Hemolytic Transfusion Reactions

and
Hemolytic disease of newborn
ADVERSE EFFECTS OF TRANSFUSION

➢ Blood transfusion is an irreversible event that carries potential

benefits and risks to the recipient

➢ “transfusion reaction” is any unfavorable transfusion-related event

occurring in a patient during or after transfusion of blood
components
HEMOLYTIC TRANSFUSION REACTIONS (HTR)

➢ occur either at the time of transfusion (immediate) or a few days after

transfusion (delayed)

➢ Common causes:
✓ transfusion of incompatible RBC
✓ transfusion of ABO-incompatible plasma containing products
✓ chemically or physically induced
IMMEDIATE HEMOLYTIC TRANSFUSION REACTION (IHTR)

➢ occurs very soon after or during transfusion of incompatible RBCs

➢ Reaction period: occur within minutes after the start of transfusion or within
a few hours after the transfusion is completed.
➢ The RBCs are rapidly destroyed releasing hemoglobin and RBC stromata
into the circulation
➢ signs and symptoms can occur within minutes after starting the transfusion
➢ Common signs and symptoms:
✓ Hemoglobinuria
✓ abnormal bleeding at the surgical wound site
✓ hypotension
➢ ABO-incompatible transfusions may be life-threatening, causing shock,
acute renal failure, and disseminated intravascular coagulation (DIC)
PATHOPHYSIOLOGY
✓ The underlying cause of IHTR is transfusion of an incompatible whole blood
or RBC product to a recipient
✓ Common antibodies associated with IHTR: anti-A, anti-Kell, anti-Jka, and
anti-Fya

THERAPY AND PREVENTION

✓ Patient care in IHTR is focused on prevention and supportive measures

✓ monitor the patient closely for risk factors to DIC, hypotension, and acute
renal failure
✓ renal diuresis and to prevent renal failure
✓ improve renal blood flow and induce diuresis
✓ Hypotension
✓ Blood component fresh frozen plasma (FFP), cryoprecipitate, and platelet
concentrates
✓ Extravascular IHTR usually does not require therapeutic intervention
DELAYED HEMOLYTIC TRANSFUSION REACTION (DHTR)

➢ result of an anamnestic response in a patient who has previously been

sensitized by transfusion, pregnancy, or transplant

➢ appear 7–10 days post-transfusion

➢ Clinical signs and symptoms are usually mild; severe DHTR cases and
fatalities are uncommon. Unexpected or unexplained decreases in
hemoglobin or hematocrit values following transfusion should be
investigated as a possible delayed hemolytic transfusion reaction
PATHOPHYSIOLOGY

➢ Two different types of DHTR have been identified:

✓ Secondary (anamnestic) response to transfused RBCs
✓ Primary alloimmunization

➢ SIGNS AND SYMPTOMS

✓ mild than IHTR because of the extravascular hemolysis and may be
undetected clinically
✓ In DHTR, complement is not activated; therefore, no intravascular
hemolysis occurs
THERAPY AND PREVENTION

✓ Renal function can be supported with intravenous fluid therapy to maintain a

normovolemic status
✓ Only symptomatic anemia should be treated with RBC
✓ Clinical signs and symptoms of hemolysis or DIC should be monitored to
reduce the risk of renal failure
IMMEDIATE NON-HEMOLYTIC TRANSFUSION REACTIONS

A. FEBRILE NONHEMOLYTIC TRANSFUSION REACTION (FNHTR)

➢ Occurs in about 1 percent of transfusions
➢ Along with allergic reactions, FNHTR is one of the most common adverse
transfusion reactions
➢ Associated with: 10C temperature rise having no medical explanation other
than blood component transfusion

➢ PATHOPHYSIOLOGY
✓ caused by: leukocyte antibodies in the patient’s plasma
✓ directed against antigens present on monocytes, granulocytes, or
lymphocytes
✓ Alloimmunization by prior blood transfusion, tissue transplantation, or
pregnancy is the causative stimulus for antibody formation
➢ SIGNS, SYMPTOMS
✓ fever with chills and rigors, headache, cold feeling, mild dyspnea, and mild
nausea/vomiting

➢ THERAPY AND PREVENTION

✓ Blood component: Leukoreduced-RBC’s
B. ALLERGIC TRANSFUSION REACTION

➢ allergic reaction is of the immediate hypersensitivity type

➢ Allergic reactions are generally mild to moderate reactions and refer to
signs and symptoms limited to the skin and gastrointestinal tract.

