TRANSFUSION MEDICINE: COMPONENT THERAPY At the end of this unit, the learners must be able to: 1. differentiate the various components as to the manner of preparation, storage and indications.
A. Review of Terms a. b. c. d. e. f.
Massive blood transfusion Multiple transfusions Chronic transfusions Autologous blood transfusion Allogeneic blood transfusion Voluntary non-remunerated blood donor i. Directed donor ii. Replacement donor iii. Altruistic donor
g. Blood Derivatives/Blood Components h. Apheresis i. Intermittent flow centrifugation ii. Continuous flow centrifugation
i. j. k.
Therapeutic bleeding and therapeutic plasma exchange Universal donor & universal recipient Blood substitutes
B. Blood Components Component
Whole blood
Indication
Volume expansion, increase oxygen
Storage (Temp in °C, Shelf Life) 1-6, depends on anticoagulant
Content: Composition, Volume, QA 450-500 ml: RBC (40%) Plasma Platelets WBCs
Preparation & other remarks Must be ABO & Rh compatible Inc Hgb 1g/dL Inc Hct by 3% Stored or transfused as collected
Irradiated WB
Volume expansion, increase oxygen in patients at risk to TAGVHD & FNHTR
1-6, depends on anticoagulant 28 days from irradiation whichever comes first
450-500 ml: RBC (40%) Plasma Platelets
Must be ABO & Rh compatible Inc Hgb 1g/dL Inc Hct by 3% 15-25 Gy (US, Phil) 25-50 Gy (New Zealand, Australia) Special labelling
RBCs
Increase oxygen in normovolemia or high risk of circulatory overload
1-6, depends on anticoagulant (if closed system) 24 hours (if open system)
RBC irradiated
RBC aliquots
Increase oxygen in normovolemia or high risk of circulatory overload and/or TA-GVHD & FNHTR
1-6, depends on anticoagulant
Increase oxygen in neonates/infants
1-6, 24 hours in CPD-A1
250-300 ml: RBC (> or =80%) Plasma (=20%) Additive solutions (optional) - Toxicity - Cost - Allergies
Must be ABO & Rh compatible Inc Hgb 1g/dL Inc Hct by 3%
250-300 ml: RBC (< or =80%) Plasma (>/=20%)
15-25 Gy (US, Phil) 25-50 Gy (New Zealand, Australia)
Volume varies (usu 10-25 ml)
Must be ABO & Rh compatible (10ml/Kg in a unit) Inc Hgb 1g/dL Inc Hct by 3%
Sedimentation or centrifugation of FWB (8-24 hrs)
28 days from irradiation whichever comes first
Syringe or Pedi-Pak RBC leukoreduced
Increase oxygen in patients prone to
1-6, depends on anticoagulant (if
250-300 ml -same as RBCs-
Must be ABO & Rh compatible
FNHTR Prevent TRALI, EBV, CMV & HTLV trans
closed system) 24 hours (if open)
<5 x 106 WBCs >/= 85% RBC recovery
Inc Hgb 1g/dL Inc Hct by 3% Sedimentation or centrifugation of FWB (8-24 hrs) Some cases of hypotension/allergic reaction
Washed RBCs (and deglycerolized RBCs)
Washed – for PNH, IgA deficiency Frozen – rare phenotype, autologous, military inventory
Up to 10 years when frozen at 65, 24 hours when washed, 1-6
Washed (180 ml): 70-80% RBC <5 x 108 WBC Deglycerolized (180 ml): <300 mg Hgb <1% glycerol 80% RBC Saline Dextrose <1% WBC, platelets
Must be ABO & Rh compatible Inc Hgb 1g/dL Inc Hct by 3%
Platelets (RD)
Thrombocytopenia, DIC, bleeding
20-24, 5 days with agitation
50-70 ml: Platelets >/= 5.5 x 1010, pH 6.2 40 to 70 ml plasma 8.3 x 105 WBC Coagulation factors
Increases platelet by 5-10k/microliter Prepared from WB within 4 hrs of collection
Pooled: 4 hours
No crossmatching required Type specific
Platelets (SD)
Thrombocytopenia, DIC, bleeding to limit HLA alloimmunization & limit exposure Platelet refractoriness
20-24, 5 days with agitation
