Transfusion Reactions

what are the top 3 most common reported cases of transfusion related mortalities?

TRALI, HTR, TACO

which sign/symptom of a transfusion reaction is defined as an increase of ≥ 1ºC (2 ºF) over the pre-transfusion temp and ≥ 38 ºC (100.4 ºF) during or within 4 hours of the completion of transfusion?

fever

which sign/symptom of a transfusion reaction is defined as elevated blood pressure exceeding 140 over 90 mmHg?

hypertension

which sign/symptom of a transfusion reaction is defined as ≥ 30 mmHg drop in systolic BP resulting in systolic BP of ≤ 80 mmHg during or within 4 hours of the completion of transfusion?

hypotension

which sign/symptom of a transfusion reaction is defined as abnormal deficiency in the concentration of oxygen in arterial blood where PO2/ Oxygen saturation is less than 90% on room air?

hypoxemia

which sign/symptom of a transfusion reaction is defined as new onset of decreased urinary output (<500 ml output per 24 hours)?

oliguria

which sign/symptom of a transfusion reaction is defined as a drop in BP accompanied by a drop in cardiac output including rapid heart rate (increase to ≥ 100 beats per minute), rapid breathing, cutaneous vasoconstriction, pallor, sweating, decreased or scanty urine production agitation and/or loss of consciousness that required fluid resuscitation?

shock

the most common ____ transfusion reactions are the mild urticarial allergic reaction and febrile non-hemolytic transfusion reaction.

acute

which form of an acute allergic transfusion reaction is best described below:

• reaction that develops due to a pre-existing antibody in the patient directed against an antigen present in the donor plasma or a pre-existing antibody in the donor plasma against an antigen present in the patient

• usually arise within seconds or minutes of start

• signs and symptoms: urticaria, pruritis, flushing

• preventive measures: pre-medication with antihistamines 30 minutes before transfusion may be helpful in recipients with history of multiple urticarial reactions

• treatment: in some cases after stopping transfusion, unit may be restarted slowly after antihistamine if symptoms resolve

mild, urticarial

which form of an acute allergic transfusion reaction is best described below:

• usually caused by hypersensitivity of recipient to allergens in donor plasma

• may moderate to severe allergic reactions or even the most severe allergic reactions and can be life-threatening, usually characterized by intractable hypotension or shock with loss of consciousness

• occur in IgA deficient recipients who demonstrated Anti-IgA

• Usually arise within 1 – 45 minutes

• the faster the onset of symptoms, the more severe the reaction will be

• signs and symptoms: urticaria, hypotension, bronchospasm (wheezing), angioedema, stridor, abdominal pain, localized edema on the eyes and lips

• preventive measures: pre-medicate with antihistamines, prednisone or parenteral steroids

• for reactions that are severe and unresponsive to pre-meds, provide washed red cells, washed or PAS-C plateletpheresis, SD plasma and/or IgA-deficient blood products

• treatment: stop transfusion; give IV fluids, epinephrine, antihistamines, corticosteroids and beta-2 agonists

anaphylactoid/anaphylactic

which form of an acute transfusion reaction is best described below:

• tends to occur in recipients who have had multiple transfusions and multiple pregnancies

• as a temperature increase of ≥ 1 ºC (2 ºF) above the pre-transfusion temperature and ≥ 38 ºC (100.4 ºF), without signs of hemolysis

• fever may be observed any time during or up to 4 hours after transfusion

• most likely caused by antibodies in the recipient’s plasma reacting against antigens present on donor’s WBCs and/or platelets; or by cytokines released from WBC and platelets into the donor plasma during product storage

• signs and symptoms: fever, chills, rigors, headache, vomiting

• preventive measures: transfuse leukocyte-reduced blood products, PAS-C plateletpheresis, and premedicate with anti-pyretics (acetaminophen) in patients with history

• if severe, provide washed cellular products

• treatment: antipyretic medication (acetaminophen, no aspirin)

• diagnostic testing: rule out hemolysis (DAT, inspect for hemoglobinemia, repeat patient ABO)

