Risks of Blood Product Administration Flashcards
What is NAT testing?
Nucleic Acid Amplification Testing
-For HIV, Hepatitis C, Hepatitis B
Reduces window periods:
-HIV : 9 days
-HCV: 7.4 days
-HBsAg: 38 days
Able to detect surface antigens faster than seroconversion.
Reduces the period between acquiring the disease and testing positive for it.
-35% of exposed patients will develop acute virus
-1% will develop fulminant hepatitis (severe liver impairment/failure)
-85% disease resolves spontaneously
-9% chronic persistent hepatitis (benign)
-3% chronic active hepatitis
-1% cirrhosis
-1% hepatocellular carcinoma
Hepatitis B Virus
-Commonly mild presentation
-85% of patients-chronic state
-20% chronic carriers develop cirrhosis
-1-5% develop liver cancer
Hepatitis C Virus
Requires Hep B as a “helper”; therefore, HBV screening prevents this
Hepatitis D
Not a known transfusion pathogen; comes from fecal contaminated water sources
Hepatitis E and A
Describe the risk of transmission of Human Immunodeficiency Viruses
HIV 1 and HIV 2:
-NAT testing implemented in 1999 for blood
-Heat pasteurization, nanofiltration since mid-1980s for coagulation factors and albumin
-Very low risk of blood transfusion transmission
Human T-Cell Lymphotropic Virus-1 and -2:
-Assay introduced in 1998, now minimal risk of transmission with blood transfusions
What is Cytomegalovirus?
Commonly transmitted via blood transfusions.
-In donors, latent virus persists permanently in WBCs (The latent virus persists permanently intracellularly so there is a life long potential for reactivation of the infection or potential for transmission through blood donation or donor organs).
-Can be fatal in immunocompromised patients
At risk:
-Premature neonates
-Organ and bone marrow transplant recipients
-Patient with depressed immune system
Immunocompromised patients should receive leukocyte reduced blood.
What is West Nile Virus?
(mosquito-borne flavivirus)
-Epidemic in Midwestern states in 2002
-Often asymptomatic but may develop encephalitis/meningitis
-Death rate 5-10%
-NAT testing began 2003
-Transmission through blood transfusion rare
What is Zika Virus?
(mosquito-borne flavivirus)
-Leads to congenital deformations in babies borne to infected mothers (microcephaly)
-Self-limiting infection like dengue – with low-grade fever, conjunctivitis, rash and muscle/joint aches
-However, Guillain-Barré syndrome and other neurologic conditions have been documented.
What is Epstein-Barr Virus?
-Cause of mononucleosis, associated with Burkitt lymphoma, nasopharyngeal cancer
-Transmission through blood transfusion rare (whether immunocompromised or not)
What are Prions?
Abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins, found most abundantly in the brain.
-leads to brain damage and the characteristic signs and symptoms of the disease.
-Prion diseases are usually rapidly progressive and always fatal.
-Creutzfeldt-Jakob disease (CJD)
Variant Creutzfeldt-Jakob disease (vCJD)
-Same prion that causes Bovine spongiform encephalitis (BSE) or “Mad Cow Disease”
-Both are fatal degenerative neurologic diseases
-BSE epidemic in UK 1984-Feb 2004
-158 cases vCJD
-Only one case of transfusion related vCJD (persons who spent more than 6 month in the UK from 1980 to 1996 or 5 years in Europe are prohibited from donating blood)
Describe minor allergic reactions to proteins in donor plasma.
-Urticaria occurs in 0.5-4% of all transfusions
-Usually occurs with FFP or platelets
-Symptoms: itching, swelling, rash (histamine release)
-Tx: diphenhydramine, saline washed RBCs
-Washing of platelets is ineffective so if patient needs plts or FFP, pretreat with antihistamine and steroids 1 hour prior to the transfusion.
Describe Anaphylactic reactions to transfusions.
Rare, but severe
-Dyspnea, bronchospasm, angioedema, hypotension
-Causes could be due to a hereditary immunoglobulin A deficiency or other protein anomalies.
-Treatment: stop transfusion, epi, methylprednisolone
-Treated RBCs, pretreatment for FFP, platelets
What are the 3 leading causes of death from blood transfusion?
1) TRALI
-1: 5,000 units transfused
2) Acute hemolytic transfusion reaction
-1: 12,000 units transfused
3) Sepsis from bacterial contamination
-1: 6 million units transfused
What is the most frequent infectious risk from transfusion?
Bacterial contamination of platelets.
