MANAGEMENT OF ACUTE TRANSFUSION REACTIONS DR SHABNEEZ HUSSAIN F.C.P. S HAEMATOLOGY (AKUH) CONSULTANT HAEMATOLOGIST FATIMID FOUNDATION

OUTLINE Definition Types of transfusion reactions Hemolytic Febrile non hemolytic Allergic Anaphylactic/ anaphylactoid Pulmonary transfusion reactions Bacterial contamination Clinical and laboratory management of transfusion reactions

What is a transfusion reaction? Any unfavorable transfusion related event, occurring in a recipient during or after transfusion.

Types of transfusion reactions Immediate Delayed HEMOLYTIC FEBRILE NON HEMOLYTIC ALLERGIC ANAPHYLACTIC TRALI BACTERIAL CONTAMINATION TACO PHYSICAL OR CHEMICAL RBC DAMAGE DEPLETION OR DILUTION OF COAGULATION FACTORS/ PLATELETS DELAYED HEMOLYTIC ALLOIMMUNIZATION POST TRANSFUSION PURPURA TA-GVHD IMMUNOSUPPRESSION IRON OVERLOAD AIR EMBOLISM

Typical causes of transfusion associated deaths Acute hemolysis (ABO incompatible) Acute pulmonary edema Bacterial contamination Delayed Anaphylaxis External hemolysis (>40C) Damaged red cell component Ta-GVHD

IMMEDIATE HEMOLYTIC TRANSFUSION REACTION

Definition Occurs soon after transfusion of incompatible RBC Reaction period: 1-2 hours Surgery: hypotension/haemoglobinuria/ abnormal bleeding

SIGNS/SYMPTOMS Fever Chills Facial flushing Chest pain Back or flank pain Hypotension Abdominal pain Nausea Dyspnea Haemoglobinemia Haemoglobinuria Shock Anemia Oligouria/anuria Pain at transfusion site Generalized bleeding Urticaria Diarrhea DIC

Treatment Perform immediate bedside procedure Mannitol / furosemide to induce renal diuresis and to prevent failure Hypotension: IV fluids and dopamine FFP/cryoprecipitate and platelet for bleeding diastheis Vital signs/coagulation status and renal output

Prevention Storage Do not warm RBC >37 C Ensure correct identification Do not add medications to blood Specimen collection labeling and testing Never sign out blood by name only

Febrile non hemolytic

Definition 1% of all transfusions 1C rise in temperature above patient’s baseline temperature during or within 24 hours after transfusion with a minimum recorded temperature being 38C

Pathophysiology Leukocyte antibodies (HLA) in patient’s plasma Stimulus: prior transfusion/tissue transplant/ pregnancy Release of pyrogens from transfused WBC

Signs and symptoms Fever ± chills Rarely hypotension Severe: cyanosis/tachycardia/ tachypnea/ dysnea / cough/transient leukopenia

Differentials IHTR Bacteremia Drugs

Prevention Leukoreduction: pre-storage or bedside (≤ 5 × 106) Washed red cell concentrate — 107 WBCs (1-2 log leukodepletion) Frozen deglycerolized red cells — 106-107 (2-3 log leukodepletion) Centrifugation and buffy coat removal — 108 WBCs (1 log leukodepletion) Premedication: paracetamol

Leukoreduction To minimize: Febrile nonhemolytic transfusion reactions HLA alloimmunization platelet refractoriness in multitransfused patients Prevention of transmission of leukotropic viruses such as EBV and CMV. 

Pre storage over post storage It eliminates the accumulation of inflammatory cytokine It removes the intact leukocytes as against filtration, at the bedside, where leukocyte fragments after storage can pass through filters Minimize the risk of leukotropic virus transmission as leukocytes disintegrate and release the intracellular organisms after 72 hours of storage in blood components.

Allergic / urticarial transfusion reaction

Definition Common Donor plasma has an allergen Patient plasma has IgG/IgE Or vice versa Release of histamine and leukotrienes Vasodilation Swelling/welts: itching

Signs/symptoms Erythema (redness) Pruritis (itching) Hives (raised firm red welts) ± fever Severe : angioneurotic edema/laryngeal edema/bronchial asthma

Treatment Mild: Diphenhydramine, can stop transfusion then resume Severe: aminophylline/epinephrine /corticosteroids

Prevention Repeated allergic reactions: washed Premedication with antihistamine

Anaphylactic/anaphylactoid

Definition Immediate hypersensitivity Spectrum : Hives …..pruritis….shock …. Death Any organ : lung, vessels, nerves, skin, GIT Differentiating feature : Fever is absent Signs and symptoms occur after transfusion of a few ml of plasma containing component

Pathophysiology IgA deficiency who develop anti IgA by sensitization from transfusion or pregnancy Histamine and leukotrienes Anaphylactic: Ig A deficient Anaphylactoid: normal levels of IgA but have limited type specific anti IgA that reacts with light chain of donor IgA

