Blood transfusion

BLOOD TRANSFUSION
Ranjita Pallavi, MD
Internal Medicine
PGY 3

Introduction
 1988: “ No single criterion should be used as an
indication for red cell component therapy and that
multiple factors related to the patient's clinical
status and oxygen delivery needs should be
considered”
National Institutes of Health Consensus Conference on Perioperative Red Blood Cell
Transfusions

Guidelines for red cell transfusions and volume
replacement in adults
Uptodate 2010

Red Cell Transfusion
 Treatment of symptomatic anemia
 • Prophylaxis in life-threatening anemia
 • Restoration of oxygen-carrying capacity in case of
hemorrhage
 • RBC are also indicated for exchange transfusion
 w Sickle cell disease
 w Severe parasitic infection (malaria, babesiosis)
 w Severe methemoglobinemia
 w Severe hyperbilirubinemia of newborn

Red Cell Transfusion
 RBC transfusion is not routinely indicated for pharmacologically treatable
 anemia such as:
 • Iron deficiency anemia
 • Vitamin B12 or folate deficiency anemia
 Dosage and administration
 • One unit of RBC will raise the hemoglobin of an average-size adult
 by ~1g/dL (or raise HCT ~3%)
 • ABO group of RBC products must be compatible with ABO group
 of recipient
 • RBC product must be serologically compatible with the recipient
 (see Pretransfusion Testing). Exceptions can be made in
 emergencies (see Emergency Release of Blood Products).
 • Rate of transfusion
 w Transfuse slowly for first 15 minutes
 w Complete transfusion within 4 hours (per FDA)

AABB Guideline Update
 AABB Guideline makes three recommendations:
 Adhering to a restrictive transfusion strategy (7 to 8 g/dL)
in hospitalized, stable patients;
 Adhering to a restrictive strategy in hospitalized patients
with preexisting cardiovascular disease and considering
transfusion for patients with symptoms or a hemoglobin
level of 8 g/dL or less; and
 Considering symptoms as well as hemoglobin
concentration during transfusion decisions.

Choice of component
 Whole blood: use for patients who have bled
acutely and massively after receiving
approximately five to seven units of red cells
plus crystalloids
 Red cell preparations containing minimal
plasma: use for Chronic anemia since volume
replacement is not required

Choice of component
 Irradiated blood products
- inactivates lymphocytes
- immunocompromised bone marrow or organ transplant recipients
 Washed RBC’s
- removes about 99% of plasma proteins, electrolytes and antibodies
- plasma proteins may cause serious anaphylactic reactions
 Leukoreduced products:
- filtered blood
- usually for chronically transfused patients
- potential transplant recipients
- patients with previous transfusion reactions

Choice of component
 Autologous blood
- an individual may donate his or her own
blood to be stored and used for transfusion
at a future date
- considered acceptable by some
Jehovah's Witnesses if the blood does
not leave the bedside for processing
- damages cells to some degree, and less
than 10 to 15 liters is recommended

Platelets
 Thrombocytopenia or dysfunction of platelets in the
presence of bleeding
 Prophylactic : plt.counts below 10,000-20,000
 Prophylactic preoperative : plt.counts below 50,000
 Microvascular bleeding in surgical patient with platelets
< 50,000
 Neuro/ ocular surgery > 75,000
 Massive transfusion with microvascular
bleeding with platelets < 100,000
 Qualitative dysfunction with microvascular bleeding
(may be > 100,000)

Fresh Frozen Plasma
 Initial therapeutic dose : 10-15 ml/kg
 Isolated factor deficiencies
 Reverse warfarin therapy
 Correction of coagulopathy associated with liver disease
 Used in patients who have received massive blood
transfusion with microvascular bleeding
 Complications (PATCH) : Platelets – dec, Potassium –
inc., ARDS, Acidosis, Temp dec., Citrate intoxication,
Hepatitis
 Antithrombin III deficiency
 TTP ( Thrombotic thrombocytopenic purpura )
 Do not use for volume

