Cancer-associated venous thrombosis in adults (second edition): A British Society for Haematology Guideline.

A shared decision on the most appropriate agent for the treatment of cancer-associated thrombosis should consider the following factors, which should be reassessed as patients continue along their cancer care pathway: risk of bleeding; tumour site; suitability of oral medications; potential for drug-drug interactions; and patient preference and values regarding choice of drug. Continuing anticoagulation beyond 6 months in patients with cancer-associated venous thromboembolism and active cancer is recommended.

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.

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.

Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update.

This is a collaboration between the British Society of Gastroenterology (BSG) and the European Society of Gastrointestinal Endoscopy (ESGE), and is a scheduled update of their 2016 guideline on endoscopy in patients on antiplatelet or anticoagulant therapy. The guideline development committee included representatives from the British Society of Haematology, the British Cardiovascular Intervention Society, and two patient representatives from the charities Anticoagulation UK and Thrombosis UK, as well as gastroenterologists. The process conformed to AGREE II principles and the quality of evidence and strength of recommendations were derived using GRADE methodology. Prior to submission for publication, consultation was made with all member societies of ESGE, including BSG. Evidence-based revisions have been made to the risk categories for endoscopic procedures, and to the categories for risks of thrombosis. In particular a more detailed risk analysis for atrial fibrillation has been employed, and the recommendations for direct oral anticoagulants have been strengthened in light of trial data published since the previous version. A section has been added on the management of patients presenting with acute GI haemorrhage. Important patient considerations are highlighted. Recommendations are based on the risk balance between thrombosis and haemorrhage in given situations.

Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update.

This is a collaboration between the British Society of Gastroenterology (BSG) and the European Society of Gastrointestinal Endoscopy (ESGE), and is a scheduled update of their 2016 guideline on endoscopy in patients on antiplatelet or anticoagulant therapy. The guideline development committee included representatives from the British Society of Haematology, the British Cardiovascular Intervention Society, and two patient representatives from the charities Anticoagulation UK and Thrombosis UK, as well as gastroenterologists. The process conformed to AGREE II principles, and the quality of evidence and strength of recommendations were derived using GRADE methodology. Prior to submission for publication, consultation was made with all member societies of ESGE, including BSG. Evidence-based revisions have been made to the risk categories for endoscopic procedures, and to the categories for risks of thrombosis. In particular a more detailed risk analysis for atrial fibrillation has been employed, and the recommendations for direct oral anticoagulants have been strengthened in light of trial data published since the previous version. A section has been added on the management of patients presenting with acute GI haemorrhage. Important patient considerations are highlighted. Recommendations are based on the risk balance between thrombosis and haemorrhage in given situations.

Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study.

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Factors associated with non-prescription of oral anticoagulant treatment in non-valvular atrial fibrillation patients with dementia: a CPRD-HES study.

Dementia is a common comorbidity in patients with atrial fibrillation (AF) and treatment guidelines recommend oral anticoagulant (OAC) therapy for AF patients with dementia unless concordance cannot be ensured by the caregiver. Despite this, the literature reports a low prescribing of OAC treatment in these patients. This study investigated possible factors associated with non-prescribing of OAC treatment in dementia patients newly diagnosed with non-valvular atrial fibrillation (NVAF) at age ≥ 65 years between 2013 and 2017 using the Clinical Practice Research Datalink and Hospital Episodes Statistics databases. Of 1090 dementia patients newly diagnosed with NVAF, 693 (63.6%) patients did not have a prescription for an OAC in the year following their diagnosis. The likelihood of experiencing a thromboembolic event was high, with 97% of the population having a CHA2DS2-VASc score > 2; however, little difference in the presence of stroke risk factors was observed between the prescribed and non-prescribed groups. The presence of bleeding risk factors was high; only 28 (2.6%) of patients did not have a previous fall or a HAS-BLED bleeding risk factor. A history of falls [OR = 0.76, 95% confidence intervals (CIs) (0.58, 0.98)], previous major bleed [OR = 0.56, 95% CI (0.43, 0.73)] and care home residence [OR = 0.47, 95% CI (0.30, 0.74)] were associated with not having an OAC prescription. The results suggest that dementia patients with NVAF and certain risk bleeding risk factors are less likely to be prescribed an OAC. Further work is needed to establish possible relationships between bleeding risk factors and other potential drivers of OAC prescribing.

Haematological management of major bleeding associated with direct oral anticoagulants - UK experience.

