Introduction to Transfusion Kathleen M. Madden MD Jay S. Raval MD Department of Pathology

Objectives Understand indications for transfusions Describe the expected laboratory response patients should achieve with transfusion Explain the indications for blood component modification Highlight key facts of UNM’s Massive Transfusion Protocols

Who does not need a RBC transfusion? A. 54 y/o F with ovarian cancer, no other medical problems, starting chemotherapy, Hgb 8.9 g/dL B. 75 y/o M, history of myocardial infarction, admitted with pneumonia, Hgb 7.4 g/dL C. 22 y/o F involved in a motor vehicle collision, hypotensive and tachycardic, Hgb 11.4 g/dL

Who does not need a RBC transfusion? A. 54 y/o F with ovarian cancer, no other medical problems, starting chemotherapy, Hgb 8.9 g/dL B. 75 y/o M, history of myocardial infarction, admitted with pneumonia, Hgb 7.4 g/dL C. 22 y/o F involved in a motor vehicle collision, hypotensive and tachycardic, Hgb 11.4 g/dL

The main indication for RBC transfusion is tissue ischemia secondary to decreased O2 transport https://www.researchgate.net/figure/Oxygen-transport-by-Hb-within-RBC-10_fig2_321474640

Emergency RBC transfusion indications include: Active hemorrhage Hypovolemic shock Laboratory evidence of ischemia Lactic acidosis Acute decrease in Hgb/Hct Clinical evidence of decreased O2 transport Dyspnea, tachypnea, tachycardia

Non-emergent RBC transfusion indications include: Hgb <7g/dL (Hct <21%) Hgb <8-10 g/dL (Hct <24-30%) in a patient with a known cardiac history No symptomatic anemia (yet) at these transfusion thresholds

Considerations when transfusing RBCs One RBC unit should increase the Hgb by 1g/dL and Hct by 3% in a 70 kg adult Same as 4 mL/kg in a child Single-unit transfusions should be ordered for non-bleeding patients Additional units ordered after reassessing patient and rechecking post-transfusion Hgb/Hct TRICC Trial: restrictive (hgb 8) vs liberal (hgb 10) transfusion strategy in ICU patients. Lower mortality, fewer cardiac events (especially MI and pulmonary edema), and lower multiorgan dysfunction in the restrictive group. Also decreased RBCs transfused by 54% and decreased RBC exposure by 33% Transfuse one unit, reassess clinical situation

ASH/AABB Transfusion Recommendations Don’t transfuse more units of blood than absolutely necessary Don’t transfuse RBCs for iron deficiency without hemodynamic instability Don’t perform serial blood counts on clinically stable patients Don’t transfuse group O negative blood except to O negative patients and in emergencies to women of childbearing potential. TRICC Trial: restrictive (hgb 8) vs liberal (hgb 10) transfusion strategy in ICU patients. Lower mortality, fewer cardiac events (especially MI and pulmonary edema), and lower multiorgan dysfunction in the restrictive group. Also decreased RBCs transfused by 54% and decreased RBC exposure by 33% Transfuse one unit, reassess clinical situation http://www.choosingwisely.org/societies/american-association-of-blood-banks/

How long will it take you to get your RBC units? Type and Screen must be up to date for type-specific RBCs Type and Screen takes 30-60 minutes if no antibodies are present Electronic Crossmatch Pt has >1 Type and Screen and no history of or current antibodies or ABO discrepancies Very rapid Antibodies present - additional time needed to identify antibody and provide antigen-negative or crossmatch compatible blood

Emergency Release RBCs Can be provided if your patient is hemorrhaging and unstable and There is no current type and screen There is not time for the Blood Bank to provide antigen-negative or crossmatch compatible RBCs O-negative RBCs: women and girls of child-bearing age O-positive RBCs: all men and women who appear >50 years old *Uncrossmatched blood must be approved by the Transfusion Medicine Service*

Plasma Pearls Source of all coagulation factors as well as fibrinogen 1 IU/mL of both pro- and anti-coagulant factors Approximately 400mg fibrinogen INR of plasma is variable but can be as high as 1.5

Indications for Plasma transfusion Bleeding with decreased coagulation factors (INR >1.5-2.0) Prior to major surgical procedure with INR > 1.5-2.0 Therapeutic plasma exchange for selected conditions Specific factor replacement when factor concentrates are unavailable

When is plasma not indicated? Non-bleeding patient with elevated INR Volume replacement Protein source for nutritional support If your bleeding patient has an elevated INR and you are unsure if they need plasma, you can order a ROTEM for whole blood evaluation of their ability to clot.