Cryoprecipitate
 10 ml: fibrinogen (150-250 mg), VIII (80-145 U),
fibronectin, XIII
 1U/ 10kg fibrinogen 50 mg/dL (usually a 6- pack)
 Hypofibrinogenemia (congenital or acquired)
 Microvascular bleeding with massive BT (fibrinogen <
80-100mg/dL)
 Bleeding patients with vWD (or unresponsive to DDAVP)

Pre – Transfusion
 Does the patient need the transfusion?
 Does the patient want the transfusion?
- Consent
 How many units to Cross?
 Massive Transfusion Protocol activation

Pre-transfusion
- Obtain Informed consent, risks and benefits of procedure, witness
- Type and Screen, crossmatch
- Inform Blood bank for product availability
- Fill up Blood Requisition Form
- Escort for pick-up of form, blood product if available
- IV access, at least 18 gauge to allow adequate flow, standard filter
- observe for 5-10 minutes initially for adverse side effects and then
at regular intervals thereafter

Pre-transfusion
- “Type and Screen” on order review, Now STAT or via phlebotomy
- Order Label, Pink top EDTA tube, Green ID band, Biohazard bag
- Countersign Label and Green ID band with your initials
- Put sticker label to green ID band then attach green ID band to
patient’s arm (cross check with patient’s admission ID band-name
and MR #)
- Place sticker from green ID band at Pink top tube
- Put pink top tube in the biohazard bag with excess green ID band
and send it to blood bank/escort pick-up (don’t send by
“shoot”/pneumatic tube)

Blood Bank Practices
1) Crossmatching (50 min)
2) Confirms ABO and Rh typing
3) Detects antibodies to the other blood group
systems
4) Detects antibodies in low titers or those that do
not agglutinate easily

Type and screen vs Type and crossmatch
 T&S -determines ABO and Rh status and the
presence of most commonly encountered
antibodies – risk of adverse rxn is 1:1000
 -takes about 5 mins
 T&C -determines ABO and Rh status as well as
adverse rxn to even low incidence antigens – risk
of rxn is 1:10,000
 -takes about 45 mins

Adverse effects from transfusion
 Volume overload: Administration of blood products greater than the
normal blood volume of patient in a 24-hr period
 Hypothermia: caused by chilled blood, cause cardiac dysrhythmias,
use blood warming device
 Citrate intoxication: in massive transfusions, Tx. Stop transfusion, if
symptomatic give calcium. ( common in hepatopathy)
 Hyperkalemia:occurs in stored RBC or irradiated products, also in pt.
already hyperkalemic, avoid by using new blood

Types of Reactions
Immune mediated transfusion reactions
 Febrile non hemolytic tranx rxns
 Immune mediated hemolysis
---Acute and delayed hemolytic reactions
 Anaphylactic transfusion rxns
 Urticarial transfusion rxns
 Post-transfusion purpura
 GVHD
 TRALI (pulm leuko-agglutinin reactions)

Types of Reactions
Non immune mediated transfusion reactions
 Physical reactions: thermal i.e. heat or cold induced
 Infectious; Hepatitis B/C, malaria, HIV, CMV, Chagas
dx, CJ Virus, West Nile virus
 Chemical; citrate toxicity, hypo/hyperkalemia, iron
overload
 Acute hypotensive reaction: mediated by bradykinins
and occurs in patients with faulty bradykinin metabolism
on ACE I
 Osmotic injury
 Congenital and acquired hemolytic anemia

Immunologic rxns
classicbloodtranxrxnsareusuallyimmunologicandoccur2/2tointeractionsofinherited/
acquiredAbwithforeignAgfromtransfusedblood
Incidence of rxns
SHOT trial (serious hazards of tranx)
-most common cause is tranx of non-matched blood mostly
2/2 to clerical error
-2x more common in infants than adults
-more common in pxts with hematological and oncological
conditions

Case scenario 1
 A 35-year-old woman was hospitalized for anemia 2/2
sickle cell disease, she is receiving 2 units of PRBC. After
her 1st unit of blood she developed a temp of 38.3 C
(101.0 F). She has no other symptoms.
On exam she appears anxious but her vital signs are stable
with Bp 120/70mmHg, HR 80bpm 18cpm Pox 98% 0n
RA
She has no skin rash and her urine color is amber
What are your differential diagnosis and how would you
manage this pxt?

