Transfusion
Medicine
Cynthia H. Ho, M.D.
July 2012
Introduction


Average volume of blood in an adult is 5 liters.
Volume of blood products
 Packed red blood cells (PRBCs): 250-350 mL
per unit.
 Fresh frozen plasma (FFP): 250–300 mL per
unit.
 Platelets: 40–50 mL per unit (single donor),
250-350 mL per unit (pheresis).
 Cryoprecipitate: 10–12 mL per unit.
Red Blood Cells
 RBC
antigens are
polymorphic, inherited,
carbohydrate or protein
structures on RBC
membranes.
 Immunization against
blood group antigens
occur through transfusion,
pregnancy, and needle
sharing.
What is in a bag of donor
blood?
 Anticoagulants


Citrate
Heparin
 Preservatives



Citrate
Adenine
Dextrose
Byproducts of RBC Storage
 Citrate

Causes hypocalcemia when patients are
given large volume transfusions.
 Potassium


Na/K pump inactivation.
Hemolysis.
 Microaggregates
of platelets, WBCs, fibrin
can cause pulmonary edema.
Red Blood Cells


One unit of PRBC will increase Hgb by 1g/dL and
increase Hct by 3%.
Indications for transfusion
 Acute blood loss: Depends on 1) risk of tissue hypoxia,
2) symptoms, 3) ongoing blood loss, 4) planned
interventions, 5) hemoglobin.
 Chronic anemia: Hgb is low but plasma volume is
normal. Treat underlying illness first.
 Critical illness: Consider at Hgb<7.0.
 Sickle cell disease: Acute chest syndrome, stroke,
perioperative.
 Chemotherapy-related anemia: Consider at Hgb<8.0.
Perioperative Transfusions



Blood loss
 <10% blood loss – usually no need for transfusion.
 10-20% blood loss – crystalloids usually sufficient
for resuscitation.
 >25% blood loss – blood products usually
indicated.
No clear cut off, but consider at Hgb<7g/dL. More
important to individualize to your patient.
Coronary artery disease – most cardiologists
suggest transfusion at Hgb<10g/dL (no studies to
support this practice).
Red Blood Cells




Packed Red Blood Cells (PRBC)
 Component of choice for replacement.
Leukocyte-reduced PRBC
 Filtered to remove most WBCs.
 Decreases risk of alloimmunization, transmission of viruses (including
CMV), febrile non-hemolytic transfusion reactions.
 Transplant patients, history of febrile nonhemolytic transfusion
reactions, transfusion-dependent chronic anemia, patients
receiving chemo or XRT.
Irradiated blood
 Avoids Graft vs Host disease.
 Transplant patients, immunodeficiency, neonates, patients
receiving chemo or radiation therapy.
CMV negative
 Transplant recipients.
 consider in potential transplant patients.
Red Blood Cells
Platelet Transfusions


Whole blood derived platelets contain 50mL
plasma and platelets from 5-6 donors per unit.
Apheresis units are from a single donor.





More expensive.
Circulate longer (gentle handling).
Exposure to fewer donors.
Decreased risk of infections.
Decreased alloimmunization risk has not been
substantiated.
Platelets
 One
unit raises platelet
counts by 5,000-10,000/uL.
 Give over 20-30 minutes
(~10mL/min).
 Keep >50,000 for bleeding
patients.
 Consider keep >100,000 for
intracranial hemorrhage.
Prophylactic Platelet
Transfusions
 Studies
of prophylactic transfusions in
leukemia patients with platelet counts of
10,000 versus 20,000 showed no increased
risk of bleeding when 10,000 used as
cutoff.
 Prior to invasive procedures – no
randomized trials


Lumbar puncture – 10,000.
Central lines – 20,000-30,000.
Prophylactic Transfusions
Prior to Surgery
 For
most surgeries – Keep
platelets > 50,000 – based on
retrospective studies.
 For neurosurgery, retinal
surgeries – Keep platelets>
70,000-100,000 – based on
tradition, no studies.
Adverse effects of platelet
transfusions





Increased risk of bacterial infections compared with
other blood products.
 Stored at room temperature for 5 days maximum.
 1 in 3,000 platelet units have bacterial
contaminant.
 Clinically apparent bacterial infections occur in 1
in 25,000 transfusions.
Allergic and febrile nonhemolytic transfusion
reactions.
Hemolytic transfusion reactions.
TRALI
Rh(D) sensitization
Platelet Refractoriness
 Non-immune
causes





Fever
Sepsis
Bleeding
Splenomegaly
DIC
 Immune


causes
Antibodies against
HLA or platelet
specific antigen
(HPA)
ABO incompatibility
Platelet Refractoriness
 Suspect
immune cause if 18-24 hour posttransfusion platelets increased by less
than 5,000.
 Check post-transfusion platelets 10
minutes to 1 hour after transfusion.