Why is plasma transfusion more effective at higher INR? Plasma transfusion for increased INR based on thoughts: abn coag tests = decreased coag factors, plasma will correct this abnormality, correcting this abnormality decreases the risk of bleeding Prolonged coag tests don’t necessarily mean coag factors have decreased low enough to affect clotting – need approx 30% of coag factors to form functional clot Coag factor % doesn’t decrease below this minimal hemostatic threshold until INR is 1.7 – even then this doesn’t predict bleeding Amount of decrease in INR/increase in coag factors will depend on the amount of plasma transfused and starting INR (v. low starting coag factor levels will have significant improvement in INR/PTT whereas the same amount of plasma transfused for higher starting coag factors will not affect INR/PTT as much) Hall D., Walsh T.S. (2015) FFP Transfusion in Intensive Care Medicine. In: Juffermans N., Walsh T. (eds) Transfusion in the Intensive Care Unit. Springer, Cham

Plasma Transfusions Dose is 15-20 mL/kg NOT 2 units! For a 70kg patient, this is 8 units plasma ABO compatible with the recipient Takes approximately 30 minutes to thaw plasma

Hepatic Failure Patients and Plasma Transfusion Both pro- and anti-coagulant factors made by liver Consequently liver failure resets the patient to have lower thresholds for bleeding and thrombosis PT/aPTT do not predict which patients will bleed - plasma should not be empirically given to correct lab abnormalities without bleeding

von Willebrand factor + Factor 8 What is cryoprecipitate? The big proteins: Fibrinogen Minimum Fgn: 150 mg vWF (carries factor 8) Minimum Factor 8: 80 IU Factor 13 Fibronectin The proteins “cryoprecipitate” (cold precipitate) out of solution Cryoprecipitate formed by Fibrinogen von Willebrand factor + Factor 8 In practice, cryoprecipitate is used almost exclusively to replace fibrinogen (mostly in bleeding patients)

Indications for Cryoprecipitate Transfusion Fibrinogen deficiency Target fibrinogen >100 mg/dL for adequate hemostasis Massive transfusion patients: >150 mg/dL Postpartum hemorrhage: >200 mg/dL Fgn <200 independently and significantly associated with worsening of bleeding in severe PPH Each of the first two rounds of the OB MTP have a pool of cry

Cryoprecipitate Dosing 1 pool of cryoprecipitate = 5 units 1 pool is approximately 75 mL Transfusing a 70kg patient 2 pools of cryoprecipitate should increase fibrinogen by 70 mg/dL Pediatric dosing: can call Transfusion Medicine fellow/resident for help targeting a fibrinogen goal Once thawed, the expiration is 6 hours Takes us approximately 15 minutes to thaw cryo

Which patient needs a platelet transfusion? A. 36 y/o M with a splenic laceration from a stab to the abdomen, platelet count 94 K B. 10 y/o F with B-cell acute lymphoblastic leukemia between chemotherapy cycles, platelet count 31 K C. 72 y/o F on Clopidogrel admitted with a subdural hematoma after a fall, platelet count 188 K D. 54 y/o M with AML admitted for chemotherapy, no bleeding signs, platelet count 17 K

Which patient needs a platelet transfusion? A. 36 y/o M with a splenic laceration from a stab to the abdomen, platelet count 94 K B. 10 y/o F with B-cell acute lymphoblastic leukemia between chemotherapy cycles, platelet count 31 K C. 72 y/o F on Clopidogrel admitted with a subdural hematoma after a fall, platelet count 188 K D. 54 y/o M with AML admitted for chemotherapy, no bleeding signs, platelet count 17 K

