Management of haemorrhage in patients taking DOACs/ NOACs (direct/ novel oral anticoagulants) Guideline Classification: Clinical Guideline Lead Author: Dr Rowena Thomas-Dewing, Consultant Haematologist Additional author(s): Lydia Baxter, Specialist Practitioner of Transfusion; Dr Martin Thomas, Consultant in Emergency Medicine, Elizabeth Lamerton, Principal Clinical Pharmacist Authors Division: Clinical support services and Tertiary medicine Unique ID: TWCG42(12) Issue number: 3 Expiry Date: November 2020 Contents Section Page Intro Who should read this document 2 Key messages 2 Background & Scope 3 What is new in this version 3 Explanation of terms 3 References and Supporting Documents 3 Roles and Responsibilities 4 Appendices 1 Haemorrhage protocol for patients on dabigatran 5 2 Haemorrhage protocol for patients on rivaroxaban 7 3 Haemorrhage protocol for patients on apixaban 8 Document control information (Published as separate document) Document Control Policy Implementation Plan Monitoring and Review Endorsement Equality analysis Page 1 of 8
Who should read this document? All staff involved in the care of patients on oral anticoagulants Key Messages At the present time, there are no specific reversal agents (antidote) for the majority of oral anticoagulants (rivaroxaban, apixaban etc) in the event of a bleeding complication However, there is now available a reversal agent for dabigatran only. This reversal agent is idarucizamab (Praxbind ), and is only for use in specific situations outlined below. It is important to document the timing of the last dose of the novel oral anticoagulant. Dabigatran is an oral direct thrombin inhibitor. It has a plasma half life of 12 to 17 hours. Rivaroxaban is an oral factor Xa inhibitor. It has a plasma half life of 7 to 11 hours. Apixaban is an oral factor Xa inhibitor. It has a plasma half life of 8 to 15 hours. Dabigatran is renally excreted (80%). Rivaroxaban and Apixaban are partially renally excreted. The half life of these drugs are prolonged in renal impairment. Routine coagulation tests (PT, APTT) do not directly correlate with the plasma concentration of these drugs nor are they used in monitoring purposes. In case of bleeding complications, measurement of coagulation tests like PT, APTT, Thrombin time and anti Xa assays are useful because if normal, this would indicate that a minimal anticoagulant effect of the drug was present. The administration of Beriplex (PCC) or idarucizumab (Praxbind) is not based on APTT ratio but after discussion with a Haematologist in cases of major and life-threatening haemorrhage based on timing of last dose and results of coagulation tests. Page 2 of 8
Background & Scope Direct (sometimes known as novel) oral anticoagulants like dabigatran, rivaroxaban and apixaban are licensed as an alternative to coumarins (eg. warfarin) in prevention of stroke and systemic embolism in patients with atrial fibrillation and also to prevent and treat patients with venous thromboembolism. Their advantage over warfarin is that do not require monitoring in an anticoagulant clinic. However, as with all anticoagulant drugs, they carry an increased risk of bleeding. There is no specific reversal agent (antidote) for the majority of these drugs, with the exception of dabigatran. This guideline sets out the recommended action if a patient suffers a bleeding complication while taking these drugs. What is new in this version? The guidance on management of haemorrhage in patients taking dabigatran has been revised, in light of the availability of the reversal agent idarucizamab (Praxbind ). Minor formatting changes. Policy/ Guideline/ Protocol Haemorrhage protocol for Dabigatran see Appendix 1 Haemorrhage protocol for Rivaroxaban see Appendix 2 Haemorrhage protocol for Apixaban see Appendix 3 Explanation of terms & Definitions Terms explained in document References and Supporting Documents BCSH guidelines 2012 Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban. BCSH guidelines 2014 Measurement of non-coumarin anticoagulants and their effects on tests of Haemostasis. NICE evidence summary regarding idarucizumab : https://www.nice.org.uk/advice/esnm73/chapter/key-points-from-theevidence#introduction-and-current-guidance Page 3 of 8
Roles and responsibilities Executive Medical Director Accountable to the Trust Board for ensuring compliance with this protocol in all parts of the trust. All Staff Are responsible for checking that their activity complies with the guidance in this document. All trust staff should follow these guidelines when dealing with patients who have a bleeding episode while taking one of the direct oral anticoagulant drugs. Hospital Transfusion Committee Are responsible to the Trust Board for reviewing and auditing requesting and administration practice. Are responsible for reviewing the document in conjunction with the Trust Legal Department. Hospital Blood Bank The hospital blood bank will facilitate release of Prothrombin Complex Concentrates (PCCs) for patients in a timely, safe and clinically appropriate manner. Page 4 of 8
