Overview

• Classification• Signs and

symptoms• Work-up• Therapy and

prevention

• Immediate (24hrs)– Immunologic

• IHTR & EHTR• FNHTR• Allergic or urticarial• Anaphylactic • TRALI

– Non-immunologic• Bacterial contam• TACO• Physical or chemical

hemolysis

• Delayed– Immunologic

• HTR• TA-GVHD• Post transfusion purpura

– Non-immunologic• Hemosiderosis• Disease transmision

• INTRAVASCULAR HTR– Complement cascade– Hemoglobin into plasma– Proportional to amount

of blood transfused

• EXTRAVASCULAR HTR– Liver and spleen– Bilirubin into the plasma– Antibodies fail to

activate complement or activate via C3 stage

– Kell, Kidd, Duffy BGS

• FNHTR– Increase in temperature

of 1°C or more that is associated with a transfusion and cannot be explained by any other condition

– Due to recipient alloantibodies to lymphocytes & granulocytes or platelets

– Usually in multiple pregnancies or previous transfusions

LEUKOREDUCTION/LEUKODEPLETIONLEUKOREDUCTION/LEUKODEPLETION

•Definition Of Terms:Definition Of Terms:

• Any production, method, or process that decrease the count of White Blood Cells (Leukocytes) in a blood component.

• Red Cells, Platelets, Plasma, Whole Blood

TRANSFUSION REACTIONSTRANSFUSION REACTIONS

Non-hemolytic Febrile Transfusion Reaction (NHFTR) 2.60 %

Transfusion Transfusion Reactions (19.24%)Reactions (19.24%)Excluding Transfusion reaction like TA-GVHD

which rarely occurs.

Alloimmunization

51.98% 36.38% 9.04%

OthersCMV infection

91% of Transfusion Reaction is associated 91% of Transfusion Reaction is associated to WBC to WBC

WALKER : A.J.C.P. 88(3):374-378,1987.

Total TransfusionPopulation (80%)

Transfusion ReactionsTransfusion Reactions

LEUKOREDUCTION/LEUKODEPLETIONLEUKOREDUCTION/LEUKODEPLETION

* Guidance For Industry: Pre-Storage Leukocyte Reduction* Guidance For Industry: Pre-Storage Leukocyte Reduction Of Whole Blood And Blood Components Intended For Transfusion

USFDA Center For Biologics Evaluation And Research, January 2001http://www.fda.gov/cber/guidelines.htm

“ at present, LeukoreductionLeukoreduction is not considered appropriate for the prevention of Transfusion-associated Graft- Transfusion-associated Graft-

Versus Host DiseaseVersus Host Disease owing to the availability of Irradiation Irradiation as the preferred and definitive method against this serious

adverse transfusion outcome. ”

LR METHODS AND APPLICATIONSLR METHODS AND APPLICATIONS

“ “ USFDA therefore is issuing USFDA therefore is issuing recommendations for pre-storage leukocyte recommendations for pre-storage leukocyte

reduction of Whole Blood and Blood reduction of Whole Blood and Blood components for transfusion,components for transfusion, including including

recommendations for quality monitoring of recommendations for quality monitoring of the leukocyte reduction process. the leukocyte reduction process. Bedside Bedside filtration remains available as a leukocyte filtration remains available as a leukocyte

reduction method to physicians prescribing reduction method to physicians prescribing transfusion therapy.transfusion therapy. However, it may fail to However, it may fail to

adequately remove leukocytes due to adequately remove leukocytes due to uncontrolled filtration times and uncontrolled filtration times and

temperature. ”temperature. ”* Guidance For Industry: Pre-Storage Leukocyte Reduction* Guidance For Industry: Pre-Storage Leukocyte Reduction Of Whole Blood And Blood Components Intended For Transfusion

USFDA Center For Biologics Evaluation And Research, January 2001http://www.fda.gov/cber/guidelines.htm

LR METHODS AND APPLICATIONS (PRE-LR METHODS AND APPLICATIONS (PRE-STORAGE)STORAGE)

• Conventional Centrifugation Conventional Centrifugation And Automated Component Separation:And Automated Component Separation:

• Separation of Plasma and Red cells• Economical and Simple• Buffy coat extraction from blood components to a satellite bag• Residual Leukocyte Count = “ Varies “

LR METHODS AND APPLICATIONS (PRE-LR METHODS AND APPLICATIONS (PRE-STORAGE)STORAGE)

• Filtration (Pre – Storage):Filtration (Pre – Storage):• Filters should be attached to Blood Bags using Sterile Tubing Connecting Device for sterility and Closed system (USFDA requirement)

• In line Filters are also recommended for Pre-Storage Leukoreduction

• When performed according to cGMP, outdate is unchanged

• Optimum Leukoreduction of Blood components

• Average Residual Leukocyte Count = 2 x 105 (Imugard – III: TERUMO)

• RBC recovery of 90% (Imugard – III: TERUMO)

