rainwater@mymelody.com || 1st semester, AY 2011-2012

24 – Blood Transfusion Reactions

Blood Transfusion Reactions

• Any adverse response to blood component transfusion

• Is considered with any unexpected or untoward sign or symptom occurring during or shortly after transfusion of blood or one of its components

Classifications of BTR • Immediate/Acute vs. Delayed • Immunologic vs. Non-Immunologic • Non-infectious vs. Infectious

Acute (<24 hours) Immunologic Transfusion Reactions 1. Febrile, hemolytic 2. Febrile/chill, non-hemolytic 3. Urticarial/mild allergic 4. Anaphylactic 5. Transfusion-related acute lung injury

Acute, Non-Immunologic 1. Bacterial sepsis 2. Circulatory overload 3. Air embolism 4. Hypotension associated with ACE inhibitors 5. Non-immune hemolysis 6. Adverse sequelae of massive transfusion

Delayed, Immunologic 1. Alloimmunization, RBC antigens 2. Alloimmunization, HLA antigens 3. Hemolytic 4. Graft vs. Host disease 5. Post-transfusion Purpura 6. Immunomodulation

Delayed, Non-Immunologic 1. Iron overload

Acute/Severe Delayed/Potentially Severe Other Immunologic Acute hemolytic transfusion reaction

Sickle cell hemolytic transfusion syndrome

Anaphylaxis Transfusion-related acute lung injury

Delayed hemolytic transfusion reaction (RBC antigen alloimmunization) Human leukocyte antigen alloimmunization Transfusion-associate graft-versus-host disease

Mild allergic/urticarial Post-transfusion

purpura Febrile non-hemolytic

transfusion reaction Non-immunologic Bacterial sepsis

Air embolism Circulatory overload

Viral transmission Parasitic infection Hemosiderosis

ACE inhibitor-related hypotension

Clinical Manifestations of BTR • Fever with or without chills

o Fever defined as a rise of at least 1°C during transfusion of blood or blood components, or within 1-2 hours thereafter

• Shaking chills with or without fever • Pain at infusion site or in the chest, abdomen, or

flanks • Blood pressure changes, usually acute, either

hypertension or hypotension • Respiratory distress – dyspnea, wheezing, tachypnea

or hypoxemia • Skin changes – urticarial, pruritus, flushing, localized

edema • Nausea, with or without vomiting • Darkened urine or jaundice • Bleeding or other manifestations of a consumptive

coagulopathy

Acute (<24 hours) Immunologic Transfusion Reactions

Febrile, Hemolytic Transfusion Reaction (HTR) • Etiology: red cell incompatibility • Presentation: fever, chills, hemoglobinuria,

hypotension, renal failure, DIC, back pain, pain along infusion vein, anxiety

• Management: o Stop transfusion ASAP o Institute measures to correct shock,

maintain renal circulation, and correct bleeding diathesis

• Laboratory diagnosis

1. Evidence of hemolysis – hemoglobinemia and/or hemoglobinuria

2. Blood group incompatibility 3. Positive DAT

FHTR: Mechanism

Transfusion of Incompatible Blood

Ag-Ab interaction

Complement activation

Promotion of inflammatory

events Enhanced

phagocytosis Cell-membrane

modification causing lysis

Extravascular and intravascular

hemolysis

Cytokine production

Fever Hypotension

Coagulation activation

DIC

rainwater@mymelody.com || 1st semester, AY 2011-2012

Febrile, Non-Hemolytic Transfusion Reaction (FNHTR)

• Etiology:

1. Antibodies to donor WBC’s

2. Accumulated cytokines in platelet units

• Presentation: temperature rise >1°C associated with transfusion without any other explanation; sometimes, no fever, only chills or rigors

• Evaluation: rule out FHTR

• Management: antipyretic premeds (may not always work)

o Leucocyte-reduced component

o Removal of plasma

Urticarial/Mild Allergic Transfusion Reactions

• Etiology: release of histamines and other anaphylatoxins from ab reactions to donor plasma proteins

• Presentation: urticaria, pruritus, flushing, localized erythema near IV site

• Evaluation and management: o Usually resolves with D/C of BT,

antihistamines

o BT may be resumed at slower rate, close monitoring

• Prevention: premedication with antihistamines

Anaphylactic Transfusion Reactions

• Etiology: Ab interaction to donor plasma (IgE-mediated response to transfused protein)

• Presentation: sudden onset of flushing, chills, vomiting, diarrhea, hypotension, urticarial, bronchospasm (respiratory distress, wheezing), local edema, anxiety, no fever

• Evaluation: rule out HTR

• Management: D/C BT

o Standard measures for anaphylaxis – epinephrine, corticosteroids, circulatory support

Transfusion-Related Acute Lung Injury (TRALI)

• Etiology:

1. Reaction of antineutrophil Abs and/or anti-HLA Class I and II Abs to the corresponding antigens between donors and recipients, occurring in the pulmonary vasculature and resulting in endothelial damage. Transfused donor antibodies are responsible. Multiparous donors and previously-transfused donors are often implicated (likely allouimmunized).

2. “2-Hit Theory” – interaction between primed pulmonary leukocytes in patients with underlying illness (pro-inflammatory states) and biologically active response modifiers introduced by transfusion.

