Department of Pathology
Division of Laboratory Medicine

Transfusion Manual
March 2014

 


ADVERSE REACTIONS TO TRANSFUSION

SYMPTOMS AND SIGNS OF TRANSFUSION REACTION

Fever > 1°C

Shortness of Breath

Chills

Headache

Itching

Chest/back pain

Nausea

Wheezing

Heat at infusion site

Facial flushing

Coughing

Hemoglobinuria

Uneasy feeling

Cyanosis

Hypotension

Myalgia

Dyspnea

Abnormal bleeding

Urticaria (Hives)

Pulmonary edema

Oliguria/anuria

Rash

Jaundice

STEPS TO TAKE WHEN TRANSFUSION REACTION SUSPECTED

ACUTE REACTIONS WITHIN 24 HOURS OF TRANSFUSION

Tranfusionist Functions

Patient related

  • Stop Transfusion.
  • Keep intravenous (IV) line open with saline.
  • Do not disconnect unit before notifying physician.
  • Contact treating physician for directions for patient care and administer supportive/definitive care.
  • Notify the transfusion service ASAP at Ext. 4-8537.
  • Rule out clerical error by RECHECK of Unit, transfusion tag and patient identification.
  • Order a transfusion reaction workup in EPIC, collect transfusion reaction specimen .
  • Complete form HSC 7173 Report of Possible Transfusion Reaction and send to laboratory. (For OR/Outpatient).
  • For barcode blood administration complete flowsheet questions in Epic related to transfusion reaction.
  • Send actual unit to laboratory only when directed to do so.
  • Defer future transfusions until workup complete.

Laboratory Functions

  • Clerical check: Bag, label, paperwork, sample.
  • Visual check of pre and posttransfusion plasma (Reliable only when >50 mg/dL hemoglobin present).
  • Perform direct antiglobulin test (DAT) on posttransfusion sample.
  • Report findings to transfusion service manager and staff pathologist.
  • Additional studies at direction of transfusion services physician.

RECOGNITION, MANAGEMENT, AND PREVENTION OF SPECIFIC TRANSFUSION REACTIONS

Reactions by Type:

ACUTE IMMUNE INTRAVASCULAR HEMOLYTIC

Detection

  • Usually caused by transfusion of ABO-incompatible red blood cells (RBCs).
  • Fever, chills, hypotension, pain along IV line, back or chest, hemoglobinuria or oliguria, and bleeding or oozing are signs and symptoms that can appear after administration of as little as 10 to 15 ml.
  • Death occurs in approximately 1 of 30 patients who receive ABO-incompatible RBC.

Management

  • Transfusion must be stopped and not restarted , and intravenous fluids must be kept running.
  • The unit needs to be returned to the blood bank for investigation.
  • Mainstays of therapy include vigorous treatment of hypotension and maintenance of renal blood flow.
  • Low-dose dopamine therapy.
  • Urinary output monitoring
  • Administration of a diuretic prn (e.g., mannitol).
  • If disseminated intravascular coagulation develops, platelets, fresh frozen plasma, and cryoprecipitate may be required.
  • Staff will follow OHSU policies for investigating, managing and reporting this reaction (see EVENT REPORTING AND INVESTIGATION).

Prevention

  • Proper identification of the patient, from sample collection through blood administration, and assurance of proper labeling of samples and components.

IMMUNE, EXTRAVASCULAR

Detection

  • Patient is often asymptomatic.
  • Diagnosis usually occurs from laboratory testing (such as, direct antiglobulin test [DAT], crossmatch, bilirubin).

Management

  • Generally no treatment is required, although the patient may need an additional transfusion.
  • Once a problem is identified, avoidance of incompatible component transfusion is desirable.

 

NON-IMMUNE HEMOLYTIC

Detection

  • May occur in the blood container or during administration due to physical disruption from temperature changes, mechanical forces, or contact with non-isotonic fluids.
  • Hemoglobinuria may be the only sign.