200-400 ml: Platelets >/= 3 x 1011 300 ml of plasma pH 6.2 coagulation factors
Through apheresis Increases platelet by 30-60K/microliter
Platelet aliquots
Neonates with <50,000/microliter
20-24, 5 days with agitation
5 to 10 ml
Increases platelets by 50,000 to 100,000 per 5-10ml/Kg
Platelets (irradiated)
Thrombocytopenia, DIC, bleeding in patients prone to TA-GVHD
20-24, 5 days with agitation
200-400 ml: Platelets >/= 3 x 1011 300 ml of plasma pH 6.2 coagulation
HLA compatible
HLA compatible
factors Platelets (leukoreduced)
Thrombocytopenia, DIC, bleeding in patients prone to FNHTR
-same-
Platelets >/= 5.5 x 1010, pH 6.2 40 to 70 ml plasma 5 x 105 WBC Coagulation factors
SD: HLA
FFP PF24
Replacement of all coagulation factors/multiple coagulation factor deficiency Actively bleeding Reversal of warfarin TTP
-18 for 1 year -65 for 7 years
Stable and labile factors 1 IU/ml
Prepared from WB within 24 hrs of collection then frozen within 6 (ACD) to 8 (CDP, CD2D, CPD-A1) hours
Factor VIII (80 units of AHF) Fibrinogen (150 mg) Factor XIII, von Willebrand Fibronectin 15-25 ml of plasma Albumin, factors II, V, VII, IX, X, XI and ADAMTS13
WB CPD or CPD-A1, frozen, thawed to a slurry at 1-6, centrifuged Increases fibrinogen by 5-10 mg/dL ABO compatible
Cryoprecipitate
Fibrin glue manufacturing Hemophilia A VWD FXIII deficiency Hypofibrinogenemia
Cryo-poor plasma/plasma cryo-reduced
Plasma exchange for TTP Source of specific factors
Thawed, use within 24 hours, if not can be stored 1-6 after thawing up to 5 days including initial 24 (reduced amounts of V, VII, VIII & X) -18, 1 year 20-24 or Thawed, 6 hours Pooled: 4 hrs
-18 or colder 1year
Prepared from FFP after thawing & obtaining cryoprecipitate, frozen within 24 hours
COMPATIBILITY TESTING At the end of this unit, the learners must be able to: 1. classify and explain the different crossmatching procedures; 2. apply learned concepts to resolution of incompatible crossmatches; 3. master the techniques of the major and minor crossmatches; 4. analyze the applications of other laboratory tests; and 5. understand the present and future trends in blood banking automation. A.
Limitations a. Cannot guarantee RBC viability b. Cannot totally eliminate transfusion reactions
B.
Pre-transfusion testing a. ID, collection & prep of samples i. Donor sample: 1. By collecting facility: ABO & Rh grouping, disease transmission, antibody ID if w/ possible sensi. 2. By transfusing facility: confirm ABO & Rh using attached segment ii. Patient sample: 1. ABO & Rh, antibody screening
b. Selection of donor units: i. Crossmatch C.
Importance of Serologic Crossmatch: a. Final ABO compatibility check b. Antibody against untested Ag c. Can be eliminated if (a.k.a. Type & Screen): i. No clinically significant antibodies were detected in the antibody screening process ii. No detection of clinically significant unexpected antibodies
STEP
REAGENT
PURPOSE OF REAGENT
CLINICAL SIGNIFICANCE
SALINE – ROOM TEMPERATURE
NSS
- IgMs, cold agglutinins & wide thermal range abs
-most ABO incompatibilites
SALINE - 37° C
NSS/LISS
-detection of IgG antibodies, potentiator
- Potent Rh antibodies
ALBUMIN OR HIGH PROTEIN TEST
22% BSA
-reduce zeta potential between RBCs
-increases strength of immediate spin agglutination
ANTIGLOBULIN PHASE
AHG
- Detect IgG and C’ bound to RBC membrane
-Identify patients who demonstrate clinically important Ab...
