG and TEM between those with vaginal delivery (VD) and CS at each time point. Paired sample -test with post hoc Bonferroni correction was utilised to compare laboratory markers over time.  Women in both groups had a median of three postpartum VTE risk factors, with higher body mass index and parity post-VD. In both the groups, TG and TEM parameters suggested hypercoagulability at T2 compared with T1, with resolution at T5. There were minimal differences between groups, apart from T2 with shorter clot formation time and higher maximum clot firmness in the VD group.  TG and TEM illustrate hypercoagulability associated with pregnancy and delivery. The pattern of postpartum hypercoagulability seen in women with VTE risk factors was similar irrespective of mode of delivery. Further research is required to establish the effect of labour on TG/TEM in the absence of low molecular weight heparin use.
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http://dx.doi.org/10.1055/s-0039-3402807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946610PMC
January 2020

Pulmonary embolism mortality trends in the European region-too good to be true?

Lancet Respir Med 2020 01;8(1):e2

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital National Health Service Foundation Trust, London SE5 9RS, UK.

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http://dx.doi.org/10.1016/S2213-2600(19)30448-5DOI Listing
January 2020

Space Medicine in the Era of Civilian Spaceflight.

N Engl J Med 2019 06;380(25):e50

King's College Hospital NHS Foundation Trust, London, United Kingdom

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http://dx.doi.org/10.1056/NEJMc1905104DOI Listing
June 2019

Direct oral anticoagulants for the management of venous thromboembolism in patients with HIV - a single centre experience.

Br J Haematol 2019 09 5;186(5):e148-e151. Epub 2019 Jun 5.

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1111/bjh.15986DOI Listing
September 2019

What are the difficulties in conducting randomised controlled trials of thromboprophylaxis in myeloma patients and how can we address these? Lessons from apixaban versus LMWH or aspirin as thromboprophylaxis in newly diagnosed multiple myeloma (TiMM) feasibility clinical trial.

J Thromb Thrombolysis 2019 Aug;48(2):315-322

King's Thrombosis Centre, Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, SE5 9RS, UK.

Routine thromboprophylaxis (TP) in newly-diagnosed multiple myeloma (NDMM) patients comprises either aspirin for standard risk patients or low molecular weight heparin for high risk patients. Studies using DOACs in cancer patients include few with myeloma. The aim of this feasibility clinical trial was to establish the foundations for creating a multicentre trial and identify any safety concerns with apixaban. Patient perspectives were sought. NDMM patients were stratified according to VTE risk and randomised to either standard TP or apixaban 2.5 mg BD and reviewed every 3 weeks throughout their chemotherapy. Two focus groups were carried out on 2 occasions at King's College Hospital and Guy's Hospital, London. Each lasted an hour, were recorded, transcribed and themes explored using NVivo 11. Ten patients were recruited, 2 considered high risk and received apixaban and 8 standard risk; 4 randomised to aspirin and 4 to apixaban. Five patients and 2 carers participated in the focus groups. There were no major bleeding or VTE events. Patients were not aware of the thrombotic risk associated with cancer. There is a lack of both written and verbal information on this topic. Myeloma patients were happy to be included in more than one trial simultaneously. Our study provides information on the difficulties facing physicians and patients on obtaining evidence of the safety of DOACs in the context of myeloma. Despite patients being happy to co-recruit into thromboprophylaxis trials along with chemotherapy trials this is not current practice.EudraCT Number: 2015-002668-18.
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http://dx.doi.org/10.1007/s11239-019-01891-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599493PMC
August 2019

Women's views, adherence and experience with postnatal thromboprophylaxis.

Thromb Res 2019 01 22;173:85-90. Epub 2018 Nov 22.

Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital Foundation NHS Trust, UK.

Introduction: Based on current guidelines, many women qualify for postnatal thromboprophylaxis following childbirth, however, little information exists on how adherent women are and their experiences to both pharmacological and mechanical forms of thromboprophylaxis.

Materials And Methods: Women requiring postnatal thromboprophylaxis were given questionnaire packs exploring their beliefs about enoxaparin, anti-embolic stockings (AES) and intermittent pneumatic compression devices (IPCD). Women were also asked to complete a diary recording when doses of enoxaparin were injected, along with an estimation of the number of hours the AES were worn each day, if at all. Results were entered onto SPSS and analysed.

Results: Sixty-seven women completed the questionnaire packs. Adherence to enoxaparin therapy was relatively high (82.4%). Women self-reported sub-optimal adherence levels to the AES, with 24% stating they never wore them once home. Reasons for this included being mobile, feeling hot and feeling as if they were cutting circulation off in the legs. Women reported a high level of acceptance of IPCD post caesarean section and would be happy for IPCD to be applied again in future deliveries, if required.

Conclusions: Although many women are adherent to postnatal TP, our findings suggest that adherence to AES is sub-optimal following discharge from hospital and therefore their usefulness is questionable. Front-line clinical staff should discuss the importance of adherence to postnatal TP, in order to avert preventable venous thromboembolic events.
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January 2019
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