Management

  • The transfusion should be stopped and the institutional policy for investigation should be followed.
  • If an immunologic cause of hemolysis is excluded, possible causes of a nonimmune hemolytic transfusion reaction should be investigated.
  • Intravenous fluid therapy should be used to maintain urinary output.

Prevention

  • Strict adherence to proper handling, storage, and administration of blood components should minimize the possibility of nonimmune hemolysis.

SIMPLE ALLERGIC

Detection

  • Development of local or generalized symptoms, usually urticaria (hives) with or without itching or localized edema.

Management

  • Transfusion should be interrupted until symptomatic relief is achieved following antihistamine administration.
  • Transfusion may be safely restarted in patients with hives alone who respond to antihistamine therapy.

Prevention

  • Routine pre-transfusion administration of antihistamines is not clinically indicated. In a few patients who have had previous episodes of transfusion-related urticaria, pre-transfusion prophylaxis with antihistamines provides symptomatic benefit. Steroids can also be helpful in selected situations. Reducing the plasma content of cellular components (washing) and avoidance of plasma administration, if clinically possible, may be necessary for some patients.

ANAPHYLACTIC

Detection

  • Acute respiratory distress due to laryngeal edema and bronchospasm with hypotension; rapid death.

Management

  • The transfusion must be stopped and not restarted.
  • The patient should receive appropriate airway management and additional supportive care as needed.
  • Volume support.
  • Epinephrine may be indicated.
  • For IgA-deficient recipients with anti-IgA, subsequent transfusions should be with IgA-deficient components, if possible. For others, plasma reduction of components (washing) will minimize the risk of possible recurrence.

Prevention

  • Washed cellular products.
  • Premedication with antihistamines and steroids.

SEPTIC

Detection

  • Caused by bacteria introduced into the blood bag which multiply and may elaborate toxins.
  • Most commonly associated with platelet transfusion; occasionally seen after red cell transfusions; rare with transfusion of frozen plasma and cryoprecipitate.
  • Very high fever, rigors, profound hypotension, often complaints of nausea with or without diarrhea are key signs and symptoms; death.

Management

  • The transfusion must be stopped and not restarted.
  • The bag, tubing and other fluids being administered should be returned to the blood bank for immediate investigation to include a Gram stain and culture of remaining component in the bag (and occasionally of the intravenous fluid). Before instituting antimicrobial therapy, it is important to obtain blood cultures from the patient because finding the same organism in the patient's blood culture as in the bag establishes the diagnosis with a high degree of certainty.
  • If the patient is receiving antibiotics at the time of transfusion, blood cultures from the patient may be negative for the organism in question. Because of the high likelihood of fatality, broad-spectrum antibiotics should be administered immediately upon suspicion of bacterial contamination.
  • Supportive care for other symptoms associated with sepsis should also be undertaken immediately.

Prevention

  • Pre-transfusion culture of all platelet units.
  • Inspection for abnormal color, clots.

FEBRILE, NON-HEMOLYTIC TRANSFUSION REACTION

Detection

  • Diagnosis of exclusion characterized by fever (defined as an increase in temperature by greater than one degree centigrade above pre-transfusion baseline), sometimes accompanied by shaking chills or rigors, and is frequently seen in non-anesthetized patients during or within one to two hours after transfusion, especially following transfusions with platelets and granulocytes.

Management

  • Because fever may be the first indication of acute hemolysis in RBC transfusions or of bacterial contamination of a component, transfusion must be suspended pending further evaluation.
  • An institutional protocol should be followed to rule out a more severe reaction.

Prevention

  • Pre-treatment with anti-pyretics (Tylenol).
  • Use leukodepleted blood products.

TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)

Detection

  • Otherwise unexplained acute respiratory distress frequently accompanied by fever and usually requiring oxygen for relief.
  • Symptoms often develop during transfusion and always within 6 hours of transfusion..
  • Portable chest radiograph shows bilateral infiltrates and no cardiomegaly or other causes of pulmonary edema.
  • Resolution usually within no more than 2-3 days.

