Transfusion Guidelines Instruction Course

Jessica Jacobson, MD

Director, Blood Bank and Transfusion Medicine

Bellevue Hospital Center

Requirements for Blood Bank Samples- Identification

• Label must be placed immediately after drawing blood while still at the patient’s bedside.

• Label must include at least two identifiers. – These could be the name of patient;

MR#; assigned name, if the patient’s name is unknown; complete date of birth.

• Patient ID wrist band (bracelet) must correspond to the label on the blood sample.

• Patient related data on the blood requisition slip must correspond to that of patient ID band and the sample label.

Requirements for Blood Bank Samples

• Blood must be collected in pink top tube after the patient has been properly identified.

• Sample must be signed or initialed by the practitioner who drew the blood.

• Blood sample should be transported directly to the Blood Bank

Requirements for Blood Bank Samples- 2nd Stick

• To ensure patient safety, one sample is not enough for any new patient.

• A second sample, with a second venipuncture and patient identification procedure, must be drawn and sent to the Blood Bank for ABO and Rh confirmation.

• The second sample can be drawn either by the same person within an arbitrarily chosen 10 minute interval or simultaneously by two different persons.– The second tube will have a

separate accession number.

1. Type and Screen

2. ABO Rh Confirmation

Blood Bank Laboratory Testing Turn-Around-Times

• STAT Samples– 60 minutes for Type

and Screen (T&S)– 10 minutes for ABO &

Rh type• For Rh-negative

patients an additional 20 minutes is required

– 45 minutes for Antibody Screen

– STAT TAT is determined by actual incubation and centrifugation times

– Antibody ID may take hours or days depending upon what RBC antibody(s)

Requirements for Blood Unit Pick-Up• Anyone who is trained may

pick-up blood from the Blood Bank.

• A transporter can not pick-up blood for multiple patients.

• Blood will only be issued to a given transporter for one patient at a time.

• For the OR multiple units can be picked-up for the same patient as long as they are transfused within 30 minutes of pick-up time

• Pick-up slip must be presented to the Blood Bank. – The contents of this slip

should include the same patient data as that on the T&S sample.

• If the patient’s identifier data is changed within the interval between sample drawing and blood pick-up, a new sample with appropriate labeling and computer order must be submitted to the Blood Bank.

BLOODBANK2 units,

please

Blood Bank Pick-Up Forms

Pick-Up Form Emergency Release Form

Form is pale blue

Unless an MD is actually picking up the blood all patient data must be ADDRESSOGRAPHED

Must know patient’s NAMEMust know patient’s MRN

MD must sign for emergency release

Emergency Release Blood

• Emergency release blood implies obtaining blood which, because of urgency related time constraints, is not completely tested for a given patient.

• Only physicians can pick-up emergency release blood, because only physicians are allowed to fill out an emergency release form.

• Physician requesting emergency release must accurately know and record at least two patient identifiers (NAME and MRN) on the emergency release form and pick-up form and sign the form with his/her MD ID#.

Emergency Release Blood

• Type O (Rh-positive or Rh-negative) uncrossmatched RBCs will be issued for patients with a yet undetermined ABO Rh type

• Type specific uncrossmatched RBCs will be issued when the T&S and ABO Rh Confirmation specimens have been typed What ABO type of

RBCs will be released?

Requirements for Blood Unit Pick-Up

• No blood may be released if above conditions are not satisfied

• All blood picked-up must be directly transported to the site intended for transfusion

• Any blood unit that is kept outside Blood Bank or Blood Bank monitored refrigerator for longer than 30 minutes cannot be returned to Blood Bank for use in another case

• Transfusion must be completed within 4 hours of issuance from Blood Bank

Blood transfusion should start within 30 minutes of issuance

Requirements for Blood Unit Pick-Up

• By law, the Blood Bank is obligated to know and document who the recipient of each unit is.

• Therefore in case of a rare emergency need for blood in life threatening condition, the physician requesting emergency release of blood must at least know and document on emergency release and pick-up forms two patient identifiers and clearly sign with his/her MD ID#. – In this situation where type and screen sample

is either not submitted or tested, the Blood Bank can only release Type O PRBCs.

