Acute Transfusion Reactions Clinical Symptoms and Laboratory Investigation

Acute Transfusion Reactions

Types of Transfusion Reactions Acute Hemolytic Febrile Allergic Anaphylactic Transfusion Related Acute Lung Injury (TRALI) Bacterial Contamination (Sepsis) Circulatory Overload

Acute Hemolytic Transfusion Reactions (AHTR) Pathophysiology: -Transfusion of ABO incompatible RBC -Other antibodies -Transfusion of ABO incompatible Plasma Incidence: Acute Hemolytic: 1/6000-1/20,000 Fatal: 1/100,000-1/600,000 5 5

Acute Hemolytic Transfusion Reactions (AHTR) Pathophsiology: When incompatible blood is given, antibodies and complement in the recipient plasma attack the antigens on the donor RBC. Hemolysis ensues The antigen-antibody complex activate the Hageman factor (factor XII), which acts on the kinin system to produce bradykinin Bradykinin increases capillary permeability and dilates arterioles, both which cause hypotension 6 6

Acute Hemolytic Transfusion Reactions (AHTR) Activation of the complement system results in the release of histamine and serotonin from mast cells resulting in bronchospasm. DIC Renal damage occurs for several reasons, blood flow is reduced because of hypotension and renal vasoconstriction, free hemoglobin can cause a mechanical obstruction, and if DIC occurs fibrin thrombi can be deposited in the renal vascular 7 7

Signs and Symptoms of AHTR Fever Chills Nausea and Vomiting Diarrhea Hypotension Flushed appearance and Dyspnea Chest pain and back pain Pt is restless, and has a headache Hemoglubinuria, and possible diffuse bleeding 8 8

Symptoms under GA Many signs and symptoms will be masked by general anesthesia. Hypotension, hemoglobinuria, and diffuse bleeding may be the only clues that a transfusion reaction has occurred. 9 9

Management of AHTR Management has 3 main objectives: 1-Maintenance of systemic blood pressure 2-Preservation of renal function 3-Prevention of DIC 10 10

Therapeutic Approach *Keep urine output >1/ml/kg/hr with fluid & IV diuretic (furosemide) *Analgesic( may need morphine) *Low dose dopamine *Haemostatic components (PlT,Cryo,FFP) for bleeding 11 11

The Most Common Cause of Acute Immediate Intravascular Hemolysis Failure to identify the patient with the donor unit at the time of administration Collecting pre-transfusion specimen from the wrong patient Incorrectly labelled specimens Unlabelled specimens that are labelled after leaving the bedside (in the lab or at the nursing station)

Non immune Hemolysis *Improper shipping or storage temp. * Using small needle size * Improper use of blood warmer * Bacterial contamination 13 13

Febrile Reactions (FNHTR) Definition: *Temperature increase of greater than 1 degree centigrade within 1-2 hours for which no other cause is identifiable. *The response occurs in 0.5-6% of RBCs transfused *Up to30% of PLT transfused 14 14

Symptoms Raises temperature >1°C (fever) Chills with fever Shaking : Raises temperature >1°C (fever) Chills with fever Shaking Antipyretics are drugs that reduce fever (i.e., acetaminophen)

Febrile Reactions (FNHTR) Pathophysiology: 1-Patients who receive multiple transfusions often develop antibodies to the HLA antigens on the passenger leukocytes During subsequent RBC transfusions, febrile reactions may occur as a result of antibody attack on donor leukocytes 2-Generation of leukocyte-derived cytokines during storage 16 16

Febrile Reactions (FNHTR) TREATMENT: *Antipyretic (Acetaminophen, no aspirin) Prevention: 17 17

Minor Allergic Reactions *Soluble antigens in the donor plasma react with IgE bound to mast cells causing histamine release. *Allergic reactions can cause urticarial reactions in 1-3% of all transfusions *The pt. may have itching, swelling, and a rash as a result of histamine release 18 18

Therapeutic/Prophylactic Approach *Antihistamine,treatment or premedication(PO or IV) *Transfusion restart slowly after Antihistamine if symptom resolve Prevention: 19 19

Anaphylactic Reactions This occurs in : *Pts with hereditary IgA deficiency *Ab against C4-Haptoglobin-Ethylene Oxide Incidence: 1/20,000-1/50,000 of transfusions Symptoms: NO fever Hypotension Skin flushing Cardiac arrhythmia Nausea Cardiac arrest Diarrhea Laryngeal edema 20 20

Laboratory evaluation in Anaphylaxis *-Perform quantitative IgA test *-Perform Anti IgA 21 21

Therapeutic/Prophylactic Approach *Trendelenberg position *Epinephrine(Adult dose :0.2-0.5 ml of 1/1000 solution SC IM , in sever cases 1/10000 IV *Antihistamines,corticosteroids, beta-2 agonists Prevention: *transfusion of IgA –deficient components or Washed cellular components 22 22

