Adverse effects of transfusion Flashcards
How many deaths per year are caused by hemolytic transfusion reaction
1 per million
USFDA (21CFR 606.170b)
notification is required for any fatality related to transfusion
Four transfusion reactions that present with fever
Febrile (FNHTR), AHTC, DHTR, bacterial contamination
Symptoms of Febrile Nonhemolytic Transfusion reaction
Fever >1 degree increase, increase blood pressure, chills, rigors, increase heart rate (*No resp distress and no drop in b.p.)
What percentage of transfusions have FNHTR
1%
What causes Febrile transfusion reactions
Cytokines released from Donor WBCs upon transfusion
How do you decrease the odd of acquiring FNHTR
Leukoreducing blood products prior to storage, or bedside leukoreduction (not as effective)
Treatment of FNHTR:
anti-pyretics: acetominephin, IB profin- both for fevers, for the rigors: demoral, neparadine
Successful Leukoreduction in products
> 5.0 x 10^6 (normal 5.0 x 10^9)
Symptoms of acute hemolytic transfusion reaction
Fever, chills, rigors, DECREASE B.P. decrease urine output (red/pink urine) decrease haptoglobin, increase LD, increase Bilirubin.
Treatment of AHTR
supportive
Free hemoglobin in the blood: what it does
scavenges nitrus oxide- vessels contract (especially in kidneys), cold clammy feeling
What causes AHTR
IgM, IgG-if high titer can fix complement when binding close together. (wrong blood type, Jka (clustering))
What causes DHTR
either low titer antibody (previous, but undetectable levels) or new antibody formation that is created in response to transfused red cells, red cells live ~120 days- attack rbcs still present.
Type of hemolysis DHTR
Extravascular- antibodies bind to red cell- red cell is removed from circulation by the spleen.
Symptoms DHTR
low grade fever, hgb drops, jaundice because hgb is broken down into bilirubin in the liver. decrease haptoglobin.
how can DHTR be diagnosed/proven
through identification of new antibody post transfusion
Bacterial contamination in blood products symptoms
fever, decrease in blood pressure (sepsis)
Differentiating Bacteria vs. AHTR
typically by the blood product provided (NOT ALWAYS) bacteria associated more with platelets- RT, AHTR most often associated with RBCs due to the fact that this is what is being hemolyzed in most cases. Hemolysis can also come from type incompatible plateelts.
Usual bacterial contamination
Gram positive more common, typically from skin contamination. Gram negative- endotoxins are the harmful portion, these can be in the cases of donors being bacteremic at the time of donation.
Treatment
antibiotics and supportive
How to avoid
diversion pouch with skin plug, pathogen reduction, sample and culture from original unit- wait 24 hours before releasing. Platelet pregnancy test (PGD test) has GN on the left, GP on the right and sample well in the center, put the same it will gravitate to both sides and colorimetric change will indicate contamination. Controls are located on the outsides of both the GN and the GP well.
Respiratory Distress Transfusion Reaction (2)
TRALI and TACO
TRALI- what it is?
Transfusion related acute lung injury
TRALI-what causes it?
Donor factor- HLA antibodies, HNA antibodies and ‘bioactive lipids’. Host factor- underlying condition with increase inflammation. It’s believed that both the Donor, and host factors combined ‘2 hit model’ cause TRALI
TRALI- Prevention?
“blood centers should attempt to mitigate TRALI” 1) decrease female plasma donors 2) limit number of previous pregnant donors 3) Test antibodies in donor plasma (HLA or granulocyte antibodies) if positive should be deferred from future donations
TRALI-symptoms
Dyspnea, Xray (white out of lungs), pulmonary edema, increase respiratory rate decrease oxygen saturation, fever, decrease blood pressure (85%)
what is specifically happening in the lungs during TRALI?
neutrophils marginate when activated bind to vessels to break through in body neutrophils marginate (forming a border to) in vessels. Avioli in the lungs, not bound to venules- bind to capillaries in lungs- capillaries are very delicate and damaged by the neutrophils- this is the first site of small vessels hit after being transfused
TACO symptoms
Transfusion associated circulatory overload. Pulmonary edema, X-ray (basal, increase pressure to lower part of lungs) increase b.p. dyspnea, increase respiratory rate, decrease oxygen saturation, increase heart rate.
Differentiating TACO and TRALI
TRALI- Xray-“white out” TACO “basal lungs”
Who is affected by TACO
it’s volume overload, heart disease patients, kidney disease patient and smaller people
What Transfusion reactions have the highest percentage of fatalities
TRALI and TACO
Impact of histamine in body
Laryngeal edema (wheezing) bronchoconstriction/vasodialation
symptoms of allergic reaction-transfusion reaction
Laryngeal edema (wheezing) bronchoconstriction/vasodialation, respiratory distress, increase respiratory rate, hives, itching, GI symptoms nausea, vomiting, cramping. decreased blood pressure
Cause of allergic reactions
IgE antibodies- depends on how much binding takes place and how much histamine was released.
