Laboratory Medicine Updates - April 20, 2007

University of Virginia Health System

Medical Laboratories

"Quality You Expect, Service You Deserve"

LABORATORY MEDICINE UPDATE

April 20, 2007

This edition contains a synopsis of the principal blood components, component compatibility, and transfusion reactions.  Transfusion medicine physicians are available at all times by calling the Blood Bank at 924-2273.  We appreciate your continuing to report immediately to the Blood Bank all adverse events related to Transfusion other than minor allergic reactions.

 

Blood Product Descriptions

Product

Approximate Volume

(Shelf life)1

Product Preparation Time2

Description

Indication

Expected Adult Increment

Red Blood Cells (RBC)

330mL

(42 days) 1

If no unexpected antibodies present:

15 min

Hct ~ 60%

Increase red cells in symptomatic anemia

Hct 3%

Hgb 1g/dL

Apheresis Platelets

200-300mL

(5 days) 1

15 min

Minimum 3x1011 platelets

Leukoreduced3

Bleeding due to thrombocytopenia or dysfunctional platelets

30,000-60,000 platelets/µL

Fresh Frozen Plasma or Plasma, Frozen within 24 Hours of Collection

250-350mL

(1 year frozen,

24 hours thawed)

30 min

Contains all coagulation factors

Coagulopathy

Dosed at 2-6 units (10-20mL/kg), to increase factor activity ~20%

Cryoprecipitate

10-15mL/unit

(1 year frozen, 4 hours pooled, 6 hours thawed)

30 min

Contains fibrinogen, FVIII, FXIII, vWF, fibronectin

Fibrinogen replacement

von Willebrand factor replacement if allergic to concentrates

Dosed at 1 unit/10kg; expected increase in fibrinogen ~50-75mg/dL

 

1 Shelf-life is from time of collection except where noted.  Irradiation, if performed, decreases shelf-life of RBCs to 28 days or the original outdate, whichever is less.  In general, when platelets are received from the blood collection center, they have about 3 days shelf-life remaining.

 

2 After an acceptable patient sample has arrived in the Blood Bank, it takes about 40-45 minutes to complete an ABO/Rh and antibody screen (also know as type and screen).  This is optimal timing, bleeding patients throughout the hospital and Blood Bank staffing may impact this timing. If the patient is found to have an unexpected antibody (e.g., anti-D, anti-E, anti-Kell, etc) the timing for RBC preparation is extended because the Blood Bank must identify these antibody (-ies) and find RBC units lacking the correlating antigen(s).  This could take several hours or longer.  Uncrossmatched, group O RBCs may always be made available immediately.

 

3 Leukoreduced RBCs may be ordered for patients to reduce the likelihood of alloimmunization to HLA antigens, provide for a reduction of cytomegalovirus risk, and to reduce the likelihood of a febrile transfusion reaction in patients who have previously experienced such reactions.  Apheresis platelets are collected as leukoreduced products.

 

If a transfusion reaction is suspected, the transfusion should be stopped and the Blood Bank should be notified.  Other than for mild allergic reactions, a transfusion reaction investigation must be performed by Blood Bank staff and physicians.  For mild allergic reactions, if the signs and symptoms improve the transfusion may be restarted.  See pages 3 and beyond for a discussion on categories and management of transfusion reactions.

 

BLOOD PRODUCT COMPATIBILITY

 

Red Blood Cells ABO and Rh Compatibility

 

DONOR

RECIPIENT

A

B

O

AB

Rh Positive

Rh Negative

A

 

 

 

 

B

 

 

 

 

O

 

 

 

 

 

AB

 

 

Rh Positive

 

 

 

 

Rh Negative

 

 

 

 

 

 

 

FFP, FP24 and Cryoprecipitate ABO and Rh Compatibility

 

DONOR

RECIPIENT

A

B

O

AB

Rh Positive

Rh Negative

A

 

 

 

 

B

 

 

 

 

O

 

 

AB

 

 

 

 

 

Rh Positive

 

 

 

 

Rh Negative

 

 

 

 

 

For platelets, ABO-identical products are preferred, but are not mandatory.  The 5-day shelf life precludes maintenance of a sufficient inventory to assure that all patients receive ABO-identical platelets.  If plasma-incompatible platelets are issued, these have been screened to assure only low anti-A and/or anti-B titers are present, as appropriate, for the recipient's blood group.  ABO major incompatibility usually results in adequate increments; however, some patients have greater increments with ABO major-compatible product.  Platelet products may contain small quantities of red blood cells; therefore, the Blood Bank will inform clinical staff if an Rh-negative patient receives an Rh-positive platelet so that RhIG administration may be considered.