Transfusion-related acute lung injury (TRALI) Definition : * Acute Onset * Hypoxemia O2 saturation<90% *The onset of signs and symptoms occur during or within 6 h of transfusion * No pre-existing ALI before transfusion *No temporal relationship to an alternative risk factor for ALI *Bilateral lung infiltration on the Chest-XRAY 23 23

Transfusion-related acute lung injury (TRALI) Incidence :1/5000-1/190,000 blood and blood components transfused *Packed red cells and -Cryo-FFP can cause TRALI * 15ml of blood component are sufficient to cause TRALI 24 24

Transfusion-related acute lung injury(TRALI) Etiology: The antibody-mediated model (Ab to HLA Class-HNA) 25 25

Transfusion-related acute lung injury (TRALI) Common symptoms and signs: Fever Progressive dyspnea Cyanosis Hypoxemia Hypotension or Hypertension (rarely) 26 26

Transfusion-related acute lung injury (TRALI) Management : *Supportive *Transfusion of the suspected blood product should cease immediately * Oxygen therapy *Mechanical ventilation in severe TRALI * No diuretics * Corticosteroids in TRALI: unproven 27 27

Transfusion-related acute lung injury (TRALI) Prognosis : *Most patients recover within 48–96hr h *Hypoxemia and radiological evidence of pulmonary infiltration can persist for 7 days in 20% of patients *70% patients require mechanical ventilation *In-hospital mortality: 5–10% 28 28

Transfusion-related acute lung injury (TRALI) Prevention : No universally agreed approach to donor management 1-It is suggested that donors implicated in TRALI and who have demonstrable antibodies should be permanently disqualified from the donor pool 2-Deferring multiparous female 3-Using male donor plasma 4-Washed blood products 29 29

Bacterial Contamination *The source of the bacteria can be donor blood, donor skin flora, or contaminants introduced during collection, processing, and storage. *Numerous gram-positive and gram-negative organisms can occur: Staphyloccus aureus, Klebsiella pneumoniae, Serratia marcescens,Pseudomonas and Staphyloccus epidermidis. 30 30

Bacterial Contamination Bacterial sepsis; Incidence :Pooled RDP :1/700 1 Unit of RBC:1/31,000 Rate of bacterial infection/contamination is higher with platelets is because they are stored at room temperature and the units are generally pooled between 6 and 10 donor units. 31 31

Bacterial Contamination Presentations: Fever Chills Tachycardia Hypotension Shock * The patient may also develop DIC and acute renal failure. 32 32

Bacterial Contamination MANAGEMENT Other products from the same donor can be quarantined *Return clamped blood unit& tubing attached for culture Collect blood samples for blood culture Broad spectrum antibiotic therapy 33 33

Bacterial Contamination PREVENTION : *Inspect all blood products for visual evidence of contamination *The first 40 ml of blood collected is diverted in a pouch to reduce risk of transmitting organisms from skin 34 34

Circulatory Overload High risk patients are: Adults >60y & infants Incidence : <1% of transfusions Symptoms : Dyspnea, Orthopnea, Cyanosis, Tachycardia & Hypertension D.D: TRALI 35 35

Circulatory Overload Treatment: Stop transfusion Upright posture Oxygen therapy IV diuretic (furosmide) Phlebotomy Prevention: * Administer transfusion slowly (1ml/kg/hr) * Use of diuretics 36 36

When a Reaction is Suspected…

Signs & Symptoms GENERAL Nervous System Respiratory Fever Chills Muscle ache,pain Back pain Chest pain Headache Heat at the site of infusion or along vein Nervous System Apprehension, impending sense of doom Tingling, numbness Respiratory Tachypnea Apnea Dyspnea Cough wheezing

Signs & Symptoms Gastrointestinal Renal Cardiovascular Cutaneous Nausea Vomiting Pain, abdominal cramping Diarrhea (may be bloody) Renal Changes in urine volume Changes in urine color Cardiovascular Heart rate Blood Pressure Circulatory Bleeding Cutaneous Rashes, Hives(urticaria) Itching

Signs in an Unconscious Patient Weak Pulse Fever Hypotension Visible hemoglobinuria Increased operative bleeding Vasomotor instability Tachycardia, brachycardia, hypotension Oliguria/anuria

Remember Reactions from different causes can exhibit similar manifestations; therefore, every symptom should be considered potentially serious and transfusion should be discontinued until the cause is determined

Immediate Actions to Take Stop TX immediately and keep an IV open with 0.9 Saline Check vital signs every 15 minutes Do clerical check at bedside of identifying tags and numbers, Check labels,forms,and Ids Notify the attending physician and the laboratory immediately Send bags &patient’s blood to BB Collect blood specimen and first voided urine