How many liters of blood are in the human body
5 liters
If dilated how many liters of blood can the human body hold?
22 Liters
Treatment of allergic reaction
anti-histamines. Epinephrin causes vasoconstriction (can premed with antihistamines and steroids)
Mild allergic reactions from transfusion
just skin reaction- itching hives, pretty mild, take anti-histamine
Moderate allergic reactions
some edema (peri-orbital around the eyes) some GI symptoms, Itching and scratching, take anti-histamine (maybe steroid)
Post transfusion purpura
delayed reaction for platelets. HPA-1a antibodies (among others) molecular mimicry takes out transfused platelets as well as auto platelets.
prevalence of homozygous HPA-1b
1% of population- not easy to find donors. if they are transfused with HPA-1a, will probably make the antibody
Vasovagal reactions
“prefaint or presyncope” dizziness, sweating nausea, vomiting, weakness, pallor, hypotensin and bradycardia. LOW PULSE RATE.
reactions to volume depletion
high pulse rate.
Paresthesias
tingling sensations- reaction to citrate anticoagulant are not uncommon- provide calcium as a treatment.
Highest risk of sepsis comes from:
Platelets, higher related fatality than any other transfusable blood component: 1 in 6000 apheresis plts have bacteria
High percentage of bacterial contamination- what day of platelet
storage days 4 and 5 of platelet- 95% of septic transfusion reations and 100% fatalities are linked to longer outdate platelets
Isolated hypotenstion
buildup of bradykinen- ACE enzyme breaks down bradykinen, people on ACE inhibitor aren’t able to break down Bradykinen.
A.C.E. inhibitor
angiotensin- converting enzyme. helps relax blood vessels
Known transfusion-Transmitted infections (19)
Syphillis, Prions, Rickettsia, Malara, Babesia, Chaga’s, Leismaniasis, Toxoplasmosis, Filariasis, West Nile, CMV, HBV, HAV, HCV, HIV, HTLV, Parvo, EBV, Zika
Theoretical transfusion transmitted infections (8)
SARS, monkey pox, smallpox, encephalitis viruses, chikungunya, Lyme, Relapsing fever, Q fever (not been proven to show transmission)
Immune related acute adverse effects of transfusin (4)
acute hemolysis, allergy, TRALI, Febrile
immune delayed adverse effects of transfusion (5)
delayed hemolysis, graft vs. host disease, post-transfusion purpura, immune suppression, alloimmunizatin
Non immune acute (5)
TACO, Mechanical hemolysis, hypothermia, electrolyte disturbances, citrate toxicity
Non immune delayed
iron overload
Pulmonary edema
lungs filled with fluid, (In TRALI-due to leaky blood vessels not heart failure)
Cause of TRALI
donor white blood cell antibodies or HLA antibodies, attach recipient white blood cells and cause them to leukoagglutinate (occurs in lungs, small capillaries of avioli cannot handle) these get caught up in the lungs and relase damaging enzymes.
What percentage of TRALI cases are fatal?
5-10% die, most patients recover within a few days
ARDS
adult resipratory distress syndrome- often misdiagnosed as this when it’s actually TRALI
Treatment for TRALI
mechanical ventilation and supportive care
Blood units associated with TRALI
any plasma containing blood unit
two types of TRALI
antibody-mediated and non antibody mediated
Antibody mediated TRALI
usually plasma units and half of apheresis platelet cases. HLA or neutrophil antibodies, antibody usually from donor, antibody alone usually does not cause TRALI
Non antibody mediated TRALI
red cell units and half of apheresis cases, negative for white cell antibodies. Neutrophil-priming (two-hit hypothesis) event #1 causes neutrophils to be primed, event number 2 causes them to be activated. (1. underlying condition 2. transfusion) could be caused by ‘biologically active substances, like lipids’
what type of antibody is most fatal in TRALI
HNA antibodies are more associated with fatalitites
what is the most common/concerning TRALI antibody specificity
HNA-3a
TRALI mitigation strategies
using solvent-detergent treated plasma, use of platelet additive solutions, use of pathogen reduced platelets no donation of products that cause TRALI by people with history of pregnancy
TACO
transfusion associated circulatory overload. reported incidence of this is increasing, still under-recognized 2-6% of transfused patients can occur with any blood products
TACO risk factors
very young (less than three) or old (older than 60) chronic renal failure, congestive heart failure, higher number of blood products infused, higher fluid balance per hour, faster transfusion rates, any critical illness
Difference between TACO and TRALI
TRALI- White out pulmonary edema TACO- only bottom of the lungs. TRALI increase temp TACO unchanged temp. TRALI-HYPOTENSION TACO-HYPERTENSION. TACO-significant diuretic. TRALI- decrease WBC count. TACO- positive fluid balance
Prevention of TACO
avoid unnecessary transfusion, identify underlying risk factors, use of diuretics, use 4-PCC for warfarin reversal instead of FFP, close monitoring and awareness
TA-GVHD
manifests 3-30 days usually 8-10 days, signs/symptoms rash, fever, diarrhea, increase liver functions and pancytopenia, no effective treatment, mainly fatal due to involvement of the bone marrow
Types of irradiation
X-ray or Gamma irradiation of cellular products
Fludarabine
Purine analogues, treatment for patients with CLL leukemia or lymphoma malignancies
What does irradiation do to the units
inactivated donor lymphocytes, prevents the proliferation so they cannot mount an attack against host
Irradiation vs. leukocyte reduction filters
filters do not remove enough leukocytes to prevent GVHD, still needs irradiation even if leukoreduced
Minimum dose of irradiation for units
25Gy to the center 15Gy to the edges of entire bag minimum
Indications of irradation of units
Premature, intrauterine transfusion, congenital immunodeficiencies, hodkin disease, hematologic malignancies, peripheral blood stem cell/marrow transplantation, granulocyte components, fudarabine therapy, HLA matches or from directed donors
HSCT irradiated products for how long?