Management

  • Symptomatic support for respiratory distress must include oxygen administration and may require intubation and mechanical ventilation. Lasix not helpful. Steroids of dubious value but often given.

Prevention

  • Most cases of TRALI occur with blood from Multiparous donors. Plasma for infusion is no longer collected from such donors.

VOLUME OVERLOAD

Detection

  • Key signs and symptoms include increased central venous pressure, pulmonary edema and peripheral edema. Usually afebrile.
  • Most common in elderly, in patients with severe cardiopulmonary disease or renal failsure, or in infants or elderly patients who are anemic but not actively bleeding.

Management

  • Treatment includes stopping the transfusion, positioning the patient as upright as possible, administering oxygen, and using a diuretic if necessary.
  • Severe and persistent symptoms of pulmonary edema should be treated aggressively with diuretics.
  • In some patients, therapeutic phlebotomy may be necessary.
  • The differential diagnosis should exclude other causes of acute pulmonary edema, eg, TRALI or acute myocardial infarction.

Prevention

  • Prevention includes pre-transfusion recognition of the at-risk patient, avoidance of unnecessary fluids, use of concentrated components, and appropriate infusion rates.

OTHER REACTIONS

  • Hypothermia: Warming fluids and inspired gases, increasing ambient temperature, and applying warming devices directly to the patient should alleviate or obviate coagulopathy in hypothermic patients.
  • Citrate toxicity: Symptomatic hypocalcaemia and hypomagnesaemia can be treated with replacement of calcium and magnesium.
  • Potassium effects: No preventive measures are generally recommended. In selected patients, use of fresh RBCs stored for less than 5 days (RC5) or washed older red blood cells may be reasonable when patient potassium intolerant.
  • Air embolism: Close attention to the return line to recognize and prevent air from being infused is the best preventive measure.  

DELAYED & LONG-TERM EFFECTS (beyond the first 24 hours after transfusion)

RED CELLS ALLOIMMUNIZATION

Detection

  • Newly positive antibody screen and/or
  • Positive DAT in a recently transfused patient.
  • In delayed hemolysis, patients experience an unexplained lack of therapeutic benefit from the transfusion and may have abnormal laboratory findings.

Management/Prevention

  • Delayed Hemolysis:
    • The only therapy required is to alleviate symptoms, including possible additional transfusions of antigen negative blood for persistent anemia.
    • Prevention is not possible using current methods.

    Alloantibody Formation:

    • Except for chronically transfused patients (See Transfusion of Patients with Sickle Cell Disease), no measures to prevent primary alloimmunization are indicated.
    • It is important to record the identity of any existing alloantibodies and to inform the patient and treating physician, because the antibody concentration may decrease below limits of detection.
    • Two alternative strategies are used to support genetically anemic patients. Some institutions perform full antigen typing of each patient when the program of chronic transfusion begins, then transfuse only antigen-identical RBCs (for the major RBC antigen systems) to prevent alloimmunization. The other strategy is to transfuse these patients just like any other recipient until alloimmunization occurs, then RBCs that are antigen negative are provided.

PLATELETS ALLOIMMUNIZATION/REFRACTORINESS

Detection

  • If suspected, checking the 1 hour posttransfusion platelet count increment after two infusions of fresh ABO matched platelets is very helpful. If the platelet increment is less than 15, then alloimmunization is more likely and additional testing is indicated.
  • More common in women and in patients who are dependent on platelet transfusions.
  • Order “Platelet Refractory Workup”.
  • Transfusion Medicine service will consult and assist in obtaining the most appropriate platelet product.

Management

  • Alloimmunization is best managed by use of platelet crossmatching. The addition of HLA matching helps identify crossmatch compatible units in patients who are highly alloimmunized.
  • Directed donations from blood relatives is another strategy that helps find compatible products.
  • Severe refractoriness that is unresponsive to HLA-matched or crossmatch-compatible platelets is often an insurmountable clinical problem.
  • High-dose intravenous immunoglobulins (IVIG), plasma exchange, splenectomy, and continuous platelet infusions have occasionally been tried but their effectiveness has not been proven in controlled clinical trials.

