Transfusion Medicine

Meredith Reyes, MD

Overview

Blood Components
Collection
Indications
Modifications

Pre-transfusion Testing
Transfusion Reactions

Collection of Blood
Products

Whole blood donation

Whole Blood
Separation

Collection of Blood
Products

Apheresis

Plateletpheresis
Leukapheresis
Erythrocytapheresis
Plasmapheresis
Stem Cell collection

Blood
products
Cellular Components:
Red blood cells
- Leukocyte-reduced

RBCs

- Washed RBCs
- Irradiated RBCs

Platelets
- Whole

blood derived platelets

- Single-donor platelets (Apheresis
Platelets)

Granulocytes

Blood products

Acellular Components:
Fresh-frozen plasma (FFP), Thawed
plasma
Cryoprecipitate
Factor concentrates (VIII, IX)*
Albumin*
IVIG*
* Provided by pharmacy

Red Blood
Cells

Prepared from whole blood

or apheresis donation
250-300 mL
200-250 mL RBCs + < 50 mL plasma
+ preservative/additive solution

Stored 21-42 days at 1-6C

Hct 55-65%

RBC
Compatibility

Indications for RBC

units

Increase O2 carrying capacity

Symptomatic anemia
Acute or chronic hemorrhage

Acute loss of >30% of blood volume

Hemolysis
Marrow failure
Hb < 8.0 gm/dL

Dont just look at hemoglobin level!

Need to consider cardiac output, volume status,
patient history, etc.

Exceptions
Sickle cell anemia
Cardiac or pulmonary disease

TRICC Trial

Transfusion Requirements in
Critical Care
Restrictive transfusion
Hemoglobin maintained at 7-9 gm/dL
Averaged 2.6 units RBCs

Liberal transfusion
Hemoglobin maintained at 10-12 gm/dL
Averaged 5.6 units RBCs

All outcomes evaluated favored

restrictive transfusion group

Contraindications for
RBC units

Acute blood loss <20-30% blood

volume
Crystalloids often adequate

Nutritional anemias
Almost never indicated for Hb
10 gm/dL

Expected Results of
RBC Transfusion

Dependent upon:

Recipient blood volume

Pretransfusion Hb level
Clinical condition (hemolysis, fluid balance, active
bleeding)
Hb content of unit

With one RBC unit for average adult:

Hemoglobin - 1 gm/dL
Hemotocrit - 3%
May take 24 hours to see full effect

RBC transfusion suppresses recipient red cell

production!
Ordering only one unit of RBCs is ok!

What is the difference

between a Type & Screen
and Type & Cross?

The difference is

Type & Screen

ABO type and antibody screen/identification
Valid for 3 months if no transfusion or
pregnancy history
Valid for 3 days if transfused or pregnant

Type & Cross (Crossmatch)

ABO type and antibody screen/identification
Requested number of units crossmatched for
patient and taken out of inventory

Should only be ordered if you anticipate transfusion!

Pre-Transfusion Testing

ABO/Rh type 5 minutes

Antibody screen 25 minutes
Antibody identification 1 hour or
much more

Time required for units

Uncrossmatched Group O-neg RBCs - <

5 minutes
Uncrossmatched type specific RBCs ~
15 minutes
Crossmatched RBCs 30-45 minutes
Full ABO type, screen & crossmatch 1
hour
Patient with multiple alloantibodies
may take many hours!
FFP 30-45 minutes for thawing
Cryo 15 minutes for thawing

When to order RBC

units

When you are ready to transfuse!

After units are out of refrigeration they must be
transfused within 4 hours!

To be returned to stock units must be out of

refrigeration < 30 minutes
Temperature must not be >10 C

Many units are wasted because they are not

transfused in time
If not ready just order a type & screen or type
& cross

Cannot be re-issued if sterility

compromised

How do you give an

RBC unit?