• Presentation: o Evidence of acute lung injury (ALI): Acute

onset, hypoxemia (O2 sat’n <90% of room air), bilateral infiltrates on CXR in the absence of lung failure

o TRALI: new ALI occurring during transfusion or within 6 hours of completion; no other temporally associated ALI risk factors

o Reaction typically includes fever, chills and hypotension within 1-2 hours of transfusion

o Hypoxemia may require intubation

o Symptoms subside rapidly, CXR becomes normal/returns to baseline within 96 hours, clinical recovery in 48-96 hours

• Evaluation: rule out HTR; CXR

• Management: D/C BT; supportive care

• Prevention: defer implicated donors

Acute, Non-Immunologic

Transfusion-Associated/Bacterial Sepsis

• Etiology: bacterial contamination

o Subclinical/unrecognized bacteremia in the donor, skin contaminants at phlebotomy sites

o RBC contaminants: Yersinia Pseudomonas

o Platelets – most susceptible to bacterial growth

Common infecting agents: Staphylococcus

Streptococci Propionebacterium

• Presentation: fever, chills, hypotension, nausea, vomiting, diarrhea, hemolysis, rapid progression to circulatory compromise, renal failure, shock, DIC

• Evaluation: rule out HTR; culture of component, patient culture; Gram stain

• Management: o Broad spectrum antibiotics

o Treat complications

Circulatory Overload

• Etiology: volume overload

Patients at risk: children, elderlies with cardiac, renal, pulmonary compromise

Patients in states of plasma volume expansion (normovolemic chronic anemia, thalassemia, etc.)

• Presentation: cough, dyspnea, cyanosis, orthopnea, chest discomfort, rales, headaches, distention of jugular veins, restlessness, tachycardia

• Evaluation: CXR

• Management: D/C BT; supportive care (O2, diuresis, phlebotomy 250 increments)

• Prevention: transfuse in aliquots

Air Embolism

• Etiology: air infusion via line (air tends to lodge in the RV and prevents air from entering PA)

• Presentation: sudden shortness of breath, acute cyanosis, pain, cough, arrhythmia

• Evaluation: X-ray for intravascular air

• Management: place patient of left side with legs elevated above chest and head

rainwater@mymelody.com || 1st semester, AY 2011-2012

Hypotension associated with ACE inhibitors

• Etiology: transient hypotension caused by activation of bradykinin. Associated with use of bedside reduction filters and apheresis procedures – ACE inhibitors block normal metabolism of bradykinin

• Presentation: flushing, hypotension

• Evaluation: rule out anaphylaxis, AHTR, TRALI, bacterial contamination

• Management: o Withdraw ACE

o Avoid albumin volume replacement in plasmapheresis

o Avoid use of bedside leukocyte filters

Non-immune-mediated hemolysis

• Etiology: physical/chemical destruction of blood (heating, freezing, drugs, wrong priming solution, small bore needles, pressure pumps)

• Presentation: intravascular/extravascular hemolysis

• Evaluation: R/O HTR

• Management: identify and eliminate cause

Complications of massive transfusion (hypocalcemia, hypothermia)

• Definition: administration of blood components over a 240-hour period in amounts that equal or exceed the total blood volume of the patient

• Adverse sequelae: 1. Citrate toxicity – hypocalcemia

2. Hypothermia – cardiac arrhythmia

3. Hypo/hyperkalemia

4. Dilutional coagulopathy – microvascular bleeding

5. DIC

Delayed, Immunologic

Alloimmunization, RBC antigens, HLA Antigens

• Etiology: immune response to foreign antigens on RBC’s, or WBC’s and platelets (HLA)

• Presentation: positive blood group antibody screening test

o Platelet refractoriness, delayed hemolytic reaction, hemolytic disease of the newborn

• Evaluation: antibody screen, DAT

• Management: o Avoid unnecessary transfusions

o Use leukocyte-reduced blood products

Delayed Hemolytic Transfusion Reaction • Etiology: repeat stimulation and accelerated

(anamnestic) appearance of the antibody in a previously alloimmunized patient upon reexposure to the offending antigen

• Presentation: fever, decreasing Hgb, jaundice, DAT positive

• Evaluation: antibody screen, DAT, tests for hemolysis • Management:

o Identify antibody o Transfuse compatible cells as needed

Transfusion-Associated Graft-versus-Host Disease (TAGVHD)

• Etiology: lymphocytes from an immune competent donor engraft recognize the patient’s antigens as foreign and mount an attack on host tissues

• Presentation: rash, diarrhea, hepatitis, mucositis, and pancytopenia; mortality approaches 90%

• Evaluation: skin biopsy, HLA typing

• Management: supportive; no specific measures have been proven effective

• Prevention: gamma irradiation of blood components

Post-transfusion Purpura

• Etiology: recipient platelet antibodies (apparent alloantibody) destroy autologous platelets

• Presentation: abrupt decline in platelet count within days to 2-3 weeks post-BT, usually self-limited, resolves within 2-3 weeks without treatment

• Evaluation: platelet Ab screen and identification

• Management: self-limited, IV Ig

Immunomodulation

• Etiology: incompletely understood – interaction of donor WBC or plasma factors with recipient immune system

• Presentation: increased renal graft survival, infection rate, post-resection tumor recurrence rate (controversial)

• Prevention: o Avoid unnecessary transfusions

o Autologous transfusion

o Leukocyte-reduced red cells and platelets

Delayed, Non-Immunologic

Iron overload: Hemosiderosis

• Etiology: multiple transfusions, typically after 100 RBC units

• Presentation: diabetes, cirrhosis, cardiomyopathy • Evaluation: serum ferritin, liver enzymes, endocrine

function tests • Management: iron chelation – desferrioxamine,

deferiprone

Transfusion-Transmitted Infections

Estimated Risk of Transfusion Transmission of Viral Diseases in the USA with Current Testing HIV 1 and 2 1:2,000,000 – 3,000,000 Hepatitis C 1:2,000,000 – 3,000,000 Hepatitis B 1:200,000 – 500,000 HTLV I and II 1:2,00,000 West Nile Virus Seasonal, regional variability