Post Transfusion Reaction blood samples to be collected from the recipient: Repeat ABO, Rh, IAT and Crossmatch. Visual check for hemolysis and compare with pre transfusion sample. DAT (Direct Antiglobulin Test) Collect 5-7 hours post transfusion to check for bilirubin Free hemoglobin determination Clotted specimen EDTA specimen 1st voided urine specimen post-tx’n

Immediate Actions to Take Treat patient symptoms as per physician instructions Take vitals Pulse Temperature Blood Pressure Document thoroughly Complete reaction form Send form, bag, tubing and set to laboratory

Did the patient develop fever? Yes Acute hemolytic FNHTR TRALI Bacterial contamination (Sepsis) No Allergic Anaphylactic Hemolytic, FNHTR or TRALI How high did the temperature rise? <2°C >2°C Consider: Acute hemolytic FNHTR TRALI Bacterial contamination Concomitant clinical factors Typically seen in Bacterial contamination (Sepsis)

When did the fever present? Immediately/at start of transfusion: Bacterial contamination Acute hemolytic Concomitant clinical factors During or at the end of the transfusion: •FNHTR Bacterial contamination Acute hemolytic TRALI Concomitant clinical Several hours after transfusion: FNHTR Bacterial contamination TRALI Concomitant clinical factors

اسلايدهاي سيستم هموويژلانس- ويژه پزشكان تنگي نفس علل : TRALI TACO Anaphylaxis Other Causes Clinical Guide To Transfusion ; Canadian Blood Service ;Chapter10;p:82-111;July2006 اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

Minor Allergic Reactions كهير علل : Minor Allergic Reactions Anaphylaxis TRALI Other Causes اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

Bradykinin mediatedHypotension - افت فشار خون علل : Bradykinin mediatedHypotension - -Sepsis -AHTR -TRALI -Other Causes

GOOD LUCK

Investigation of transfusion reactions.

Investigations of transfusion reaction are necessary for : Diagnosis Selection of appropriate therapy Transfusion management Prevention of future transfusion reaction اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

Investigations should include correlations of clinical data with laboratory result

Important clinical data : Diagnosis Medical history of pregnancies, transplant, and previous transfusion. Current medication Clinical signs and symptoms of the reaction. اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

Important clinical data : 5. Question related to the transfusion: Amount of blood transfused to cause the reaction. How fast , how long ? The use of blood warmer. Any filter used ? Other solutions. Any drugs given at the time of transfusion اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

Laboratory investigation outline of transfusion reaction. Immediate procedures Clerical checks. Visual inspection of serum and plasma for free hemoglobin ( pre and post transfusion ) Direct anti – globulin test. ( post transfusion EDTA sample ) اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

2. As required procedures ABO grouping and RH typing, pre and post transfusion Major compatibility testing , pre and post transfusion Antibody screening test , pre and post transfusion Alloantibody identification Antigen typings Free hemoglobin in first voidedurine post transfusion Unconjugated bilirubin 5 – 7 hours post transfusion. اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

اسلايدهاي سيستم هموويژلانس- ويژه پزشكان 3. Extended procedures Gram stain and bacterial culture of unit Quantitative serum Hemoglobin. Serum Haptoglobin , pre and post transfusion Peripheral blood film. Coagulation and renal output study Urine hemosiderin اسلايدهاي سيستم هموويژلانس- ويژه پزشكان

What Happens in the Lab…

Laboratory Actions when Notified of Suspected Reaction Quarantine all other crossmatched units When Reaction form, unit, set, tubing, urine received Centrifuge specimen Clerical Check Review Symptoms To determine extent of investigation required

Clerical Check Check test results vs. interpretation Check tag information with bag information (unit number, ABO/Rh) Check Pre-transfusion specimen information with tag information (name, number) Check that information on pre-transfusion specimen is identical to post-transfusion

Visual Inspection Compare plasma color of pre-transfusion and post-transfusion specimens Is post-transfusion specimen hemolyzed? If yes, ensure that hemolysis is not due to difficult collection (recollect if necessary) If still yes, notify physician immediately Check contents of unit for hemolysis Check blood in tubing for hemolysis

Direct Antiglobulin Test (DAT) To determine if there is in vivo sensitization May be negative if intravascular hemolysis has occurred If positive, perform monospecific DAT to determine if it is IgG, C3 or both

Extended Testing ABO/Rh on pre and post transfusion specimens ABO/Rh on donor unit Antibody screen on pre and post transfusion specimens Antibody Investigation, positive DAT on pre transfusion specimen and donor unit

Reporting Classified as to type of reaction given symptoms and investigation outcome Should be signed off by laboratory physician or designate Reference for follow up for any attending physician questions regarding future transfusions given the patient’s clinical need Patient should be informed of reaction and outcome

Reporting Should include future pre medication or special requirements, if applicable Examples Antihistamines Anti pyretics Washed blood (when anaphylactic reactions are under investigation and results are not back yet) Antigen negative blood if a clinically significant antibody is identified

Reporting Hospitals should report all severe and fatal reactions to the blood supplier