Febrile non hemolytic tranx rxns
 Most common, usually benign without sequelae
 Concerning because initial presentation is similar to more adverse
rxns. i.e. fever, chills +/- mild dyspnea.
 15% will have a rxn in the future with subsequent tranx
Etiology
1. Class 1 HLA ab directed against contaminating wbc in red cell
conc. Although these are not always found
2. 2/2 to cytokines IL-1, 6,8 and Tnf alpha generated in stored
blood/products.
3. Determining factor is age of blood products
Management
Discontinue tranx, rule out hemolysis i.e. check labels, repeat type and
cross, coombs test
Antipyretics +/- meperidine for chills and rigors

Prevention
• Leukoreduction: evidence is scarce but few studies have shown a
decrease in number of reactions.
• Although tylenol and antihistamine premedication is widely used there
are no evidence to support that their use actually prevents rxn.

Case scenario 2
 A 35-year-old woman was hospitalized for anemia 2/2 sickle cell disease,
she is receiving 2 units of PRBC. Her 1st unit of blood was transfused without
events but 5minutes into her 2nd unit, She complains of new flank pain and
fever.
On exam she appears very anxious, diaphoretic and in acute distress, she is
febrile to 38.8C with Bp 100/60mmHg, HR 101 bpm, 18cpm, Pox 98% 0n
RA
She has no skin rash but is oozing out of IV sites and her urine color is now
reddish brown.
Labs: elevated Bun/creat, increased PTT, PT and decreased HCT.
What is the diagnosis and how would you manage this patient?

Acute hemolytic rxns
 Medical emergency
 Occurs due to rapid transfused RBC destruction by
preformed recipients Abs
 Mostly 2/2 to ABO incompatibility-typically type O
receiving non O blood. May occur with other blood
types
 IgM mediated complement fixation leading to rapid intra
vascular hemolysis
 Most common causes are clerical or procedural errors
 Complications includes DIC, shock, ARF 2/2 to ATN

Clinical presentation
Classic presenting triad of Fever, flank pain and reddish brown urine from
hemoglobinuria is rarely seen
DIC may be presenting mode
Labs
Direct Coombs +, Pink plasma, Lactate, FDP in DIC
Management
1. Stop transfusion, alert blood bank to start search for clerical error since
another patient may be at risk
2. R/o tranx rxn i.e. check labels, repeat type and cross with unit, check urine for
hemoglobin
3. Supportive care; ABC +/-pressors
4. cardiac monitoring because of risk of hyperkalemia
5. Infuse NS to maintain BP and promote diuresis, avoid LR and dextrose because
calcium in LR will promote clotting in IV line and dextrose will increase
hemolysis. Maintain urine output >100-200ml/hour
6. With DIC early heparinization 10u/kg/hr may be beneficial

Delayed hemolytic transfusion rxns
Generally occurs within 2-10 days of tranx
Usually due to senescent Ab response on re-exposure to a foreign red cell
Ag
History of previous pregnancy, transfusion or transplant
Usually extra vascular and is less severe than acute
Other Abs often Rh and Kidd
Falling HCT, low grade fever, slight increase in indirect bili, spherocytes on
blood smear
Diagnosis
New +DAT and new Ab test when new blood is ordered
Txt
None in the absence of rapid hemolysis
Avoid offending Ag in future tranx

