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Policy # 123456 | Last Revised: September 26, 2012 page 1 of 13 Policy and Procedure

Subject: Massive Transfusion Policy (MTP) for Adult & Pediatric Patients

Purpose: To outline the process and steps for rapid preparation and issue of blood components for trauma patients and other patients in surgical extremis due to massive bleeding. Responsibility: Physicians, Registered Nurse (RN), Blood Bank, Laboratory, Pharmacy Definitions: 1. Adult Massive transfusion: the actual or anticipated transfusion of blood products and other intravenous fluids to replace greater than patient’s blood volume within 24-hour period. 2. MTP Pack: composed of 4 units of packed red blood cells, 4 units of thawed fresh frozen plasma and 5 units (1 pooled pack) of platelets with cryoprecipitate between packs (adult only). 3. Pediatric Massive transfusion: the actual or anticipated transfusion of blood products and other intravenous fluids to replace greater than the patient’s estimated blood volume within twenty-four (24) hour period and/or need for transfusion equal to half of the patient’s estimated blood volume at one time, such as within one hour. Estimates of total blood volume vary by age (Appendix A).

Policy Content: I. MTP is to be used for: A. Trauma/surgical patients with massive blood component requirements and anticipated volume of blood replacement preclude waiting for laboratory evaluation and to limit excessive use of banked blood. 1. Methods used may include but not limited to auto transfusion, use of the cell saver, Tranexamic Acid, Recombinant Factor VIIa (rFVIIa) or Prothrombin Complex Concentrate (PCC)/Factor IX Complex, and damage control surgery. II. Interdepartmental responsibilities are defined as: A. Attending surgeon / ACC / PCCM / anesthesiologist / emergency physician 1. Initiates the MTP 2. Communicates with blood bank 3. Terminates the MTP

Policy # 123456 | Last Revised: September 26, 2012 page 2 of 13 Policy Content- continued: B. Registered Nurse (RN) 1. ED Charge Nurse (CN), operating room Circulator Nurse, or Bedside RN assigns to another RN the task of blood administration 2. CN assigns personnel to be recorder 3. CN designates personnel to pick-up blood from blood bank. 4. Maintains direct communication with blood bank regarding patient status and blood needs. C. Laboratory Personnel 1. Performs laboratory tests as STAT 2. Adheres to the every hour for three consecutive hours STAT laboratory testing D. Blood Bank 1. Designates a staff MTP coordinator once notified by the department/unit in which the patient receiving the therapy resides. 2. Places tracking record (x15847) on the first pack 3. Validate the patient’s name and medical record number with ED charge nurse, operating room circulating nurse or patient’s RN. 4. Switches to type specific units as soon as the patient’s ABO-Rh type is established when un-cross matched “O-pos” or “O-neg” PRBC units were used initially. Note: Packed red blood cell units have minimal residual plasma; therefore, low risk of exposure to AntiA or AntiB hemolysins. In addition, Michigan Blood screens units for AntiA and AntiB hemolysins 5. Monitors and provides total number of units dispensed by category when requested. E. Pharmacy/Pharmacist 1. Responds immediately by sending a pharmacist on activation of an Emergency Department Trauma Code or Adult Critical Care Unit 2. Collaborates with and prompts the attending to order Tranexemic Acid and calcium chloride as indicated by clinical status and facilitates timely drug delivery. 3. Continues to support the attending physician with calcium chloride intervals, PCC or rFVIIa administration, and timely drug delivery when the MTP transitions from emergency department to critical care. 4. Assists with Tranexamic Acid, PCC, rFVIIa, and calcium chloride dosing per recommendations (Appendix B). 5. Ensures all medications given for massive transfusion are ordered and documented in the electronic health record (EHR)

Procedure Content: Criteria for Initiation of MTP Steps: Key Points: 1. The ACC, PCCM, OR, ANES, ED, OB, and/or 1. Note: For in-house resource STAT Trauma LD attending physician determines initiation of the Surgeon Consult call ASCOM # ______MTP with any of the following triggers/criteria: (Trauma Attending call first) or ______(Resident). a. When upon 5 minutes of admission the patient has 1) Base deficit negative 6 mEq/L 2) INR greater than 1.5