– If patient’s ABO type is known, ABO type specific uncrossmatched blood will be issued.

NAME

MRN

Requirements for Blood Unit Pick-Up

• The only situation where physicians can administer blood without first submitting patient identifiers is when the blood is taken directly from the ER trauma blood refrigerator. – 2 identifiers must be

submitted after the patient’s ID is determined

• The red blood cell units kept in the ER trauma refrigerator are Type 0 and are intended only to be used in exceedingly critical situations.

Universal RBC Type is OYou can safely give type O red blood cells to any patient

Requirements for Obtaining Plasma, Platelets, and Cryoprecipitate

• For any blood product an active type & screen is required.

• If the patient’s type is unknown, the Blood Bank will try to issue type AB plasma products in emergency release situations.– This is especially true for FFP and

P24 since the volume is 200 ml per unit

– Platelets of any ABO type may be issued depending upon inventory.

– ABO type for cryoprecipitate is not particularly important due to low volume.

• If the patient’s type is known, type-specific products will be given preferentially.

Universal Plasma Type is AB

Requirements for Administering Blood Products

• In non-emergent situations a separate consent for transfusion must be obtained

• No blood product may be administered before establishing agreement between the data on:– Patient’s two identifiers.– Blood unit’s data in relation to

patient’s identifier data, blood unit number, ABO/Rh, expiration date/time.

– Blood infusion record (crossmatch form) data in relation to patient’s identifier data, blood unit number, ABO/Rh, expiration date/time.

Consent Form

Requirements for Administering Blood Products

• If under any circumstance, the patient is unidentifiable or there is a discrepancy between patient, unit, and blood infusion record (cross-match form), BLOOD UNITS MUST BE RETURNED to the Blood Bank without administering.

• CALL to notify Blood Bank• DO NOT TRANSFUSE THE

UNITS!

Requirements for Administering Blood Products

• The patient’s ID band must be attached to the patient, if they have to be removed in rare instances.

• There are two ways of reattaching the patient’s ID band : – Taping it to the patient – Pinning it to the patient’s

gown.

• If the patient’s ID band is removed the patient’s medical record (chart) cannot be used to identify the patient.

Requirements for Administering Blood Products

• In the operating room at Bellevue, one of the two individuals identifying the patient, blood unit, and the blood infusion record (crossmatch form) must be an anesthesia attending.

• Outside of the OR, one of the two individuals identifying the patient, blood unit, and the blood infusion record (crossmatch form) must be a RN

MandatoryDouble Check

Requirements for Administering Blood Products

• During each blood product transfusion ALL of the questions directed to the tranfusionist on the blood infusion record (Crossmatch Form) must be accurately completed.

– These questions include: Date, Time, tranfusionist’s name and MD ID#, verifier’s name and MD ID#, recipients vital signs (Temp, Pulse rate, Respirations, BP) before, 15 minutes after transfusion is started and at the end of transfusion.

• At the end of transfusion, date, time, volume transfused, and transfusionist’s signature must be recorded on the appropriate section of the blood infusion record (Crossmatch Form).

• Signatures MUST be legibleCrossmatch Form is a duplicate form1st sheet is white (patient chart record)and 2nd sheet is pink (returned toBlood Bank)

Transfusion Triggers

• Red Blood Cells– Hgb <7 g/dL and

symptomatic anemia– Hgb <9 g/dL with

significant cardiovascular, cerebrovascular or respiratory

– Blood loss >20% (or >750 mL) refractory to fluid resuscitation

• Platelets– Platelet count <10K per uL with

or without active bleeding– Platelet count <50K per uL with

bleeding or undergoing major surgery

– Platelet count <100K per uL in patient undergoing neurosurgery or ophthalmic procedure or with intracranial hemorrhage