Signs and symptoms

Treatment Stop transfusion IV line open with saline Epinephrine immediately Corticosteroids or aminophylline Airway patency Vital signs

Prevention Washed PRBC Transfuse blood components from donors lacking IgA

Pulmonary transfusion reactionS TRALI TACO TAD Pulmonary transfusion reactionS

Pulmonary transfusion reactions PRIMARY SECONDARY Reactions occur in the wake of another transfusion reaction in which the lung is not the mainly affected tissue. Reactions with predominant pulmonary injury and respiratory distress Haemolytic transfusion reactions Hypotensive/anaphylactic reactions Transfusion transmitted bacterial infections Transfusion-related acute lung injury (TRALI) Transfusion-associated circulatory overload (TACO) Transfusion associated dyspnea (TAD)

Transfusion-related acute lung injury

Pathophysiology Immune: Occurs due to passive transfer of leukocyte antibodies or neutrophil priming substances accumulated in stored blood Antibodies bind to neutrophil, actin polymerizes  entrapment  release of reactive oxygen species and toxic enzymes  leakage of protein rich fluid and neutrophil emigration Non-immune: TRALI occurs after transfusion of stored platelet and erythrocyte concentrates 

Risk factors HNA and HLA antibodies in multiparous female donors Anti HNA3a :severe and fatal TRALI

Signs and symptoms Non cardiogenic pulmonary edema, Hypoxemia, Respiratory distress, Fever, Cyanosis, hypotension In ventilated patients, sudden drop in arterial oxygen tension, copious frothy ooze from endotracheal tube TRALI improves within 48 hours Pulmonary infiltrates remain till 7 days

Diagnostic tests X ray: bilateral generalized lung infiltrates (white lung) Pao2/Fio2 : < 300 mmHg, Pulse oximetry <90%

Treatment Stop transfusion Respiratory and hemodynamic support

Prevention If caused by patient anti leukocyte antibodies: leukoreduction If caused by donor anti leukocyte antibodies: defer donor (controversial)

Transfusion-associated circulatory overload

TACO Transfusion can cause rise in central venous pressure and heart failure Elevated transvascular fluid filtration and lung edema

Risk factors Advanced age or very young age Congestive cardiac or renal failure patients

Clinical features Mostly within 1 to 2 hours after beginning transfusion chest tightness, headache, dry cough, tachycardia, tachypnea, elevated blood pressure Engorgement of neck vessels S3 on auscultation Positive fluid balance

Diagnostic tests X ray: Pulmonary edema ± cardiomegaly Pulmonary artery occlusion pressure >18mmHg

Treatment Rapid reduction of hypervolemia Respiratory and cardiac support Oxygen therapy Intravenous diuretics Correction of cardiac arrhythmias and decreased myocardial function

Prevention Usual transfusion rate : 200ml/hr With TACO : 100 ml/hr or less Aliquots of donor units RBC instead of whole blood

Transfusion associated dyspnea Respiratory distress associated with transfusion Those reactions that are not assigned to other pulmonary transfusion reactions

Bacterial contamination

Definition Yersinia enterocolitica Endotoxin Bacteria in cold temperature (peudomonas , E coli)

Signs and symptoms Rapidly or within 30 mins after transfusion Dryness, flushing of skin Fever Hypotension Shaking Chills Muscle pain Vomiting Abdominal cramps Bloody diarrhea Haemoglobinuria Shock Renal failure DIC

Treatment Stop transfusion IV line: fluid support Send bag and patient’s blood sample for Cultures Broad spectrum antibiotics Dopamine Respiratory ventilation Maintenance of renal function

Prevention Occurs at the time of phlebotomy During component preparation or processing Thawing of blood in waterbath Visual inspection for colour change before release (brown/purple discolouration /clots/ hemolysis) Infused within 4 hours

Transfusion reaction …… what will you do ???

Immediate bedside procedure STOP TRANSFUSION Keep IV line open with saline Notify physician Perform bedside clerical checks Return unit /set/attached solution to the blood bank Collect appropriate blood specimen Document reaction

Laboratory investigation outline Immediate: Visual inspection of serum and plasma for free hb (pre and post transfusion) Direct coombs’ test (post transfusion) As required: ABO and rh (pre and post) Major compatibility test (pre and post) Antibody screening (pre and post) and identification Antigen typing Free hb in the first voided urine post transfusion Indirect bilirubin 5 to 7 hours post transfusion

Laboratory investigation outline Extended procedure: Gram stain and culture of unit and patient Quantitative serum Hb Serum haptoglobin (pre and post) Serial Hb , haematocrit and platelet count Peripheral blood smear Coagulation and renal output studies Urine for haemosiderin