Objectives
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
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)
Non immune mediated 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
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
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
Class 1 HLA ab directed against contaminating wbc in red cell conc. Although these are not always found
2/2 to cytokines IL-1, 6,8 and Tnf alpha generated in stored blood/products.
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
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
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?
Transfusion associated
GVHD
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
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
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
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?
Pulmonary embolism
Antileukocyte antibodies
Allergy to donor plasma proteins
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.
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
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
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
Conclusion
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.
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