The lack of antidotes for activated factor X-inhibitor direct oral anticoagulants (DOACs) means that management of bleeding consists largely of existing supportive therapies. This study aimed to: (i) examine the relative frequency of DOAC-related major bleeding in relation to DOAC prescriptions over the study period; (ii) describe the presentation and haematological management of DOAC-related major bleeding; and (iii) evaluate the association between the use of prothrombin-complex-concentrate (PCC) and in-hospital mortality. Over a 3-year period, 32 UK hospitals submitted data on haematological management of DOAC-related bleeding. Data consisted of 421 episodes (67%, 21%, 11% and 1% on rivaroxaban, apixaban, dabigatran and edoxaban respectively) of major bleeding on DOACs. The proportion of major bleeds on DOACs and DOAC prescriptions increased throughout the study. Overall, 44% and 37% of patients presented with gastrointestinal bleeding and intracranial haemorrhage (ICH) respectively. Drug concentrations were seldom measured. Compared to no PCC, there was a borderline evidence that receiving low dose PCC (≤25 iu/kg) was associated with better outcomes in terms of mortality (sub-distribution hazard ratio: 0·15; 95% confidence interval: 0·02-1·19; P = 0·07): but this was not the case for higher doses. DOAC concentrations are seldom measured. There was no evidence of benefit for PCC on in-hospital mortality.

Suspected cancer symptoms and blood test results in primary care before a diagnosis of lung cancer: a case-control study.

Aim: To compare symptoms and blood test results prior to cancer diagnosis in individuals who developed lung cancer and those who did not. Patients & methods: Nested case-control study, lung cancer patients were matched to up four controls with no record of cancer. Differences in symptoms and blood test results were investigated in the 2-year period prior to diagnosis. Results: 26,379 lung cancer patients were matched to 92,125 controls. Elevated C-reactive protein (CRP) was independently predictive of lung cancer at every 2-month interval 12 months prior to diagnosis. Elevated CRP in conjunction with at least one symptom was associated with greater than fourfold higher odds of lung cancer. Conclusion: CRP may be a prediagnostic marker for lung cancer, and when present with other symptoms could facilitate the investigation of high-risk individuals.

Can we use biomarkers of coagulation to predict which patients with foot and ankle injury will develop deep vein thrombosis?

BACKGROUND: Our aim was to determine whether plasma levels of Tissue Factor (TF), Vascular Cell Adhesion Molecule 1 (VCAM-1), Interleukin 6 (IL-6) or D-dimer after foot and ankle injury could predict which patients would develop deep vein thrombosis (DVT). METHODS: Patients aged 18-60 years with acute foot and ankle injury had venous blood sample to measure TF, VCAM-1, IL-6 and D-dimer within 3 days of injury. Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic. RESULTS: 21 of 77 patients were found to have DVT (27%). There was no statistically significant association between levels of TF, VCAM-1, IL-6 or D-dimer and subsequent development of DVT. CONCLUSION: Tissue Factor (TF), Vascular Cell Adhesion Molecule-1 (VCAM-1), Interleukin-6 (IL-6) and D-dimer levels were not associated with development deep vein thrombosis in patients with acute foot and ankle injury.

A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study).

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality.

Does thromboprophylaxis reduce symptomatic venous thromboembolism in patients with below knee cast treatment for foot and ankle trauma? A systematic review and meta-analysis.

BACKGROUND: Our aim was to determine the evidence for thromboprophylaxis for prevention of symptomatic venous thromboembolism (VTE) in adults with foot or ankle trauma treated with below knee cast or splint. Our secondary aim was to report major bleeding events. METHODS: MEDLINE and EMBASE databases were searched for randomized controlled trials from inception to 1st June 2015. RESULTS: Seven studies were included. All focused on low molecular weight heparin (LMWH). None found a statistically significant symptomatic DVT reduction individually. At meta-analysis LMWH was protective against symptomatic DVT (OR 0.29, 95% CI 0.09-0.95). Symptomatic pulmonary embolism affected 3/692 (0.43%). None were fatal. 86 patients required LMWH thromboprophylaxis to prevent one symptomatic DVT event. The overall incidence of major bleeding was 1 in 886 (0.11%). CONCLUSIONS: Low molecular weight heparin reduces the incidence of symptomatic VTE in adult patients with foot or ankle trauma treated with below knee cast or splint.

The effect of active toe movement (AToM) on calf pump function and deep vein thrombosis in patients with acute foot and ankle trauma treated with cast - A prospective randomized study.

