Clinical Guidelines PROMOTING EXCELLENCE IN TRANSFUSION MEDICINE. Nova Scotia Provincial Blood Coordinating Program

Transcription

1 Clinical Guidelines PROMOTING ECELLENCE IN TRANSFUSION MEDICINE Nova Scotia Provincial Blood Coordinating Program Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia March 2013 Version 2.0

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3 Guideline prepared by: Susan Cairns BN RN Utilization Transfusion Practice Coordinator Nova Scotia Provincial Blood Coordinating Program 7th Floor Centennial Building, Room South Park Street Halifax, Nova Scotia B3H Y29 Phone: (902) March 2013 Version 2.0 2

4 CONTENTS 1. Background Guideline Development Membership Overview of New Recommendations Guideline Definitions Therapeutic goals Selection of blood component therapy Red Cells Platelets Plasma and Cryoprecipitate Communication Massive Transfusion Algorithm Explanation of Algorithm References Appendix A Preprinted Physician Order for facilities with platelets. 20 Appendix B Preprinted Physician Order for facilities without platelets. 22 Appendix C Selected C.S.A. Z Standards Pertinent to Massive Transfusion Appendix D Conflict of Interest Declaration for Massive Transfusion Working Group Copyright and Adaptation of These Guidelines The Nova Scotia Provincial Blood Coordinating Program (NSPBCP) encourages the sharing and exchange of these guidelines for clinical and educational purposes. Please include the recommended citation below to indicate the source document. If you wish to reproduce these in whole or in part for any purposes, written permission must be obtained from the NSPBCP. Recommended Citation: Nova Scotia Provincial Blood Coordinating Program Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia (2013) March 2013 Version 2.0 3

5 1 Background The Nova Scotia Provincial Blood Coordinating Program (NSPBCP) is a provincial program of the Quality, Safety and Wait Time Improvement branch of the Nova Scotia Department of Health and Wellness. The NSPBCP was created in January 2003 and provides leadership in promoting excellence in transfusion medicine. The NSPBCP collaborates with health care providers in the DHAs/IWK and Canadian Blood Services (CBS) in order to support the appropriate management and safe administration of blood and blood products to patients in Nova Scotia. As a provincial program, the strategic directions of the NSPBCP are determined by a Program Advisory Council, while working groups advise and support the NSPBCP in the development of blood related standards. The NSPBCP developed the Guideline for Massive Transfusion in Nova Scotia in 2010 in response to the identified need by the Nova Scotia Provincial Blood Contingency Plan to provide guidance and standardization for the use of blood and blood components in patients who are massively bleeding. Since 2010, recent literature has provided updates to the care of the massively bleeding patient requiring revision of this guideline. The guideline and information on massive transfusion has been prepared specifically for use in Nova Scotia however the NSPBCP encourages the exchange and sharing of the information contained within for clinical and educational purposes. The information in this document is intended as suggested guidelines, procedures, and forms to provide clinical guidance to healthcare professionals on the use of blood components/products during the management of massive blood loss. The appendices in the Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia have also been reviewed and updated to support the implementation of the massive transfusion guideline. The appendices provide pre-printed order forms, data collection tools and log forms. March 2013 Version 2.0 4

6 2 Guideline Development Membership The following Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia has been prepared in collaboration with the provincial Massive Transfusion Working Group (MTWG). The Nova Scotia Provincial Blood Coordinating Program (NSPBCP) would like to acknowledge the tremendous and diligent work of the provincial working group, which provided invaluable contributions in the development of this guideline. Massive Transfusion Working Group Dr. Guy Brisseau Medical Director of Trauma Nova Scotia Trauma Program Dr. Robert Green Department of Emergency Medicine QEII Health Sciences Centre Dr. Eiad Kahwash Medical Director, Canadian Blood Services, Nova Scotia and Prince Edward Island Dr. Blaine Kent Chief, Division of Cardiac Anesthesia QEII Health Sciences Centre. Surgical Director, Perioperative Blood Management Program Dr. R. Grayson Lloyd Department of Anesthesia Valley Regional Hospital Kentville, NS Dr. Samuel Minor General Surgery, Critical Care Medicine QEII Health Sciences Centre Halifax, Nova Scotia Dr. Irene Sadek Medical Director, Blood Transfusion Services, Capital District Health Authority Dr. Romesh Shukla Chief of Women s and Obstetric Anesthesia IWK Health Centre Dr. Craig Stone Department of Anesthesia Cape Breton Regional Hospital Sydney, NS Dr. Natalie Yanchar Medical Director IWK Trauma Care Dorothy Harris Hospital Customer Service Representative, Canadian Blood Services, NS/NL Chris Nickerson Program Manager, Emergency Health Services Nova Scotia Trauma Program Heather Mingo Conservation Nurse Coordinator Perioperative Blood Management Program Michelle Rogerson Regional Manager Production CBS, NS/PEI Maria Wadden Medical Laboratory Technologist Transfusion Medicine Quality Specialist Cape Breton Regional Hospital Sydney, NS NSPBCP Dr. David Anderson Clinical Advisor Marina Hamilton Program Manager Susan Cairns Utilization Transfusion Practice Coordinator Declaration of Conflict of Interest Members of the MTWG completed the Conflict of Interest form with one member reporting they have previously conducted research for and presently hold stock in the manufacturing company for activated recombinant Factor VII (rfviia), Novo Nordisk Inc. March 2013 Version 2.0 5