– Bleeding or immediately pre-op in patient with documented platelet dysfunction

Transfusion Triggers

• Plasma– Bleeding or immediately

prior to invasive procedure and PT >17 sec, (INR >1.5) and/or aPTT >40 sec

– Disseminated Intravascular Coagulation (DIC) with uncontrolled bleeding

– Warfarin reversal (if Vitamin K contraindicated or not sufficiently rapid)

– TTP/HUS/HELLP syndrome / therapeutic plasma exchange

• Cryoprecipitate– Deficiency of factors I

(fibrinogen) or XIII– Fibrinogen <100 mg/dL – Bleeding in patients with Von

Willebrand Disease when concentrates are not available

– Disseminated intravascular coagulation (DIC) – if bleeding and plasma not raising fibrinogen level

– Uremia with bleeding if not responsive to other therapy

Blood Product Modifications

• Leukocyte reduced– <5.0X106 WBC per product– Decreases febrile non-

hemolytic transfusion reactions

– Products are considered CMV safe

• Irradiated– Required for patients at

risk of developing transfusion associated GVHD

• Washed– Available for patients who

have had severe allergic transfusion reactions or have IgA-deficiency

• Sickle-negative– RBC donor has been

tested to determine if their RBCs will sickle under oxidative stress

– Required for patients with Sickle Cell Disease

Adults: Expected Results from Transfusion

• 1 unit PRBCs should increase a patient’s Hgb by 1 g/dl or Hct by 3%

• 1 single donor platelet (SDP) should increase a non-bleeding patient’s platelet count by 30-50 X109 per liter

• A 1-hour post platelet count is helpful in determining if a non-bleeding patient has become refractory to platelet transfusions

Dosing Plasma in Adults

• Plasma should be dosed at 10-15 ml/kg

• For adults this is roughly 4-6 units of plasma

• In vivo half-life of Factor VII is 2-5 hours

• Plasma should be given immediately pre-procedure

• If using plasma to replace FVII, you will need to give 10-15 ml/kg every 4-6 hours

NOTE: INR of P24 and FFP is approximately 1.1-1.2

Pediatrics: Expected Results from Transfusion

• 10 ml/kg dose of PRBCs should increase the Hgb by 1 g/dl

• 10 ml/kg dose of plasma is required to attain therapeutic levels of factors

• 10 ml/kg dose of SDPs should increase the platelet count by 30-50 X109 per liter

Adverse Effects of Transfusion

• Infectious– Viral– Bacterial

• Non-infectious• Transfusion

Reactions

Transfusion-Related Fatalities Reported to FDA

What to do if you suspect a transfusion reaction?

• Stop the transfusion!– Do not restart the transfusion– Only with urticaria may the unit be restarted after the

symptoms have resolved• Report ALL suspected reactions!• Monitor and assess the patient• Notify the Blood Bank• Check to verify that the name and MRN on the blood unit

matches the patient’s wrist band• Return the blood unit to the Blood Bank• Draw a post-transfusion specimen and send to Blood

Bank for work-up• Provide supportive care to the patient if necessary

Clinical Symptoms of a Transfusion Reaction

• Fever• Chills• Infusion site pain• Change in BP• Respiratory distress• Hives• Bleeding

Infectious Risks of Transfusion

What is Blood Tested For?• Lab Testing Helps Ensure Blood Safety

• Tests are done on each unit of blood:– ABO blood grouping – Rh type – Red cell antibody screen – Antibodies to hepatitis B Core – Hepatitis B Surface Antigen – Antibodies to hepatitis C – Antibodies to HIV-1 – Antibodies to HIV-2 – Antibodies to HTLV I/II - (human T-Lymphotrophic Virus Types I and II) – Nucleic Acid Amplification Testing (NAT) for hepatitis C (window period is 35 days)– Nucleic Acid Amplification Testing (NAT) for HIV (window period is 9 days)– Nucleic Acid Amplification Testing (NAT) for West Nile virus – Syphilis (RPR)– Antibodies to T. cruzi (Chagas Disease)

Impact of Viral Testing on Safety

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20

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Year of Introduction of Test

Volunteer DonorsHBsAg

ALT

CUE

HIV-1

Anti-HBc

HCV 1.0

HIV-1/2HCV 2.0

HTLV 1.0

HCV 3.0p24 Ag

HTLV 2.0

HTLV-I/II

HCV/HIVNAT

WNV NATHBsAg 3Bacterial detection

Chagas?Babesiosis?Andromeda strain?