➢ Two mechanisms:
✓ The donor plasma has a foreign protein (allergen) in which immunoglobulins
in the patient’s plasma react (IgE, IgG or both)
✓ The donor plasma has reagins (IgE or IgG or both) that combine with
allergens in the patient plasma.
➢ SIGNS, SYMPTOMS
✓ urticaria, pruritus, and localized or generalized rash.
✓ oropharyngeal or upper respiratory symptoms

➢ THERAPY AND PREVENTION

✓ In patients with histories of repeated allergic reactions, plasma is often
removed from blood components
C. ANAPHYLACTIC AND ANAPHYLACTOID REACTION

➢ are of the immediate hypersensitivity type of immune system response

➢ Anaphylaxis can range from mild urticaria (hives) and pruritus to severe
shock and death. Any organ of the body can be involved, such as the lungs,
blood vessels, nerves, skin, and gastrointestinal tract.

➢ PATHOPHYSIOLOGY
✓ Associated with: IgA deficient patients who have developed anti-IgA
antibodies (transfusion or pregnancy)
✓ Anaphylactic: seen in patients deficient in IgA who have class specific IgA
antibodies
✓ Anaphylactoid: seen in patients having normal levels of IgA but a limited
type-specific anti-IgA that reacts with light chain (kappa or lambda) of the
donor’s IgA.
D. TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)

➢ Other names: Noncardiogenic, Pulmonary edema (NCPE), Pulmonary

Hypersensitivity Reaction, Allergic Pulmonary Edema

➢ PATHOPHYSIOLOGY
✓ Most consistent finding is leukocyte antibodies in donor or patient
plasma
✓ Anti-leukocyte antibodies in donor or patient plasma could initiate
complement-mediated pulmonary capillary endothelial injury
➢ SIGNS, SYMPTOMS
✓ TRALI is usually characterized by chills, cough, fever, cyanosis,
hypotension, and increasing respiratory distress shortly after transfusion
of blood component volumes that usually do not produce hypervolemia.

➢ THERAPY AND PREVENTION

✓ adequate respiratory and hemodynamic supportive treatment
✓ TRALI pulmonary infiltrates usually clear after several days
✓ If TRALI is caused by patient anti-leukocyte antibodies (Leukoreduced
RBC, platelets)
E. TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO)

➢ Transfusion-associated circulatory overload (TACO) is a good example of

an iatrogenic transfusion reaction
➢ Patients at significant risk include children, elderly patients, and patients
with chronic normovolemic anemia, cardiac disease, thalassemia major, or
sickle cell disease

➢ PATHOPHYSIOLOGY
✓ transfusion of a unit at too fast a rate
✓ Hypervolemia associated with transfusion leads to congestive heart failure
and pulmonary edema
➢ SIGNS AND SYMPTOMS
✓ dyspnea, coughing, cyanosis, orthopnea, chest discomfort, headache,
restlessness, tachycardia, systolic hypertension (greater than 50mmHg
increase), and abnormal electrocardiogram results

➢ Therapy and Prevention

✓ Rapid reduction of hypervolemia and patient respiratory and cardiac support
are primary goals
✓ Oxygen therapy and intravenous diuretics should be used appropriately
✓ If more rapid fluid volume reduction is necessary, therapeutic phlebotomy
can be used
✓ Cardiac arrhythmias or decreased myocardial function should be corrected
✓ Usual rate of transfusion: 200 mL/hr; for TACO: <100 mL/hr
F. BACTERIAL CONTAMINATION REACTIONS

➢ Bacterial contamination of blood components usually occurs at the time of

phlebotomy, during the component preparation or processing, or during
thawing of blood components in water baths
➢ septic reaction can have a rapid onset and lead to death
➢ most are caused by blood components contaminated by: Yersinia
enterocolitica (Pseudomonas, E.coli)