>5,000-10,000 rise suggests non-immune
mediated cause.
<5,000-10,000 rise suggests immunemediated cause.
Contraindications to platelet
transfusions
 TTP
 ITP
 HIT
 Aplastic
anemia
 MDS
***Unless life-threatening bleeding.
Plasma
 Acellular



component of blood
90% water
7% protein and colloids
2-3% nutrients, crystalloid, hormones, and
vitamins
 Proteins
– Fibrinogen, vWF, protein C,
protein S, and soluble clotting factors
(V,VII,IX,XI).
Plasma
 Give
transfusions over 20-30 minutes.
 One unit is 200-280mL.
 Give 8-10mL/kg.
 If critically ill, give 30mL/kg.
Plasma
 FFP
is frozen at -18°C or colder within 6
hours of collection.


Can be stored for one year.
Thawed over 20-30 minutes.
 F24


is most commonly used in the U.S.
Frozen within 24 hours of collection.
Virtually equivalent to FFP except
decreased amount of fibrinogen, factors V,
VIII, and XI.
Indications for plasma
transfusion
 Give
over 20-30 minutes (~10mL/min).
 Bleeding associated with clotting factor
deficiencies, prior to invasive procedures,
reversal of warfarin.
Adverse reactions to Plasma
transfusions
 Febrile
non-hemolytic and allergic
reactions.
 TRALI.
 Anaphylaxis (IgA deficiency).
 Infections.
Cryoprecipitate
 Contains
Factor VIII, fibrinogen,
fibronectin, von Willebrand's factor and
Factor XIII.
 Give 2-10 units for every 10 kg -> will raise
fibrinogen 60-100 g/dL.
 Indications: Bleeding associated
fibrinogen deficiency (<100), e.g. DIC.
Transfusion-related labs
 Type
and cross: Matches patient's blood to
specific donor units.
 Type and screen: Tests patient's serum for
common antigens. Good for 72 hours.
 Direct Coomb’s DAT: Tests if patient's cells are
IgG or complement coated (e.g. hemolytic
transfusion reactions, autoimmune hemolytic
anemia). IN VIVO.
 Indirect Coomb’s: Tests patient's serum with
common antibody (other than ABO) to RBC's
(e.g. autoimmune hemolytic anemia, delayed
hemolytic transfusion reaction). IN VITRO.
Pre-Transfusion Medications




Fever from a transfusion is usually due to febrile nonhemolytic transfusion reaction and responds to
antipyretics.
However, fever can also occur with bacterial
contamination or more serious transfusion reactions
(TRALI). Therefore, do not routinely pre-treat with
acetaminophen.
Unless the patient has a history of allergic reactions or
shows signs of an allergic component to a febrile
non-hemolytic transfusion reaction (flushing, hives, or
pruritus) there is no benefit from the use of
antihistamines for febrile reactions.
Diphenhydramine should be reserved for
pretreatment or treatment of possible allergic
reactions in patients who have had a history of a mild
allergic reaction.
Labs after Transfusion
 In
the absence of increased red blood
cell destruction or sequestration, the
expected rise in Hgb is usually not
measurable until 24 hours after transfusion,
when the plasma volume has had time to
return to normal.
 Checking platelets 1-2 hours after
transfusion may be helpful to determine if
platelets increase appropriately or if
possible alloimmunization has occurred.
 When to draw post-transfusion labs
depends on what your goal is,
anticipated ongoing losses, anticipated
procedures (anesthesia), etc.
Transfusion reactions







Hemolytic transfusion
reactions
Febrile non-hemolytic
transfusion reactions
Allergic transfusion
reaction
Bacterial
contamination
TRALI
Circulatory overload
Anaphylaxis
 Post-transfusion
purpura
 Graft versus host
disease
 Hypothermia
 Electrolyte
abnormalities
Febrile Non-hemolytic
Transfusion Reaction
 Increase
in temperature by 1°C with no
other explanation.
 Antibody-leukocyte or antibody-platelet
reactions -> cytokine release -> fever.
 Fever and chills usually occur shortly after
a transfusion has begun.