After H. Alter

Risk of Infection from Allogeneic Blood Transfusion

Virus Risk

Hepatitis C <1:1,000,000

Hepatitis B 1:140,000

HTLV I & II 1:640,000

HIV <1:2,000,000

Infectious Risks of Blood Transfusion, Blood Bulletin, volume 4, No. 2, December 2001.

Bacterial Contamination of Platelets

• Major cause of transfusion related fatalities– Clusters of infection/deaths

– RDP Contamination = 1:2-4,000

– SDP Contamination = 1:15,000

– Fatalities = ~ 1:40,000 (underreported)

• Fatalities typically due to gram negative organisms

Other Rare Transfusion Transmitted Infections

• Emerging Blood-Transmitted Infections

– Malaria• Risk 1:4,000,000

– Chagas Disease (Trypanosoma cruzi)• The risk of transmission is 12-25% if

transfused T. cruzi seropositive blood

– Babesiosis (B. microti)• In Connecticut, the risk of

acquiring babesiosis from a transfused unit of packed RBCs was estimated at about 0.17%

– Parvovirus B-19• Viremic donors 0.025%

– Hepatitis A • Transfusion risk is 1 in 1,000,000

– Variant Creutzfeld Jacob Disease (vCJD)

• 4 documented cases in UK– 66 Patients know to have been

transfused with blood from patient who later died from vCJD

– West Nile Virus– Dengue Virus

• Other agents with viremic phase but not yet proven to be transfusion-transmitted

– Human herpes virus- 8 (HHV-8-Kaposi's sarcoma virus)

– Borellia (Lyme disease)– Avian flu virus– SARS

Non-infectious Risks of Transfusion

If not Infectious, What are the Risks?

Mis-transfusion, 66%

TRALI, 7%Delayed Reaction

AcuteReaction

Infections, 2%

GVHD

Post-TxPurpura

Non-Infectious Risks• Human Error and

Clerical Errors• Improper

Administration of the Blood Product

SHOT DATA 1996-2003

How common are errors?

• Risk of an error occurring during transfusion of a blood component is 1:16,500

• Risk of an ABO incompatible transfusion is 1:100,000

• Risk of death as a result of an 'incorrect blood component transfused' is around 1:1,500,000

Clerical Errors

• Sample drawn on the wrong patient– It is vital to check the name and patient ID number

every time you draw a blood sample for testing• Blood is hung on the wrong patient

– It is vital to check that the name and patient ID number on the unit of blood matches that on the patient’s ID band

• Labeling error– Label tubes as you draw or use them rather than

batch labeling. When batching, the risk of a tube switch exists

– Sample tubes must be labeled at the patient’s bedside/chairside

Sample Collection Errors at BHC Identified by the Blood Bank

Total Sample Errors Identified by Bellevue Blood Bank

0

200

400

Num

ber

ABO Discrepancies 2 9 5 13 6 7 7 7 4 6 6

Specimen Not Signed 80 129 117 134 135 169 146 106 67 102 147

Total by Service 128 189 176 214 201 267 205 169 131 157 210

2Q07 3Q07 4Q07 1Q08 2Q08 3Q08 4Q08 1Q09 2Q09 3Q09 4Q09

Where do the Errors occur? SHOT Errors, 1996-2003, n=2340

Collection, Administration, 48.4% Hospital Blood Bank, 29%

Prescription, sampling, request, 19.7%Blood Center, 1.7%

Other, 1%

Unknown, >1%

Serious Hazards of Transfusion Study in UK

Transfusion Errors• Transfusion errors in New York State*

– Erroneous administration (1/19,000 units)• ~50% of errors occurred outside the blood bank

– Blood bank errors• 29% of errors occurred in the blood bank (wrong test, issuance of wrong unit

etc.)

