blood transfusion reaction
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Classification
- immediate immunologic transfusion reactions
- acute intravascular hemolysis (acute hemolytic transfusion reaction)
- urticarial reactions
- anaphylaxis (anaphylactic transfusion reaction)
- febrile non-hemolytic reactions
- platelet alloantibodies
- transfusion-related acute lung injury
- delayed immunologic transfusion reactions
- delayed immune hemolysis
- graft vs host disease
- transfusion-related immune suppression
- immune-mediated thrombocytopenia (ITP)
- immediate non-immunologic effects
- volume overload (transfusion-associated circulatory overload)
- citrate toxicity
- air embolism
- potassium overload
- delayed non-immunologic effects
- infectious complications
- viral transmission
- transmission of bacteria & bacterial endotoxins
- transmission of parasites
Etiology
immediate immunologic transfusion reactions
- acute intravascular hemolysis (acute hemolytic transfusion reaction)
- clinical errors: misidentification of patient or patient's blood specimen accounts for the majority of fatal transfusion reactions
- caused by ABO incompatible plasma or red cells
- involves complement-fixing IgG & IgM antibodies
- urticarial reactions
- recipient sensitized to donor antigens
- anaphylaxis (anaphylactic transfusion reaction)
- febrile non-hemolytic reactions
- recipient response to donor leukocytes (antibodies)
- donor leukocyte cytokines
- platelet alloantibodies
- HLA or platelet-specific antibodies, i.e. anti-PLA-1
- transfusion-related acute lung injury
- donor antibodies reacting with recipient leukocytes causing leukocyte aggregation in the pulmonary capillary bed[4]
delayed immunologic transfusion reactions
- delayed immune hemolysis
- sensitization to RBC antigens (not ABO):
- esp. Rh, Kidd, Duffy, MNS antigens
- anamnestic production of non-complement fixing IgG antibodies
- extravascular removal of antibody-coated RBCs
- sensitization to RBC antigens (not ABO):
- graft vs host disease
- proliferation of donor-derived HLA-incompatible transfused lymphocytes
- occurs in immune compromised recipients & patients who receive blood components from relatives
- transfusion-related immune suppression
- immune-mediated thrombocytopenia (ITP)
- prior pregnancy sensitizes women to platelet antigen-1 (PLA-1)
immediate non-immunologic effects
- volume overload (transfusion-associated circulatory overload)*
- citrate toxicity: sudden drop in serum ionized Ca+2
- air embolism: accidental infusion of air
- potassium overload
* restrictive cardiomyopathy may result in volume overload at low transfused volumes[8]
delayed non-immunologic effects
- transfusion hemosiderosis
- 1 mg of iron/ mL of packed RBCs
infectious complications
- viral transmission
- failure to recognize asymptomatic donors infected with HIV-1, HIV-2, HTLV-1, HTLV-2, hepatitis viruses, CMV, West Nile virus, dengue virus & others
- transmission of bacteria & bacterial endotoxins
- unrecognized bacteremia in donor
- contamination during processing
- bacterial contamination of donor platelets is the most common cause
- E. coli & Pseudomonas are associated with refrigerated components
- Yersinia, Serratia & Salmonella are associated with platelets
- Acinetobacter, Klebsiella, Anaplasma
- Staphylococcus aureus (1 in 2500 platelet transfusions)
- transmission of parasites
- donors infected with parasites, i.e. Plasmodium (malaria), Trypanosomes (Chagas' disease), babesiosis, leishmaniasis
- transmission of prions
Epidemiology
- immediate immunologic transfusion reactions
- urticarial reactions
- incidence: 1-3% of all transfusion
- anaphylaxis
- incidence: < 1:1000
- febrile non-hemolytic reactions
- incidence: 1-3%; more common in multiply transfused patients
- platelet alloantibodies
- incidence: high-frequency of platelet alloantibodies in multiply transfused patients
- transfusion-related acute lung injury: rare
- urticarial reactions
- delayed immunologic transfusion reactions
- delayed immune hemolysis
- incidence: 1 in 5000 (occurs in previously transfused patients or multiparous women)
- graft vs host disease
- incidence: < 1 in 1000
- transfusion-related immune suppression
- incidence: common; frequently unrecognized
- immune-mediated thrombocytopenia (ITP)
- most common in women
- delayed immune hemolysis
- immediate non-immunologic effects
- volume overload (transfusion-associated circulatory overload)
- incidence: common
- citrate toxicity
- incidence: rare except in massive transfusions (> 12 units/hour in an adult)
- air embolism
- incidence: extremely rare, greatest risk with intra-operative blood salvage systems
- potassium overload
- incidence: rare unless patient with pre-existing renal failure or acidosis
- volume overload (transfusion-associated circulatory overload)
- delayed non-immunologic effects
- transfusion hemosiderosis
- incidence: common in chronically transfused patients
- transfusion hemosiderosis
- infectious complications
- viral transmission
- incidence: (risk per unit of component transfused)
- HIV: < 1 in 200,000
- hepatitis B: < 1 in 200,000
- hepatitis C: < 1 in 3000
- HTLV: < 1 in 60,000
- CMV: 50-100% of donors are infected
- incidence: (risk per unit of component transfused)
- transmission of bacteria & bacterial endotoxins