CATEGORIES AND MANAGEMENT OF TRANSFUSION REACTIONS



REACTION

ETIOLOGY (USUAL CAUSE)

SIGNS AND SYMPTOMS

PREVENTIVE & THERAPEUTIC CONSIDERATIONS

Acute (<24 hours) Transfusion Reactions - Immunologic

Hemolytic (immune mediated)

  • ABO incompatible RBCs
  • Other complement binding red cell antibody.

Chills, fever, anxiety, shock (hypotension), pain at infusion site, chest/back/flank pain, dyspnea, hemoglobinuria, hemoglobinemia, renal failure with oliguria, DIC (oozing from IV sites)

To maintain blood pressure, administer as clinically indicated:

  • Vasopressor (e.g., levophed)

Maintain renal output >100mL/hour with fluid replacement and, for diuresis, administer as clinically indicated:

  • Diuretic (e.g., furosemide 1mg/kg body weight or 20-80mg IV)

Maintain airway.

Monitor coagulation and watch for DIC.

Request appropriate labs, which may include:

  • CBC (Complete Blood Count)
  • Coagulation studies:
    • PT (Prothrombin Time)
    • PTT (Partial Thromboplastin Time
    • Fibrinogen Level
  • DIC studies
    • D-Dimer Test
  • Renal function studies:
    • BUN and Creatinine
  • Hemolysis studies:
    • Bilirubin
    • Haptoglobin
    • Hemoglobinemia, Hemoglobinuria

Febrile Nonhemolytic Transfusion Reaction (FNHTR)

  • Antibody to donor WBCs
  • Accumulated cytokines in transfused product

Fever (temperature increase ≥ 10C) during or up to 2 hrs. after transfusion and not explained by patient's underlying clinical process, chills, headache, vomiting

Administer as clinically indicated:

  • Antipyretic (e.g., acetaminophen 325-650 PO/PR every 4 hours)

Mild Allergic Reaction

Antibody to donor plasma proteins

Urticaria, pruritis, flushing

Administer as clinically indicated:

  • Antihistamine (e.g., diphenhydramine 25-50mg PO/IM/IV every 6 hours)

If the signs and symptoms improve, continue transfusion of same unit.

Severe Allergic Reaction or Anaphylaxis

Antibody to donor plasma proteins (e.g., IgA, haptoglobin, C4)

Hypotension, bronchospasm (respiratory distress, wheezing), local edema, anxiety, urticaria

  • o Administer as clinically indicated:
  • Antihistamine (e.g., diphenhydramine 25-50mg PO/IM/IV every 6 hours)
  • Epinephrine (e.g., 0.3-0.5mg {0.3-0.5mL of 1:1000 solution} SQ every 20 minutes)
  • Vasopressor (e.g., levophed)
  • Corticosteroids (e.g., methylprednisolone 125mg IV every 6 hours)

Send for IgA studies.

Transfusion-related acute lung injury (TRALI)

WBC antibodies in donor (occasionally in recipient), other WBC-activating agents in components

Hypoxemia, respiratory failure, hypotension, fever, bilateral pulmonary edema

Administer oxygen.

Intubate (mechanical ventilation) if necessary.

Acute (<24 hours) Transfusion Reactions - Nonimmunologic

Transfusion associated sepsis

Bacterial contamination

Fever, chills, hypotension during or up to several hours after transfusion

Administer the following as clinically indicated:

  • Antibiotic (review gram stain and culture results of blood product to determine which antibiotic to administer)

Circulatory overload

Volume overload

Dyspnea, orthopnea, cough, tachycardia, hypertension, headache, edema

Administer the following as clinically indicated:

  • Diuretic (e.g., furosemide 1 mg/kg body weight or 20-80mg IV)

Nonimmune Hemolysis

Physical and/or chemical destruction of RBCs (e.g., blood warmer >42OC, infusing drugs or hypotonic solutions through same line, using small bore needle, etc.)