Policy # 123456 | Last Revised: September 26, 2012 page 3 of 13 Procedure Content: Criteria for Initiation of MTP-continued Steps: Key Points:

3) Hgb less than 10 g/dL 4) Systolic blood pressure is less than 90 mm/Hg / Persistent hypotension 5) Progressive acidosis b. The anticipated blood loss is requiring b. Refer to Appendix A for pediatric 10 units of packed red blood cells (PRBCs) thresholds/triggers or greater in adults. c. Four (4) units of PRBC / 4 units of fresh frozen plasma (FFP) / 5 units of platelets are required within one hour and additional units are anticipated. Initiation and Implementation of MTP Steps: Key Points:

1. The ACC, PCCM, OR, ANES, ED, OB, LD attending physician initiates the “Mass Transfusion Careset” (Adult) or the “Mass Transfusion PEDS Careset” through the EHR and ensures a stat type and screen has been ordered and obtained.

2. Laboratory will perform the following initial 2. Type and cross match must be drawn with initial STAT laboratory tests and every hour for 3 hours blood sample until MTP is terminated. a. PT b. PTT c. Fibrinogen d. Hemoglobin e. Platelet Count f. ABG g. Ionized Calcium (after 1st MTP Pack) h. Thromboelastogram (TEG) if available h. Physician determined

3. For patients admitted through the emergency department:

1) First administer 4-6 units of emergent 1) Blood bank green “pick up” slip with physician uncrossed PRBCs / 2 pre-thawed FFP in signature is required one time per patient to the ED prior to the initiation of the MTP. replace used un-cross matched blood Refer Clinical Policy Blood/Blood Components Administration (Adult) (CPRO-B0O-S0927) and Clinical Policy Blood/Blood Components

Policy # 123456 | Last Revised: September 26, 2012 page 4 of 13 Administration (Pediatric)( CPRO-B0P-S1399) for blood and blood component administration: Procedure Content: Initiation and Implementation of MTP - Continued Steps: Key Points: 2) Second, the ACC, PCCM, OR, ANES, ED, OB, LD Attending Physician or designee under direct supervision of the attending physician with activate the MTP process.

2. ED CN, Operating Room Circulator Nurse or Patient’s RN:

a. Calls or delegates the phone call task a. Call made to ______alerting the Blood Bank of MTP initiation.

b. Assigns personnel to pick up blood from the b. A green “pick up” slip must be accompanied and Blood Bank. submitted to Blood Bank with each MTP pack pick up occurrence per laboratory regulatory process. The ice chest from Blood Bank will contain one MTP Pack

c. Assigns a separate RN to administer blood c. Refer Clinical Policy Blood/Blood Components products. Administration (Adult) (CPRO-B0O-S0927) and Clinical Policy Blood/Blood Components Administration (Pediatric)( CPRO-B0P-S1399) for blood and blood component administration

1) Cryoprecipitate should be given between 1) Additional needs for cryoprecipitate must be the first and the second MTP Pack. requested through direct communication with the Blood Bank.

2) All blood products transfused must be warmed prior to administration

d. Assigns the task of recorder to another RN. Recorder

1) Documents fluid, blood product, and total volumes administered in the intake/output section of the EHR upon discharge from respective nursing departments.

2) Completes the MTP tracking form 2) Note: tracking form is not a permanent part

Policy # 123456 | Last Revised: September 26, 2012 page 5 of 13 (x15847) and reports concurrently during of the medical record. MTP the number of packs infused.

3) Completes and validates blood slip documentation is per Blood Bank policy.

e. Monitors for and documents the occurrence of massive transfusion complications (Appendix C)

Procedure Content: Termination of MTP Steps: Key Points:

1. Attending physician evaluates the termination of the MTP after 2 MTP Packs have been administered. a. Provider /coordinator contacts the Blood Bank for number of total units dispensed.

b. Total blood administered by components is documented in both the EHR and the progress notes

2. The ACC, PCCM, OR, ANES, ED, OB, LD 2. Call made to blood bank Attending Physician will terminate the MTP by promptly notifying the Blood Bank.