Anaphylactic reactions
-life threatening emergency
-Occurs within a few seconds to minutes following tranx
-Characterized by rapid onset of anaphylaxis
-Can occur with all blood products but generally seen with serum albumin,
plasma protein fractions or coagulation factors
Incidence
1 in 20-50 thousand
Mechanism
Presence of class specific IgG and anti IgA abs in pxts who are IgA def
-Selective IgA def is fairly common, occurring in 1/300-500 people but majority
of them do not develop Abs
-Ahaptoglobinemia with antihaptoglobin Abs is similar and occur primarily in
East Asian
Treatment
As in all cases of anaphylaxis: stop tranx, epi 0.3ml of 1.1000 soln IM
Consider IV epinephrine drip
ABC +/- pressor support

Prevention
Establish diagnosis: usually after the fact
Use IgA def products for all further tranx (extra washed red cells or platelets)
Urticarial reactions
-Allergenic products in blood products activates IgE in recipient leading to
histamine release from mast cells and basophils
-Only rxn in which tranx can be resumed
-Give benadryl 25-50mg IV/PO if urticaria is extensive

Case scenario 3
 30 year old kidney transplant recipient on chronic
Immunosupressive therapy admitted for anemia and
received 2 units of non irradiated PRBC from his sister 3
days ago develops skin bullae, diarrhea and abdominal
cramps
VS: notable for low grade fever of 37.9C otherwise normal
PE: Jaundice, swollen skin with multiple bulla
Labs; new thrombocytopenia, elevated LFT, increased
bilirubin.
What is your diagnosis?

 Very rare (0.1-1%) complication seen in Immuno-compromised
individuals esp in solid tumor cancer pxts on chemo, but can occur with
acute/chronic leukemia, lymphomas, new borne with erythroblastosis
fetalis and transplant pxts
 Different from transplant GVHD by it’s effect on bone marrow (BM
aplasia)
 It occurs in immuno-compromised recipients of blood products from
donors with identical HLA haplotypes. They are heterozygous for a HLA
haplotype for which the donor is homozygous .e.g. genetically identical
relatives
HLA ag are shared by donor and recipient, thus donor lymphocyte are
engrafted by recipient because they are the only Ag seen by the host.
On the flip side the donor lymphocytes view the recipient’s tissues as
foreign leading to immunologic activation and GVHD.
 Bone marrow aplasia is the primary cause of death
Transfusion associated GVHD

Skin: Swollen, erythroderma and bullae formation- most common
GI: Diarrhea and abdominal cramps
Liver: Elevated LFT and Hyperbilirubinemia
Heme: Bone marrow aplasia, persistent thrombocytopenia
Skin manifestation of GVHD
Generalized swelling, erythroderma and bullous
formation

 Non Irradiated whole blood
 PRBC
 Platelets
 Granulocytes
 Fresh non frozen plasma
It has not been seen with frozen deglycerolized RBC, FFP or Cryoprecipitate
Treatment
Poor response to standard immunosuppressive therapies,
Thalidomide has been tried with variable success.
Prevention
Key since response to treatment is poor
Gamma irradiation and leuko-reduction of products
Avoid blood products from genetically identical donors
Implicated products

Case scenario 4
 A 35-year-old woman was hospitalized for thrombotic thrombocytopenic
purpura for which she underwent therapeutic plasma exchange with
fresh frozen plasma. After 7 days of treatment, she had improved
sufficiently to allow for weaning from daily transfusions; however, at the
conclusion of plasma exchange, she developed a cough and a temperature
of 38.3 C (101.0 F), with progression of respiratory symptoms to severe
dyspnea, with some wheezing.
On physical examination, the blood pressure is 120/80 mm Hg. There is
no rash or hives. She is tachycardic and cyanotic on cardiopulmonary
examination. Oxygen saturation is 80% on room air, and a blood gas
study shows an arterial PO2 of 55 mm Hg. A chest radiograph reveals
diffuse opacifications of both lungs and a normal-sized heart and no
pleural effusion.
Which of the following is the most likely cause for this patient's reaction?
1. Pulmonary embolism
2. Antileukocyte antibodies
3. Allergy to donor plasma proteins
4. Circulatory overload

Transfusion related acute lung injury
 New acute lung injury occurring during or within 6 hour
of blood product tranx
 All blood products have been implicated
 May progress to ARDs
 Immune mediated non cardiogenic pulm edema
Risk factors
No definite risk factors but prolonged storage of blood
products, massive tranx, cytokine txt, multiparity,
thrombocytopenia and active infections have been
implicated in a number of studies.