Platelets: the Goldilocks of Blood Components Platelet-rich plasma solution Storage requirements: Oxygen-permeable bag Kept at room temperature Gently agitated/rocked Must “rest” for 12 hours before bacterial testing can be started Highest-risk blood component for bacterial contamination and septic transfusion reactions http://simpsons.wikia.com/wiki/Goldilocks

Indications for Platelet Transfusion: Quantitative Defects Platelet Indications Platelet Count Prophylactic - Inpatient <10 K Prophylactic – Outpatient <20 K Prior to Invasive Procedure <50 K Active Bleeding Intracranial/Central Nervous System Bleeding <100 K Intraocular Bleeding < 100 K

Indications for Platelet Transfusion: Qualitative Defects Platelet dysfunction Antiplatelet medications Congenital platelet functional defects Following surgery using cardiopulmonary bypass

Platelet Dosing For a 70kg adult, 1 unit of platelets should increase the platelet count by 25-50K For pediatric patients, the dosing is 10-15 mL/kg

How long will it take to get your platelets? After collection and before expiration we have about a 3-3.5 day window to transfuse platelets On a good day, the Blood Bank has 7-9 platelet units for the hospital and cancer center You may be asked to give half-units to your patients (should see a 15-25K increase in platelet count) when we have a shortage and are trying to get more platelets You may be asked to hold on transfusing non- emergent patients until we can bring more platelets into the inventory

Blood Components & Indications Plasma Cryoprecipitate RBCs Platelets Bleeding w/INR >1.5 – 2.0 (coagulopathic) Massive hemorrhage Therapeutic plasma exchange Factor deficiency w/o concentrate Low fibrinogen <10K (inpt) - prophylactic <20K (outpt) - prophylactic <50K active bleed/major surgery <100K CNS/eye injury/surgery Massive hemorrhage Aspirin/Plavix use with active bleed When not to use plasma: INR >1.5-2 but not bleeding, for volume, as a protein source for nutrition Decreased tissue oxygenation Symptomatic anemia Massive hemorrhage

Blood Product Modification Leukoreduction Washing Irradiation

Leukoreduction All cellular products (RBCs, platelets) are leukoreduced Main reasons for leukoreduction: Decrease incidence of febrile non- hemolytic transfusion reactions Prevention of CMV transmission Prevention of HLA alloimmunization Considered equivalent to CMV seronegative products HLA antibody formation requires donor lymphocytes to present HLA Class I antigens https://blood.ca/en/blog/2016-11/things-we-do-safety-leukoreduction

Washed Blood Products Removal of plasma proteins to decrease hypersensitivity to blood products 1-2 L of saline is used to remove ~99% of plasma Indications may include: IgA deficiency History of severe allergic/anaphylactoid reactions to blood transfusions IgA deficient patients: may develop anti-IgA and exposure to IgA leads to anaphylaxis. Either need intensely washed products or blood products from other IgA deficient donors Removing unwanted antibodies: may be considered in patients who have repeated severe allergic or anaphylactic transfusion reactions despite premedication with Benadryl and Solu-Medrol

Issues with providing washed blood products Washing changes expiration of blood products Platelets = 4 hr RBCs = 24 hr Takes approximately 1 hour for washing process, then time for transportation to UNMH. Products must also be taken into Blood Bank inventory and then allocated Quantitatively and qualitatively inferior unit secondary to washing process

How does irradiation work? Used for cellular products RBCs Platelets Granulocytes Ionizing radiation damages the DNA of the irradiated cell but leaves normal cellular function intact Indication for irradiation: prevent Transfusion- Associated Graft vs Host Disease (TA-GVHD) Irradiated cells are unable to replicate but can still work. Plasma and Cryo DO NOT need to be irradiated.