POSTTRANSFUSION PURPURA

Detection

  • The clinical findings in posttransfusion purpura are also similar to ITP, except for a recent history of a blood transfusion (within the preceding 5 to 10 days).
  • An unexplained purpuric rash, bruising, or bleeding from mucous membranes 5 to 10 days after transfusion, usually after transfusion with RBCs.
  • Patients developing this complication have developed an anti-platelet antibody (usually against a platelet antigen called Pl A1) at the time of a previous, often remote, pregnancy or transfusion. Subsequent transfusion triggers immune mediated destruction of the patient's own platelets resulting in a profound thrombocytopenia during which platelet levels often drop to <10,000/µl.
  • Occurs particularly in parous women or in previously transfused recipients who lack the most common platelet antigen, HPA1a (formerly PL A1).
  • Patients at risk for posttransfusion purpura are not identifiable, using current methodologies, before symptoms occur.

Management

  • Spontaneous platelet recovery occurs within two weeks.
  • Patients may be treated with corticosteroids, plasma exchange, high dose IV immunoglobulin.
  • Plasma exchange has been successful in some cases.
  • Once the reaction occurs, transfusion should be restricted to components from donors who are negative for the appropriate antigen (usually Pl A1 negative platelets). 

TRANSFUSION ASSOCIATED GRAFT-VERSUS-HOST DISEASE (TA-GVHD)

Detection

  • Rash, fever, or gastrointestinal symptoms and unexplained cytopenias between 4 and 10 days after transfusion are key signs and symptoms.
  • TAGVHD is likely when the donor is HLA homozygous haplotype-identical with the patient or was a biologic family member, or the recipient's immune system was significantly compromised.

Management

  • The disease is virtually always fatal due to the profound bone marrow aplasia and management is not well defined and is rarely successful. The disease does not respond to treatment regimens used for ordinary GVHD in the transplant setting.

Prevention

  • Prevention of TAGVHD is relatively simple; gamma irradiation of cellular (and some advocate all) blood components to at least 25 Gy in the center of the bag will inhibit lymphocyte mitosis without affecting other cellular functions. Leukoreduction does not eliminate TA-GVHD.

IMMUNOMODULATORY EFFECTS

    • The relationship between transfusion and possible increased incidence of infections or earlier cancer recurrence remains unresolved.

IRON ACCUMULATION

Detection

  • Transfusion hemosiderosis (excess tissue iron deposition) may be clinically silent until it is far advanced.
  • Long-term ferritin monitoring may assist in assessing total body iron burden.
  • Liver and endocrine dysfunction create significant morbidity.
  • The most serious complication is cardiotoxicity, which causes arrhythmias, congestive heart failure, and death.

Management

  • Iron overload should be anticipated in patients who are chronically transfused with RBCs. Treatment using iron-specific chelation agents, such as parenteral deferoxamine, should be initiated early in the course of chronic transfusion therapy when the serum ferritin level reaches 1000 to 2000 µg/L. Long-term maintenance of serum ferritin levels below 2500 µg/L is associated with improved survival.
  • To reduce transfusion requirements, chronically transfused patient with clinical hypersplenism may benefit from splenectomy. Use of erythrocytapheresis for patients with sickle cell disease reduces iron exposure, but the process is expensive and increases donor exposure. Recombinant human erythropoietin, hydroxyurea for sickle cell patients, and allogeneic bone marrow transplantation provide promise as alternatives to RBC transfusion.