7 3 Overview of New Recommendations The Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia developed by a multi-disciplinary working group representative of medical experts and health care professionals from both adult and pediatric facilities throughout Nova Scotia was initially developed in Membership included representatives from hematology, anesthesiology, emergency medicine, critical care, nursing, medical laboratory technology, transfusion medicine, Canadian Blood Services, Perioperative Blood Conservation Program and the Nova Scotia Trauma Program. Since 2010, there has been new literature and information regarding the care of the patient who is massively bleeding. For this reason, the Guideline for Massive Transfusion in Nova Scotia has been revised to reflect current recommendations. The Massive Transfusion Working Group (MTWG) was reconvened by the NSPBCP with the intent to review the relevant literature and to provide advice on best practice for the care of the massively bleeding patient. The document has also been renamed to accurately indicate the scope of clinical practice intended in the document Guideline for the Appropriate Use of Blood Components/Products during a Massive Transfusion in Nova Scotia. The key areas of discussion were: The National Advisory Committee on Blood and Blood Products (NAC) Massive Transfusion Consensus Conference 2011 key findings include a lack of evidence to support the use of 1:1:1 blood component ratios as the standard of care, the importance of early use of tranexamic acid, the expected value of an organized response plan, and the recommendation for an integrated approach including antifibrinolytics, rapid release of red blood cells, and a foundation ratio of blood components adjusted by results from either traditional coagulation tests or clot viscoelasticity or both. The MTWG reviewed the recommendations from the NAC Massive Transfusion Consensus Conference 2011 and determined the transfusion ratio in NS will continue at 1:1:1 (RBC: Plasma: Platelets). The earlier introduction of tranexamic acid in the resuscitation process has been shown to reduce blood loss in trauma (CRASH-2 Trial) and surgical patients. The MTWG has recommended tranexamic acid be administered earlier in the resuscitation process. Recombinant Factor VIIa (rfviia), also known as NiaStase (eptacog alfa, activated), is licensed in Canada for hemophilia A/B patients with inhibitors to Factor VIII or Factor I, respectively, for the treatment of bleeding episodes (including treatment and prevention of those occurring during and after surgery). (NiaStase Product Monograph) In 2012, NAC revised the transfusion policy framework for the off-label use of rfviia in massive bleeding. Given the absence of evidence of benefit and with evidence of the risk of harm, the NAC recommends that rfviia no longer be used for the off-label indications of prevention and treatment of bleeding in patients without hemophilia. (Lin et al, 2012, p. 10) In Nova Scotia, the MTWG agreed with the evidence and recommends the off-label use of rfviia should be very limited and only considered in very rare situations, as discussed in this document, with the knowledge there is risk of harm with the use of this product. For this reason, the Massive Transfusion Algorithm reference to the use of rfviia is presented with a warning label. All other corrective measures as outlined in this document are to be attempted prior to the administration of rfviia. The NSPBCP will continue to collect and evaluate the utilization data for rfviia. March 2013 Version 2.0 6

8 4 Guideline Massive bleeding may be the result of trauma, gastrointestinal bleeding, obstetrical hemorrhage, ruptured aortic aneurysm, or surgical procedures. Implementation of a Massive Transfusion Protocol (MTP) promotes early and aggressive coagulation factor therapy as well as the limitation of crystalloid infusion, the prevention of coagulopathy, hypothermia and acidosis (the Lethal Triad ), and permission for moderate hypotension (Shaz et al, 2009, p. 1766). Figure 1: The interplay between metabolic acidosis, hypothermia and progressive coagulopathy in trauma (modified from Moore & Thomas Memorial lecture, with permission from Excerpta Medica Inc.) (as cited in Spahn & Rossaint, 2005, p.133) The objective of the guideline is to provide clinical guidance to healthcare professionals on the use of blood and blood components during the management of massive blood loss. Guidelines should not replace specific decisions for individual patients, and do not substitute for the shared decisions between any patient and doctor (or other health professional) which are unique to each circumstance. Guidelines provide evidence-based background information and consensus-based recommendations for consideration when making individual decisions. While this guideline provides perimeters for the use of blood components and products in children, there is minimal literature regarding the care of the pediatric patient experiencing trauma induced coagulopathy and massive transfusion. (Shaz et al, 2009, p. 1766) 4.1 Definitions Mollison et al (1997) defined massive blood loss as the loss of one blood volume or more within a 24 hour period, (as cited in Stainsby, MacLennan, Thomas, Isaac, Hamilton, 2006, p. 634) the normal adult blood volume being approximately 7% of ideal body weight in adults and 8-9% in children (Stainsby, MacLennan, Hamilton, 2000, p. 487). Fakhry & Sheldon (1994) gave alternative definitions that may be more helpful in the acute situation include a 50% blood volume loss within 3 hours or a rate of loss of 150 ml/min (as cited in Stainsby et al, 2006, p. 634) or requiring four (4) units (or 40 ml/kg in children) of RBCs in four (4) hours in the setting of major bleeding. March 2013 Version 2.0 7