- incidence: < 1 in 500,000 as cause of death
- transmission of parasites
- incidence: rare in the USA
- viral transmission
Pathology
- immediate immunologic transfusion reactions
- acute intravascular hemolysis
- urticarial reactions
- plasma constituents can react with patient's IgE on mast cells
- anaphylaxis
- anti-IgA antibodies in IgA-deficient individuals
- platelet alloantibodies
- anti-platelet antibody, anti-PLA-1
- transfusion-related acute lung injury
- donor antibodies reacting with recipient leukocytes causing leukocyte aggregation in the pulmonary capillary bed[4]
- febrile transfusion reaction
- results from donor leukocyte cytokines or recipient alloantibodies directed against donor leukocytes
- delayed immunologic transfusion reactions
- delayed immune hemolysis
- sensitization to RBC antigens (not ABO)
- anamnsetic production of non-complement fixing IgG
- extravascular removal of antibody-coated RBCs
- graft vs host disease
- proliferation of donor-derived HLA-incompatible transfused lymphocytes
- reactions affect the bone marrow, liver, skin & GI tract[4]
- immune-mediated thrombocytopenia (ITP)
- prior pregnancy sensitizes women to platelet antigen-1 (PLA-1)
- delayed immune hemolysis
- immediate non-immunologic effects
- volume overload
- citrate toxicity
- sudden drop in serum ionized Ca+2
- air embolism
- potassium overload
- delayed non-immunologic effects
- transfusion hemosiderosis
- deposition of iron in heart, liver, lungs & bone marrow
- infectious complications
- viral transmission
- related to transmitted virus
- transmission of bacteria & bacterial endotoxins
- shock & disseminated intravascular coagulation (DIC)
- high mortality
- transmission of parasites
- related to transmitted parasite
- viral transmission
Clinical manifestations
immediate immunologic transfusion reactions
- acute intravascular hemolysis (acute hemolytic transfusion reaction)
- fever
- tachycardia
- hypotension
- dyspnea
- acute renal failure
- pain at infusion site
- chest pain
- flank pain & abdominal pain
- incidence < 1:50,000
- urticarial reactions
- rapid onset of hives, rash, wheezing during or after transfusion
- anaphylaxis
- sudden hypotension, hypoxemia, respiratory distress, stridor[6] during transfusion
- abdominal pain, angioedema [4]
- febrile non-hemolytic reactions
- platelet alloantibodies
- fever
- edema
- failure to maintain increased platelet count after transfusion
- petechiae, purpura & severe thrombocytopenia within days with anti-PLA-1
- transfusion-related acute lung injury
- fever/chills, tachycardia, dry cough, hypoxemia
- non-cardiogenic pulmonary edema
- acute respiratory distress syndrome
- occurs 2-6 hours after initiation of transfusion
delayed immunologic transfusion reactions
- delayed immune hemolysis
- anemia; fever; arthralgia; renal failure (mild)
- delayed hemolytic reaction typically occurs 4-13 days (2-10 days)[4] after transfusion
- graft vs host disease
- several days to 1 month after transfusion
- dermatitis, maculopapular rash[4]
- gastrointestinal & liver dysfunction[4]
- immune suppression
- high mortality
- transfusion-related immune suppression
- frequently subclinical;
- increased risk of bacterial infections
- increased cancer progression
- immune-mediated thrombocytopenia (ITP)
- thrombocytopenia occurring >= 1 week after transfusion .
immediate non-immunologic effects
- volume overload (transfusion-associated circulatory overload)
- citrate toxicity
- air embolism
- potassium overload
- hyperkalemia in massively transfused or smaller patients .
delayed non-immunologic effects
- transfusion hemosiderosis
- deposition of iron in heart, liver, lungs & bone marrow .
infectious complications
- viral transmission
- related to transmitted virus
- transmission of bacteria & bacterial endotoxins
- shock & disseminated intravascular coagulation (DIC)
- high mortality
- transmission of parasites
- related to transmitted parasite
Laboratory
immediate immunologic transfusion reactions
- acute intravascular hemolysis (acute hemolytic transfusion reaction)
- red plasma & urine: hemoglobinuria
- plasma free hemoglobin;
- direct antiglobulin test (Coomb's test) is positive
- serum bilirubin & DIC panel
- repeat cross match
- urine hemoglobin
- haptoglobin in serum
- febrile non-hemolytic reactions
- platelet alloantibodies
- anti-platelet antibody, anti-PLA-1
- transfusion-related acute lung injury
- anaphylaxis or anaphylactoid reactions
delayed immunologic transfusion reactions
- delayed immune hemolysis
- complete blood count (CBC): drop in hemoglobin
- serum LDH: increased
- serum bilirubin: hyperbilirubinemia;
- positive direct antiglobulin (Coomb's) test
- reticulocyte count: increased
- serum haptoglobin: decreased
- a new alloantibody appears in
- immune-mediated thrombocytopenia (ITP)
- platelet count: thrombocytopenia occurring >= 1 week after transfusion
- anti-platelet antibody anti-PLA-1 (HPA-1a)
- graft vs host disease
- abnormal liver function tests
- complete blood count (CBC): pancytopenia
immediate non-immunologic effects
- citrate toxicity
- sudden drop in serum ionized Ca+2
- potassium overload (hyperkalemia)
- serum potassium elevated
- elevated serum BNP with volume overload[4]
delayed non-immunologic effects
- transfusion hemosiderosis
- iron studies abnormal
- high serum iron
- high serum ferritin .