23 gauge needle or larger (18

gauge preferred)
Run at 2-5 mL/min
Maximum time to transfuse 4 hours
Vital signs within 15 minutes of start

Compatible solutions
0.9% normal saline

Modified RBC units

Leukocyte-reduced RBCs
Pre-storage (95% of RBCs used at
MHH & LBJ)
Post-storage (using issued filter)
Indications:
Prevention of HLA alloimmunization
Prevention of febrile non-hemolytic
transfusion reactions
Prevention of CMV transmission
Prevention of transfusion associated
immunosuppression

Modified RBC units

CMV negative RBCs

Donor is seronegative for CMV

Indications:

Protect patient from severe CMV infection

Premature infants (<1200 gms) born to CMV
seronegative mothers
CMV-seronegative pregnant women
CMV-seronegative bone marrow and hematopoietic
progenitor cell or solid organ transplant recipients
CMV-seronegative patients who are severely
immunosuppressed

**Leukocyte-reduced PRBCs are considered

equivalent to CMV seronegative units with
regard to risk of CMV transmission

Modified RBC units

Washed RBCs

99% of plasma is removed

Shelf life of 24 h after washing
180 ml and Hct 75%
Indications:
History of severe or frequent allergic
transfusion reactions
IgA deficiency
Hyperkalemia, especially in a child or
infant

Modified RBC units

Irradiated RBCs
RBCs exposed to cesium

Crosslinks T-lymphocyte DNA

Prevents proliferation

Changes expiration date to 28 days after

irradiation

Indication:

Prevention of transfusion-associated GVHD

Transfusion
Associated GVHD

Partial match between recipient and

donor HLA type
Donor lymphocytes arent recognized
as foreign, proliferate and attack the
recipient tissues

Or due to severe
immunosuppression in recipient
Signs appear within 3-50 days
fever, skin rash, diarrhea, marrow
aplasia
mortality rate ~90%

Patients at risk for TAGVHD

Congenital immunodeficiencies
Intrauterine transfusion
Recipients of blood from 1st degree
relatives or HLA matched units
Bone marrow or stem cell transplant
recipients
Hodgkins disease recipients
NOT indicated for HIV patients

Modified RBC units

Frozen RBCs
RBCs frozen in glycerol & stored up to
10 years
Used to preserve rare blood types
RBCs must be washed multiple times
prior to transfusion

Expire 24 hours after thawing and washing

VERY expensive

Platelets

Whole blood derived platelets

Random donor platelets

50 mL
Dose

10-15 mL/kg
4-6 units for an average adult

Stored 5 days at room temperature with

agitation
Must transfuse within 4 hours after pooling
Expected increment of 5-10K/L/unit (or 2060K/ L/dose)
$50/unit (max of $300/dose)

Platelets

Apheresis platelets

Single donor platelets

Also referred to as
Jumbo platelets
100 mL
Dose

1 apheresis unit

Stored 5 days at room temperature with

agitation
Expected increment of 30-40K/L/dose (unit)
$500/unit!
Advantage = single donor

Less infectious risk

Less risk of HLA alloimmunization

Platelets

Express ABO antigens

Will get best increment with ABO
compatible platelets

DO NOT express Rh antigens

Can give regardless of Rh type
However, platelets contain a small
amount of RBCs

Rh-negative woman of child-bearing age

should receive Rh negative platelets

Indications for
Platelets

Thrombocytopenia

<10,000 in uncomplicated patients

<20,000 if febrile or septic
<50,000 if bleeding or undergoing major
surgery
<100,000 for neurosurgery or ophthalmologic
procedures

Thrombocytopathy

Congenital defects
Drugs (ASA, Plavix)
External agents (cardiac bypass or ECMO)

Failure of expected
platelet increment

Consumption (after 24 hours)

Fever
Infection
Drugs (Amphotericin)
Bleeding
Hepatosplenomegaly
DIC

Anti-HLA or platelet-antigen antibodies

(after 10-60 minutes)

Modified Platelet Units

Washed platelets
Leukocyte-reduced platelets
Irradiated

Contraindications for
Platelets

TTP/HUS
Heparin-induced thrombocytopenia
(HIT)
ITP (relative contraindication)
Uremia-related platelet dysfunction

DDAVP
Cryoprecipitate
RBC transfusion (keep HCT > 30%)