We don’t have a set standard, definitely require irradiated blood products during and for at least 1 year after transplantation, AABB acknowledges that we don’t have the evidence to determine how long they need to be provided irradiated products for. Must be given from the initiation of conditioning chemoradiotherapy, should be continued while patient- is on GVHD prophylaxis usually six months post transplant. Lymphocytes >1x10^9
HSCT donors considerations
If donor for HSCT is to be transfused up to 7 days prior to or during the harvest should be irradiated, same with autologous donors
Hodgkin Lymphoma special requirements for units
all adults and children with diagnosis, at any stage of the disease should have irradiated red cells annd platelets for life
Purine analogue drugs
fludarabine, cladribine and deoxycoformicin, need to receive irradiated blood components indefinitely, these are commonly used to treat cancer by disrupting DNA
Acute Leukemia patients special needs
not necessary to irradiate red cells or platelets except for HLA selected platelets or donations from family
alemtuzumab
anti-CD52 therapy, patients must be given irradiated blood products
ATG
antithymocyte globulin, recent switch from horse to rabbit ATG that is more immunosuppressive in patients with aplastic anemia. Recommendation of irradiated units, though cannot make a firm recommendation on how long irradiated blood product need to be provided for.
what is a substitution for irradiated blood products
pathogen reduction
Platelet safety measurements
before release of platelets, needs to be 1. culture based testing 2. point of care testing at hospital (PDG) 3. pathogen reduction technology.
If platelet is positive for bacteria
per FDA need to identify organism and then contact and counsel donor if appropriate
Arm scrub for donors
chlorhexidine or betadine
septic transfusion reaction rate
1/100,000 for passive recording 1/10,000 for active recording, 95-100% of cases of septic reactions were on days 4 and 5 of platelet life
6 or 7 platelets
platelets can now be used on day 6 or 7 if test is done for bacterial detection on the day of transfusion
FDA new rule 2018 regarding platelet contamination
Must be checked on day four or five for bacterial testing, would required aerobic and anaerobic testing, testing daughter bags as opposed to mother bag. otherwise pathogen reduction technology
Acute conditions to report for transfusion reactions
Fever, chills, flushing, red urine or other indicators of hemolysis, changes in blood pressure or pulse, dyspnea, unexplained pain, anaphylaxis or moderate to severe allergy, fatalities, maybe urticaria, simple rash or volume overload
Testing in acute hemolytic transfusion reaction
examination of post-transfusion serum: hemolysis, DAT ABORH of post sample. Examination of post transfuision urine, perform clerical check of paperwork. Further testing if any of the others are abnormal or positive: repeat ABORH repeat crossmatch, repeat antibody screen and ID, blood markers for hemolysis (LD, bilirubin, haptoglobin)
Intravascular hemolysis
immediate, destruction by complement, occurs in circulation, free hemoglobin in urine and serum, decreased haptoglobin, systemic reaction
Extravascular hemolysis
delayed hours or days, destruction by macrophage, occurs in spleen or other extravascular sites, no free hemoglobin, few if any simptoms, rarely life-threatening
Clinical signs and symptoms of AHTR
patient discomfort, low blood pressure and high pulse, fever and chills, loss of conscioiusness, feeling of impending doom, pain in back, chest or at infusion site, difficulty breathing
Outcome of AHTR
death, renal failure, DIC
treatment of AHTR
Stop transfusion ASAP! Keep IV line open, don’t close the line!!! Start saline administration, keep well hydrated, support blood pressure, do not transfused additional units of same time!!
