ABO Compatibility and Blood Products

5/30/2019

Overview

• Blood Products ABO Compatibility and Blood • ABO Compatibility Products • HSCT Product Processing on Day of Transplant • Adverse Transfusion Events Transfusion Support of the HSCT Patient • Transfusion Support Issues • Iron Overload Renee LeBlanc, BSN, RN Transfusion Services Office Seattle Cancer Care Alliance

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Blood Composition Whole blood processing to express off Platelet Rich Plasma

Plasma: 55% of blood (90% H²0, 10% solutes)

RBCs: 44% of blood (erythrocytes)

WBCs: less than 1% (leukocytes)

Platelets: less than 1%

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Express off majority of plasma into satellite bag to INDICATIONS FOR TRANSFUSION make Plasma/FFP with platelet concentrate remaining When, What and Why

Thromb- Bleeding Anemia cytopenia- Infection Oozing

Platelets RBC Platelets Granulocytes Plasma Standard Standard Prolonged neutropenia Threshold Threshold and infection Cryoprecipitate 10K unresponsive to 21% - 26% treatment w/certain attributes

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Concentric Layers of Flowing Blood Red Blood Cells

Axial stream RBC’s

BLOOD TYPING REVIEW Minor Red Cell Antibodies

Distribution of Blood Types in the United States

Image By InvictaHOG - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1088507

RED BLOOD CELLS RED BLOOD CELLS

Things that delay RBCs – Antibodies, Volume Reduction and Washing Effect of daratumumab or similar drugs on Lab Testing Red Cell Antibodies: ▪ Alloantibodies ▪ Anti-A & Anti-B are expected ▪ Daratumumab binds to CD38 on RBCs and interferes with antibody screening by masking the ▪ All others are unexpected detection of “minor” antibodies ▪ Autoantibodies ▪ Warm autoantibodies are IgG immune responses to a pt’s own RBCs ▪ Cells must be treated with DTT to disrupt daratumumab binding ▪ Cold autoantibodies are generally not clinically significant. ▪ If pt shows sx of reaction, warmer use is indicated. ▪ Additional processing time

▪ Kell blood group proteins are also sensitive to DTT Antibody Testing is done in 3 Antibodies that are always phases: considered to be potentially clinically significant: ▪ 1. Immediate spin at 37o to Post DTT treatment it is impossible to know if the patient had Kell blood group proteins detect “cold” antibodies ▪ ABO (A, B) ▪ If not, the pt may have anti-K antibodies 2. Tubes are then incubated at ▪ Rh (D, C, c, E, e) 37o to detect “warm” ▪ Duffy (Fya, Fyb) antibodies – 10 to 60min ▪ Kidd (Jka, Jkb) ▪ SCCA standard to genotyping or phenotyping before daratumumab is given – to determine if the depending on process ▪ Kell (K, k) 3. AHG phase for indirect ▪ SsU (S, s, U) pt has Kell on their RBCs. antibody testing (Uhl, 2016)

(Smith, 2016)

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Acute Hemolytic Transfusion Reaction ABO Compatibility + Preventing Hemolytic Transfusion Reactions for Antibodies RBC’s ABO mismatched BMT Transplants Antibody Coated RBC’s

Complement Activation

Membrane Damage and Cell Death Hypotension, shock, renal failure, DIC

Blood Type ABO Compatibility Concepts

• Red Cell Type – Forward (Front) Type A • Antigens exist on the RBC Cell Wall A – What ABO type are the RBC’s A • A and B antigens are expressed on the cell wall A A • Antibodies exist in the Plasma A • Serum Type – Reverse (Back) Type • RBC’s do not have Plasma • (Actually not true – there is ~ 20-40ml) – What antibodies (Anti-A, Anti-B) are present • Platelets have Plasma but no RBC’s • (Actually not true – there is ~ 1-3ml)

Type A Case Study - Background Patient B B

B Mrs. Mary Jones A •57yo, Myelofibrosis A A B •Scheduled for PBSC Transplant

A • URD B A B •Her ABO type O positive A •Donor ABO type A positive

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Type O Patient Case Study – ABO Pre-Transplant A B A O positive Antibodies to both type A and to B RBC’s B Anti-A and Anti-B

A RBC’s – Give type O positive

B A Platelets – Give any type Plasma – Give any type

There are no RBC’s in Platelets or Plasma. A B There is no such thing as Anti-O

Post Transplant Blood Component Support Case Study – ABO Post-Transplant ABO mismatched Transplant Patient O positive Donor A positive Give Components that are compatible with what the recipient: was, is, and will be. RBC’s – Give type O positive

All ABO mismatched recipients get ABO type O RBC’s Platelets, Plasma – Give compatible with Type A (Full volume A, AB. Or Reduced Volume O, B or PAS)