9 Table 1: Classification of hemorrhage in the adult Symptom Class I Class II Class III Class IV Blood Loss (ml) Up to Greater than 2000 Blood Loss Up to 15% 15% - 30% 30% - 40% Greater than 40% Pulse rate Less than Greater than 140 Blood Pressure Normal Normal Decreased Decreased Pulse Pressure (mm Hg) Normal or Increased Decreased Decreased Decreased Respiratory Rate Greater than 35 Urine Output (ml/hr) Greater than Negligible Capillary refill Normal Slow (>2 sec) Slow (>2 sec) Undetectable Extremities (color) Normal Pale Pale Pale + cold Complexion Normal Pale Pale Ashen CNS/ Mental status Slightly Anxious Mildly Anxious or Anxious, confused, Confused, lethargic, Alert Aggression aggressive / drowsy unconscious Fluid Replacement None Crystalloid/colloid Blood + crystalloid Blood + crystalloid Note. Adapted from British Committee for Standards in Haematology Blood Transfusion Taskforce (BTT) 2001 and American College of Surgeons (ACS), Therapeutic goals It is imperative to recognize major blood loss early and institute effective action promptly if shock and its consequences are to be prevented. (Stainsby et al, 2006, p. 634) Sauaia et al (1995) found coagulopathy is present in 65% of patients requiring massive transfusion and hemorrhage may account for 33% of in-hospital deaths, particularly in the first 24 hours (as cited in Shaz et al, 2009, p. 1760). Hewson et al (1985) and Ferrara et al (1990) stated coagulopathy after hemorrhage is thought to be a secondary event because of the triad of depletion and dilution of coagulation factors, acidosis, and hypothermia (as cited in Shaz et al, 2009, p. 1760) associated with massive transfusion. Iserson and Heustis (1991) have stated that hypothermia increases risk of end organ failure and coagulopathy (as cited in Stainsby et al, 2006, p. 636) and may be prevented by prewarming of all resuscitation fluids, external warming devices such as warm air blankets, thermal caps, heated respiratory gases and the use of temperature controlled blood warmers. (ACS, 2008, p. 67) 4.3 Selection of blood component therapy Group specific blood components or compatible blood components (if group specific are not available) should be given as soon as possible. Table 2: ABO Compatibility for RBCs, Plasma, and Platelets Recipient Donor ABO Group ABO Group RBCs Plasma Platelets UNKNOWN O AB AB O O O, A, B, AB O, A, B, AB A A,O A, AB A, AB B B, O B, AB B, AB AB AB, A, B, O AB AB Note. Adapted from Canadian Blood Services (2007). Clinical Guide to Transfusion. March 2013 Version 2.0 8

10 4.3.1 Red Cells Hemoglobin and hematocrit levels should be monitored, although the hemoglobin level may be a poor indicator of blood loss in the acute situation. Red cells are rarely indicated when the hemoglobin concentration is greater than 100 g/l but almost always indicated when it is less than 70 g/l. (British Committee for Standards in Haematology Blood Transfusion Taskforce, 2001) Schwab et al (1986) advise it is acceptable to give group O Rh (D) positive RBCs to females of non-childbearing potential and to males with unknown blood group (as cited in Stainsby et al, 2006, p. 637). Children and women with childbearing potential should receive Group O Rh (D) negative RBCs (CSA Standard Z902-10, page 56) Platelets Platelets should be transfused when the count falls below 75 x 10 9 /L in the acutely bleeding patient or below 100 x 10 9 /L in patients who have sustained a CNS injury (ACS, 2008) or for those with multiple high-velocity trauma (Stainsby et al, 2006, p. 638). If Rh positive platelets are given to a female with childbearing potential and the patient is later determined to be Rh negative, consider passive immunization with an anti-d agent such as WinRho. For the purpose of massive transfusion, 1 adult dose of platelets = one buffy coat unit of platelets = 4 random donor platelets = one unit of apheresed platelets Plasma and Cryoprecipitate It is essential laboratory tests for coagulation (PT/INR, PTT and fibrinogen) be monitored frequently and may require interpretation by a hematologist. Plasma is less inflammatory than artificial colloid, albumin or lactated ringers (University Health Network, Ont.) therefore plasma should be initiated as soon as possible. Early and intensive therapy with plasma and platelets appear to be associated with better patient outcomes. (McClelland, 2007) For trauma patients presenting with exsanguinating hemorrhage, coagulopathy correction beginning with aggressive FFP administration may improve resuscitation and outcome. (Gonzalez et al, 2007, p. 119) In vitro evidence has shown clot formation and strength improves with higher fibrinogen levels. During massive blood loss replacement, fibrinogen may be the first coagulation factor to decrease critically. Fibrinogen concentrate or cryoprecipitate should be administered if significant bleeding is accompanied by thromboelastometric signs of a functional fibrinogen deficit or a plasma fibrinogen level less than g/l; an initial fibrinogen dose of 3-4 g or 50 mg/kg of cryoprecipitate, approximately equivalent to units in a 70 kg adult, may be employed. (Rossaint et al, 2010) March 2013 Version 2.0 9

11 4.4 Communication Treating clinicians will determine when to transfer patients based on the medical needs of the patient and the resources/capabilities of the sending institution or patient care unit. In situations where the Massive Transfusion Protocol has been activated in one facility and the patient is to be transferred to another facility, the Massive Transfusion Protocol will need to be activated in the second facility as well. Inpatients Transfers of massively bleeding inpatients should be facilitated through existing routine transfer processes. Trauma Patients Transfers of trauma patients should be facilitated through The Nova Scotia Trauma Program. The Provincial Trauma Team Leader can be contacted at , if inter-facility transport is being considered. Initiation and Termination of MTP To minimize miscommunication, the physician leading the resuscitation efforts or delegate should initiate and terminate the MTP with the blood bank. Similarly, within the blood bank each MTP should be coordinated by a single blood bank technologist. 5 Massive Transfusion Algorithm The recommendations have been summarized in algorithm format and should be displayed in highrisk clinical areas, e.g. emergency departments, intensive care units, operating rooms, labor/delivery/recovery unit and blood transfusion laboratories. The algorithm provides a description of the goals of treatment, the key steps for treatment and blood components/product administration utilization during the treatment of massive bleeding. Documentation should consist of a minimum dataset that must record: type of blood component or replacement fluid, time given, amount (dosage), indication for replacement, effectiveness of the transfusion. Full traceability of blood components transfused is imperative. Accurate documentation of blood components given, reason for transfusion and any adverse reactions observed, is necessary in order to enable audit of outcome and satisfy compliance with standards for full traceability (CSA Standard Z902-10). March 2013 Version