Mechanical hemolysis
improper storage or handling of blood, heated or frozen, improper administration pressure pump or too small needle bore, incompatible IV fluids or medications added, bypass circuit or blood pump, bacterial contamination
Fever after transfusion
TRALI, Bacteria, Hemolysis or underlying disease. If all of these can be excluded may diagnose non-hemolytic febrile transfusion reaction
Febrile reaction units
most common with platelets, caused by white blood cell incompatibilities, most common donor white blood cells are lysed by recipient wbc antibodies, cells release pyrogens that cause fever, chills and flushing.
Avoidance of febirle reactions
leukoreduction of components, premedication with anti-pyretics (tylenol)
Allergic Transfusion reaction
Mild- reaction of patient IgE antibodies against transfused plasma, soluble substance (probably a protein) in plasma is the target. Antigen antibody reaction releases histamine and other anaphylotoxins from basophils and mast cells urticaria hives itching
Severe allergic transfusion reaction
More thanlocalized skin rash and itching, may involve facial swelling, laryngeal edema and difficulty breathign if this occurs stop transfusion, do not continue with same unit after treatment
Anaphylaxis
severe, life-threatening allergic reaction, occurs within minutes of the start of transfusion, difficulty breathing closure of airways can have GI cramping and pain, stop transfusion and call for help needs immediate treatment with epinephrine patient may end up on ventilator
Transfusion of patients with moderate allergic reactions
pre-medication with anti-histamines, pre medication with steroids, close observation, use of washed cellular products avoidance of plasma, autologous blood if possible
1 bacteria in RBCs
Yersinia entercolitica= 51% (#2 is pseudomonas fluorescens=27%)
Acute Fever (4)
AHTR, TRALI, septic, Febrile
Delayed Fever (2)
DHTR, TA-GVHD
Acute non-fever (4)
TACO, Urticarial, Anaphylaxis, premedicated
Delayed non-fever (2)
PTP, Iron overload
PTP
post transfusion purpura, typically in multiparous women, has antibodies against platelets HPA-1a etc. and destroys platelets including own platelets after transfusion with ‘incompatible’ Patient should be tested to identify antibody causing reaction for future avoidance
Symptoms of AHTR
fever, chills, back/flank pain, sense of impending doom, hemoglobinemia/uria, DIC, decreased LDH, elevated bilirubin, decreased serum haptoglobin
Window for increased hemoglobinuria and decresed haptoglobing in AHTR
1-2 days and then values slowly return to normal
Percentage of Febrile reactions in transfusion
1-2% of all transfusions
Febrile caused by
accumulated cytokines in unit (IL-6, TNF etc.) These can be increased in older units due to activation and release cytokines by WBCs over time
Febrile symptoms/signs
fever and chills comes on acute, increase in temp greater than 1 degree
Clinical signs and symptoms of Septic reation
Rapid high fever, rigors and shock
TRALI fatality percent
20% fatal
TRALI and TACO comparison of cardiac dysfunction
TRALI has no cardiac dysfunction, TACO has tachycardia and hypertension
Most common HLA group that causes TRALI reaction
HLA-II (34-47%) HLA1 and HNA have similar percentage rates for causality (4-28% ish)
TRALI two hit method
Typically something primes the endothelium and PMNs in the patient and then when unit is transfused they are activated
Signs and symptoms of Anaphylaxis
Severe hypotension, GI symptoms, swelling of throat (fevers are rare!!)
Drug for chills/rigors
meperidine
anamnestic response
rapid IgG production upon re-exposure to antigen. Most common cause of DHTR
Transfusion hemosiderosis
Excessive iron deposition in recipient, significance comes over years of constant transfusion
Iron in each unit of RBCs
225mg of Iron
Iron overload more common in these patients:
chronic renal failure, aplastic anemia, congenital hemolytic anemias (sickle cell)
Citrate toxicity results in
hypocalcemia, manifesting particularly in liver dysfunction, hypothermic or shock in patients
Potassium complications
excess potassium in red cells (predominantly in irradiated units) transport pumps can become damaged, hypokalemia is more frequently observed because potassium depleted donor cells reaccumulate potassium ion intracellularly and citrate metabolism causes further movement of potassium into the cells.
Hyperkalmeia can be a problem in these patients:
Pre-existing hyperkalemia, renal failure, premature infants, newborns receiving large transfusions, cardiac surgery or exchange transfusion
When does bilirubin peak in patient after hemolytic event
3-6 hours as free hemoglobin is metabolized
normal oxygen saturation
95-100%
Treatment ofr acute hemolytic transfusion reaction
Diuretic, analgesics, pressors to manage hypotension and management for DIC
Diuretic drug
furosemide
analgesics
medicines used to relieve pain, acetominephan
Treatment of hypotension
PRESSOR- low dose dopamine, fludrocortisone, midodrine