References: Blood ,Blood Components Administration - Adult pdf (Blood and Blood Component Administration- Adult # CPRO-BOO-SO927)

Blood ,Blood Components Administration –Peds pdf (Blood Component Pediatrics Procedure # CPRO-BOP-S1399)

Consent for Transfusion of Blood and Blood Products (X04161); Spanish (X09809)

Recombinant Factor VIIa/Factor IX Pharmacy Department 2011 protocol

Mikhail, S. (2004). Massive transfusion in trauma: process and outcome. Journal Trauma Nursing, 1 1(2), 55-60.

Stanford Mass Transfusion Guidelines 2005

Dutton R, et al. Indications for Early Red Blood Cell Transfusion. J Trauma 2006; 60(6)S35-40.

Ketchum L, et al. Indications for Early Fresh Frozen Plasma, Cryoprecipitate, and Policy # 123456 | Last Revised: September 26, 2012 page 6 of 13 Platelet Transfusion in Trauma. J Trauma 2006; 60(6) S51-58.

Fox C et al. Damage Control Resuscitation for Vascular surgery in a Combat Support Hospital. J Trauma 2008: 65 (1).

Moore E, et al. Military-Civilian Collaboration in Trauma Care and the Senior Visiting Surgeon Program, N Engl J Med 2007;26:3357.

Holcomb J, et al. Increased Plasma and Platelet to Red Blood Cell Ratios Improves Outcome in 466 Massively Transfused Civilian Trauma Patients. Annals of Surgery 2008;248(3):447-458.

Beekley A, et al. Lessons Learned from Modern Military Surgery. Surgical Clinics of North America 2007;87:157-184.

Hoyt D, et al. Management of Coagulopathy in the Patients with Multiple Injuries: Results from an International Survey of Clinical Practice. J Trauma 2008; 65(4):755-765.

Dehmer JJ, et al. Massive transfusion and blood product use in the pediatric trauma patient. Seminars in Pediatric Surgery 2010;19:286-291.

Hendrickson JE, et al. Implementation of a pediatric trauma massive transfusion protocol: one institution’s experience. Transfusion 2011.

Hendrickson JE, et al. Coagulopathy is prevalent and associated with adverse outcome in transfused pediatric trauma patients. The Journal of Pediatrics. 2011 Sep.

Pickett PM, et al. Massive Transfusion Protocol in Pediatric Trauma. International Anesthesiology Clinics 2011;49(2):62-67.

Children’s Healthcare of Atlanta, Trauma Massive Transfusion Protocol, 2009

Profilnine® SD [package insert]. Los Angeles, CA: Grifols Biologicals, Inc; October 2008.

Bruce D, Nokes T. Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. Crit Care 2008;12:105-111.

Shick K, Fertmann J, Karl-Walter J, Hoffmann J. Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care 2009:13:191-206.

Spahn D, Cerny V, Coats T, et al. Management of bleeding following major trauma: a European Guideline. Crit Care 2007;11:R17.

Policy # 123456 | Last Revised: September 26, 2012 page 7 of 13 The CRASH-2 Collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomized, placebo-controlled trial. Lancet 2010;376:23-32.

Morrison J., Dubose J., Rasmussen T., & Midwinter M. (2011). Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Archives of Surgery. 147(2),113-119. doi:

Riskin, D.J., Tsai, T.C., Riskin, L., Hernandez-Boussard, T., Purtill, M., Maggio, P.M., Spain,D.A., & Brundage, S.I. (2009), Massive Transfusion Protocols: The Role of Aggressive Resuscitation Versus Product Ratio in Mortality Reduction. Journal of the American College of Surgeons. 209 (2), 198-205. doi:10.1016/j.jamcollsurg.2009.04.016

Key Words: Blood, trauma, hemorrhage MTP

Policy # 123456 | Last Revised: September 26, 2012 page 8 of 13 APPENDIX A PEDIATRIC DEFINITIONS, CRITERIA AND DOSING

Management of the pediatric trauma patient in hemorrhagic shock depends upon accurate assessment of blood loss and size-appropriate goals for resuscitation Definition – Massive transfusion is defined as actual or anticipated transfusion of blood products and other intravenous fluids to replace greater than the patient’s estimated blood volume within twenty-four (24) hour period and/or need for transfusion equal to half of the patient’s estimated blood volume at one time, such as within one hour. Estimates of total blood volume vary by age (see below).