12 BLOOD COMPONENT / BLOOD PRODUCT USE DURING A MASSIVE TRANSFUSION IDENTIFY AND TREAT ACTIVE BLEEDING (Obstetrical, Surgical, Trauma, Medical) STABILIZE AND TRANSPORT TO REFERRAL CENTRE Care should be initiated within the resources and capabilities of the sending institution, which will vary depending on the hospital. ACTIVATE MTP if patient is bleeding with anticipation of ongoing blood loss or bleeding requiring at least four (4) units of RBCs (adults) or 40 ml/kg (children) in four (4) hours. Establish or assign patient identification If the patient is transferred to another facility, the MTP will need to be activated in the second facility. CALL BLOOD TRANSFUSION SERVICE/BLOOD BANK (BTS/BB) TO ACTIVATE MTP Provide contact information of physician leading the MTP Provide patient information BTS will notify the BTS/BB Medical Director as appropriate MEDICAL-SURGICAL INTERVENTIONS Prior to initiation of treatment, send STAT: CBC, INR/PTT, Fibrinogen, Electrolytes, Creatinine, Mg ++, Ionized Ca ++, serum lactate, Group and Screen, Blood Gas (blood work done based on facility s capabilities) Consider cell salvage Warm all fluids Perform surgical/interventional radiology interventions as appropriate If treatment is within 3 hours of injury, consider tranexamic acid 1 gram IV over 10 minutes followed by 1 gram IV over 8 hours. Anticoagulant reversal o Oral vitamin K 1 antagonists - (e.g. Warfarin/Acenocoumarol) INR 1.7 to PCC 40 ml IV and - vitamin K 1 (Phytonadione) 10 mg IV INR 5.1 or Intracranial Hemorrhage or unknown INR - PCC 80 ml IV and - vitamin K 1 (Phytonadione) 10 mg IV o o Heparin - Protamine 1 mg IV for every 100 units of Heparin Direct thrombin inhibitors/direct factor a inhibitors (Apixaban/Dabigatran/Rivaroxaban) - no known antidote. Replace fluid loss with appropriate fluid replacement. Transfuse RBCs, plasma and/or platelets as needed. Plasma will not reverse the anticoagulant effects of these drugs. INITIAL TRANSFUSION MANAGEMENT ADULTS: o RBCs 6 units and o Plasma 1500 ml and o Platelets* 1 adult dose PEDIATRICS: o RBC 15 ml/kg and o Plasma ml/kg and o Platelets* 5-10 ml/kg *In hospitals where platelets are not inventoried and the patient will be managed on site, consider requesting platelets from CBS. MAINTAIN Ionized calcium greater than 1.13 mmol/l Urine output greater than 0.5 ml/kg/h Systolic blood pressure greater than 70 mmhg Temperature greater than 35ºC ph greater than 7.10 MAINTAIN Hemoglobin above 70 g/l with RBCs: Adults: 2-10 units Pediatrics: 15 ml/kg Platelet count above 75x 10 9 /L OR above 100 x 10 9 /L (CNS injury) with Platelets: Adults: 1 adult dose Pediatrics: 5-10 ml/kg INR below 1.7 with Plasma: Adults: ml Pediatrics: ml/kg Fibrinogen above 1.5 g/l with Cryoprecipitate: Adults: 10 units Pediatrics: 1 unit/10 kg REASSESS CBC, INR/PTT, fibrinogen, blood chemistries as appropriate CONSIDER DISCONTINUING BLOOD COMPONENT THERAPY WHEN Shock has resolved Bleeding is under control Inform BTS when MTP is terminated FOR ONGOING BLEEDING Reassess for the source of bleeding Repeat blood components based on lab results and in consultation with BTS, consider other Prohemostatic Drugs: DDAVP o Adults: 10.0 mcg/m 2 IV (max 20 mcg) o Pediatrics: 0.3 mcg/kg rfviia WARNING rfviia should only be considered in rare circumstances after all other measures have been carried out and there is a likelihood the patient will survive. rfviia dosing is mg/kg IV Direct NSPBCP Version 2.0 March

13 5.1 Algorithm details - Blood Component/Blood Product Use during a Massive Transfusion Identify and treat active bleeding - Medical, Obstetrical, Surgical, and Trauma. Stabilize patient and transport to referral centre - Care should be initiated within the resources and capabilities of the sending institution, which will vary depending upon the hospital. Smaller hospitals should be encouraged to participate in regional or provincial trauma systems, to optimize local resources, to establish criteria for referral of care, and to establish pathways for communication and expeditious transfer for definitive trauma care. (NAC Massive Transfusion Consensus Conference 2011) Activate the Massive Transfusion Protocol (MTP) - Criteria for activation of the massive transfusion protocol: Bleeding with the anticipation of ongoing blood loss or requiring at least four (4) units of RBCs (adults) or 40 ml per kg (children) in 4 hours. If the MTP has been activated at one facility and the patient is to be transferred to another facility, the MTP will need to be activated at the second facility as well. o Emergency Health Services may activate the massive transfusion protocol (MTP) prior to arrival at an emergency department. o Call Blood Transfusion Service (BTS) Provide the name, location and phone number for the physician leading the MTP Patient name, age, sex, HCN, diagnosis, any known special transfusion requirements (e.g., antigen negative, CMV-negative or irradiated), treatment to date. If patient name and/or health card number (HCN) are unknown (e.g., patient not yet registered in the hospital), request that a unique anonymous identifier be provided. All patients must be identified by two independent and unique alphanumeric identifiers (American Association of Blood Banks, 2005, p. 7). Request immediate issue of uncrossmatched blood components. Upon receiving this activation, the BTS will prepare the initial MT package for adults with an unknown blood group - six units of RBCs, 1500 ml plasma and 1 adult dose of platelets. Upon confirmation of the patient s blood grouping, the blood bank should issue group specific or compatible RBCs, plasma and platelets. Note: Due to plasma requiring a thaw time, the initial package may be sent as the components are ready, i.e. the RBCs are sent first with the plasma sent once thawed. For children under 50 kg, the transfusion amounts are: RBC = 15 ml/kg and plasma = ml/kg and platelets = 5-10 ml/kg. Note: a patient sample must be collected even if uncrossmatched RBCs have been requested. BTS to notify their Medical Director of the activation of the MTP as appropriate. Medical-Surgical Interventions o Perform the following laboratory investigations prior to initiating any fluid resuscitation: Draw a group and screen as per normal sample collection policy, CBC, aptt, INR, o o fibrinogen, arterial blood gas, electrolytes, serum creatinine, ionized Ca ++, as per facility capabilities. The pre-transfusion testing may be abbreviated according to policies and procedures established by the medical director. (CSA Standard Z902-10, p. 56) Ensure adequate venous access with two large bore IV lines. Initiate fluid resuscitation with either normal saline or Ringer s lactate, start plasma/rbc infusion as soon as available. Permissive hypotension (e.g. systolic BP no higher than 90 mmhg) should be considered, particularly for penetrating torso trauma. (Tien et al, 2007, p. 205) March 2013 Version