Give Platelets that do not have plasma with antibodies to either original or • There are no RBC’s in platelets or Plasma. donor ABO types • There is no such thing as Anti-O

Platelet Type O HSCT Product Processing Plasma Reduced A B ABO Mismatched Transplants B

A Major ABO Mismatch B Patient Antibodies directed toward Donor RBC’s A Minor ABO Mismatch Donor Antibodies in PLASMA directed toward Patient RBC’s B A B B

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Case Study – Transplant Donor Type A Major ABO Mismatch Patient Antibodies directed toward (Patient O, Donor A) B A Donor RBC’s A A Mary has Anti-A titers IgM 1:32 A B A Patient Type O IgG 1:128 A These titers would hemolyze type A RBC’s in the HSCT Product B B B Assure RBC’s in HSCT Product is < 20ml

Hct is checked on PBSC product A A If > 20ml RBC in product - must RBC deplete

PBSC done in Cellular Therapy Lab, Marrow done by Apheresis A B

Engraftment of Donor RBC’s Donor Type A Major ABO Mismatch Patient ABO type O, Donor ABO type A A Patient Antibodies directed toward B Donor RBC’s Patient Vascular A A Patient Bone Space Marrow Space A A A B B A A A A Patient Type O B A A B B A A A A A RBC Deplete A A

A A A A A A B B A Major ABO Mismatch

Case Study 2- Background Case Study 2 – Transplant (Patient A, Donor O) Mr. Mike North •45yo, AML Donor has Anti-A titers IgM 1:512 •Plan for Bone Marrow Transplant IgG 1:256 • URD These titers would hemolyze type A RBC’s in the Patient

•His ABO type A positive Assure Plasma in HSCT Product is < 200ml •Donor ABO type O negative If > 200ml Plasma -> Plasma deplete

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Donor Type O Minor ABO Mismatch Donor Type O Minor ABO Mismatch

B B Donor Antibodies directed toward Donor Antibodies directed toward A Patient RBC’s A Patient RBC’s

B B Patient Type A Patient Type A A A A A B B A B B A A A A B A B

A A A A A A Plasma B Deplete B

Engraftment of Donor RBC’s Patient ABO type A, Donor ABO type O Instruction Examples

Patient Vascular Patient Bone Space Marrow Space B B B

B B

Minor ABO Mismatch

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RN collection of the Type and Screen 2 Person Verification at Time of Blood Draw: Always at the Bedside

Collector legibly writes initials, collection date and time on specimen label and requisition

MUST MATCH Second Verifier legibly writes initials on specimen label and EXACTLY requisition attesting to verification of exact match

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Verification Right Patient and Right Product: Verification Right Product for Order: Patient to Transfusion Report Unit to Transfusion Report

*Verification occurs with Patient and 2 RN Verification of RN/RN or at the ID band MUST bedside match Transfusion 1. Component Name Report EXACTLY 2. Unit Number *Pt states Name 3. Expiration has not passed and DOB 4. Component Blood Type *RN spells out 5. Pt’s Blood Type patient’s full name 6. Special processing and MRN 7. Blood board - HSCT

*2nd RN verifies this information on BOTH RNs attest by Transfusion Report signing the Transfusion Record If ID and Transfusion Report do not match exactly, you must return unit to Blood Bank This is your FINAL safety check before beginning transfusion. Strict attention is critical.

Prolonged Engraftment Platelets

Cord BMT GVHD Medications Patient high titers against the donor red cell type

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POOLED PLATELETS APHERESIS PLATELETS (AKA RAPS)

Whole blood derived from 5 different PLATELETS From a random single donor donors are “pooled” previous to storage ▪ also called Pre-storage pooled Necessary for the clotting process ▪ Can be large volume - generally PLATELETS platelets 220mL to 500mL ▪ PSPP pooled in closed system allows ▪ Suitable for most patients for same storage as apheresis ▪ Apheresis only for Aplastic Anemia pts to reduce # of donors they are Processing ▪ Suitable for most patients exposed to ▪ Not for Aplastic Anemia Processing Minimum Required: ▪ Leukoreduction ▪ Appropriate substitution for pts receiving ❖Not appropriate for most platelet ▪ Irradiation HLA selected apheresis platelets Minimum Required: refractory pts ▪ Leukoreduction Additional: ▪ TRAP Trial demonstrated no significant ▪ Irradiation ▪ Volume Reduction difference in lymphocyte antibody Apheresis platelets with Platelet ▪ Washed development as long as product is LR Additional: Additive Solution (PAS) ▪ Volume Reduction ▪ Washed ▪ Treated the same as regular Apheresis platelets ▪ Can substitute for out of blood group

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HLA DIRECTED APHERESIS PLATELETS Apheresis How do you know your patient needs them, how do you monitor your patient?