Granulocytes

Collected via apheresis

Donor stimulated with dexamethasone & G-CSF

250-300 mL
Should be given once daily for at least 5 days
Indications
Persistent fever or infection not responding to
antimicrobial therapy
Severe neutropenia (<500/L)
Reversible bone marrow hypoplasia

Must have CMV-negative donor to prevent CMV

transmission
Must be given within 24 hours of collection

Fresh Frozen Plasma

(FFP)

Whole blood plasma

200 -250 ml

Also collected by apheresis = Jumbo FFP

400-600 mL

All coagulation factors and other proteins

Stored frozen for 1 year
Dose
10-15 mL/kg
2-4 whole blood units OR 1-2 Jumbo FFP

Expect 20-30% increase in all factor levels

Plasma Compatibility

Indications for FFP

Coagulopathy due to multiple

factor deficiencies
Liver disease
Reversal of nutritional Vit K
deficiency or Warfarin overdose
Massive transfusion
TTP/HUS
PT/PTT > 1.5 x normal

Cryoprecipitate

Made from 1 unit partially thawed FFP

15 mL
Fibrinogen, factor VIII, VWF, factor XIII
Stored 1 year frozen, 6 hours thawed
If pooled must be given in 4 hours
Dose
1 unit/10 kg
10-20 units in average adult

Indications for cryo

Fibrinogen deficiency
Von Willebrand's disease
Uremic thrombocytopathy
Factor XIII deficiency
Topical fibrin glue
**Not for replacement of Factor
VIII!

Other products

Albumin
Factor concentrates
Factor VIII
Factor IX

IVIG

The number one risk of

transfusion is
A.
B.
C.
D.

Hemolytic reaction
Infectious disease
TRALI
Circulatory Overload

The #1 infectious risk

of transfusion is
A.
B.
C.
D.
E.
F.

Hepatitis B
Hepatitis C
HIV
Bacterial Contamination/Sepsis
HTLV 1/2
Malaria

Risks of Transfusion

Infectious disease
Units tested for HIV, Hep B, Hep C,
syphilis, WNV, HTLV, Chagas disease
HIV 1 : 2 million
Hep C 1 : 2 million
Hep B 1 : 250,000
Bacterial infection of clinical importance

1:25,000 for platelets

1:250,000 for RBCs

Transfusion Reactions

STOP the transfusion

Send all tubing and a patient sample to the
blood bank
Labs

Bilirubin
LDH
Haptoglobin
Urine hemoglobin

Blood Bank Work-up

Clerical check & visual inspection

Pre & Post transfusion ABO re-type (patient & unit)
Pre & Post transfusion Direct Antiglobulin Test
(Direct Coombs)

Hemolytic Transfusion
Reaction

Acute (within 24 hours) or delayed

(within several days)
Incompatible RBCs

Due to ABO incompatibility (IgM)

Intravascular hemolysis
Due to alloimmunization from prior
transfusion and/or pregnancy (usually
IgG) Extravascular hemolysis

Most common cause = clerical error

Also low titer antibodies not detected on
initial screen (Rh and Kidd)

Pathophysiology

Hypotension
Vasoconstriction,
renal ischemia
Platelet activation

Hemolytic Transfusion
Reactions

Signs and Symptoms:

Fever, Chills/rigors
Anxiety
Flushing/Pallor
Chest/ abdominal/ back pain
N/V/D
Dyspnea
Hypotension
Hemoglobinuria
Jaundice
Oliguria/anuria
Pain or oozing at transfusion site

Hemolytic Transfusion
Reactions

Treatment = supportive
IV fluids for hypotension
Diuretics - maintain urine output at
30-100 mL/h
Low dose dopamine (severe cases)
Heparin

Hemolytic Transfusion
Reactions

Prevention
Blood type & antibody screen every 3 days
Minimum of 2 identifiers used to ID patient
(NOT room number), initials of
phlebotomist

Labeling of specimen at bedside

Maintain patient blood type & antibody

history records
Barcoded bracelets, transfusion safety
officers, transfusion team

RBC Autoantibodies

Antibodies that react with all RBCs,

including the patients own
Causes: medications, autoimmune
disease, idiopathic
May or may not be clinically significant