– Multiple errors • 20% involved errors at blood bank and on floor or lab

• Increased scrutiny of hospital reporting by regulatory agencies

* JV Linden et al (2000) Transfusion, 40: 1207

Administration Errors

• What can be added to a line during a transfusion?– Normal saline (0.9%)– ABO compatible plasma– 5% Albumin– Plasma protein fraction

• What can never be added to a line during a transfusion?– Lactated Ringer’s solution

• Contains 3 mEq/L ionized calcium– 5% Dextrose– Hypotonic sodium chloride solutions– Almost all MedicationsRunning any of the above “never solutions” along with blood risks

hemolyzing the transfused cells.

Alloimmunization

• Chronically transfused patients can develop antibodies to WBCs as well as RBCs

• Antibodies to WBCs– Can cause febrile non-hemolytic transfusion reactions

• May avoid or reduce frequency and severity by leukoreduction or pre-medication with antipyretics

• Antibodies to RBCs– Can cause either acute (AHTR) or delayed hemolytic

reactions (DHTR)– Can lead to hemolytic disease of the newborn– May affect the availability of blood

Alloimmunization

• Incidence: – RBC Antigens: 1:100 (1%)

– HLA Antigens: 1:10 (10%)

• Etiology: Immune response to foreign antigens on RBC, WBCs, and platelets (HLA)

• Presentation: Positive blood group antibody screening test, platelet refractoriness, delayed hemolytic reaction, hemolytic disease of the newborn

Impact of RBC Alloimmunization

• Hemolytic Transfusion Reactions– Acute– Delayed

• May make laboratory evaluation more complicated

• Delay and Difficulty in providing compatible blood for transfusion

• Hemolytic Disease of the Newborn

Recognition of Acute Transfusion Reactions

• Signs and symptoms that may be associated with any type of acute transfusion reaction– Fever

• 1C (2F) increase in body temperature associated with transfusion

– Shaking chills (rigors) with or without fever– Pain at the infusion site or in the chest, abdomen, or

flanks– BP changes

• Usually acute either hypertension or hypotension

Types of Acute (<24 hours) Transfusion Reactions (TXRs)

• Immunologic

– Hemolytic

– Fever/Chill

– Urticarial

– Anaphylactic

• Non-Immunologic

– Hypotension associated with ACE inhibition

– TRALI

– Circulatory overload (TACO)

– Non-immune hemolysis

– Air embolus

– Hypocalcemia

– Hypothermia

Hemolytic Transfusion Reactions

• Acute hemolytic transfusion reactions may be either immune-mediated or nonimmune-mediated

• Immune-mediated– Occur when a patient has an antibody directed against a RBC

antigen on the transfused RBCs or when the plasma in the transfused blood product contains an antibody to an antigen on the patient’s own RBCs

• Nonimmune-mediated– Occur when RBCs are damaged prior to transfusion– Generally results in hemoglobinemia and hemoglobinuria

without significant clinical symptoms.

Acute Immune-Mediated Hemolytic Transfusion Reactions

• Incidence: 1:38,000 to 1:70,000 – Some reports as high as 1:25,000 transfusions

• Occur during or within 24 hours after transfusion• Can be fatal• Most often due to clerical and sample identification

errors• Hemolysis can be intravascular or extravascular• Intravascular

– Most often due to ABO blood group mismatch

Acute Immune-Mediated Hemolytic Transfusion Reactions• Signs and Symptoms

– Chills– Fever– Hypotension– Renal failure with

oliguria– DIC– Back pain– Pain along infusion vein– Anxiety– Pain at infusion site

– Hemoglobinurea

– Hemoglobinemia• Can detect 2.5 to 5 ml

RBC hemolysis

Acute Immune-Mediated Hemolytic Transfusion Reactions

• Treatment– Immediately discontinue the transfusion – Maintain venous access for emergency management. – Anticipate hypotension, renal failure, and DIC. – Prophylactic measures to reduce the risk of renal failure may

include • Low-dose dopamine (1-5 mcg/kg/min)• Vigorous hydration with crystalloid solutions (3000 mL/m2/24 h)• Osmotic diuresis with 20% mannitol (100 mL/m2/bolus followed by 30

mL/m2/h for 12 h).