What does What exactly is a PRA? platelet refractory What now? Platelet Reactive mean? Alloantibody Test that identifies what Poor (more than antibodies a patient is Identify issues like: once) or no response ▪ Splenomegaly making against platelet HLA to platelet ▪ Fevers types. ▪ Reactions Represented as a % transfusions. Check for better response to Pooled What this test means: Plts Once antibodies are identified, BWNW uses a program that compares these So then, what qualifies as a antibodies against the typing of all known transfusion “failure?” No other possible reason donors (the blood bank population). If the Send a Platelet (Reactive) patient has an antibody against a An Incremental increase of ≤ 5K with common HLA type (such as A2) then the Alloantibody Workup PRA will automatically be high Pre count done immediately Basic (PRA).* If 68% of the “population before transfusion & post count has that HLA type then the pt’s PRA will be at done 15 min to 1hr after least 68%. Add in completion. antibodies against additional HLA types and the PRA can be as high as Platelets, Granulocytes, 100% Plasma, RBC’s, PBSC

HLA DIRECTED APHERESIS PLATELETS Plasma-Stored versus PAS-Stored Platelets How do you know your patient needs them, how do you monitor your patient?

Management and Complications My Patient’s PRA is

100% - what now? In some cases donors are not available Initiate a MAP referral The pt. may be managed Transfusion Service will with pooled plts and/or identify matched donors an antifibrinolytic like and may recruit donors to Amicar. donate just for this pt. This Follow each MAP transfusion to is a limited resource so evaluate for response. good management is needed. Long Term: Good communication is key PRA should be rechecked every Notify Transfusion Service in month0 while receiving advance for known procedures that MAPs. will require transfusion. Minimize # of Not all HLA matched donors will transfusions to limit also be an ABO and/or Rh match, exposure to donors. so some special circumstances may need management

LESS COMMON BLOOD PRODUCTS In the Clinic Setting Blood Component Attributes

Granulocytes Donor Recruitment Indicated for patients with… ▪ Family donors can be considered but only if there is …neutropenia expected to last >2 no chance they would be potential HSCT donors weeks ▪ Donors can donate once a week …infections with specific attributes ▪ Yearly cap is 12 times in a year (rolling 12 …unresponsive to antibiotics or months) Modifying the Blood Product antifungals ▪ i.e. Pulmonary infiltrates To reduce adverse effects st 1 2 transfusions will take inpatient Collection to assess reaction ▪ Donors are treated with G-CSF and dexamethasone Standard premeds: the day before collection diphenhydramine, acetaminophen, ▪ Cells are then collected by apheresis the next hydrocortisone, methylprednisolone morning or dexamethasone ❖ Always a risk the donor will be deferred. Processing ▪ Irradiation ▪ Do not order leukoreduction

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Irradiation Leukoreduction

Applied to red cells and platelets • Leukoreduction Inactivates Lymphocytes that cause Transfusion Related Graft vs. Host – Removes WBC that may cause alloimmunization against Disease (tGVHD) platelets – Reduce unwanted effects caused by WBC’s releasing cytokines during storage

• CMV Negative/Safe – Virus exists in WBC, therefore Leukoreduced blood products are considered CMV Safe

Reduced Volume Washed Blood Components

Plasma removed from product down to 100ml • Indication RV results in some platelet loss and platelet activation – Rarely used. Removes essentially all plasma proteins from component – Life Threatening Allergic Reactions (Anaphylaxis) Indications • Small recipient size • How • Severe fluid restriction issues – Normal saline added to bag • Allergic reactions – centrifuged -> plasma removed • ABO compatibility • Effect – Removes donor plasma proteins PAS platelets may substitute for RV if for: – Adverse Effect of washing - Cell loss (~ 20% of cells) •ABO compatibility •Mild-moderate allergic transfusion reactions

Suspected Transfusion Reaction Recognized 1) STOP TRANSFUSION 2) Notify MD (consider RRT) 3) Assess patient frequently - vital signs, lung, skin 4) Maintain IV access. Do not flush or use blood set. 5) Perform Clerical Check 6) Determine if samples needed: a) Order TransReact in Cerner; send two EDTA tubes, blood bag, infusion set, & PSBC transfusion reaction form to Blood Bank Lab STAT ADVERSE TRANSFUSION EVENTS b) If urine is red/dark, send urine sample to Lab c) Hives only-No samples required, send PSBC transfusion reaction form to Blood Bank lab

Image source: http://www.bestchinanews.com/Explore/4783.html 7) Treat symptoms per MD orders 8) Document in medical record

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Acute Hemolytic Transfusion Reaction (AHTR) Transfusion reactions can Signs and Symptoms occur… ▪ An antigen/antibody reaction usually due to ABO incompatible blood. Transfusion … at any time during the infusion or up to several hours after it is completed. Reactions ▪ Fever ( ≥38C or an increase of 1 ▪ 80% of AHTRs are due to clerical errors in labeling degree Celsius or greater of a …with any type of blood or blood bsln temp 38C) component including red cells, plasma, ▪ WBIT: wrong blood in tube ▪ Chills platelets, or cryoprecipitate.