-platelets are stored up to 5 days at room temperature
Organisms implicated in plt infections:
-Gram + staph* and strep
-Gram – serratia, e. coli, enterobacter
-Gram + implicated in more cases but -Gram – implicated in more fatalities
Treated with amoxicillin or cephalosporins
What are S/Sx of bacterial contamination of blood?
Fever, chills, tachycardia, emesis, shock, DIC, acute renal failure, CV collapse
What is the treatment for suspected bacterial contamination of blood?
Stop transfusion, obtain blood cultures, supportive measures, broad spectrum antibiotics
What are the two causes of Acute Hemolytic Transfusion Reactions?
1) Presence of Antibodies
-Antibodies (Anti-A, Anti-B)
-Antibodies formed as a result of prior exposure to Donor RBCs, Donor platelets, and/or Donor proteins
2) Due to a transfusion of white cells or white cell antibodies
What are RBC antigens?
-Antibodies that fix complement, cause immediate intravascular hemolysis:
Anti-A, Anti-B, Anti-Kell, Anti-Kidd, Anti-Lewis and Anti-Duffy, Anti-Ss
-> 300 different antigens on RBC
Rh Antibodies don’t fix complement but can cause serious hemolytic reaction
Describe the patho of Acute Hemolytic Transfusion Rxn.
Occurs both intravascular and extravascular.
-Antigen-antibody complexes form, activating Hageman factor (XII)
-Bradykinin is released
-↑ Capillary permeability & dilated arterioles → hypotension
-Complexes also activate coagulation cascade—30-50% develop DIC
-Also causes release of histamine/serotonin from mast cells → Bronchospasm
Leads to RBC hemolysis → acute renal failure, DIC, & Death
Describe the effects of Hemoglobin being released into blood during an Acute Hemolytic Transfusion Rxn
-Initially, Hgb binds to Haptoglobin and Albumin
-But once those are saturated, Hgb circulates unbound until excreted by the kidneys.
Renal damage occurs due to several mechanisms:
-Blood flow ↓ due to systemic hypotension, renal vasoconstriction
-Damage to tubules by free Hgb or Antigen-antibody complexes
-Fibrin thrombi in renal vasculature
What are the S/Sx of an Acute Hemolytic Transfusion Reaction?
-Fever, chills
-Nausea, vomiting, diarrhea
-Rigors
-Hypotension, tachycardia from bradykinin
-Flushed and dyspneic from histamine
-Chest and back pain
-Diffuse intravascular occlusion by red cells
-Restless-sense of impending doom
-With renal failure-oliguria, hemoglobinuria
Many are masked by GA.
-Hypotension, microvascular bleeding, hemoglobinuria may be the only initial clues of hemolytic rxn
What is the treatment of an Acute Hemolytic Transfusion Reaction?
Stop the transfusion!
3 main management objectives:
1) Maintain systemic blood pressure with volume, pressors, inotropes
2) Preserve renal function
-Urine output promoted with fluids
-Diuretics (mannitol or furosemide or both)
-Sodium bicarbonate to alkalinize the urine
3) Prevent DIC:
-Prevent hypotension
-Support cardiac output to prevent stasis and hypoperfusion
Consider steroids and H1/H2 blockers to decrease bronchospasm
What is the definitive test for acute hemolytic reactions? (!)
Coombs test
-Direct antiglobulin test
-Examines recipient RBCs for surface immunoglobulin and complement
-Clumping is positive coombs test = antibodies are bound to surface of RBC.
-If positive, additional tests needed
What is a Delayed Hemolytic Transfusion Reaction?
Occurs 4-8 days up to 1 month post transfusion.
-After apparently “compatible” cross match, transfused red cells are eliminated from the circulation after short interval following transfusion
-Due to previous sensitization which waned over time to be undetectable in testing
-Commonly involve antibodies against Rhesus, Kell, Kidd, or Duffy antigens, not ABO
-Typically antibody-coated RBC sequestered extravascularly
-Lysis occurs in the spleen and renal system
What are the S/Sx of a Delayed Hemolytic Transfusion Rxn?
Evidence of hemolysis by 1st or 2nd week after the transfusion.
Symptoms less severe, self-limiting
May be identified by:
-Low-grade fever
-Increased bilirubin with or without mild jaundice
-And/or an unexplained reduction in hgb concentration
Tx: Supportive Care
How do you diagnose a Delayed Hemolytic Transfusion Rxn?
Diagnosis confirmed by positive direct antiglobulin tests (Coombs test)
What are the 3 components of compatibility testing?