Hemoglobinuria, hemoglobinemia

  • Identify and discontinue cause
  • Supportive therapy

Hypocalcemia (ionized calcium)

Rapid citrate infusion (massive transfusion of citrated blood, delayed metabolism of citrate, apheresis procedures)

Paresthesia (frequently perioral and acral present early), tetany, arrhythmia

  • Calcium infusion while monitoring ionized calcium levels in severe cases
  • PO calcium supplement for mild symptoms during apheresis procedures

Hypothermia

Rapid infusion of cold blood, especially with use of central line or during massive transfusion.

Cardiac arrhythmia

  • Employ blood warmer

Delayed (> 24 hours) Transfusion Reactions - Immunologic

Primary alloimmunization, RBC antigens

Immune response to foreign antigens on RBCs leading to anti-RBC antigen

  • Positive blood group antibody screening test
  • Delayed serologic/hemolytic transfusion reaction (DS/HTR), see below
  • Hemolytic Disease of the Fetus/Newborn
  • Avoid unnecessary transfusions to decrease exposure and thus decrease risk for alloimmunization

 

Delayed Serologic/Hemolytic Transfusion Reaction (DS/HTR)

Anamnestic immune response to red blood cell antigen(s).

  • Fever, decreasing hemoglobin and haptoglobin, increasing bilirubin with mild jaundice, positive antibody screen
  • Send sample to Blood Bank
  • Check CBC, bilirubin, haptoglobin
  • Transfuse compatible RBCs as needed (RBCs should lack the antigen to which the antibody correlates).

Alloimmunization, HLA and/or HPA antigens

Immune response to foreign antigens on WBCs and/or platelets leading to anti-HLA and/or anti-HPA (e.g., anti-PlA1)

  • Platelet refractoriness
  • Neonatal Alloimmune Thrombocytopenia (NAIT)
  • Avoid unnecessary transfusions to decrease exposure and thus decrease risk for alloimmunization
  • Leukocyte-reduced blood to decrease risk for developing anti-HLA

Graft-vs.-host disease (GVHD)

Donor lymphocytes engraft in recipient and mount attack on host tissues

Erythroderma, maculopapular rash, anorexia, nausea, vomiting, diarrhea, hepatitis, pancytopenia, fever

  • Prevent by irradiation of cellular blood components for patients at risk
  • Corticosteroids and cytotoxic agents for treatment (greater than 90% fatality rate even with treatment)

Post transfusion purpura (PTP)

Recipient platelet antibodies (apparent alloantibody) destroy autologous and transfused platelets

Thrombocytopenia and bleeding (e.g., purpura, hematuria, vaginal bleeding, etc.) 8-10 days after transfusion

  • Corticosteroids
  • IVIG
  • Plasmapheresis

Delayed (> 24 hours) Transfusion Reactions - Nonimmunologic

Iron overload

Multiple transfusions (typically >100 RBC units) in transfusion-dependent patient.  Each RBC unit contains about 225 mg iron.

Excess iron deposits in pancreas, liver and heart leading to diabetes, cirrhosis, cardiomyopathy

  • Send iron studies (e.g., ferritin level)
  • Iron chelator

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Signs of Transfusion Reaction in an Unconscious Patient

  • Unexpected change in vital sign(s)
  • Hives
  • Hematuria
  • Oozing at surgical and/or access site
  • Oliguria/anuria

 

Reactions from different causes can exhibit similar manifestations; therefore, every symptom should be considered potentially serious.

Selected Acute Transfusion Reactions

Whenever an acute adverse transfusion reaction is suspected, immediately:

  • Stop the transfusion
  • Check patient bracelet, blood bank bracelet, blood product, and compatibility tag for clerical errors
  • Maintain IV access with normal saline
  • Notify the patient's physician and the Blood Bank (924-2273). (Mild cutaneous allergic reactions do not require notification of the Blood Bank.  The transfusion may be restarted after antihistamine medication at the treating physician's discretion if the reaction is not progressing.)