  • rule out bacterial contamination if indicated, HLA antibody screen

febrile non-hemolytic transfusion reaction (FNHTR)

which form of an acute transfusion reaction is best described below:

• caused by transfusion of bacterially contaminated blood products due to introduction of skin flora during collection, unrecognized asymptomatic bacteremia in donor or contamination during component processing

• platelets are more likely to be contaminated than red cell products

• usually occurs during or shortly after transfusion

• fever is usually high, ≥ 38.5 ºC (101.3 ºF)

• signs and symptoms: fever, chills/rigors, hypotension, nausea/vomiting, an increase of 2 ºC (3.6 ºF) over the pre-transfusion temp

• preventive measures: blood collection facilities must perform health screening history of donors, pay meticulous attention to phlebotomy site, perform bacterial testing of all plateletpheresis units as require, and removal from inventory other products from same implicated donation

• blood bank must examine unit prior to transfusion for any signs of bacterial contaminations

• transfusionist must change blood tubing every 4 hours, hang blood promptly (within 30 minutes of issue and finish within 4 hours), and observe prompt recognition and reporting of suspected septic reactions

• treatment: broad-spectrum antibiotics

• diagnostic testing: gram stain and culture of implicated donor unit, culture of patient sample, and rule out hemolysis (DAT, inspect for hemoglobinemia, repeat patient ABO)

transfusion associated sepsis (bacterial contamination)

which form of an acute transfusion reaction is best described below:

• rapid destruction of RBCs during, immediately after, or within 24 hours of cessation of transfusion

  • clinical and laboratory signs of hemolysis are present

  • severity related to amount of blood infused; reactions possible with as little as 10 – 15 ml RBCs

  • caused most often by pre-existing antibodies in the recipient reacting with the donor ABO or other antigens

  • rarely, it is caused by transfusion of ABO incompatible plasma, usually platelets, with the donor antibodies reacting with the recipient’s RBCs

  • caused by non-immune etiologies such as concurrent medications, use of blood warmer or infusion pump, incompatible solutions, bacterial contamination, or improper blood storage

• signs and symptoms: fever generally defined as ≥ 1 ºC (2 ºF) rise in temperature to ≥ 38 ºC (100.4 ºF), the most common sign of HTR, chills, hemoglobinuria, hypotension, renal failure with oliguria, hemorrhage (DIC), back pain, pain along infusion site, anxiety

acute hemolytic transfusion reaction (AHTR)

which form of an acute transfusion reaction is best described below:

• preventive measures:

  • follow all patient and specimen identification procedures scrupulously to ensure proper identification at time of specimen collection and at infusion of blood product

  • perform all pre-transfusion serological testing according to policy and procedure

  • retype donor unit as required, observe patient closely for first 15 minutes

  • give transfusion slowly for first 15 minutes

  • second, confirmatory ABORh of the patient required on separately collected specimen on all patients

  • use barrier methods such as blood product administration module (BPAM) to exactly match the patient to the scanned donor unit

  • phenotype matching if needed

  • transfuse ABO plasma compatible platelets or low titer isohemagglutinin group O platelets or PAS- C group O platelets

  • document all events in an error tracking system

• treatment: stop transfusion, keep urine output >1 mL/kg/hr with fluids and IV diuretics, analgesics, Pressors for hypotension, Hemostatic components (platelets, plasma or cryoprecipitate) for bleeding

• diagnostic testing: clerical check, DAT, visual inspection (free Hgb)

  • repeat patient ABO, on pre and post-transfusion samples

  • further tests as indicated to define possible incompatibility (such as antibody screen, compatibility testing, antibody ID, elution)

  • further tests as indicated to detect hemolysis (H&H, LDH, Total and Direct bilirubin, reticulocyte count, haptoglobin and urinalysis)

acute hemolytic transfusion reaction (AHTR)

which form of an acute transfusion reaction is best described below:

• an underreported adverse reaction to transfusion

• a condition where the recipient cannot effectively process the infusion volume due to high rate (rapid transfusion) and/or large volume of the infusion or an underlying cardiac or pulmonary pathology

• can occur after only a few mL up to 6 hours after transfusion

• fairly common among children and elderly, chronic anemic patients, patients with compromised cardiopulmonary system and patients with compromised renal function