14 o o o o o o Infuse all fluids including RBCs, plasma and crystalloid via a rapid infuser with in-line warmer. Infuse Group O RBCs (Rh negative to children and women of child-bearing age). For infants under 4 months of age, only RBCs that are negative for hemoglobin S should be transfused. (CSA Standard Z902-10, p. 56) Employ cell salvage if available. If blood loss is from a clean surgical field in a patient without underlying malignancy, initiate cell salvage procedures where available. (Capital Health, 2010) RBCs, platelets, plasma, and cryoprecipitate must be infused as per hospital policy. Perform all appropriate surgical and interventional radiology interventions in order to control bleeding. Ensure all required relevant services are notified, including surgery, interventional radiology, anesthesia and critical care. If treatment can be initiated within 3 hours of injury, consider administering tranexamic acid intravenously 1 gram over 10 minutes followed by an infusion of 1 gram over 8 hours. (Dzik et al, 2011, p. 3) It is recommended tranexamic acid be included in the pharmacy stock in operating rooms and emergency departments. Discontinue all anticoagulants and consider the specific antidotes as follows: o Table 3: Anticoagulants and Antidotes Anticoagulant Examples Antidote Heparin Sodium Unfractionated Heparin (UFH) Low Molecular Weight Dalteparin (Fragmin ) Protamine sulfate 1 mg/100 Units (Note: Protamine Sulfate does not fully Heparin (LMWH) Enoxaparin (Lovenox ) reverse LMWH) Tinzaparin (Innohep ) Heparinoid Danaparoid (Orgaran ) No specific antidote Vitamin K Antagonists Acenocoumarol (Sintrom ) vitamin K 1 (Phytonadione) 10 mg IV Warfarin (Coumadin ) AND Prothrombin Complex Concentrate INR 1.7 to ml INR greater than or equal to 5.1 or Intracranial Hemorrhage or unknown INR - 80 ml Direct Thrombin Inhibitors Argatroban (Argatroban ) No specific antidote Bivalrudin (Angiomax ) Dabigatrin (Pradax ) Factor a Inhibitors Direct Apixaban (Eliquis ) Rivaroxaban (arelto ) No specific antidote Indirect Fondaparinux (Arixtra ) Antiplatelet agents Acetylsalicylic Acid (Aspirin ) Platelet transfusion Clopidogrel (Plavix ) Dipyridamole (Persantine ) Dipyridamole & ASA (Aggrenox ) Glycoprotein IIb/IIIa inhibitors o Abciximab (ReoPro ) o Tirofiban (Aggrastat ) Prasugrel (Effient ) Ticagrelor (Brilinta ) Ticlopidine (Ticlid ) Adapted from University Health Network, Policy & Procedure Manual, Massive Transfusion Protocol-Clinical Note. Dose of antidote may be reduced if anticoagulant has already been held several hours earlier. Hematology consultation recommended. March 2013 Version

15 o Direct thrombin inhibitors / direct factor a inhibitors (dabigatran/rivaroxaban) No known antidote. Replace fluid loss with RBCs, plasma and/or platelets. The anticoagulant effect of apixaban, dabigatran or rivaroxaban will NOT be reversed by administration of vitamin K or plasma. Atlantic Collaborative Recommendations for Managing the Bleeding Patient on Apixaban, Dabigatran or Rivaroxaban Moderate to severe bleeding a reduction in Hgb 20g/L, symptomatic bleeding in an organ or critical area, 1 e.g. intraocular, intracranial, intramuscular, retroperitoneal, intra-articular or pericardial bleeding. Life-threatening bleeding a reduction in Hgb 50g/L, symptomatic intracranial bleed, hypotension requiring 1 inotropic agents, e.g. dopamine, bleeding requiring surgery. There is insufficient evidence to recommend the use of Prothrombin Complex Concentrates (octaplex or Beriplex P/N), FEIBA or rfviia (NiaStase ) for the reversal of these medications. 4 Initial transfusion management o Adults - 6 units RBCs, 1500 ml plasma, 1 adult dose of platelets o Pediatrics ml/kg RBCs, ml/kg plasma, 5-10 ml/kg platelets o In hospitals where platelets are not inventoried and if the patient will be managed on site, consider requesting platelets from CBS. o Women with child bearing potential and children should receive Rh negative blood components. o Reassess bleeding rate between doses of blood products. Repeat CBC, INR/PTT, fibrinogen and blood chemistries as appropriate (serum lactate q4hours). Document transfusions and relevant laboratory tests. o For ongoing massive bleeding, order blood products based on the last available laboratory tests. March 2013 Version

