Campbell Tait

Guidelines on oral anticoagulation with warfarin - fourth edition: Guideline

The writing group was selected to be representative of UK based experts. This guidance is an update of the previous guideline written in 2005 and published in 2006 (Baglin et al, 2006). The guidance is updated with reference to relevant publications since 2005. Publications known to the writing group were supplemented with additional papers identified by searching PubMed for publications in the last 5 years using the key word warfarin and limits clinical trial, randomized control trial, meta-analysis, humans, core clinical journals, and English language. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH (British Committee for Standards in Haematology), the British Cardiovascular Society and the British Society for Haematology Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the indications for and management of patients on warfarin. This guideline replaces the previous BCSH guidelines on oral anticoagulants (Baglin & Rose, 1998; Baglin et al, 2006).

Guideline on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. A United Kingdom Haemophilia Center Doctors' Organisation (UKHCDO) guideline approved by the British Committee for Standards in Haematology.

Summary.  Evidence‐based guidelines are presented on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. They include details of therapeutic products available in the UK and they update and replace previous United Kingdom Haemophilia Centre Doctors’ Organisation guidelines.

Guideline on the management of bleeding in patients on antithrombotic agents

The guideline writing group was selected to be representativeof UK-based medical experts. The MEDLINE and EMBASEdatabases were searched systematically for publications in Eng-lish from 1966 to June 2011 and 1980 to June 2011 respec-tively, using the following strategy: Approved and proprietarynames of the antithrombotic agents described in the guidelinewere combined with terms relating to antidote, reversal, haem-orrhage, (activated) prothrombin complex concentrate, factorVIII inhibitor bypass activity (FEIBA), Beriplex, Octaplex,recombinant activated factor VII (rFVIIa), Novoseven, freshfrozen plasma, tranexamic acid, antifibrinolytic, platelet trans-fusion, and desmopressin. Identified papers were also searchedfor additional references. The writing group produced the draftguideline which was subsequently revised by consensus bymembers of the Haemostasis and Thrombosis task Force of theBritish Committee for Standards in Haematology (BCSH).The guideline was then reviewed by a sounding board ofapproximately 50 UK haematologists, the BCSH and theBritish Society for Haematology Committee and commentsincorporated where appropriate. Criteria used to quote levelsand grades of evidence are as outlined in: http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html.The objective of this document is to guide healthcareprofessionals on the management of patients receivingantithrombotic drugs who experience significant bleeding orwho require emergency surgery or an invasive procedure.Guidance on reversal of vitamin K antagonists (VKAs;warfarin, phenprocoumon, acenocoumarol (sinthrome) andphenindione has been described previously (Keeling et al,2011).Antithrombotic drugs are used increasingly in patientgroups at greater bleeding risk. Although major haemorrhageis infrequent, management can be difficult especially withantithrombotics for which there are no specific reversalagents. Bleeding during antithrombotic therapy is associatedwith high morbidity and mortality (Linkins et al, 2003; Eikel-boom et al, 2006; Mannucci & Levi, 2007). Before any anti-thrombotic treatment is started, the risks and benefits shouldbe carefully considered. In this guideline we consider themanagement of bleeding in patients on the more widely usedantithrombotic agents including heparin, anti-IIa and anti-Xainhibitors, oral VKAs, anti-platelet drugs as well as the fibri-nolytic agents.

Guidelines on the investigation and management of venous thrombosis at unusual sites

Department of Haematology, Glasgow Royal Infirmary, Glasgow, Department of Haematology, Addenbrooke’s Hospital, Cambridge, Department of Haematology, Aberdeen Royal Infirmary, Aberdeen, Department of Haematology, Imperial College at Hammersmith Hospital, London, Department of Cardiovascular Science, Royal Hallamshire Hospital, Sheffield, and Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UK

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).

FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations

Summary.  In patients with severe haemophilia and inhibitors, regular factor VIII inhibitor bypassing activity (FEIBA) prophylaxis has been shown to reduce the frequency of bleeding by up to 85% and to improve patient quality of life. FEIBA is well tolerated; the incidence of thrombotic events and of allergic reactions is extremely low. The concept of prophylaxis in haemophilia patients with inhibitors is relatively new and some clinicians may be unsure of how to use FEIBA in this context. These treatment recommendations, based on published evidence plus the collective experience of a group of haematologists (with practical knowledge of managing inhibitor patients with FEIBA prophylaxis), are intended to provide guidance to clinicians considering initiating and maintaining patients on FEIBA prophylaxis with specific focus on practical aspects of patient selection, dosing, monitoring and stop criteria.

British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism (PE)

### Outcomes of outpatient care for low-risk pulmonary embolism (PE) Recommendations ### Inclusion and exclusion criteria for OP management or early discharge Recommendations

British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism

The following is a summary of the recommendations and good practice points for the BTS Guideline for the initial outpatient management of pulmonary embolism. Please refer to the full guideline for full information about each section.

Oral anticoagulant agent-associated bleeding events reporting system (ORANGE) study.

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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.