1) ABO and Rhesus (Rh) determination
2) The antibody screen (Indirect Coomb’s test) is performed to identify recipient antibodies against RBC antigens other than ABO
-While the Coombs test looks for antibodies on the surface of the RBCs, Indirect Coombs looks at free flowing antibodies directed against RBCs
3) The Cross-Match, in which donor RBC’s are mixed with recipient serum
-Detects antibodies in low titers or that don’t agglutinate easily
-Assures optimum safety
-Incident of serious reaction after transfusion with ABO and Rh compatible blood (screen) is < 1%
What are the different White Cell Related Transfusion Reactions?
-Febrile reactions
-Transfusion-Related Acute Lung Injury (TRALI)
-Graft-versus-Host Disease (GVHD)
-Transfusion-Related Immunomodulation (TRIM)
When are febrile rxns most likely to occur?
In patients who receive multiple RBC or platelet transfusions.
-Develop antibodies to human leukocyte antigens (HLA) on passenger WBCs
-On a subsequent transfusion, the antibodies attack the WBC antigen
-Febrile reaction in 2% of PRBC, FFP, platelet transfusions
-Leukoreduction reduces or prevents these reactions
-Chills, resp distress, anxiety, HA/Myalgia
-Tx: Tylenol
-Coombs test will be negative
What is Transfusion-Related Acute Lung Injury (TRALI)?
-Noncardiogenic form of pulmonary edema
-Has been associated with administration of all blood components containing plasma
-Most frequent with FFP, platelets (pheresis)
-Incidence 1:5000 transfusions, mortality of 5-8%
-Most common cause of transfusion-related death reported to FDA
What is the patho of TRALI?
Usually donor anti-leukocyte antibodies activate recipient WBCs.
-The donor WBC antibodies were made after a previous transfusion.
TRALI requires presence of pre-existing or pre-disposing inflammatory condition in recipient
i.e trauma, sepsis, surgery
Activated leukocytes sequestered in lung → capillary endothelial damage and ↑ permeability of the lung tissue.
What are the S/Sx of TRALI?
-Clinical appearance similar to ARDs
Within 6 hours of transfusion:
-Dyspnea, fever, chills, labile BP
-Noncardiogenic pulmonary edema
-Bilateral infiltrates (CXR)
Treatment:
-Oxygen, ventilator with low TVs
-No diuretics or corticosteroids needed
What are risk factors for Transfusion associated circulatory overload (TACO)?
Impaired myocardial function & rapid, aggressive fluid therapy.
What are the S/Sx of TACO?
Associated with signs and symptoms of cardiac dysfunction (hx of CHF, low EF, etc.) and/or volume overload.
What are ways to prevent TRALI?
1) Restrictive transfusion strategy
-Greater volumes of blood components = ↑ risk of TRALI
2) Universal leukoreduction
-Will get rid of anti-leukocyte antibodies in both donors and recipients
3) Frequent source of anti-leukocyte antibodies are multiparous female donors and other donors who have had multiple transfusions
-Limit these donors
What is Graft vs Host Disease?
PRBCs and platelets contain significant numbers of viable donor lymphocytes.
-When transfused into an immunocompromised individual, the donor lymphocytes may become engrafted, proliferate, and establish an immune response against the recipient
-In other words, the engrafted lymphocytes reject the host.
-progresses from bone marrow suppression to pancytopenia
Who are patients at risk for GvH Disease?
T-cell immune deficits, bone marrow transplants, Hodgkin’s lymphoma and maybe other hematologic malignancies, neonates who have undergone a exchange transfusion in utero, babies weighing less than 1200 gm at birth, other immunocompromised patients and Patients receiving blood from a first degree relative.
What types of products can cause GvH Disease?
Only reported after transfusion of cellular blood components
-Not after FFP, cryoprecipitate
How can you prevent GvH Disease?
Irradiate cellular blood products to inactivate the lymphocytes in transfused blood.
-For immunocompromised patients
-For direct donor units from 1° relatives
-Leukoreduction decreases incidence but does not prevent GVHD
-Irradiation only effective means to prevent GVHD
What is Transfusion-Related Immunomodulation (TRIM)?
Allogenic blood transfusions associated with immunosuppression &/or proinflammatory effects
-First seen in renal transplant patients (less likely to reject organ if received a blood transfusion)
-Likely due to transfused WBCs
-Adverse effects of immunosuppression: increased recurrence of malignancies, increased rate of infections, and increase in mortality in the short term.
How does Transfusion-Related Immunomodulation (TRIM) occur?
During blood storage, bioactive substances such as cytokines, cell membrane breakdown products, and complement accumulate leading to an inflammatory response and multiorgan dysfunction.
-Consider Leukoreduction of all blood products