16 For ongoing bleeding o Reassess for source of active bleeding. o Repeat blood components based on lab results and in consultation with BTS. Consider: DDAVP - Adults 10 mcg/m 2 Maximum 20 mcg. Pediatrics 0.3 mcg/kg rfviia - Given the absence of evidence of benefit and with evidence of the risk of harm, the NAC recommends that rfviia no longer be used for the off-label indications of prevention and treatment of bleeding in patients without hemophilia. (Lin et al, 2012, p. 10) The NAC recognizes the reported use of rfviia in clinical trials may differ from situations where rfviia may be used as a last ditch effort (Lin et al, 2012, p. 10) to save a patient. Only consider rfviia in rare circumstances where there is a reasonable expectation the patient will survive their injuries and after all other transfusion and therapeutic measures have been carried out including: hemostatic measures to correct a. bleeding surgical and/or interventional radiology b. acidosis (ph greater than 7.1) c. hypocalcemia (ionized calcium greater than 1.13 mmol/l) d. hypothermia (temperature greater than 35 0 C) aggressive blood component support a. the patient has received 8 or more units of red blood cells (RBCs) in 24 hours or more than 4 units RBCs in the first hour of resuscitation (for pediatric cases, more than 1.5 times the infant/child blood volume). RBCs to maintain a hemoglobin greater than 80 g/l b. platelet transfusions to maintain a platelet count of greater than 100 x 10 9 L for head trauma or neurosurgery patients, or a platelet count greater than 50 x 10 9 L for all other patients c. plasma transfusions if the PTT is greater than 1.5 times normal or if the INR is greater than 1.7 d. cryoprecipitate to maintain a fibrinogen greater than 1.5 g/l administration of antifibrinolytics a. tranexamic acid 10 mg/kg b. DDAVP 10 mcg/m2 (adult dose) maximum dose - 20 mcg 0.3 mcg/m2 (pediatric dose) maximum dose - 20 mcg In situations where the attending physician requests rfviia, the request will be assessed and approved on a case-by-case basis by the Blood Transfusion Service/Blood Bank (BTS/BB) physician based on the medical screening clinical recommendations listed above. The following questions may serve as a guide: o What is the patient clinical presentation and the rationale for use? o What blood components have already been infused? o What is the fibrinogen level, the INR, ph and the platelet count? o Is the patient hypothermic? For these other indications the requesting physician should contact the BTS/BB physician on call to provide specific criteria about the indication for requesting rfviia. The BTS/BB physician will determine if the prerequisites have been met and if rfviia should be issued. March 2013 Version

17 rfviia is dosed according to body weight. rfviia should be rounded to the nearest vial size to avoid wastage. Dosing for massive (life threatening) bleeding (trauma patients, perioperative patients, obstetrical bleeds) is an initial dose of mg/kg. (Moltzan et al, 2008) The dose may be repeated in 30 minutes if bleeding does not stop. If bleeding continues, a third dose may be given 2 hours later (maximum 3 doses). Goals of Treatment Maintain: ionized calcium greater than 1.13 mmol/l urine output greater than 0.5 ml per kg/h systolic blood pressure greater than 70 mmhg temperature greater than 35 o C ph greater than 7.10 Transfusion Guidelines Table 4: Transfusion guideline based on laboratory results Laboratory Results Product and Dose Hemoglobin less than 70 g/l Adults units RBCs Hemoglobin less than 100 g/l for patients with cardiac Pediatrics - 15 ml/kg RBCs disease Platelet less than 75 x 10 9 /L OR 100 x 10 9 Adults - 1 adult dose of platelets /L CNS injury^ Pediatrics ml/kg Adults ml plasma INR greater than 1.7 Pediatrics ml/kg plasma Fibrinogen less than 1.5 g/l Adults - 10 units cryoprecipitate Pediatrics - 1 unit cryoprecipitate per 10 kg ^ Do not rely on platelet count within 12 hours of cardiopulmonary bypass or within 24 hours ingestion of antiplatelet agent; administer maximum of 2 doses of platelets empirically. Note. Adapted from University Health Network, Policy & Procedure Manual, Massive Transfusion Protocol Clinical and CBS, 2007 Fibrinogen is the first coagulation factor to decrease in massive bleeding and in vitro evidence has shown a higher fibrinogen level improves clot formation and strength. While there have not been randomized control trials to substantiate a higher level, literature and European guidelines have increased the target fibrinogen levels to 1.5 g/l to 2.0 g/l. Consider discontinuing blood component therapy when o there is resolution of shock and o bleeding is under control Inform blood transfusion service when control of bleeding has been regained, or when resuscitation efforts have been withdrawn. March 2013 Version

18 6 References American Association of Blood Banks Guidelines for Massive Transfusion American College of Surgeons Committee on Trauma. (2004) Advanced Trauma Life Support for Doctors 7 th edition. Chicago American College of Surgeons Committee on Trauma. (2008) Advanced Trauma Life Support for Doctors 8 th edition. Chicago British Committee for Standards in Haematology: Stainsby, D., MacLennan, S., Thomas, D., Isaac, J., Hamilton, P.J. (2006) Guidelines on the management of massive blood loss. Br J Haematology, 135(5), British Committee for Standards in Haematology (2004) Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant, British Journal of Haematology, 126, British Committee for Standards in Haematology Blood Transfusion Taskforce (2001) Guidelines for the clinical use of red cell transfusions. British Journal of Haematology, 113, British Committee for Standards in Haematology Blood Transfusion Taskforce (2003) Guidelines for the use of platelet transfusions. British Journal of Haematology, 122, British Committee for Standards in Haematology Blood Transfusion Taskforce (2004) Transfusion guidelines for neonates and older children. British Journal of Haematology, 124, Canadian Blood Services (2007). Clinical Guide to Transfusion - Fourth Edition Canadian Standards Association. C.S.A. Standard Z Blood and blood components. (2004) Mississauga, Ontario Canadian Standards Association. C.S.A Standard Z Blood and blood components. (2010) Mississauga, Ontario Capital Health - Clinical Guide to Blood Transfusion (2010) Massive Transfusion (Section 10) Edmonton, Alberta Coats T, Roberts I, Shakur H (2004) Antifibrinolytic drugs for acute traumatic injury. Cochrane Database of Systematic Reviews, CD CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt,B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto,R, Ramana PV, Ravi RR, Yutthakasemsunt S. (2010) Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet, 376:23-32 Contreras M. (1998). Consensus conference on platelet transfusion. Final Statement. Blood Reviews, 12, March 2013 Version