- iron studies abnormal
infectious complications
- viral transmission
- donor screening
- serologic testing
- transmission of bacteria & bacterial endotoxins
- serology as indicated
- blood cultures
- transmission of parasites
- serology as indicated
- peripheral smear for examination of parasites
Radiology
- immediate immunologic transfusion reactions
- transfusion-related acute lung injury
- chest X-ray:
- perihilar, patchy infiltrates
- bilateral infiltrates with pulmonary edema
- chest X-ray:
- transfusion-related acute lung injury
- immediate non-immunologic effects
Differential diagnosis
- transfusion-related volume overload (see blood transfusion Complications:)
Management
immediate immunologic transfusion reactions
- acute intravascular hemolysis (acute hemolytic transfusion reaction)
- stop transfusion
- clotted & EDTA-treated blood specimens along with patient's blood & tubing should be sent to lab
- send freshly voided urine to lab for free hemoglobin
- support blood pressure
- maintain urine output at 100 mL/hr with IV fluids, diuretics, & mannitol if necessary
- NaHCO3 to alkalinize urine may aid in excretion of hemoglobin
- urticarial reactions
- anaphylaxis (see anaphylaxis)
- febrile non-hemolytic reactions
- stop transfusion
- rule out acute intravascular hemolysis
- direct antiglobulin test, see Laboratory: (above)
- consider causes of fever unrelated to transfusion[4]
- treatment: antipyretics, glucocorticoids
- prevention:
- platelet alloantibodies
- prevention: use of leukocyte filters for transfusion of cellular blood products
- transfusion-related acute lung injury
- stop transfusion
- respiratory support
- vasopressors for hypotension
- prevention:
- leukocyte depletion filters or washed RBCs
- eliminate multiparous women as blood donors[4]
delayed immunologic transfusion reactions
- delayed immune hemolysis
- prevention
- wallet card identifying alloantibodies
- transfusion with compatible blood
- patient education
- prevention
- graft vs host disease
- prevention:
- use of irradiated blood products (at least 2500 rads) if transfusing with relative's blood or in immunocompromised recipients[4]
- use of irradiated blood components is an absolute requirement in stem cell transplant recipients
- prevention:
- transfusion-related immune suppression
- prevention: autologous blood transfusion
- immune-mediated thrombocytopenia (ITP)
immediate non-immunologic effects
- volume overload (transfusion-associated circulatory overload)
- treat as cardiogenic pulmonary edema
- prevention: slow or incremental transfusion; careful monitoring; diuretics
- citrate toxicity
- prevention: treatment with calcium gluconate or chloride washed RBCs in small recipients
- air embolism
- place patient on left side with head down & feet up
- potassium overload
- prevention: use of washed RBCs
delayed non-immunologic effects
- transfusion hemosiderosis
- prevention:
- minimize unnecessary transfusion
- erythropoietin may be useful
- iron chelation therapy
- prevention:
infectious complications
- viral transmission
- transmission of bacteria & bacterial endotoxins
- empiric coverage for gram-positive & gram-negative organisms[4]
- prevention:
- proper skin preparation with blood donation
- good blood banking practices
- deferring donors with febrile illnesses
- use of leukocyte-depleted blood components
- transmission of parasites
- prevention:
- donor screening
- development of serologic tests
- prevention:
Notes
More general terms
More specific terms
- anaphylactic transfusion reaction
- hemolytic transfusion reaction
- transfusion-associated volume overload; transfusion-associated circulatory overload
- transfusion-related acute lung injury (TRALI)
Additional terms
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 615-616
- ↑ The Washington Manual of Medical Therapeutics, 29th edition, Carey, CF et al (eds), Lippincott-Raven, Philadelphia, 1998, pg 272-73
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 790
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2015, 2018, 2022.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009 Apr 9;113(15):3406-17. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19188662
- ↑ 6.0 6.1 Sandler SG, Vassallo RR. Anaphylactic transfusion reactions. Transfusion. 2011 Nov;51(11):2265-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22023182
- ↑ Delaney M, Wendel S, Bercovitz RS et al Transfusion reactions: prevention, diagnosis, and treatment. Lancet. 2016 Dec 3;388(10061):2825-2836. Epub 2016 Apr 12. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27083327
- ↑ 8.0 8.1 NEJM Knowledge+ Hematology