Pathogenesis
-Abs against HLA
-2 hit hypothesis:
1st hit is an underlying pulm pathology that leads to localization of
neutrophils in the pulm vasculature
2nd hit is the transfusion of blood products containing sensitized
neutrophils Ab leading to release of vasoactive Cytokine and pulm
edema
 Leading cause of transfusion related fatalities in the USA
 1 case for every 1000-2400 units transfused
 6-9% mortality rate
Epidemiology

 Acute onset of respiratory distress (hypoxemia) during or shortly after
blood tranx. On the average within 1-2 hours post tranx
 Fever, tachycardia, tachypnea, +/-hypotension
 In intubated pxts; elevated peak airway pressures, pink frothy airway
secretion
 CXR bilateral patchy alveolar infiltrates, normal cardiac picture
 Labs; eosinophilia and transient drop in neutrophils, Leuko-agglutinin
testing
Diagnosis
Clinical presentation and CXR findings
-Labs; granulocyte/ leuko-agglutinating abs, decline in C3 or C5 levels
12-36 hours after onset of symptoms followed by rise 4-7 days later

(a) Bilateral patchy alveolar infiltrate in TRALI (b) Complete resolution
a b
Criteria for the diagnosis of TRALI
• No acute lung injury immediately before transfusion
• New acute lung injury:
1. acute onset lung injury,
2. no circulatory overload or PA pressures <18mmHg,
3. bilateral pulm infiltrate on Cxr,
4. Hypoxemia:Pa02/FiO2 <300, or sat <90% on RA.
• Onset within 6 hours after transfusion
• No temporal relation to an alternate risk factor for acute lung injury
Popovsky TP et al TRALI; definition and review. Crit care Med 2005

Ddx includes
 Acute fluid overload: ↑ JVP, ↑SBP and widened pulse pressure
during dyspneic episode, ↑ pulm vascular markings on CXR
 Hemolytic transfusion rxns
 IgA mediated anaphylaxis in IgA def patients
Management
-Mostly supportive with abrupt resolution in symptoms within a few days
-A majority of patients may require mechanical ventilation
-Diuretics play no role in management since it is microvascular damage
and not due to volume. It has been shown to actually worsen TRALI
Prognosis
Increased risk of recurrence if they receive products from the implicated
donor but no risk from other donors

POSTTRANSFUSION PURPURA
 occurs primarily in women sensitized by pregnancy
 severe degrees of thrombocytopenia, often lasting days to weeks,
develop about 5 to 10 days following transfusion of a platelet-
containing product such as red cells, platelets, whole blood
 Usually self limited, but high mortality if severe thrombocytopenia
 preferred therapy is IVIG in high doses (400 to 500 mg/kg per day,
usually for five days); alternatively, 1.0 g/kg per day for two days can
be given for severe thrombocytopenia. Plasmapheresis is also a option
 usually takes about four days for the platelet count to exceed
100,000/microL

Approach to patients who are unwilling or unable
to receive RBC transfusions
 reduce blood loss by phlebotomy and obtain
necessary testing in pediatric tubes
 EPO is often of benefit
 Most cases, concurrent use of oral or parenteral
iron is also recommended with increase of 1-2
g/dl over approx a week

Finally:
 Important numbers:
Blood bank Ext. - 6891/92/93
Patient Escort Ext. - 6500
Phlebotomy Ext. - 6201
Phlebotomy Pager - 6790, 6791,6792
STAT Lab Ext. - 6775

“Blood is still the best possible thing to have in our
veins” - Woody Allen
Blood transfusion is a lot like marriage. It should not
be entered upon lightly, unadvisedly or wantonly,
or more often than is absolutely necessary” - Beal

Blood transfusion

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