Ordering RBCs
Crossmatch will be positive
Monitor closely for signs of hemolysis

Febrile Non-hemolytic
Transfusion Reactions

Majority of transfusion reactions

Increase in temperature

1 C
2 F
No other cause for fever

All labs unchanged from pretransfusion

Febrile Non-hemolytic
Transfusion Reactions

Pathophysiology
Pyrogenic cytokines in cellular units

Pre-transfusion
WBCs in unit make cytokines during storage
Platelets

Post-transfusion
Recipient anti-WBC antibody stimulates donor
WBCs
RBCs

Febrile Non-hemolytic
Transfusion Reactions

Treatment
Anti-pyretics

Prevention
Leukoreduced units
Acetaminophen premedication*

Bacterial
Contamination

#1 infectious risk of transfusion

Mostly a problem with platelet
units
Gram positive cocci

Rarely a problem with RBC units

Yersinia enterocolitica most common

Bacterial
Contamination

Symptoms
High fever/rigors (>2 F increase)
Abdominal
cramping/nausea/vomiting
Shock

Blood product may be discolored

Bacterial
Contamination

Treatment

Stop transfusion
Culture patient and product bag
IV antibiotics
Pressor support

Prevention

Proper phlebotomy technique at donation

Careful donor history
pH testing and/or culture of platelet units

Allergic Transfusion
Reactions

45% of all transfusion reactions

More common with FFP
Symptoms
Pruritus
Urticaria

Pathophysiology

IgE in the patient reacts with donor plasma

proteins
Donor plasma has IgE which reacts with
patient plasma proteins

Allergic Transfusion
Reactions

Treatment

Benadryl
Corticosteroids
The only reaction in which the
transfusion can be resumed

Prevention
Benadryl premedication*
Washed RBCs/platelets

Anaphylactic
Transfusion Reactions

More severe allergic reaction

Pathophysiology

IgA deficient patients with anti-IgA

Almost immediate reaction

Clinical symptoms range from urticaria to

shock & cardiac arrest

Treatment

Epinephrine, corticosteroids

Prevention

Washed products
IgA deficient products

Transfusion Associated
Circulatory Overload
(TACO)
1 in 100 transfusions

High volume or rate of transfusion exceeds

ability of patients cardiovascular system to
handle additional workload

Underlying cardiovascular of pulmonary pathology

Elderly
Normovolemic anemia (thalassemia)

Symptoms:

Dyspnea, Orthopnea
Hypoxemia
Pulmonary edema
Hypertension (>50 mmHg increase in SBP)
Increased central venous pressure
Increased BNP

TACO

Treatment
Stop or slow rate of infusion

Split unit into aliquots

Washed RBCs less volume

Diuretics
Oxygen
Supportive care

Prevention

Vigilant assessment of pts ins/outs

Slow rates of infusion/aliquots
Diuretics

Transfusion Related
Acute Lung Injury (TRALI)

All components implicated

FFP most commonly

1 in 1000 transfusions
Extremely underreported

Pathophysiology
Anti-HLA in donor plasma activates
PMNs in pulmonary capillaries of
recipient capillary leakage
Anti-HLA antibodies form after prior
transfusion or pregnancy

TRALI

Symptoms
Sudden new onset hypoxemia (O2 sat
<90%) or increased FiO2 requirement
CXR with bilateral infiltrates (like ARDS)
Absent signs of circulatory overload

Pre/Post transfusion BNP ratio <2

No preexisting lung injury or ARDS

Onset within 6 hours of transfusion

TRALI

Treatment
Supportive measures

Prevention
Use of male plasma
Defer implicated donors
Test donor for anti-HLA antibodies
Compare to HLA type of patient

Other complications of
transfusion

Alloimmunization

18-47% in sickle cell patients

5-11% in thalassemia patients
20% without underlying hematologic/oncologic
disease

Iron overload
Metabolic abnormalities
Hypocalcemia
Hyperkalemia

Coagulopathy
Hypothermia
GVHD

Take Home Points

While extremely safe when used

appropriately, transfusion is still
not without risk.
Know what you are ordering and
the implications of your orders.
Blood is not a limitless resource!
Dont make assumptionscall the
blood bank!