D. Computer Crossmatch E. Emergency Crossmatch a. Abbreviated b. Incomplete crossmatch
POLYAGGLUTINATION At the end of this unit, the learners must be able to: 1. understand the present and future trends in blood banking automation. A.
Definition a. Red cells that are agglutinated by a large proportion of adult human sera regardless of blood group. b. Usually non-reactive with autologous serum
B. Classification a. Acquired/Microbial associated (Transient, common) ▪ T, Tk, Acquired-B, Th, VA b. Inherited/Non-microbial associated (permanent & irreversible) • Tn, CAD, NOR • HEMPAS (hereditary erythroblastic multinuclearity w/ a positive acidified serum) a chronic dyserythropoietic anemia C.
Laboratory testing a. Detection i. Not easily detected 1. Natural polyagglutinins are destroyed during the manufacturing process 2. Antibodies are low in titer 3. Apparent during crossmatching (esp minor) b. Confirmation and classification i. RBC should be tested with several cord blood sera and with several normal group AB adult sera ii. Enzymes and Sulfhydril compounds iii. Lectins iv. Adsorption and elution v. Aged sera vi. Dilution
D.
Clinical Significance a. Hemolytic anemia & HTR
b. Hemolytic uremic syndrome c. Breast cancer and other malignancies d. Leukemia
ADVERSE EFFECTS OF BT At the end of this unit, the learners must be able to: 1. enumerate and discuss the common types of transfusion reactions; 2. apply the basic principles of laboratory tests in analyzing cases regarding transfusion reactions; A. Classifications a. Acute/Immediate vs delayed b. Immunologic vs. Non-immunologic c. Infectious/TTI/TTD vs. non-infectious
• Immediate (24hrs) – Immunologic • IHTR • FNHTR • Allergic or urticarial • Anaphylactic • TRALI – Non-immuno-logic • Bacterial contamination • TACO • Physical or chemical hemolysis
• Delayed – Immunologic • EHTR • TA-GVHD • PTP – Non-immunologic • Hemosiderosis • Dse transmission
Acute Transfusion Reactions Febrile Allergic Pulmonary AHTR TAS FNHTR Mild Severe TACO TRALI Delayed Transfusion Reactions Serological hemolytic TAGVHD PTP iron Overload B. Risk management of adverse reactions a. Pathogen inactivation b. Proper donor screening c. Proper blood utilization
C. Assignment – complete table below: Reaction
AHTR (immunemediated)
AHTR (nonimmune)
Transassociated sepsis
S&S
Pain: abdomen, chest, flank, back, infusion site Feeling of impending doom Hemoglobinuria Hemoglobinemia Hypotension Renal failure Shock DIC Fever/chills asymptomatic hemoglobinuria renal dysfunction
Fever/chills (=/> 2ºC) Rigor Hypotension Shock
Cause
Work-up
Management (Treatment & Prevention) Follow SOP Discontinue transfusion Maintain IV & BP Treat DIC if present
Naturally occurring or previously formed Abs against donor Ag’s
DAT (+) L Hgb H LDH H Bilirubin L haptoglobin
Chemical or mechanical damage
DAT (-)
Follow SOP Maintain IV & BP Maintain renal blood flow Discontinue transfusion Clerical verification Notify physician
Bacterial contam
DAT (-) GS blood bag Culture bag Culture patient
Discontinue transfusion Maintain vascular access Consider antibiotic Follow SOP Implement bacterial detection intervention
A. Transfusion-Transmitted/Associated Diseases a. Viruses: i. Hepatitis (A, B, C, D, E, G) ii. HIV Types 1 and 2 iii. HTLV I and II iv. West Nile Virus v. CMV vi. EBV vii. Parvovirus B19 viii. Human Herpesvirus 6 and 8 b. Bacteria i. Syphilis ii. Tick-borne bacterial agents
c. Parasites i. Babesia microti ii. Trypanosoma cruzi iii. Malaria d. Prion i. Creutzfeld-jakob disease
OTHER TESTS FOR ANTIBODY DETECTION At the end of this unit, the learners must be able to: 1. apply the basic principles of laboratory tests in analyzing cases regarding transfusion reactions; A. Neutralization/Hemeagglutination inhibition B. Adsorption and elution C. Antibody screening