Less common, but fever and chills can
occur hours after transfusion.
 Usually
resolves after 8-10 hours.
What to do if your patient has
a fever during a transfusion




Stop the transfusion
R/o hemolysis
 Confirm patient and donor blood type
 Repeat type and cross
 Evaluation for hemolysis – BMP, CBC, LFT, LDH, DAT,
haptoglobin, U/A with microscopy
R/o infection
 Examine your patient, consider blood culture is bacterial
contamination suspected.
Treatment
 Tylenol.
 Consider hydrocortisone for patients with history of severe
FNTR with fever despite Tylenol.
 Consider demerol for patients with significant chills from
FNTR
Allergic Transfusion Reaction







Can present as urticaria, pruritis, vasomotor instability,
bronchospasm, anaphylaxis.
Most common presentation is pruritis followed by
urticaria.
Due to antibodies (IgE or other) against donor
plasma proteins.
Severity is not dose related.
Common – occurs in 1% of transfusions.
Treatment – stop transfusion, give 25-50mg
diphenhydramine, monitor. Restart transfusion if
urticaria gone.
Do not restart transfusion if patient has fever,
bronchospasm, dyspnea, hypotension, tachycardia.
Bacterial Contamination



Contamination occurs from skin at the time of
collection.
Some bacteria grow optimally at room
temperative but others grow optimally under
refrigeration (Pseudomonas, Yersinia,
Enterobacter, Flavobacterium).
Presents with fever, rigors, skin flushing,
abdominal cramps, myalgias, DIC, renal
failure, cardiovascular collapse (warm shock).
Bacterial Contamination

Treatment



Stop transfusion,
check labs (r/o
acute intravascular
hemolysis)
Send culture of
donor blood
Start broad
spectrum antibiotics

Between 1998 and 2000


Transfusion transmitted
bacteremia
 9.98 per million single
donor platelets
 10.64 per million pooled
platelets
 0.21 per million RBC units
Fatal reactions
 1.94 per million single
donor platelets
 2.22 per million pooled
platelets
 0.13 per million RBC units
Transfusion Related Acute
Lung Injury
 Occurs
in 1,000 to 5,000 transfusions.
 Range in presentation - mild dyspnea,
desaturation, fever, chills, hypotension,
respiratory failure.
 CXR with acute development of bilateral
infiltrates.
 Develops within 1-6 hours of transfusion.
 Non-cardiogenic pulmonary edema
(PCWP<18).
Circulatory Overload



More common among elderly and patients
with predisposition to volume overload (renal
failure, CHF).
As a general rule, unless a patient is actively
hemorrhaging, do not transfuse faster than 23mL/kg/hour.
Slowest rate of transfusion in 4 hours per unit of
PRBC. Can ask blood bank to give blood in
smalller aliquots if needed to slow down the
rate further.
Post-transfusion Graft versus
Host Disease







Occurs in bone marrow transplant patients.
Immunocompetent donor WBCs attack host
tissues.
Fatal in 90% of cases.
Occurs 8-10 days after transfusion.
Pancytopenia, rash, liver test abnormalities,
multiorgan failure.
No effective treatment.
Irradiated leukocyte reduced PRBC
decreases risk of GVHD.
Post-transfusion Purpura