19 CRASH-2 collaborators, Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. (2011) The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet, 377: , e1091-e1092. Development Task Force of the College of American Pathologists (1994). Practice Parameter for the use of fresh frozen plasma, cryoprecipitate and platelets. JAMA, 271, Dzik WH, Blajchman MA, Fergusson D, Hameed M, Henry B, Kirkpatrick AW, Korogyi T, Logsetty S, Skeate RC, Stanworth S, MacAdams C, Muirhead B. (2011) Clinical review: Canadian National Advisory Committee on Blood and Blood Products Massive Transfusion Consensus Conference 2011: report of panel. Critical Care, 15:242 doi: /cc10498 Donaldson MD, Seaman MJ, Park GR. (1992). Massive blood transfusion. British Journal of Anaesthesia, 69, Eastridge BJ, Malone D, Holcomb JB. (2006). Early Predictors of Transfusion and Mortality After Injury: A Review of the Data-based Literature. The Journal of Trauma Injury Infection and Critical Care. Supplement Volume 60, Number 6, S20-S25 Gonzalez EA, Moore FA, Holcomb JB, Miller CC, Kozar KA, Todd SR, Cocanour CS Balldin BC, McKinley BA. (2007). Fresh Frozen Plasma Should be Given Earlier to Patients Requiring Massive Transfusion. The Journal of TRAUMA Injury, Infection, and Critical Care. 2007; 62 (1): Gruen RL, Mitra B. Tranexamic acid for trauma Lancet doi: /s (11) Hardy JF, De Moerloose P, Samama M (2004). Massive Transfusion and coagulopathy: pathophysiology and implications for clinical management. Journal of Anaesthesia, 51, Hebert P, Wells G, Blajchman M, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E and the Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group. (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. New England Journal of Medicine, 340 (6), Hellstern P, Haubelt H. (2002). Indications for plasma in massive transfusion. Thrombosis Research, 107 (2002) S19-S22 Hiippala ST. (1998). Replacement of massive blood loss. Vox Sanguinis, 74 (Suppl. 2), Horsey PJ. (1997). Multiple trauma and massive transfusion. Anaesthesia, 52, Iserson KV, Huestis DW. (1991). Blood warming: current applications and techniques. Transfusion, 31, Ketchum L, Hess JR, Hiippala S. (2006). Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma. The Journal of Trauma Injury Infection and Critical Care. Supplement Volume 60, number 6, S51-S58 Lin Y, Moltzan CJ, Anderson DR on behalf of the National Advisory Committee on Blood and Blood Products. (2012) The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework. Transfusion Medicine DOI: /j x March 2013 Version

20 Malone DL, Hess JR, Fingerhut A. (2006). Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol. The Journal of Trauma Injury Infection and Critical Care. Supplement Volume 60, number 6 S91-S96 McClelland DBL, Fourth Edition (2007). Handbook of Transfusion Medicine. Pp. 36. United Kingdom Blood Services Mikhail J. (2004). Massive transfusion in trauma: process and outcomes. Journal of Trauma Nursing Moltzan, C.J., Anderson, D.A., Callum, J., Fremes, S., Hume, H., Mazer, C.D., Poon, M.C., Rivard, G., Rizoli, S., Robinson, S. (2008). The evidence for the use of recombinant factor VIIa in massive bleeding: development of a transfusion policy framework. Transfusion Medicine, 18: Nova Scotia Provincial Blood Coordinating Program (2013) Atlantic Collaborative Recommendations for Managing the Bleeding Patient on Dabigatran or Rivaroxaban v 2.1 Rossaint, R., Bouillon, B., Cerny, V., Coats, T.J., Duranteau, J., Fernández-Mondéjar, E., Hunt, B.J., Komadina, R., Nardi, G., Neugebauer, E., Ozier, Y., Riddez, L., Schultz, A., Stahel, P.F., Vincent, J- L., Donat R Spahn, D.R. (2010) Management of bleeding following major trauma: an updated European guideline Critical Care 14:R52 Royal Children s Hospital Massive Transfusion Protocol (2005) Laboratory Services, Doc. No. MH- W-001, Version 2 Shaz BH, Dente CJ, Harris RS, MacLeod JB, Hillyer CD. (2009) Transfusion Management of Trauma Patients. Anesthesia & Analgesia. 2009; 108(6): Spahn DR, Rossaint R. (2005). Coagulopathy and blood component transfusion in trauma. British Journal of Anaesthesia, 95 (2): Stainsby D, MacLennan S, Hamilton PJ. (2000). Management of massive blood loss: a template guideline. British Journal of Anaesthesia, 85, Stanford Hospital & Clinics Massive Transfusion Guidelines - Aug 2007 Tien H, Nascimento Jr B, Callum J, Rizoloi S. (2007) An approach to transfusion and hemorrhage in trauma: current perspectives on restrictive transfusion strategies. Canadian Journal of Surgery, 50(3), Schwab CW, Shayne JP, Turner J. (1986). Immediate trauma resuscitation with type O uncrossmatched blood: a two-year prospective experience. Journal of Trauma, 26, University Health Network (Ontario) - Policy and Procedure Manual, Massive Transfusion Protocol Clinical March 2013 Version