Appendices Appendix 1 Haemorrhage protocol for patients taking dabigatran Stop dabigatran and note time of last dose Request FBC, U&E/eGFR, coagulation screen, and thrombin time (TT) Contact Haematology Specialist trainee via pager 07623625698 or 07623615092 (or via switchboard out of hours) Consider oral charcoal if taken <2 hours previously APTT and TT normal: No/ minimal anticoagulant effect present APTT and TT prolonged: Dabigatran anticoagulant effect may be present Follow general principles in managing haemorrhage and contact Haematologist EARLY in case of major or life-threatening haemorrhage Minor Bleed Major Bleed Life-threatening or Uncontrolled Bleed Mechanical compression if feasible Maintain BP and urine output Manage as for Major Bleed Delay next dose of dabigatran or discontinue treatment Optimise tissue oxygenation Control haemorrhage: Refer to Major Haemorrhage protocol PLUS: Idarucizamab (Praxbind ) see below for details Give tranexamic acid 1g IV Aim for platelet count >50 (>100 in event of haemorrhage) Page 5 of 8
Dabigatran Reversal Idarucizumab (Praxbind), is a licensed product that binds specifically to dabigatran to block the anticoagulant effects of dabigatran and its metabolites. Idarucizumab will not reverse the action of other anticoagulant medicines. The action is specific to dabigatran. It must not be given unless the patient has taken dabigatran Idarucizumab is licensed for use in adults treated with dabigatran etexilate (Pradaxa), when rapid reversal of its anticoagulant effects is required: for emergency surgery or urgent procedures in life-threatening or uncontrolled bleeding. The recommended dose of idarucizumab is 5g given intravenously as 2 consecutive infusions of 2.5g/50 ml over 5 to 10 minutes each or as 2 consecutive 2.5 g bolus injections. Administration of a second 5 g dose of idarucizumab may be considered in the following clinical situations only when approved by a haematologist: recurrence of clinically relevant bleeding together with prolonged APTT and/or TT or; if potential re-bleeding would be life-threatening and prolonged APTT and/or TT or are observed or; patients require a second emergency surgery or urgent procedure and have prolonged APTT and/or TT. Further information is available in the evidence summary from NICE See References and Supporting Documents Supply: One pack of idarucizumab injection ( 2 x 2.5g vials) is stored in the fridge in the Trauma Room of the Emergency Department. To locate further stock check the on-line search tool using ida http://intranet/policies-resources/on-line-system/c/find-that-drug/ If a dose is given, the pharmacy department must be notified immediately to ensure replacement stock is ordered. Page 6 of 8
Appendix 2 Haemorrhage protocol for patients taking rivaroxaban Note: No specific reversal agent Stop rivaroxaban and note time of last dose Request FBC, U&E/eGFR, coagulation screen, AntiXa assay Contact Haematology Specialist trainee via pager 07623625698 or 07623615092 (or via switchboard out of hours) Consider oral charcoal if taken <2 hours previously PT normal: minimal anticoagulant effect present PT prolonged: Rivaroxaban anticoagulant effect may be present Follow general principles in managing haemorrhage and contact Haematologist EARLY in case of major or life-threatening haemorrhage Minor Bleed Major Bleed Life-threatening or Uncontrolled Bleed Mechanical compression if feasible Maintain BP and urine output Manage as for major bleed Delay next dose of rivaroxaban or discontinue treatment Optimise tissue oxygenation Control haemorrhage: Refer to Major Haemorrhage protocol Give tranexamic acid 1g IV Plus Beriplex 50 units/kg after discussion with Haematologist For confirmed haemorhage, administer Beriplex 50 units/kg without delay Aim for platelet count >50 (>100 in event of haemorrhage) Page 7 of 8
Appendix 3 Haemorrhage protocol for patients taking apixaban Note: No specific reversal agent Stop apixaban and note time of last dose Request FBC, U&E/eGFR, coagulation screen, AntiXa assay Contact Haematology Specialist trainee via pager 07623625698 or 07623615092 (or via switchboard out of hours) Note coagulation tests do not correlate well with apixaban levels. Follow general principles in managing haemorrhage and contact Haematologist EARLY in case of major or life-threatening haemorrhage Consider oral charcoal if taken <2 hours previously Minor Bleed Major Bleed Life-threatening or Uncontrolled Bleed Mechanical compression if feasible Maintain BP and urine output Manage as for major bleed Delay next dose of apixaban or discontinue treatment Optimise tissue oxygenation Control haemorrhage: Refer to Major Haemorrhage protocol Give tranexamic acid 1g IV Plus Beriplex 50 units/kg after discussion with Haematologist For confirmed haemorhage, administer Beriplex 50 units/kg without delay Aim for platelet count >50 (>100 in event of haemorrhage) Page 8 of 8