➢ PATHOPHYSIOLOGY
✓ Transfusion reactions attributed to bacterial contamination reactions are
commonly caused by endotoxin produced by bacteria capable of growing in
cold temperatures (psychrophilic)
✓ Bacteremia
➢ SIGNS AND SYMPTOMS
✓ septic reactions usually appear rapidly during transfusion or within about 30
minutes after transfusion
✓ dryness and flushing of the patient’s skin
✓ fever, hypotension, shaking, chills, muscle pain, vomiting, abdominal
cramps, bloody diarrhea, hemoglobinuria, shock, renal failure, and DIC

➢ THERAPY AND PREVENTION

✓ Broad-spectrum antibiotics should be immediately administered
intravenously
DELAYED NON HEMOLYTIC TRANSFUSION REACTIONS

A. ALLOIMMUNIZATION
➢ may result from prior exposure to donor blood components
➢ As an adverse effect of blood component transfusion, alloimmunization is a
significant complication
➢ Even very small amounts of donor antigenic RBCs can elicit an alloimmune
response

➢ PATHOPHYSIOLOGY
✓ exposure to foreign antigens by blood component transfusions, tissue
transplantation, or pregnancy that may cause a patient’s immune system to
produce antibodies
➢ SIGNS AND SYMPTOMS
➢ Clinical signs and symptoms may be mild, including slight fever and falling
hemoglobin and hematocrit levels; or severe, including platelet
refractoriness with bleeding

➢ THERAPY AND PREVENTION

✓ Treatment depends on the type and severity of the transfusion reaction.
Most reactions are mild and often missed clinically.
B. POST-TRANSFUSION PURPURA

➢ rare complication of blood transfusion, usually involving platelet

concentrates

➢ PTP is characterized by a rapid onset of thrombocytopenia as a result of

anamnestic production of platelet alloantibody.

➢ Usually, the implicated alloantibodies are directed against human platelet

antigens HPA-1 or HPA-3a

➢ Well defined cases of PTP are women

➢ SIGNS AND SYMPTOMS
✓ Purpura and thrombocytopenia occur about 1 to 2 weeks after
transfusion
✓ Thrombocytopenia can be severe, with platelet counts of less than
10,000
✓ bleeding from mucous membranes , GI bleeding, and hematuria

➢ THERAPY AND PREVENTION

✓ intravenous immunoglobulin (IVIG)
C. TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE (TA-
GVHD)

➢ complication of blood component therapy or bone marrow/hematopoietic

and solid organ transplantation
➢ Members of the at-risk:
✓ patients underwent cardiac surgery involving cardiopulmonary bypass
✓ patients experiencing lymphopenia or bone marrow suppression
✓ fetuses receiving intrauterine transfusions
✓ newborn infants receiving exchange transfusions
✓ patients with solid tumors undergoing chemotherapy
✓ individuals with congenital immunodeficiency syndromes, patients with
certain hematologic and oncologic disorders
✓ Patients receiving blood components from blood relatives
➢ PATHOPHYSIOLOGY
✓ TA-GVHD is caused by a proliferation of T-cell lymphocytes derived
from the donor blood that is responding immunologically to major and
minor histocompatibility antigens in the patient

➢ SIGNS AND SYMPTOMS

✓ typical skin rash see, diarrhea, fever, enlarged liver, elevated liver
enzymes, marrow aplasia, pancytopenia.
✓ rash, fever, increased liver enzymes, pancytopenia, and diarrhea.