MEDICO-LEGAL ASPECTS OF BB At the end of this unit, the learners must be able to: 1. learn the ethical implications and considerations in transfusion medicine. A. Civil lawsuits: 1. Striking or threatening to strike another person (battery and assault) • Intentional infliction of emotional distress • Invasion of privacy under civil case law 2. Being careless or reckless (negligence) • A duty was owed to the injured party • Duty was not met by the injuring party • Injured party was harmed • Failure to meet the duty owed was directly responsible for or could have been predicted to cause the harm suffered by the injured party. • Some measurable (compensable) harm (called “damages”) occurred. 3. Failing to complete an agreement (breach of contract)
4. Intruding on another’s property or privacy 5. Misbehaving on other similar ways B. Governing laws and policies 1. Doctrine of informed consent 2. Standard of care (professional & ordinary) • Is the treatment the best course of treatment? Did the professional do everything possible to avoid consequences? Are there alternatives? (note: blood pharming, blood alternatives) • Examples of adverse donor reactions: • Systemic reactions (dizziness, sweating, nausea, vomiting, weakness, apprehension, pallor, hypotension, bradycardia, syncope, convulsions) NB: pulse rate is usually high during volume depletion & low during vasovagal reactions o Common among young, lowweight, female, first-time • Bruise or hematoma • Fatigue • Local nerve injury • Arterial puncture
• Upper extremity deep vein thrombosis • Postdonation mortality 3. Respondeat superior 4. Statutes of limitation 5. Risk management/reduction • Screening & voluntary donation • Untimely notification • Component collection, processing • Proper documentation & endorsement • Quality control 6. Ethics: • Principles: Autonomy, Beneficence, Justice • Issues: • Feelings of rejection when deferred as donor • Confrontation of old diseases (diseases that they feel cured of or they have already forgotten about) • Confrontation with unrealized risks • Feelings of discrimination • Conflicting guidelines on deferral • Cases when anonymity is not possible (stem cell or HLA specific transfusions) • Recently diseased persons as blood donors 7. Morals vs. righteousness
REFERENCES: A. Textbook: a. Harmening, Denise M. Modern Blood Banking and Transfusion Practices (2012). 6th Edition. F.A. Davis Company. B. Reference Books: a. Blaney, Kathy D and Howard, Paula R. Basic and Applied Concepts of Immunohematology (2008). 2nd Edition. Mosby, Inc. . b. AABB Committee (2011). Standards of Blood Banks and Transfusion Services. 27th Edition. USA: American Association of Blood Banks. c. Fung, Mark K; Grossman, Brenda J; Hillyer, Christopher D; and Westhoff, Connie M (2014). 18th Edition. Technical Manual (AABB). Maryland, USA. d. Mcpherson, Richard A. and Pincus, Matthew (2017). Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd Edition. Philadelphia: Elsevier Inc. C. Related Websites and other materials: a. American Association of Blood Banks. Available at: http://www.aabb.org/Pages/Homepage.aspx. Accessed on November 6, 2017. b. American Red Cross. Available at http://www.redcross.org/ Accessed on November 6, 2017. c. Department of Health. Available at http://www.doh.gov.ph Accessed on November 6, 2017. d. Human Blood. Available at http://www.fi.edu/learn/heart/blood/blood.html. Accessed on November 6, 2017. e. Hematology-Blood Bank Links to Related Sites. Available at http://www.lhsc.on.ca/lab/bldbank/links.htm. Accessed on November 6, 2017. f. International Society of Blood Transfusion. Available at http://www.isbtweb.org/. Accessed on November 6, 2017. g. Medical Laboratory Observer. Available at http://www.mlo-online.com. Accessed on November 6, 2017. h. World Health Organization. Available at http://www.who.int/en/. Accessed on November 6, 2017.
Note: Regarding the pictures presented in this document, these fall into one of the following types: photographs personally taken by the document’s author, downloaded from the internet under creative commons license, or scanned/downloaded from the references listed; unless otherwise stated in the photograph or caption.
Prepared by: CRIZELDA L. SALITA, MS, RMT