– If DIC is documented and bleeding requires treatment, transfusions of frozen plasma, pooled cryoprecipitate for fibrinogen, and/or platelets may be indicated.

Febrile Non-Hemolytic Transfusion Reactions (FNHTRs)

• Most frequently reported of all reactions

– About 1% of all transfusions

• Incidence:– RBCs: 1:200 to 1:17 (0.5-0.6%)

– Platelets: 1:100 to 1:3 (1-38%)

• Increase in temperature of 1C or 2F with no other explanation

• Presentation: Chills/rigors, rise in temperature (>1C), headache, vomiting

• Most FNHTRs can be prevented

Febrile Non-Hemolytic Transfusion Reactions (FNHTRs)

• Etiology: Due to antibodies to WBCs and/or accumulated cytokines especially in platelets– Current theory is that FNHTRs are caused by

cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha (TNF), which are generated and accumulate during the storage of blood components

• Prevention:– Antipyretic pre-medication with acetaminophen

– Leukoreduced blood products

Urticarial TXRs

• Incidence: 1:100 to 1:33 (1-3%)

• Second most frequently reported reaction

• Presentation: Urticaria, pruritis, rash, flushing

• Etiology: Antibody to donor plasma proteins– Due to Type 1 hypersensitivity to donor plasma proteins

– Urticarial transfusion reactions (UTRs) occur when soluble allergenic substances in the plasma of the donated blood product react with preexisting IgE antibodies in the recipient. This causes mast cells and basophils to release

histamine, leading to hives or urticaria

Urticarial TXRs

• Lab Testing: Rule out hemolysis

• Prevention:– Antihistamines,

treatment or pre-medication (PO or IV)

– May restart transfusion of unit slowly after antihistamine if symptoms resolve

Anaphylactic TXRs

• Incidence: 1:20,000 to 1:50,000• 1:800 to 1:900 people have no detectable

IgA• Etiology: Antibody to donor plasma proteins

(includes IgA, C4)• Presentation: Hypotension without fever,

urticaria, bronchospasm (respiratory distress, wheezing), local edema, anxiety

Anaphylactic TXRs

• Treatment:– Immediate cessation of the

transfusion – Epinephrine, 0.3 mL of a

1:1000 solution intramuscularly

– Preparation, for possible administration, of an intravenous epinephrine drip

– Airway maintenance, oxygenation

– Volume maintenance with saline

– Vasopressors (eg, dopamine), if necessary

• Prevention:– Antihistamines,

corticosteroids, beta-2 agonists

– IgA-deficient blood components if IgA-deficient patient

– Washed blood products

Transfusion Associated Acute Lung Injury (TRALI)

• Incidence: 1:1,300 to 1:5,000• Etiology: Most likely caused by antibodies in donated

blood products that react with patient white cells or visa-versa– Antigen-Antibody reaction results in increasing the permeability of

the pulmonary micro-circulation so that high-protein fluid enters the interstitium and the alveolar air spaces

• Presentation: Noncardiogenic pulmonary edema, hypoxemia, respiratory failure, hypotension, fever, dypsnea, chills– Develops within 1-2 hours of transfusion. Usually present within 4-6

hours– Can be difficult to distinguish from ARDS

TRALI

• Leading cause of transfusion deaths in US for the last two reporting years

• Pulmonary edema arises from capillary injury not volume overload

• Can occur after the transfusion of any type of blood product

• Most patients (>80%) recover adequate pulmonary function within 2 to 4 days

• Observed mortality rate is less than 10%

• Patients are treated with supportive care and may require ventalitory assistance