➢ THERAPY AND PREVENTION

✓ corticosteroids, cyclosporine,methotrexate, azathioprine, and
antithymocyte globulin
✓ Blood component: Irradiated RBC
D. IRON OVERLOAD

➢ long-term complication of RBC transfusion is iron overload (aka transfusion

hemosiderosis)
➢ Patients with certain diseases are chronically dependent on RBC
transfusion support as part of therapy (congenital hemolytic anemias,
aplastic anemia, chronic renal failure)

➢ PATHOPHYSIOLOGY
✓ Accumulated iron begins to affect the function of heart, liver, and endocrine
glands.
➢ SIGNS AND SYMPTOMS
✓ muscle weakness, fatigue, weight loss, mild jaundice, anemia, mild
diabetes, and cardiac arrhythmias

➢ THERAPY AND PREVENTION

✓ Removal of accumulated tissue iron stores without lowering patient
hemoglobin levels is the treatment of choice
✓ Desferrioxamine
E. IMMUNOSUPPRESSION

➢ Immunosuppression is a generalized, nonspecific effect that diminishes the

activity of the recipient’s immune system soon after blood component
transfusion
HEMOLYTIC
DISEASE OF THE
NEWBORN (HDN)
HEMOLYTIC DISEASE OF THE NEWBORN (HDN)

➢ destruction of the red blood cells (RBCs) of the fetus and neonate by
antibodies produced by the mother
➢ Signs and symptoms:
✓ Less severe form: Mild anemia
✓ Sever form: Icterus gravis neonatorum (Kernicterus)
✓ Intrauterine death: Hydrops fetalis
❖ Oedematous, ascites, bulky swollen & friable placentA
❖ Pathophysiology:
 Extravascular hemolysis with extramedullary erythropoiesis
 Hepatic and cardiac failure
Rh HEMOLYTIC DISEASE OF THE NEWBORN

➢ More severe than ABO HDN

➢ Caused by maternal antibodies (anti-D, anti-c, anti-E) directed against
antigens present on (D antigen) fetal red cells
➢ Mother: Rh-Negative
➢ Fetus: Rh-positive

➢ Firstborn infant is usually unaffected

➢ All subsequent offspring inheriting D-antigen will be affected in case of anti-
D HDN
RECOMMENDED OBSTETRIC PRACTICE FOR HDN

➢ History; including previous pregnancies or any disease needing blood

transfusion
➢ ABO and Rh testing
➢ Antibody screening and identification
✓ To detect clinically significant IgG alloantibodies which reacts at 370C
✓ Repeat testing required at 24 or 28 weeks if first test negative
➢ Parental phenotype
➢ Amniocentesis and cordocentesis
✓ Concentration of bilirubin
✓ Spectrophotometric scan
❖ Indirect method: Increasing or un-change OD as pregnancy
advance shows worsening of the fetal hemolytic disease
(OD=450nm)
➢ Fetal blood sample can be taken and tested for: Hb, Hct, blood grouping,
DAT
PREVENTION OF Rh HDN

➢ Prevention by active immunization

➢ Use of RhIg (Rhogam)
✓ Purified anti-D
✓ After 1st pregnancy
✓ Administered within 72 hours after delivery
✓ Mother must be Rh-negative with no anti-D in the circulation
ADMINISTRATION OF RhIg

A. Full dose RhIg

✓ 30 ug of anti-D; protects up to 30 mL of D positive WB and 15 mL PRBCs
✓ Given after 12 weeks of gestation

B. Mini/Microdose RhIg
✓ 50 ug of anti-D; protects up to 5 mL D positive WB and 2. mL PRBCs
✓ Given before 12 weeks of gestation
 To determine the number of RhIg vials to be given:

1. KLEIHAUER BETKE TEST

✓ Fetal hemoglobin (HbF) resists acid elution
✓ Fetal cells: Deep pink
✓ Maternal cells: ghost cells
✓ Result will be: % fetal cells
✓ After 2,000 cells are counted, the percentage of fetal cells is determined, and the
volume of fetal hemorrhage is calculated using this formula:

Number of fetal cells × Maternal blood volume

-------------------------------------------------------------- = Volume of fetomaternal hemorrhage
Number of maternal cells
2. COMPUTE FOR NUMBER OF RHIG VIALS
# of RhIg vials: volume of FMH/30 mL
***volume of FMH: % fetal red cells x 50 (maternal blood volume)
Ex.
% fetal cells: 3%
Volume of FMH= 150
# of RhIg vials: 150/30= 5 vials of RhIg + 1
End!

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