Hairmyres Hospital MANAGEMENT OF BLEEDING AND EXCESSIVE ANTICOAGULATION IN ADULTS RECEIVING ANTI-COAGULANTS Bleeding in patients on anticoagulants, even in the absence of over-anticoagulation, can be life-threatening or can threaten the viability of a limb. Such bleeding should be treated as a MEDICAL EMERGENCY. All such cases should be discussed both with the consultant under whose care they are and with a consultant haematologist. To contact haematology medical staff: DECT phone 4320 Monday-Friday 9am-5pm Via Hairmyres switchboard outwith these times or on public holidays 1
MANAGEMENT OF LIFE-THREATENING BLEEDING AND BLEEDING THREATENING THE VIABILITY OF A LIMB PATIENTS ON WARFARIN (or other vitamin K antagonists) (Adapted from BCSH guidelines on oral anticoagulation (1998), available online at www.bcshguidelines.com) 1. OMIT WARFARIN 2. GIVE: a. 5 mg intravenous vitamin K (in 100ml 5% dextrose over 15-20 minutes) b. At discretion of treating medical staff and consultant haematologist, ONE of the following: i. DEFIX up to 50 iu/kg body weight plus FFP 2 units OR ii. FFP 15mls/kg body weight NOTES i. DEFIX contains factors II, IX and X. Its use should be avoided if possible in patients with severe hepatic impairment, unstable coronary syndromes or DIC. Because of a potential risk of thrombosis, these patients should instead receive FFP alone at a dose of 15 ml/kg. ii. The rationale for giving a small amount of FFP along with DEFIX is to provide factor VII, which is missing from DEFIX. iii. DEFIX and FFP will not be issued without prior discussion with the duty consultant haematologist (contact details as above) 2
MANAGEMENT OF LIFE-THREATENING BLEEDING OR BLEEDING THREATENING THE VIABILITY OF A LIMB PATIENTS ON HEPARIN If the patient is receiving intravenous (unfractionated) heparin: 1. Stop the heparin infusion (half life is approximately 1 hour but increases in overdose) 2. Give protamine sulphate by slow intravenous bolus (over 10 minutes). 1mg protamine neutralises about 100 units of heparin. Maximum dose of protamine is 50mg. See protocol for administration of protamine on pages 8 and 9 of this document. If the patient is receiving low molecular weight heparin: 1. Ensure that no further heparin is given 2. Give protamine sulphate by slow intravenous bolus (over 10 minutes). Neutralisation of low molecular weight heparin is incomplete and variable (see below). Maximum dose of protamine is 50mg. See protocol for administration of protamine on pages 8 and 9 of this document. NOTES: a. Low molecular weight heparin may not be fully neutralised by protamine. The percentage of anticoagulant activity neutralised depends on the brand of low molecular weight heparin. Crowther et al (British Journal of Haematology (2002, 3
116: 178-186) found the following percentage inactivations for different low molecular weight heparins: tinzaparin 85.7% inactivated dalteparin 74% inactivated enoxaparin 54.2 % inactivated. b. There is a small risk of anaphylaxis if patients receiving protamine have previously been exposed to this agent. 4
MANAGEMENT OF LIFE-THREATENING BLEEDING OR BLEEDING THREATENING THE VIABILITY OF A LIMB PATIENTS WHO HAVE RECEIVED THROMBOLYTIC AGENTS (STREPTOKINASE, tpa) 1. Give tranexamic acid 1g by infusion in 100 ml 5% dextrose over 15 minutes OR aprotinin 500 000 kallikrein inactivator units over 10 minutes followed by 200 000 units over 4 hours. 2. Give cryoprecipitate 10 units and/or 15 mls/kg body weight FFP to replenish depleted coagulation factors, guided by results of a coagulation screen. Reference: Ludlam et al (1995) Guidelines for the use of thrombolytic therapy. Blood Coagulation and Fibrinolysis 6: 273-285. 5
MANAGEMENT OF HIGH INR WITH OR WITHOUT MINOR BLEEDING IN PATIENTS ON WARFARIN OR OTHER VITAMIN K ANTAGONISTS (Adapted from BCSH guidelines on oral anticoagulation (1998), available on-line at www.bcshguidelines.com) 1. Patients with INR greater than or equal to 8 a. omit warfarin b. Give vitamin K: 0.5 1 mg intravenously (infuse over 15 minutes in 100 ml 5% dextrose) or 1 2 mg orally (iv preparation given orally - see notes below) for all patients. 2. Patients with INR less than 8 a. Omission of warfarin may be sufficient. b. In presence of risk factors for haemorrhage, consider administration of vitamin K, 0.5 mg intravenously (infuse over 15 minutes in 100 ml 5% dextrose) or 1 mg orally (give iv preparation orally see notes below). Risk factors for haemorrhage may include: Age >75 Severe hypertension History of significant GI bleed Recent (< 1 month) cerebrovascular accident Recent (<1 month) major surgery NOTES i. Administration of the intravenous preparation of vitamin K orally is UNLICENSED, although widely practised. 6
ii. Ensure that whoever monitors the patient s warfarin is informed AS SOON AS POSSIBLE of any change to warfarin dose and/or of need to give vitamin K. iii. Ensure that appropriate arrangements are in place for resumption of INR checks (eg next day) and that patient is aware of these. Protamine Injection Preparation Protamine sulphate is available as 10mg/ml in 5ml ampoules. Indication Protamine sulphate is used as an antidote to heparin. Dose The dose of protamine to be given depends on the type of heparin used and the length of time since the dose was given. No more than 50mg should be given in one dose. Heparin Bolus: Time elapsed since dose given Protamine dose per 100units of heparin Protamine dose for 5000units of heparin 30mins 1-1.5 mg 50mg 30-60mins 0.5-0.75mg 25-37.5mg 2 hours 0.25-0.375mg 12.5-18.75mg Heparin Infusions: Stop the infusion and give 25-50mg of protamine. Subcutaneous Heparin -including Low Molecular Weight Heparin (LMWH): One mg of protamine per 100units of heparin give 25-50mg as a slow IV injection and the remainder as a slow infusion over 8-16 hours or as 2hourly divided doses. Administration Protamine is given as a slow IV bolus over 10mins, at a maximum of 5mg/minute. If an infusion is required dilute with sodium chloride 0.9%, 100ml or 250ml bag. 7
Hypersensitivity to protamine. Contraindications Cautions/Monitoring Check activated partial thromboplastin time (APTT) 5-15minutes after giving protamine. Further doses of protamine may be required because protamine is cleared from the body quicker than heparin, especially LMWH. The anti-xa activity of LMWHs may not be completely reversed with protamine: refer to individual data sheets for further information and see also information given on pages 3 and 4 of this document. Please note the information provided is a guide for treating adult patients. Always refer to the product data sheet for full details 8