INFECTIOUS DISEASES

HEPATITIS

Estimated Current risk:

  • Hepatitis B: ~1 case per 200,000 transfusions
  • Hepatitis C: ~1 case per 2,000,000 transfusions

Detection

  • Posttransfusion hepatitis may be clinically overt, although the majority of cases are subclinical; a variable number of cases may become chronic.
  • Hepatitis B and C are the most frequently implicated agents. Hepatitis A is rarely seen.
  • The primary diagnosis often occurs because of unexplained elevations in liver enzymes and occasionally hyperbilirubinemia.
  • Definitive diagnosis depends on specific serologic tests (which correlate with time since infection for hepatitis B).

Prevention

  • Transmission of hepatitis B and C viruses by blood cannot be completely prevented using available methods, which include asking the donor questions about possible exposure or prior positive test results, checking to ensure donor suitability, and by applying the most recent version of serologic and nucleic acid screening.
  • Licensed vaccines are available for both hepatitis A and B. The latter is recommended for use in spouses and close family contacts of recipients infected with hepatitis B virus.

HUMAN IMMUNODEFICIENCY VIRUS (HIV), TYPES 1 & 2

Estimated Current risk:

  • 1 case per 200,000 transfusions

Detection

  • Definitive diagnosis of transfusion-transmitted HIV depends on seroconversion usually occurring within 4 to 12 weeks after transfusion, in the absence of any other risk factors. Molecular techniques can demonstrate effective identity between donor and recipient viral strains.
  • In transfusion-transmitted HIV, the diagnosis is usually made due to a "look back" to recipients of prior donations. Otherwise, onset of symptoms, such as unexplained opportunistic infections, low CD4 counts, or characteristic tumors that mark development of the acquired immune deficiency syndrome (AIDS), may be the first indication of HIV infection.
  • In some transfusion recipients, the time from injection until symptomatic AIDS may be as short as 2 or 3 years.

HUMAN T LYMPHOTROPHIC VIRUS I & II (HTLVI/II)

Estimated Current risk:

  • 1 case per 650,000 transfusions

Detection

  • HTLVI-associated myelopathy has occasionally been reported following transfusion, with onset generally occurring a few months to 2 years later, but adult T-cell lymphoma/leukemia has not yet been reported.
  • Current screening tests for HTLVI have a considerable rate of false positivity. The incidence of false positive reactions shows seasonality, with a peak incidence in the winter and spring. Some believe this may be related to flu vaccinations.

Prevention

  • Efforts to prevent HTLV infection by transfusion focus on proper donor testing using the most current version of an FDA-approved screening test and discarding all test positive units. Confirmatory procedures are still investigational.

CYTOMEGALOVIRUS (CMV)

Detection

  • Clinical disease in immunocompetent patients is rare.
  • CMV infection may lead to life-threatening, multi-system disease in immunocompromised patients, such as low-birthweight infants (<1200g), marrow transplant recipients, heart-lung transplant recipients, and CMV-negative AIDS patients.
  • Clinical manifestations in these patients include hepatitis, pneumonitis (the most common fatal complication), retinitis, central nervous system disease, gastrointestinal tract disease, and hematologic abnormalities.
  • Viral isolation from urine or saliva, or viral antigen or nucleic acid detection in tissue, is usually required to diagnose active CMV infection definitively.

Prevention

  • The risk of transfusion-associated CMV infection may be essentially eliminated by use of blood components that are leukoreduced (to <5x10 6 white blood cells) or are CMV seronegative. Leukoreduced cellular products are the preferred method for prophylaxis for patients at risk of severe CMV disease.

CREUTZFELDT-JAKOB DISEASE (Mad Cow Disease, CJD, New Variant CJD)

Estimated Current risk:

  • Extremely rare but transfusion transmission now confirmed.

Detection

  • Diagnosis is based on clinical exam and histologic inspection of infected tissues.
  • There is currently no non-invasive test that can identify patients who have been infected.

Prevention

  • American Red Cross (ARC) screens blood for an exposure history.

Policy

  • Patients who receive blood from donors who come down with CJD are notified. Additional details for patient notification in cases of CJD are defined in OHSU administrative policies.