Download Blood Transfusion Reactions

Blood Transfusion Reactions
Senior talk by
Isidore C. Okere
Objectives
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Early identification of common
transfusion rxns.
Differentiate life threatening reactions
from benign transfusion rxns.
Manage common immunologic tranx
rxns.
Types of Reactions
Immune mediated transfusion reactions
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Febrile non hemolytic tranx rxns
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Immune mediated hemolysis
---Acute and delayed hemolytic reactions
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Anaphylactic transfusion rxns
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Urticarial transfusion rxns
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Post-transfusion purpura
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GVHD
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TRALI (pulm leuko-agglutinin reactions)
Non immune mediated reactions
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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
classic blood tranx rxns are usually immunologic and occur 2/2
to interactions of inherited/ acquired Ab with foreign Ag from
transfused blood
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
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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
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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
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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
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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 are 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
Clinical presentation
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 unseen 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
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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?
Transfusion associated
GVHD
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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.
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Bone marrow aplasia is the primary cause of death
Clinical presentation
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
Implicated products
Non Irradiated whole blood
 PRBC
 Platelets
 Granulocytes
 Fresh non frozen plasma
It has not been seen with frozen deglycerolized RBC, FFP or
Cryoprecipitate
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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
Case scenario 4
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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.
2.
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Pulmonary embolism
Antileukocyte antibodies
Allergy to donor plasma proteins
Circulatory overload
Transfusion related acute
lung injury
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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.
Epidemiology
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Leading cause of transfusion related fatalities in the USA
1 case for every 1000-2400 units transfused
6-9% mortality rate
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
Clinical presentation
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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
(a) Bilateral patchy alveolar infiltrate in TRAL
b
(b) Complete resolution
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
Conclusion
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Transfusion reactions are mostly due to
clerical errors and can range from benign
reactions to life threatening emergencies
Early detection, discontinuation of
transfusion and instituting supportive care
are key to management.
Reporting of all reactions helps to improve
standard practices and reduce future
occurrences.
References
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Kleinman S, Caulfield T, Chan P, Davenport R, McFarland J, McPhedran S, et al. Toward an understanding of
transfusion-related acute lung injury: statement of a consensus panel. Transfusion. 2004;44:1774-89. [PMID: 15584994]
[PubMed]
Beauregard P et al. Hemolytic and pseudo- hemolytic reactions: AN overview of hemolytic reactions and the clinical
conditions that mimic them. Transfus Med Rev 1994; 8:184
Brittingham, TE et al. Febrile transfusion reactions caused by sensitivity to donor leukocytes and platelets J Am Med Assoc
1957 165:819
Sanders RP et al. A revised classification scheme for acute transfusion reactions. Transfusion 2007 47;621.
Stack G et al; Cytokine generation in stored platelet concentrates; Transfusion 1994
Uhlmann ET et al. Prestorage universal WBC reduction of RBC units does not affect the incidence of transfusion reactions.
Transfusion 2001 41; 997
Tobian AA et al. Transfusion premedication: a growing practice not based on evidence.. Transfusion 2007; 78;1337
Murphy MP et al. Prevention of bedside errors in transfusion medicine (PROBE-TM) study: a cluster-randomized, matchedpaired clinical areas trial of a simple intervention to reduce errors in the pre transfusion bedside check. Transfusion 2007
47:771
Shimada E et al. Anaphylactic transfusion reactions in haptoglobin-deficient patients with anti-haptoglobin Abs.
Transfusion 2002
Vassallo RR: Review IgA anaphylactic transfusion reactions Part 1. Lab diagnosis, incidence and supply of IgA def products.
Immune hematol 2004
Kopko PM, Marshall CS, MacKenzie MR, Holland PV, Popovsky MA. Transfusion-related acute lung injury: report of a
clinical look-back investigation. JAMA 2002;287:1968-71. [PMID: 11960539] [PubMed
Toy, P Popovsky et al, Transfusion-related acute lung injury; Definition and review. Crit Care Med 2005: 33:721
Thank God this nightmare is over!!!!!!!