Any change in the ▪ Flushing, urticaria … regardless of previously tolerated ▪ Considered a “Sentinel Event” and medical patient’s baseline transfusions. clinical assessment ▪ Hives emergency in association with a transfusion should ▪ Hypotension/hypertension ▪ Potentially FATAL be considered a ▪ Nausea/vomiting possible transfusion reaction. ▪ Back, chest, or flank pain ▪ Onset within 10-15 minutes ▪ Wheezing, difficulty breathing, Febrile Allergic Transfusio hypoxia Reactions – n ▪ RBC hemolysis -> Hemolytic & Reaction ▪ Peri-orbital edema Non- s Associated ▪ Fever, hypotension, nausea, vomiting, tachycardia, Hemolytic Circulator ▪ Anxiety dyspnea, chest or back pain, flushing, severe anxiety. www.pc.maricopa.edu/.../type2reaction.jpg y Overload ▪ Dark/red urine Hemoglobin induced renal failure

Mild Allergic Reaction Allergic/Anaphylactic Reaction ▪ ▪ Causes: Pre-existing antibody in the patient to a protein or allergen in Causes: Pre-existing antibody in the patient to a protein or allergen in the donor component the donor component ▪ Allergic (urticarial) ▪ Mild Allergic ▪ Most common of reactions ▪ Most common of reactions ▪ Anaphylactic ▪ Can sometimes be delayed 2-3 hrs post ▪ Shorter interval more severe ▪ Rare, but potentially fatal ▪ ▪ Symptoms: the shorter the interval the more severe the reaction ▪ Itching, hives, urticaria Well circumscribed, discrete wheals with ▪ Symptoms: erythematous raised, spreading borders ▪ Itching, hives, dyspnea, wheezing ▪ Report to transfusion services – sample ▪ Cutaneous and no fever not required. ▪ Resume slowly if ordered

Febrile Transfusion Reactions Bacterial Contamination

• Caused by sensitization to antigens on cell components, particularly • Rare leukocytes and/or cytokines produced by donor lymphocytes Fever, chills, rigors, hypotension • More common with platelets Fever defined as ≥38C AND 1C change from baseline • Sudden, severe – Usually in 1st 15min.

• Pre-medicate with acetaminophen • High Fever, rigors, hypotension, nausea, vomiting

• Leukoreduction – Pre-storage reduces incidence • Stop, notify Blood Bank, save bag for culture • Co-components must be sequestered • Culture patient

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TRALI: Transfusion Related Acute Lung Injury TACO: Transfusion Associated Circulatory Overload • Causes: Neutrophil/HLA antibodies in product react with the patient’s ❑Symptoms-new onset or exacerbation ❑ Infusion volume not neutrophils causing activation of the neutrophils in the pulmonary within 1 -2 hrs of transfusion microcirculation & subsequent pulmonary edema effectively processed ▪ SOB, cough, rales, hypoxia O2 Sat↓, ❑ • Clinical Manifestations High rate of infusion orthopnea ❑ ▪ Dyspnea Excessive volume ▪ Hypertension ❑ ▪ Cyanosis Underlying cardiac, ▪ Tachycardia pulmonary, or renal disease ▪ Hypotension ▪ Pedal Edema ▪ Fever & chills ▪ Pulmonary Edema NOT present prior to ▪ Bilateral pulmonary edema (non-cardiogenic) ▪ Jugular Vein Distention • Sx onset within 1-2 hours of transfusion ▪ Pulm Art Pressure >18mm Hg ▪ Central Venous Pressure > 12mm Hg ▪ Full presentation at 4-6 hours: return to baseline in 2-4 days ▪ ST segment and T wave changes ▪ Ventilator Support ❑Similar timeline to TRALI

PRE-MEDICATIONS When, why, and risks

ANTIPYRETICS (Acetaminophen) ANTI-HISTAMINES (H1) (Diphenhydramine ) ▪ History of febrile reactions ▪ History of allergic transfusion reactions ▪ Repeated or significant reactions ▪ Risk: Sedation ▪ Risk: Masking (neutropenic) fever due to infection

TEROIDS H2 BLOCKER (Ranitidine) S (Hydrocortisone) ▪ History of allergic transfusion reactions ▪ History of severe allergic reactions not responsive to Diphenhydramine ▪ Use when adding Diphenhydramine or increasing Diphenhydramine dose is not an ▪ Prefer to volume reduce platelets if possible option. ▪ Risk: Immunosuppression ▪ Risk: Concern for delayed engraftment in HSCT pts