• Diuretics are contraindicated

Normal Chest X-Ray

TRALI Chest X-Ray

TRALI Edema Fluid

Transfusion Associated Circulatory Overload (TACO)

• Incidence: <1%– Mayo Clinic estimated that incidence to be 1:708

• Etiology: Volume overload Pulmonary edema secondary to congestive failure can occur with transfusion-associated volume/circulatory overload (TACO)

• At risk patients include elderly patients, small children, and/or those with compromised cardiac function. – This often occurs in association with surgery, where large

fluid volumes and some blood are administered. • Presentation: Dyspnea, orthopnea, tachycardia and a

wide pulse pressure, often with hypertension, and may begin near the end of the transfusion, or within six hours. Headache is common, and seizures have been reported.

Transfusion Associated Circulatory Overload (TACO)

• In order to avoid TACO for routine transfusions of blood components, a transfusion rate of approximately 2.0 to 2.5 mL/kg per hour is acceptable. – Thus, for an average-sized adult, one unit of packed red

cells should be transfused over a 1.5 to 2 hour period. • Patients deemed to be at risk of TACO (eg, small stature

or low body weight, elderly, known or suspected poor cardiac function) can generally be safely transfused at a rate of 1 mL/kg per hour. – Such patients should also be monitored more closely

during the transfusion for signs and symptoms of TACO.

Transfusion Associated Circulatory Overload (TACO)

• Treatment consists of fluid mobilization (diuretics) and supplementary oxygen.– Noninvasive positive pressure ventilation may be

helpful in the acute management of patients with severe respiratory compromise.

• Phlebotomy in 250 mL increments, with or without reinfusion of the removed red cells, may be necessary if symptoms persist or diuresis cannot be promoted.

Other Rare Complications

• Hypothermia– Incidence: Dependent on

clinical setting– Etiology: Rapid infusion

of cold blood– Presentation: Cardiac

arrhythmia– Therapeutic/ Prophylactic

approach: Employ blood warmers

• Non-Immune Hemolysis– Incidence: Rare– Etiology: Physical or chemical

destruction of blood (heating, freezing, hemolytic drug or solution added to blood or line)

– Presentation: Hemoglobinuria– Lab testing:

• Plasma-free Hb• DAT (should be negative)• Test unit for hemolysis• Look at segments verses unit

– Therapeutic/Prophylactic approach: Identify and eliminate cause

Other Rare Complications

• Air Embolus

– Incidence: Rare

– Etiology: Air infusion via line

– Presentation: Sudden SOB, acute cyanosis, pain, cough, hypotension, cardiac arrhythmia

– Therapeutic approach: Lay patient on left side with legs elevated above chest and head

• Hypocalcemia (Ionized Ca2+)

– Incidence: Dependent on clinical setting

– Etiology: Rapid citrate infusion. Can occur with massive transfusion of citrated blood, delayed metabolism of citrate, or during apheresis procedures

– Presentation: Paresthesia, tetany, arrhythmia

Delayed (>24 hours) TXRs

• Immunologic– Alloimmunization

• RBC antigens• HLA antigens• WBC antigens

– Hemolytic– Graft-vs-Host Disease

(TA-GVHD)– Post-transfusion

Purpura

• Non-Immunologic– Iron overload

Delayed Hemolytic TXRs

• Incidence: 1:11,000 to 1:5000

• Etiology: Anamnestic immune response to RBC antigens

• Occur 5-20 days after transfusion

• Hemolysis:– Classically extravascular

– Can be intravascular• Kidd antibodies are able to fix complement and thus

can cause intravascular hemolysis

Delayed Hemolytic TXRs

• Caused by antibodies that were undetectable at the time of compatibility testing– Patients frequently “shop around” for their health care

and are thus treated at different hospitals– Without an accurate transfusion history &/or prior test

results it is possible to miss clinically significant antibodies

– >30% of antibodies disappear (become undetectable) with time, but recipients can mount an anamnestic response to further stimulation by transfusion

Delayed Hemolytic TXRs

• Presentation: Fever, decreasing hemoglobin, new positive antibody screening test, mild jaundice, often no signs or symptoms