 

1.  Febrile non-hemolytic transfusion reactions are defined as an increase of 1o C in temperature occurring within 2 hours of starting a transfusion.  Symptoms include chills, rigors, headache, nausea and vomiting.  The incidence is 0.5 - 1.0 % for RBC transfusions and 1 - 15% of platelet transfusions.  This type of reaction usually resolves spontaneously.  The clinical management includes stopping the transfusion and obtaining a new sample for serological evaluation by the Blood Bank to exclude an acute hemolytic reaction.  Antipyretics and meperidine may be considered for fever and rigors respectively.

Occasionally, transfusion results in the above-noted symptoms without an elevation of temperature.

 

2.  Allergic transfusion reactions can vary from benign to extremely severe.  Symptoms include pruritus, erythema, nausea, vomiting, tachycardia, hypotension, cardiac arrest and airway obstruction.  Fever is typically absent.  These reactions are not dose dependent.  Mild cutaneous reactions are self-limited.  Transfusing at a slower rate may lessen symptoms and discomfort.  Systemic reactions may require epinephrine, prednisone and antihistamine.  In cases of known, significant cutaneous allergic response where antihistamine premedication is ineffective, washed cellular products may be indicated.  Patients who have experienced an anaphylactic reaction from a blood transfusion must receive washed cellular products as well as premedication.



Cutaneous allergic reaction

Cutaneous Transfusion Reaction lmu092702

 

3.  Acute intravascular hemolysis occurs in approximately 1 in 75,000 RBC transfusions.  Approximately 10% of reported ABO incompatible transfusions are fatal.  The signs and symptoms include fever (usually greater than 2o C, unless masked by antipyretics), hypotension (often hypotensive shock), pain (at the infusion site, back and chest), headache, shortness of breath, hemoglobinuria and hemoglobinemia, hemorrhage, nausea, vomiting, and diarrhea.  Jaundice can occur 4-6 hours post transfusion and renal failure may develop.  Treatment includes stopping the transfusion, peripheral blood and urine samples for testing, symptomatic treatment with fluids, pressors, steroids, and furosemide.  Only group O cells should be transfused until the etiology of the reaction is resolved.  Exchange transfusion may be necessary.

 

4.  Transfusion Related Acute Lung Injury (TRALI) is an acute respiratory distress syndrome associated with transfusion.  The signs and symptoms include bilateral pulmonary edema, hypoxia, tachycardia, fever (typically 1-2o C), hypotension and cyanosis.  The incidence may be increasing and is reported to be as high as 1 in 5,000 transfusions of plasma and platelets. Mortality can be as high as 5-10%.  The pathophysiology often involves donor granulocyte or HLA antibodies reacting with antigens in a susceptible recipient. Reactive lipid products and cytokines from stored blood products have also been implicated.  The diagnosis must exclude cardiac causes, volume overload, and, if fever is present, an acute hemolytic reaction.  A chest x-ray will typically show diffuse pulmonary infiltrates producing a "white-out" appearance.  In TRALI, the central venous and pulmonary wedge pressures are normal.  Of course, volume overload and TRALI can coexist.  The clinical course is usually self-limited with most resolving completely within 72 hours.  Management chiefly includes respiratory support, although pressors may be indicated if hypotension is prolonged.  The role of steroids is unproved.

TRALI lmu092702

 

5.  Bacterial contamination of blood components can result in morbidity and mortality. Signs and symptoms include hypotension, fever (usually greater than 2o C), chills, nausea, vomiting, dyspnea, and diarrhea. In severe cases patients can develop septic shock, and disseminated intravascular coagulation leading to death. The symptoms most commonly occur during the transfusion, but may not occur until several hours after transfusion. Investigation should include Gram's stain and culture of the blood components as well as blood cultures from the patient. Immediate empirical treatment with antibiotics may be indicated.



Blood smear from a bacterially contaminated RBC unit showing numerous extracellular bacteria.

Blood Smear Bacterial Contamination lmu 092702