+ + w/ or

In-line FiltersIn-line Filters

LR METHODS AND APPLICATIONS (PRE-LR METHODS AND APPLICATIONS (PRE-STORAGE)STORAGE)

•Filtration (Pre – Storage):Filtration (Pre – Storage):

LR METHODS AND APPLICATIONS (POST-LR METHODS AND APPLICATIONS (POST-STORAGE)STORAGE)

• Filtration By Aseptic Technique Only (Post – Filtration By Aseptic Technique Only (Post – Storage):Storage):

• Filter connection done without the use of a Sterile Tubing Connecting Device (Laboratory or Bedside) is considered Open system (USFDA requirement)

• Stored @ 1 – 6 oC• Outdate is 24 hours

• Platelets outdate is 4 hours• Average Residual Leukocyte Count = 2 x 105 (Imugard – III: TERUMO)

• RBC recovery of 90% (Imugard – III: TERUMO)

• Available in Laboratory and Bedside Filters (Imugard – III: TERUMO)

LR METHODS AND APPLICATIONSLR METHODS AND APPLICATIONS

““All blood components, including those All blood components, including those leukoreduced prior to storage should be leukoreduced prior to storage should be

administered through a standard blood filter administered through a standard blood filter designed to remove clots and/or designed to remove clots and/or

microaggregates that were formed during microaggregates that were formed during blood storage.blood storage. ” ”

* Guidance For Industry: Pre-Storage Leukocyte Reduction* Guidance For Industry: Pre-Storage Leukocyte Reduction Of Whole Blood And Blood Components Intended For Transfusion

USFDA Center For Biologics Evaluation And Research, January 2001http://www.fda.gov/cber/guidelines.htm

• ALLERGIC– Recipient antibody to

donor plasma proteins– Mediated by histamine

release from mast cells

• ANAPHYLACTIC– Can be life threatening– Even with few ml– Reaction between

patient’s potent class specific anti-IgA Ab’s & IgA

• When IgA deficient recipients are previously exposed to IgA

• TRALI– Donor plasma containing

leukoagglutinins directed against recipient leukocytes

– HLA system specific– Donor is usually

multiparous

– Ag-Ab rxn gets trapped in pulmonary circulation

• Pulmonary edema• Complement activation• Sequestration &

degranulation of PMN’s

• BACTERIAL CONTAM– Sepsis– Usually from platelets– Transient bacteremia in

asymptomatic donors

– Contamination during collection, thawing or storage

– Common agents:• Yersinia enterolitica• S. Epidermidis• S. Aureus• B. subtilis

S. epidermidis, 30.2%

S. aureus, 10.5%

E. coli, 9.3%

B. cerus, 9.3%

S. cholerae-suis, 8.1%

E. cloacae, 5.8%

B-hem. Strep, 5.8%

E. aerogenes, 2.3%

10 others, 1.3% each

n = 86n = 86

Compilation of data from Clin Micro Rev Compilation of data from Clin Micro Rev 1994; 7:290-302; Transfusion 2001;41:1493-1994; 7:290-302; Transfusion 2001;41:1493-99; www.shot.demon.co.uk/toc99; www.shot.demon.co.uk/toc

• CIRCULATORY OVERLOAD– Rapid infusion of large

volumes of blood products• Very young, elderly, cardiac

patients, chronic anemia

– Rapid infusion of even small volumes

• Pre-existing cardiopulmonary disease

– Can lead to:• CHF• Pulmonary edema

• PHYS / CHEM’L HEMOLYSIS (Prior to transfusion)– Mechanical damage

• infusion through small bore• open heart surgery bypass

machines

– Thermal trauma• Freezing blood without

cryoprotectant or warming above 45°C

– Osmotic or chemical change

• Hypotonic or hypertonic solutions or drugs

• TA-GVHD– Immunocompromised

patients transfused with immunocompetent lymphocytes

• Recipients of bone marrow or peripheral stem cell transplants

• Transfusion recipients with inherited immunodeficiency syndromes

• Fetuses receiving intrauterine transfusions

• Receipients of donor units from a blood relative

• Newborns receiving exchange transfusions

• Patients with certain hematologic and oncologic

disorders

• DELAYED HTR– Anamnestic response– Previous transfusion or

pregnancy– Ab’s no longer detectable

– Mild (14 days)– Due to gradual

destruction of antibody coated RBC by macrophages and RES

– Implicated BGS:• Kell• Duffy• Kidd• Rh

• POST TRANS PURPURA– HPA antigens

• HEMOSIDEROSIS– Iron overload– Chronically transfused

(>100 units)– Each unit of RBC = 200

mg Fe

• DISEASE TRANSMISSION– Hepatitis B, C and D– Cytomegalovirus– Epstein-barr– HTLV I & II

– HIV– Treponema pallidum– Plasmodium – Babesia microti– Trypanosoma

Note: please review chapter 19 of Harmening