Age Est blood volume Premature infant 90-100 ml/kg Term infant to 3 months 80-90 ml/kg Children older than 3 months 70 ml/kg Obese children 65 ml/kg (Dehmer, 2010)

Packed Red Blood Cells (PRBC): 1 bag = 1 unit = 350 ml Fresh Frozen Plasma (FFP): 1 bag = 1 unit = 250 ml Platelets (PLT): 1 bag =1 pack = 5 units = 250 ml Cryoprecipitate: 1 bag = 5 units = 200 mL

Calcium Chloride: Pediatric Dose: 10-20mg/kg IV, max 1 gram, preferred, must have a central line Calcium Gluconate: Pediatric Dose: 50-100mg/kg/dose IV, max 2 grams Recombinant Factor VIIa: Pediatric Dose: 90-120mcq/kg IV (round dose to the nearest vial size when possible – 1mg, 2mg or 5mg vials are available). • Effective only with a pH of 7.20 or greater with hemorrhage. • After administration evaluate the need to continue MTP. Prothrombin complex concentrate (PCC)/Factor IX Complex, Tranexamic acid: NOT APPROVED FOR USE IN PEDIATRIC TRAUMA

Pediatric weight-based doses of blood product follow on the next page.

Policy # 123456 | Last Revised: September 26, 2012 page 9 of 13 APPENDIX A PEDIATRIC DEFINITIONS, CRITERIA AND DOSING

Children <10 kg: Blood products are to be physician order specific for any child <10kg. Product MTP Pack 1 MTP Pack 2 MTP Pack 3 MTP Pack 41 PRBC 25ml/kg 25ml/kg 25ml/kg 25ml/kg FFP 20ml/kg 20ml/kg 20ml/kg 20ml/kg PLT 10ml/kg 10ml/kg 10ml/kg 10ml/kg Cryo. 4ml/kg 4ml/kg2 4ml/kg2 4ml/kg2 3 Ca++? 3 Ca++? 3 Ca++? 4 rFVIIa?

Children 11 – 25kg: Product MTP Pack 1 MTP Pack 2 MTP Pack 3 MTP Pack 41 PRBC 2 Units 2 Units 2 Units 2 Units FFP 2 Unit 2 Unit 2 Unit 2 Unit PLT 1 Pack 1 Pack 1 Pack 1 Pack Cryo. 2.5 Units 2.5 Units 2.5 Units 2.5 Units (½ bag) (½ bag)2,3,4 (½ bag)2,3 (½ bag)2,3 [100 mL] [100 mL] [100 mL] [100 mL] 3 Ca++? 3 Ca++? 3 Ca++? 4 rFVIIa?

Children 26 kg and up: Product MTP Pack 1 MTP Pack 2 MTP Pack 3 MTP Pack 41 PRBC 4 Units 4 Units 4 Units 4 Units FFP 4 Unit 4 Unit 4 Unit 4 Unit PLT 1 Pack 1 Pack 1 Pack 1 Pack Cryo. 5 Units 5 Units 5 Units 5 Units (1 bag) (1 bag)2,3,4 (1 bag)2,3 (1 bag)2,3 3 Ca++? 3 Ca++? 3 Ca++? 4 rFVIIa?

1for additional MTP Packs, repeat cycle as needed 2additional cryoprecipitate available by request only, if indicated based on fibrinogen levels 3consider calcium replacement 4consider administering rFVIIa

Policy # 123456 | Last Revised: September 26, 2012 page 10 of 13 APPENDIX B SUGGESTED COMPONENT REPLACEMENT PROTOCOLS DURING TRAUMA RESUSCITATION Adult Patients

COMPONENT PROTOCOL INDICATIONS NOTES Packed Red Goal: initial 4 units of uncrossed O negative Base Deficit negative All PRBC use Blood Cells or O positive emergent blood 6 or greater warmer Enflow (PRBC) INR greater than 1.5 or Belmont times control Rapid Infuser Hgb less than 10 Use Normosol solution for adult BP less than 90 blood mmHg systolic administration