Rare, self-limited cause of thrombocytopenia after
transfusion.
Patients with history of exposure to platelet specific
antigen (usually PLA1) that they lack form an antibody.
With subsequent exposure to the platelet specific
antigen, the antibody destroys donor platelets and
triggers an autoimmune response to host platelets as
well.
Treatment – IVIg, plasma exchange, steroids,
splenectomy.
If bleeding and transfusion needed, give platelets
without the platelet specific antigen that the host is
lacking.
Risk of Transmission of Viral
Infections
 HBV
– 1 in 137,000
 HCV – 1 in 1,000,000
 HIV – 1 in 1,900,000
Type
Signs/Symptoms
Treatment
Acute hemolytic
Fever, chills, back pain, hypotension,
intravenous site burning, pallor, jaundice,
dark urine.
•Occurs during or immediately after transfusion.
•Evidence of immune-mediated hemolysis (DAT positive,
indirect hyperbilirubinemia, high LDH, low haptoglobin,
elevated retic, urine dipstick positive blood without RBC)
•Stop transfusion, maintain BP & volume.
Delayed hemolytic
Pallor, jaundice, fever.
•Occurs days to weeks after transfusion.
•Evidence of immune-mediated hemolysis (DAT+).
•Stop transfusion, monitor for severe hemolysis, send
pink top tube to blood bank.
Non-immune
hemolytic
Pallor, dark urine.
•Evidence of hemolysis (DAT negative).
•Stop transfusion, supportive treatment.
Febrile nonhemolytic
Fever, chills, malaise.
•Once hemolysis ruled out, give anti-pyretics.
Allergic reaction
Hives, rash, pruritis, wheezing, anaphylaxis.
•Hold transfusion, monitor for signs of more serious
allergy, give diphenhydramine.
•If rash only, should resolve in 30 min after treatment and
can resume transfusion.
•This is the only reaction that a transfusion reaction workup does not need to be sent.
Anaphylaxis or
Anaphylactoid
Sudden onset flushing, wheezing, and
hypertension followed by hypotension,
edema, respiratory distress, and shock.
•No evidence of incompatibility (DAT negative).
•Watch for DIC, ARF, respiratory failure, hyperkalemia.
•Stop transfusion, give 1ml/kg im epinephrine
(0.01mg/kg) of 1:1000 solution.
•Hydrocortisone 1mg/kg iv.
•Maintain BP and volume, consider dopamine, O2.
•Consider IgA deficiency.
-1-
LAC+USC HEALTHCARE NETWORK
Practice Parameters For Transfusion of Blood Products (For Adult Patients)
RED BLOOD CELLS
I.
ACUTE BLOOD LOSS
1. Evaluate for risk of ischemia
Usually Needed
Acute blood loss >30%
to 40%
Hb <6g/dL
2. Estimate degree of blood loss
3. Measure hemoglobin
Gray Zone (30%-40% rapid blood loss)
Transfuse based on clinical assessment (vital signs,
EKG changes etc.)
Hb = 6-10 g/dL
Usually Not Needed
Acute blood loss <30 to 40%
in previously healthy person
Hb >10g/dL
II.
CHRONIC ANEMIA
1. Treat with specific pharmacologic agent (B12, iron, folate, erythropoietin)
2. Transfuse to minimize symptoms and risks of anemia (typically at Hb 5-8g/dL range)
III.
DO NOT TRANSFUSE RBC
1. For volume expansion only
2. In place of specific pharmacologic therapy
3. To enhance wound healing
PLATELETS
I.
THERAPEUTIC TRANSFUSION - Patients with active bleeding or high-risk of bleeding at major surgery, and
normal platelet function
Usually Needed
<50,000/uL
II.
Gray Zone (50,000 -100,000u/L)
Transfuse based on patient’s risk for more significant bleeding
PROPHYLACTIC TRANSFUSION - Stable patient with intact vascular system and normal platelet function
Usually Needed
<10,000/uL
III.
IV.
Usually Not Needed
>100,000/uL
Gray Zone (10,000 - 50,000u/L)
Transfuse based on patient’s risk for more significant bleeding
Usually Not Needed
>50,000/uL
Platelet transfusions at higher counts may be needed for patients with platelet dysfunction
DO NOT TRANSFUSE PLATELETS - Patients with ITP, TTP, and/or Heparin Induced
Thrombocytopenia unless there is clinically significant bleeding or significant surgical challenge
FRESH FROZEN PLASMA (FFP)/THAWED PLASMA
THERAPEUTIC TRANSFUSION - Usually Needed
I.
·
·
II.
Urgent reversal of warfarin therapy when patient requires emergency major or CNS surgery or is bleeding. A
second dose may be required after 4-6 hours due to the short half-life of Factor VII.
Treatment of acute TTP or HUS
· Severe trauma with massive bleeding
PROPHYLACTIC TRANSFUSION
Usually not needed for prophylaxis when both INR is <1.7 and PTT is <45 seconds
III.
DO NOT TRANSFUSE FFP/THAWED PLASMA
·
·
When coagulopathy is correctable more effectively with specific therapy (Vitamin K, FVIII or FIX conc.)
For volume expansion
· As a nutritional supplement
CRYOPRECIPITATE
Usually Needed
· Factor XIII deficiency
· Fibrin glue
·
·
Fibrinogen deficiency
Active DIC
·
Dysfibrinogenemia
References:
1. Anesthesiology 1996;84:732-743 2. Arch Pathol Lab Med 1998;122:130-138
3. Transfusion 1998;38:796-797
4. Am J. Clin Path 2006;126:133-139
Approved: August 26, 2008 (Blood Utilization Committee)
Summary

RBC transfusions





Platelets



Transfuse for bleeding patient with decreased clotting factors.
Cryoprecipitate


One unit increases platelets by 5,000-10,000.
Check platelets after 1 hour if concern for immune mediated cause
of refractoriness to platelet transfusion.
Plasma


One unit increases Hgb by 1g/dL.
Give over 2-3mL/kg/hour, slowest is one unit over 4 hours.
Leukocyte reduction decreases risk of CMV and FNHR.
Irradiation decreases risk of GVHD.
Transfuse for bleeding patient with decreased fibrinogen <100.
Transfusion reactions


Can be acute or delayed, hemolytic or non-hemolytic.
Stop transfusion, call the blood bank!
Reference
 Hoffman:
Hematology: Basic Principles
and Practice, 5th edition. 2008 Churchill
Livingstone, An Imprint of Elsevier.