BACKGROUND: Patients with foot and ankle trauma treated with cast are advised to perform toe movements to prevent venous thromboembolism (VTE). Our aim was to determine the effect of active toe movement on asymptomatic deep vein thrombosis (DVT) and venous calf pump function. METHODS: Patients aged 18-60 years with acute foot and ankle trauma requiring below knee non weight bearing cast were randomized to intervention (regular active toe movement) or control groups (n=100). Patients had bilateral lower limb venous ultrasound to assess for DVT on discharge from clinic. Patients requiring chemical thromboprophylaxis were excluded. RESULTS: 78 completed the study. 27% sustained asymptomatic DVT, with no statistically significant difference in calf pump function or DVT incidence between groups. All DVT's occurred in the injured lower limb. CONCLUSION: Active toe movement is not a viable strategy for thromboprophylaxis in patients with acute foot and ankle trauma treated with cast.

Fibrin-based clot formation as an early and rapid biomarker for progression of postpartum hemorrhage: a prospective study.

This prospective, observational study investigated the utility of Fibtem A5 and Clauss fibrinogen as predictors of progression of postpartum hemorrhage (PPH). A consecutive cohort of 356 women experiencing 1000 to 1500 mL PPH was recruited. Fibtem and fibrinogen were measured and subsequent transfusions, invasive procedures, and bleed volume recorded. Women progressing to 8 U blood products (red blood cells [RBCs] + fresh frozen plasma [FFP] + platelets) had a median (interquartile range) fibrinogen and Fibtem A5 of 2.1 (1.8-3.4) g/L and 12 (7-17) mm, respectively, compared with 3.9 (3.2-4.5) and 19 (17-23) for those not progressing. On multivariate analysis, Fibtem was an independent predictor for progression to bleeds >2500 mL (95% confidence interval [CI], 0.85 [0.77-0.95]). Receiver operating characteristic area under the curve (95% CI) for progression to RBC transfusion was 0.67 (0.60-0.74) for fibrinogen and 0.61 (0.54-0.68) for Fibtem, and progression to >2500 mL was 0.71 (0.61-0.81) and 0.75 (0.66-0.85) for fibrinogen and Fibtem, respectively. Fibtem A5 <10 mm was associated with more prolonged bleeds (median [95% CI], 127 [44-210] compared with 65 [59-71] minutes; P = .018) and longer stay in the high-dependency unit (23.5 [18.4-28.5] compared with 10.8 [9.7-11.8] hours). Fibtem is a rapidly available early biomarker for progression of PPH.

Superficial vein thrombosis: a current approach to management.

Superficial vein thrombosis (SVT) was considered to be a benign and self-limiting condition. However, it is now appreciated that a significant proportion of those presenting with SVT will have concomitant deep vein thrombosis or pulmonary embolism, or are at significant risk of developing deep venous thromboembolism. Potential therapeutic options include topical preparations, compression therapy (stockings, bandages), medication such as non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants (therapeutic or prophylactic doses) and surgery, ligation or stripping, of superficial veins. The treatment of choice is therapeutic/intermediate dose low molecular weight heparin or prophylactic dose fondaparinux administered for 4-6 weeks. The cost-effectiveness of treatment is a concern and more targeted therapy is required.

Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction).