Fresh Frozen Goal: 1 unit of FFP for every 1 unit PRBC’s PT, PTT greater than 2 units thawed at Plasma (FFP) [utilize pre-thaw option] 1.5 times control all times in Blood and/or INR greater Bank than 1.8 •For timeliness in massive transfusion, 1:1 Ice chest of ratio of PRBC to FFP should be blood product simultaneously infused. taken to ED / OR •Monitor INR thereafter to guide FFP / ACC replacement. Platelets Goal:5 pooled units (1 Pack) after first 4 Oozing Infuse in over 5 units PRBC’s Platelet count less minutes at room than 50000 temperature. 5 pooled units (1 Pack) after each 4 units Note: Do not PRBC’s infuse by rapid blood warmer pump (Belmont). Can use Enflow warmer for platelets

Cryoprecipitate Goal:1 bag [5 units] after first MTP Pack Fibrinogen less than Infuse over 20 [1 bag=5 units=200mL] 80-100 mg/dl minutes at room Indicated thereafter based on fibrinogen temperature level from STAT lab results

Calcium Calcium Chloride: 1000mg IV over 10 After every other Calcium Chloride minutes, must have a central line MTP Pack and based preferred. Pediatric Dose: 10-20mg/kg IV, max on lab results Use calcium 1 gram. SEE APPENDIX A gluconate if no central line Calcium Gluconate: 3000mg IV over 10 minutes Pediatric Dose: 50-100mg/kg/dose IV, max 2 grams, SEE APPENDIX A Pharmacy to assist with dosing

Policy # 123456 | Last Revised: September 26, 2012 page 11 of 13 APPENDIX B SUGGESTED COMPONENT REPLACEMENT PROTOCOLS DURING TRAUMA RESUSCITATION Adult Patients

COMPONENT PROTOCOL INDICATIONS NOTES Tranexamic Preferred Adult Dose: Administer with Acid 1,000mg IVPB over 10 minutes then initiation of 1st MTP 1,000 mg IVPB infused over 8 hours pack or suspect on going hemorrhage Alternative Dosing for Limited Access: 1,000 mg IVPB over 10 minutes then repeat 1,000 mg IVPB over 10 min at 3 hours May administer intraosseous

TRANEXAMIC ACID IS NOT APPROVED FOR USE IN PEDIATRIC TRAUMA

Prothrombin Adult Dose: Consider with 2nd Profilnine® SD complex 50units/kg IV based on actual body weight. round of MTP packs (Prothrombin concentrate administered if Complex (PCC)/ Factor PCC IS NOT APPROVED FOR USE IN bleeding persists. Concentrate IX Complex PEDIATRIC TRAUMA (PCC)/Factor IX • Infuse no faster than 10ml/min. Complex)

• Avoid if patient is in DIC.

• After administration evaluate the need to continue the MTP

• BeneFix® (Factor IX) is not equivalent to Profilnine® SD (Factor IX Complex) and SHOULD NOT be used for massive OR transfusion.

Factor VIIa Adult Dose: NovoSeven® RT Weight 100 kg or less: 5 mg rFVIIa Consider after PCC (Recombinant Weight greater than 100 kg: consider failure /or 2nd round Factor VII) 6 mg rFVIIa of MTP packs Round to administered if nearest vial size Pediatric Dose: 90-120 mcq/kg IV bleeding persists. when possible (1mg, 2mg or 5 •Effective only with a pH of 7.20 or greater mg vials) with hemorrhage.

•After administration evaluate the need to continue MTP.

Policy # 123456 | Last Revised: September 26, 2012 page 12 of 13 APPENDIX C COMPLICATIONS OF MASSIVE TRANSFUSION (Greater than 20 units components)

COMPLICATION RATIONALE TREATMENT Hypothermia Banked blood is kept at 4 degrees C Blood should be administered using a warmer Hypocalcaemia High citrate load in blood additives can lead Monitor ionized calcium with to decreased levels of ionized calcium transfusions greater than 4 units Coagulopathy Multifactor: coagulation abnormalities, Aggressive resuscitation with excessive fibrinolysis, hypothermia, acidosis, warming measures, timely FFP dilutional coagulopathy. and Platelet (which also have Fibrinogen) administration. Immunomodulation: New emerging detrimental effect of older Awareness of age of blood Enhanced acute blood. Stimulation of cytokine release noted products, potentially note and inflammatory with blood older than 14 days associated document age of blood. response with worse outcome in trauma patients.

Policy # 123456 | Last Revised: September 26, 2012 page 13 of 13