• signs and symptoms: acute respiratory distress, dyspnea or tachypnea, tachycardia, elevated BP, acute or worsening pulmonary edema, evidence of positive fluid balance, JVD, S2 heart sound (gallop), fever (not a universally accepted symptom, but a common one), chest tightness, elevated BNP, elevated CVP, distended neck veins

• preventive measures: treating or ordering clinician to alert Blood Bank if the recipient is a “volume sensitive” patient

  • good Patient Blood Management by using “transfuse and assess” instead or ordering multiple units

  • diuretic measures, monitor fluid input/output, adjust volume and rate (slow infusion), limit non-blood fluids during transfusion, split or divide units if possible

• treatment: stop transfusion, place the patient in a sitting position if possible, give O2 if clinically warranted (rarely may require ventilator support), administer diuretics if not contraindicated, and if symptoms persist, therapeutic phlebotomy is appropriate

• diagnostic testing: pulse oximetry (low and/or dropping), chest x-ray (edema), rule out pneumothorax, effusion, other causes of distress, differentiate with TRALI, BNP or NT Pro-BNP

  • recipients will have a post-transfusion brain natriuretic peptide (BNP) level of at least 100 pg/mL, and a post-transfusion:pre-transfusion BNP ratio of 1.5

  • an arterial blood gas study may be appropriate to differentiate TACO from TRALI

transfusion associated circulatory overload (TACO)

which form of an acute transfusion reaction is best described below:

• syndrome that is clinically similar to adult respiratory distress syndrome (ARDS), but usually resolves in 96 hours

• presents as an acute hypoxemia with PaO2/fraction of inspired oxygen (FIO2) ratio of 300 mmHg or less and/or SpO2 < 90% on room air, combined with chest x-ray showing bilateral infiltrates in the absence of left atrial hypertension (i.e., circulatory overload).

  • onset is abrupt in association with transfusion

  • can occur only after a few mL, as small as 15 ml, up to 6 hours after, with most cases becoming evident within 1 – 2 hours

• believed to be an immunologic reaction where the donor HLA and/or granulocyte antibodies react with neutrophils in the recipient’s lung, resulting in neutrophil activation which alters the vascular permeability, ending in pulmonary edema

• all plasma-containing blood products, including frozen plasma, platelets, cryoprecipitate and RBCs have been implicated

• patients who have experienced an episode are NOT at greater risk for a second episode

• signs and symptoms: acute onset, hypoxemia, respiratory failure, hypotension, fever, bilateral pulmonary edema, pink frothy secretions in intubated patients, cyanosis, and no evidence of circulatory overload/left atrial hypertension

  • a transient neutropenia and leukopenia may also be observed

transfusion related acute lung injury (TRALI)

the following three main conditions need to be distinguished from ____:

• anaphylactic transfusion reactions

• TACO

• transfusion-related sepsis.

transfusion related acute lung injury (TRALI)

fever and pulmonary edema are NOT associated with anaphylactic reactions. true or false?

true

key distinctions between TACO and TRALI are that the pulmonary edema in ____ is cardiogenic and responsive to diuretics.

transfusion associated circulatory overload (TACO)

high fever with hypotension and vascular collapse are NOT prominent features of transfusion-related sepsis. true or false?

false

respiratory distress is frequently associated with septic reaction. true or false?

false

there is no method to predict which patients will develop TRALI. true or false?

true

there are no confirmatory or exculpatory laboratory findings; TRALI is largely a diagnosis of ____.

exclusion

the following are all _____ transfusion reactions (8):

• allergic reaction – mild, urticarial

• allergic reaction – anaphylactoid/anaphylactic

• febrile non-hemolytic transfusion reaction (FNHTR)

• transfusion associated sepsis (bacterial contamination)

• acute hemolytic transfusion reaction (AHTR)

• transfusion associated circulatory overload (TACO)

• transfusion related acute lung injury (TRALI)

acute

the most common ____ transfusion reactions are delayed hemolytic transfusion reaction (DHTR) and delayed serological transfusion reaction (DSTR).