What is TA-GVHD? Graft-vs-host reaction that occurs after transfusion due to Immunologically competent donor cells Antigenic difference between graft and host detected by the donor cells Inability of the host to reject the donor cells effectively Affected organs include skin, GI tract, bone marrow, spleen, liver Mortality >90% Mortality is secondary to overwhelming sepsis from bone marrow failure Only way to survive is to have a stem cell transplant ready https://www.sciencedirect.com/science/article/pii/S0001581416300986

What are the common indications for irradiation? Hematopoietic stem cell transplant recipients Congenital Cellular Immune Deficiency Intrauterine/neonatal transfusions Infants up to 6 months old All pediatric malignancies Hematologic malignancies Transfusion from family members or HLA-matched products Treatment with purine analogs, anti-thymocyte globulin, or Alemtuzumab Cong Cellular Deficiency: can be suspected or confirmed (why we irradiate neonates to 6 mo) - includes SCID, DiGeorge, Ataxia Telangiectasia, Wiskott-Aldrich

When is irradiation NOT indicated? Solid organ transplantation Adult solid organ tumors Autoimmune diseases HIV/AIDS Caveat: if patient is severely lymphopenic (ALC < 500) or treated with medications for which irradiation is indicated, cellular blood products will be irradiated

Changing gears to massive transfusions

What is a massive transfusion? Acute administration of >1/2 estimated blood volume in 3 hours Replacement of 10% of the total blood volume/minute Anticipated replacement of total blood volume in 24 hours Pediatric patients: transfusion of >40 mL/kg RBCs Definitions are retrospective based on amount of bleeding or blood products replaced over a period of time

When should you consider activating the MTP? If you think any of the above circumstances apply to your patient OR If your patient is bleeding and you are concerned that it is already uncontrolled or it may become uncontrolled, activate the MTP!

How will activation of the Massive Transfusion Protocol help your patients? Protocol is designed to mimic whole blood resuscitation Each round of the MTP contains RBCs, Plasma, and Platelets Having the MTP Protocol set up in advance streamlines the allocation and rapid delivery of blood products to patients MTP is designed so that once activated, you do not need to continuously reorder blood products

Important points to remember when ordering a MTP for your patient You must choose the appropriate MTP in powerchart Pediatric Massive Transfusion Trauma/Surgical Massive Transfusion Obstetric Massive Transfusion You MUST initiate and sign the powerplan You MUST call the Blood Bank to notify them that you activated a MTP 272-2591

Information to provide to the Blood Bank Patient’s name and MRN Patient’s location Attending physician responsible for the patient Point of contact name and phone number For pediatric patients: estimated/known weight in kg

Adult and OB MTP Rounds Cryoprecipitate is not provided nor built into the ADULT MTP rounds. One pool of cryoprecipitate is provided with each of the first two OB MTP rounds

Pediatric MTP rounds are weight-based Cryoprecipitate is not provided nor built into the MTP rounds – it must be ordered separately Blood product dosing for pediatric patients: 15mL/kg

The most important initial labs are included in the MTP powerplans Type and screen Emergency Hemorrhage Panel (EHP) Tests included: Hemoglobin, Platelet Count, PT/INR, Fibrinogen Results in 15 minutes upon specimen arrival to the lab Hand deliver a lavender top and a light blue top tube to the lab New EHP should be sent after every round or every 30-60 minutes Important to know patient’s type before we start giving o pos/neg if no type is in system

Picking up MTP rounds The clinical service is responsible for picking up all blood products required during the MTP RBCs and other blood products are generally available for pickup at the Blood Bank unless otherwise arranged The Blood Bank will notify the Point of Contact when each new round is ready to be picked up A new round will automatically be prepared once previous round is picked up RBCs/plasma can be set to be picked up in the fridge between TSI and the MICU if necessary

Endpoints of Massive Transfusion Physician declares hemostasis based on the absence of bleeding The treating physicians agree the patient is adequately resuscitated based on normalizing vital signs Further resuscitation is deemed to be futile The point of contact must notify the Blood Bank when the MTP has ended

Remember: If your patient is bleeding and you’re concerned it is already uncontrolled or may become uncontrolled, activate the MTP

Questions?