BACKGROUND: Venous thromboembolic disease has been extensively studied in surgical patients. The benefit of thromboprophylaxis is now generally accepted, but it is medical patients who make up the greater proportion of the hospital population. Medical patients differ from surgical patients with regard to their health and the pathogenesis of thromboembolism and the impact that preventative measures can have. The extensive experience from thromboprophylaxis studies in surgical patients is therefore not necessarily applicable to non-surgical patients. This is an update of a review first published in 2009. OBJECTIVES: To determine the effectiveness and safety of heparin (unfractionated heparin or low molecular weight heparin) thromboprophylaxis in acutely ill medical patients admitted to hospital, excluding those admitted to hospital with an acute myocardial infarction or stroke (ischaemic or haemorrhagic) or those requiring admission to an intensive care unit. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). SELECTION CRITERIA: Randomised controlled trials comparing unfractionated heparin (UFH) or low molecular weight heparin (LMWH) with placebo or no treatment, or comparing UFH with LMWH. DATA COLLECTION AND ANALYSIS: One review author identified possible trials and a second review author confirmed their eligibility for inclusion in the review. Two review authors extracted the data. Disagreements were resolved by discussion. We performed the meta-analysis using a fixed-effect model with the results expressed as odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: Sixteen studies with a combined total of 34,369 participants with an acute medical illness were included in this review. We identified 10 studies comparing heparin with placebo or no treatment and six studies comparing LMWH to UFH. Just under half of the studies had an open-label design, putting them at a risk of performance bias. Descriptions of random sequence generation and allocation concealment were missing in most of the studies. Heparin reduced the odds of deep vein thrombosis (DVT) (OR 0.38; 95% CI 0.29 to 0.51; P < 0.00001). The estimated reductions in symptomatic non-fatal pulmonary embolism (PE) (OR 0.46; 95% CI 0.19 to 1.10; P = 0.08), fatal PE (OR 0.71; 95% CI 0.43 to 1.15; P = 0.16) and in combined non-fatal PE and fatal PE (OR 0.65; 95% CI 0.42 to 1.00; P = 0.05) associated with heparin were imprecise. Heparin resulted in an increase in major haemorrhage (OR 1.81; 95% CI 1.10 to 2.98; P = 0.02). There was no clear evidence that heparin had an effect on all-cause mortality and thrombocytopaenia. Compared with UFH, LMWH reduced the risk of DVT (OR 0.77; 95% CI 0.62 to 0.96; P = 0.02) and major bleeding (OR 0.43; 95% CI 0.22 to 0.83; P = 0.01). There was no clear evidence that the effects of LMWH and UFH differed for the PE outcomes, all-cause mortality and thrombocytopaenia. AUTHORS' CONCLUSIONS: The data from this review describe a reduction in the risk of DVT in patients presenting with an acute medical illness who receive heparin thromboprophylaxis. This needs to be balanced against an increase in the risk of bleeding associated with thromboprophylaxis. The analysis favoured LMWH compared with UFH, with a reduced risk of both DVT and bleeding.

The acute management of haemorrhage, surgery and overdose in patients receiving dabigatran.

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation and likely to be soon approved in Europe for treatment of venous thrombosis. Predictable pharmacokinetics and a reduced risk of intracranial haemorrhage do not negate the potential risk of haemorrhage. Unlike warfarin, there is no reversal agent and measurement of the anticoagulant effect is not 'routine'. The prothrombin time/international normalised ratio response to dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery. The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT. Commercially available DTI assays provide a quantitative measurement of active dabigatran concentration in the plasma. If a patient receiving dabigatran presents with bleeding: omit/delay next dose of dabigatran; measure APTT and thrombin time (consider DTI assay if available); administer activated charcoal, with sorbitol, if within 2 h of dabigatran ingestion; give tranexamic acid (1 g intravenously if significant bleeding); maintain renal perfusion and urine output to aid dabigatran excretion. Dabigatran exhibits low protein binding and may be removed by dialysis. Supportive care should form the mainstay of treatment. If bleeding is life/limb threatening, consider an additional haemostatic agent. There is currently no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another. Choice will depend on access to and experience with available haemostatic agent(s).

Design and rationale for REVERXaL: A real-world study of patients with factor Xa inhibitor-associated major bleeds.

BACKGROUND: The prevalence of anticoagulation treatment is increasing as an aging global population faces a high burden of cardiovascular comorbidities. Direct oral anticoagulants, including factor Xa inhibitors (FXai), are replacing vitamin K antagonists as the most commonly prescribed treatment for reducing risk of thrombotic events. While the risk of FXai-associated spontaneous bleeds is established, less is understood about their management and the effect of treatment on clinical and patient-reported outcomes. The primary objectives of the REVERXaL study are to describe patient characteristics, health care interventions during the acute-care phase, in-hospital outcomes, and associations between timing of reversal/replacement agent administration and in-hospital outcomes. Secondary/exploratory objectives focus on clinical assessments and patient-reported outcome measures (PROMs) at 30 and 90 days. METHODS: REVERXaL is a multinational, observational study of hospitalized patients with FXai-associated major bleeds in Germany, Japan, the United Kingdom, and the United States. The study includes 2 cohorts of approximately 2000 patients each. Cohort A is a historic cohort for whom medical chart data will be collected from hospitalization to discharge for patients admitted for major bleeds during FXai use within 2 years prior to enrollment of Cohort B. Cohort B will prospectively enroll patients administered any reversal/replacement agent during hospitalization to manage FXai-associated major bleeds and will include the collection of clinical outcomes and PROMs data over 3 months. CONCLUSIONS: REVERXaL will generate insights on patient characteristics, treatment approaches, and associated outcomes in patients hospitalized with FXai-associated major bleeds. These data may inform clinical practice and streamline treatment pathways in this population. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT06147830.

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

BACKGROUND: In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. METHODS: The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. RESULTS: In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. CONCLUSION: The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.