delayed

which form of an delayed transfusion reaction is best described below:

• development of antibodies to RBC antigens between 24 hours and 28 days after completion of transfusion can result in an asymptomatic case(s)

• the hemolysis associated similar to AHTR but milder

  • some patients may develop jaundice and leukocytosis

  • the hemolysis is primarily extravascular; hemoglobinuria may occur in rare cases, acute renal failure and DIC are not generally present. In some cases, the hemolysis occurs without causing clinical symptoms

• signs and symptoms: fever, decreasing hemoglobin, new positive antibody screening test, mild jaundice

• these patients presents with unexplained anemia or do not experience the expected increase in hemoglobin following transfusions

• preventive measures:

  • caused by known antibody specificities can be prevented by the transfusion of antigen negative RBCs

  • it is essential to obtain patient prior transfusion records (history) because of antibody evanescence

delayed hemolytic transfusion reaction (DHTR); delayed serological transfusion reaction (DSTR)

which form of an delayed transfusion reaction is best described below:

• the clinical manifestations typically begin 8 – 10 days after transfusion, although symptoms can occur as early as 3 days and as late as 30 days

• signs and symptoms: rash, fever, enterocolitis with watery diarrhea, elevated liver function tests and pancytopenia

  • in severe cases, bullae may develop

• may lead to profound marrow aplasia, with a mortality rate higher than 90%

• the time course of the reaction is rapid; death typically occurs within 1 - 3 weeks of the first symptoms

• preventive measures: the only reliable way to prevent this is by irradiation of cellular blood products

transfusion associated graft vs host disease (TAGVHD)

there are three (3) requirements for _____ to develop in a patient:

• there must be differences in the HLA antigens expressed between the donor and the recipient, immunocompetent cells must be present in the component, and the host must be incapable of rejecting the immunocompetent cells

• the risk depends on the degree of recipient immunodeficiency and the number of viable T lymphocytes in the blood product

• the number of viable lymphocytes in a transfusion can be affected by age, leukocyte reduction status and irradiation status of the blood product

transfusion associated graft vs host disease (TAGVHD)

which form of an delayed transfusion reaction is best described below:

• commonly associated with transfusion of RBCs or whole blood; however, it has also been associated with platelet or plasma transfusion

• this reaction is related to the presence of platelet specific alloantibodies in a patient who has previously been exposed to platelet antigens via pregnancy or transfusion

• the female to male ratio of affected patients is 5:1

• signs and symptoms: patients typically present with wet purpura and thrombocytopenia within 2 weeks after a transfusion

• the platelet count is usually <10,000/uL

• bleeding from mucous membranes and the gastrointestinal and urinary tract is common

  • mortality is primarily due to intracranial hemorrhage

post transfusion purpura (PTP)

which form of an delayed transfusion reaction is best described below:

• the production of an antibody against antigens that comes from a different person of the same species

  • this can occur against antigens in the “Human Leukocyte Antigen” (or HLA) system

  • Anti-HLA antibodies are most commonly induced by multiple pregnancies, though transfusion of blood products (especially those given before the near-universal implementation of leukocyte reduction) may also be a culprit

• signs and symptoms: platelet refractoriness

• preventive measure: provide leukocyte-reduced and irradiated cellular blood products.

• treatment: same as preventive measures and avoid unnecessary transfusions

alloimmunization , HLA

which form of an delayed transfusion reaction is best described below:

• human lacks the physiologic means to excrete excess iron; persistent increase in iron influx after transfusion of ≥20 units of RBCs

• when the accumulation of iron overwhelms the capacity for safe storage, tissue damage can ensue

  • as iron accumulates in the reticuloendothelial system, liver, heart, spleen and endocrine organs lead to tissue damage

• signs and symptoms: diabetes, cirrhosis, cardiomyopathy

• preventive measures: avoid unnecessary transfusions

• treatment: prevent the accumulation of iron stores through the use of iron chelators or therapeutic phlebotomy can reduce these complications

• diagnostic testing: Liver and cardiac iron concentration (MRI), Serum ferritin, Liver enzymes, Endocrine function tests

iron overload