• Lab testing:– Positive antibody screen– Spherocytes on peripheral screen– DAT (Classically “mixed field”)– Test for hemolysis (visual inspection for

hemoglobinemia, LDH, bilirubin, urinary hemosiderin as clinically indicated)

Delayed Hemolytic TXRs

• Prevention: Excellent patient histories and historical blood bank/blood center testing records– Enables the correct RBCs lacking the

patient’s antibody to be selected

Delayed Hemolytic TXRs

• 50% of patients who become alloimmunized will develop multiple antibodies

• 50% are anti-Rh blood group system– E most common

• 20% are anti-Kell and anti-Kidd (Jka & Jkb)

Hemolytic Disease of the Newborn

• Maternal IgG antibodies made following a previous RBC exposure cross the placenta

• IgG antibodies bind to the fetal RBCs

• The antigen-antibody complexes result in fetal RBC hemolysis and anemia

Hemolytic Disease of the Newborn

Prolonged anemia leads to increased erythropoiesis in fetal liver

This causes disruption of portal circulation, impaired albumin synthesis, decreased plasma colloid osmotic pressure

The decreased osmotic pressure of severe anemia causes cardiovascular failure, tissue hypoxia, and death in utero

Transfusion Associated Graft-vs-Host Disease (TA-GVHD)

• Incidence: Rare• Etiology: Donor lymphocytes engraft in

recipient and mount an attack on the host tissues

• Presentation: Rash, erythroderma, maculopapular rash, anorexia, nausea, vomiting, diarrhea, hepatitis, pancytopenia, fever, bone marrow fibrosis and failure

• Lab testing: – Skin biopsy– Bone marrow biopsy and HLA typing

TA-GVHD• Can develop in patients whose immune system fails

to recognize transfused WBC as foreign • Transfused WBCs (CD4 & CD8 cells) attack and kill

host’s immune system• Prevention: Irradiation of blood components for

patients at risk of developing TA-GVHD– Including:

• Low infant birth weight neonates• Congenital immunodeficiencies• Certain malignancies including Hodgkin’s Disease• Fludarabine chemotherapy• Hematopoietic stem cell transplants• HLA matched products• Blood products from blood related donors

Irradiation of Blood Products

• Since TA-GVHD depends upon:– Number of viable, immunologically

competent lymphocytes transfused

Degree of HLA similarity between donor and recipient

Immunocompetence of recipient

• Gamma irradiation reduces/eliminates lymphocyte proliferative capacity (2500cGy)

• It is necessary to irradiate all cellular blood components including RBC, platelets, and granulocytes

Post-Transfusion Purpura (PTP)

• Incidence: Rare (>250 cases in literature)– Female-to-male ratio is 26:1

• Etiology: Recipient platelet antibodies destroys autologous and transfused platelets

• Presentation: Thrombocytopenic purpura, bleeding, 8-10 days following transfusion

• The typical patient is a multiparous woman or a patient with history of previous transfusions

• Thrombocytopenia is usually severe with platelet counts below 10,000

• Can be associated with significant hemorrhage

Post-Transfusion Purpura

• Treatment– Consists of prompt initiation of IVIG at a dose of 2 g/kg

over 2 or 5 days, in split fractions– Steroids can be used in conjunction– Plasma exchange (TPE)– Transfusion of HPA-1a negative platelets (if patient is

HPA-1b) can be used in life threatening hemorrhagic circumstances

• Course– PTP is generally self-limited with full recovery within

21 days– 10-15% of patients have been reported to die from

PTP

Iron Overload

• Major problem for chronically transfused patients– Sickle Cell Anemia

– Thalassemia

• Incidence: Invariable after >100 units of RBCs, risk occurs after >50 units

• Etiology: Multiple transfusions with obligate iron load in transfusion-dependent patient

• 1 mg of iron per 1 ml of RBCs transfused (every unit of RBC contains approximately 200mg iron)

• Presentation: Diabetes, cirrhosis, cardiomyopathy