21 PRE-PRINTED ORDER Provicial Blood Coordinating Program Request for Blood/Blood Components for the Massive Bleeding Patient (Facilities with platelet inventory) Patient: Allergies: Weight: KG (Pediatrics) Items preceded by a bullet ( ) are mandatory. Items preceded by a checkbox ( ) are only to be carried out if checked. For patients outside of these indicators, contact Blood Transfusion Service (BTS) Physician. Call ###-####. MASSIVE BLEEDING (Complete all sections) Location of Patient (Select one only): ICU OR Emergency Other (specify) Indication for Use: Massive Bleeding (please specify or circle) Trauma, Surgical, Obstetrical, Medical, Other (specify) INITIAL TRANSFUSION MANAGEMENT (select either adult or pediatric) ADULT RBC 6 units FFP/FP 1500 ml Platelets 1 adult dose PEDIATRIC ml RBC (10-15 ml per kg) ml FFP/FP (10-15 ml per kg) ml Platelets (5-10 ml per kg) I have requested the release of blood for the above patient without the completion of the required pretransfusion testing and/or compatibility. In my judgement, emergency transfusion is needed and a delay may be detrimental to this patient. Physician s Signature: Date (yyyy/mm/dd): Physician s Name CPSNS No. Print Bar Code Original Patient Chart Fax Request to Blood Transfusion Service at: ###-#### Guideline for the Appropriate Use of Blood Products/Components during a Massive Transfusion in NS Version

22 Guideline for the Appropriate Use of Blood Products/Components during a Massive Transfusion in NS Version

23 PRE-PRINTED ORDER Provicial Blood Coordinating Program Request for Blood/Blood Components for the Massive Bleeding Patient (facilities without platelet inventory) Patient: Allergies: Weight: KG (Pediatrics) Items preceded by a bullet ( ) are mandatory. Items preceded by a checkbox ( ) are only to be carried out if checked. For patients outside of these indicators, contact Blood Transfusion Service (BTS) Physician. Call ###-####. MASSIVE BLEEDING (Complete all sections) Location of Patient (Select one only): ICU OR Emergency Other (specify) Indication for Use: Massive Bleeding (please specify or circle) Trauma, Surgical, Obstetrical, Medical, Other (specify) INITIAL TRANSFUSION MANAGEMENT (select either adult or pediatric) ADULT RBC 6 units FFP/FP 1500 ml PEDIATRIC RBC ml (10-15 ml per kg) FFP/FP ml (10-15 ml per kg) PLATELETS Platelets are NOT required as the patient will be transferred Request Platelets from CBS (Select either adult or pediatric) Adult 1 adult dose Pediatric ml (5-10 ml per kg) I have requested the release of blood for the above patient without the completion of the required pretransfusion testing and/or compatibility. In my judgement, emergency transfusion is needed and a delay may be detrimental to this patient. Physician s Signature: Date (yyyy/mm/dd): Physician s Name CPSNS No. Print Bar Code Original Patient Chart Fax Request to Blood Transfusion Service at: ###-#### Guideline for the Appropriate Use of Blood Products/Components during a Massive Transfusion in NS Version

24 Guideline for the Appropriate Use of Blood Products/Components during a Massive Transfusion in NS Version

25 Appendix C - Selected C.S.A. Z Standards Pertinent to Massive Transfusion The Guideline for Massive Transfusion in Nova Scotia has been developed in compliance with the C.S.A. Standard, Z902-10, Blood and blood components. Massive transfusion a procedure in which a recipient is transfused with an amount of blood that is approximately equal to or greater than his or her estimated total blood volume, within a 24 h period. 4 General 4.7 Process control The facility shall have validated operating procedures for all activities listed in Clause 1.3 (a) through (q) to ensure the quality of its products, processes, and services. These shall include procedures for the identification, documentation, review, and approval of all process changes. The facility shall perform a revalidation whenever changes are made to a validated system that could reasonably be expected to affect the results obtained during the original validation. The comprehensiveness of validation should reflect the criticality of the process and the extent of the change being made. 9 Release, storage, packing, and transportation of blood and blood components 9.3 Release of untested blood and blood components Release of blood and blood components, prior to completion of required testing, shall be done only in life-threatening situations when blood or blood components tested according to normal procedures are not available and only with the documented approval of the physician of the person receiving the transfusion. See Clause Requests, pre-transfusion testing, selection of components, and acceptance criteria 10.2 Requests There shall be unequivocal identification of the recipient before drawing blood samples. This shall include verification of the recipient s identification number or, if this not available, the alternative procedure in Clause shall be used. If inaccuracies or discrepancies are discovered during the identification process, blood samples shall not be collected until the inaccuracies or discrepancies have been satisfactorily resolved There shall be a written procedure for the establishment of positive identification in situations where recipients do not have an identification number. March 2013 Version

26 Note: Such circumstances can occur in instances where specimens are drawn outside of the health care facility or when pre-operative tests are performed on an outpatient basis Recipient blood samples At the time of blood sample collection, in the presence of the recipient, the tube shall be labeled and the person taking the sample shall verify that the information on the label of the sample matches the identity of the recipient. All documentation that accompanies a recipient blood sample shall contain sufficient information to unequivocally link it with the recipient and the sample Selection of blood components Recipients shall be transfused with ABO group-specific whole blood or ABO group-compatible red blood cells Special circumstances Infants under four months In the case of massive transfusion including exchange transfusion, only red blood cells that have been screened and found negative for hemoglobin S should be transfused Massive transfusion When a recipient receives a massive transfusion, the pre-transfusion testing may be abbreviated, provided the abbreviated testing is in accordance with policies and procedures established by the medical director Emergency transfusion In situations where delaying a transfusion may be deleterious to the recipient s condition, whole blood or blood components may be released without the infectious disease tests and pre-transfusion testing required under Clauses 8.4 and 10.6; nonetheless, Clause 9.3 shall apply. Whole blood or red blood cells should be Rh-negative for (a) children; and (b) women of child-bearing age Recipients with an undetermined ABO group shall receive group O red blood cells ABO group-specific whole blood or ABO group-compatible red blood cells may be transfused prior to completion of other tests for compatibility if the recipient s ABO group has been determined by the transfusing facility without reliance on previous records. March 2013 Version