Blood Transfusion

Mukesh M Desai
Consultant Pediatric Hematologist, H.N. Hospital, Nanavati Hospital, Mumbai, India
First Created: 05/01/2005 


The transfusion is extremely safe today, however, the general perception that transfusions are unsafe persists thanks largely due to the HIV pandemic and risk of post-transfusion hepatitis. Today very often it is said, " The best blood is the one that you have not received." Preventable death due to wrong identification of blood still occurs and is largely occur due to human error. Ignorance among clinicians about how to transfuse blood adds further to these preventable deaths.

As a clinician, one will have to be aware of:

  • Indications for blood transfusion
  • Alternatives to blood transfusion
  • Administration of blood
  • Transfusion reactions
  • Informed consent for blood transfusion
  • Component therapy
  • Do's & Don'ts of blood transfusion

Ordering Blood:

Safe transfusion practice begins with the correct identification of the intended recipient. Blood samples of the recipient should be identified and labeled properly. Test recipient's blood for ABO Group, Rh type, Coomb's & crossmatch.

Steps at the Time of Issue of Blood

  • Identify intended recipient
  • Compare ABO group and Rh type of the primary label and transfusion form
  • Inspect color & expiry date of blood bag. Blood bag with clots, pinkish discoloration of plasma, purple discoloration should not be issued.
  • Record of issuing person, Date, Time and person to whom issued is to be maintained so that in case of an adverse reaction the person can be contacted to help identify the cause of transfusion reaction.

Issuing of Blood and Blood Component

  • Administer blood within half an hour of the issue from the blood bank.
  • ½ Hour time limit is empirical and is the time taken for the blood bag to reach 10 degrees Celsius temp.
  • No blood bank will accept blood back if it has reached 10-degree temp and it has to be discarded.
  • Non-medical reasons for the delay in starting blood transfusion can be avoided by properly educating transfusions.
  • Open system of blood e.g. saline washed RBC should be used within 24 hr.
  • Blood components like cryoprecipitate & FFP should be used within 6 hrs of issue.
  • In case of delay in initiating blood transfusion, return the blood bag to blood bank immediately.
  • Don't store blood or blood component in unmonitored nursing station refrigerator as storage temp for the blood of 0 to 4 degree Celsius cannot be assured and gives a false sense of security. This is a common practice in small nursing homes and ICCU and surgical theaters of most institutions.
  • Platelet bags should not be stored in a refrigerator, it should be maintained at 22 to 24 degree Celsius on a constant agitator

Steps at the Time of Infusion

  • Check all identifying information.
  • Identity the recipient on transfusion form, compatibility label, ABO group, Rh type, Donor unit identification no. & Expiry date.
  • Transfusionist must start transfusion only on physician's "written orders".

Starting the Transfusion

  • Record Date and Time of beginning and termination of blood transfusion.
  • Record amount of blood transfused.
  • Patient's record should be checked once again to verify correct identification.
  • Record patient's vital parameters prior to initiation of blood and then every 15 minutes, as changes in vital parameters are the first change to occur in case of a transfusion reaction.

Care During Transfusion

  • First half an hour is crucial.
  • Risk of catastrophic event like ABO hemolytic reaction and anaphylactic reaction is maximum in the first ½ hr.
  • Risk declines sharply after ½ hr.
  • Record vital signs every 15 minutes.
  • Increase rate of infusion to required rate.
  • Observe through out transfusion.

Rate of Infusion of Blood

  • First ½ hr is slow.
  • If no reaction, increase the rate depending on recipient's haemodynamic status.
  • If haemodynamically stable, transfuse over 2 hours.
  • If haemodynamically unstable, transfuse over 4 hours.
  • This time limit is empirical based on the time it takes the blood bag to reach room temperature. - Since blood is an excellent culture media, keeping the blood bag at room temperature for longer duration could result in bacterial overgrowth.
  • In case, medical condition of recipient demands transfusion over a longer period ask for split units of blood from blood bank and give each over 4 hours.
  • Rapid infusion may be necessary in certain clinical setting, then use mechanical devices for rapid infusion of blood. Blood pressure cuff is unsuitable for providing external pressure.

Discontinuing Blood Transfusion

  • Record time, Volume and type of component given.
  • Check patient's condition and vital parameters.
  • Return transfusion form to transfusion service i.e. blood bank.
  • Observe patient for one hour.
  • Do post transfusion monitoring: HCT, platelet counts, coagulation factors. (delayed transfusion reaction may be recognized if there is inappropriate rise in HCT.) Monitor for PTH (post transfusion hepatitis)

Blood Transfusion Filters

  • All blood component must be infused using filters.
  • Filters remove microscopic clots, cellular debris & undesirable particles.
  • Blood components like cryoprecipitate, platelets, FFP should also be infused using blood transfusion sets with filters.
  • Purified factor VIII, IX are provided by needles with inline filters
  • Standard blood transfusion filter size is 170-260 micron.
  • Microaggregate filter pore size is 20 -40 micron.
  • For routine transfusion, microaggregate filter is not necessary.
  • Microaggregate filter removes decomposed platelets, WBC and fibrin generated after 5 days of storage of blood with sizes of 20-160 micron which are pathologically implicated in ARDS, TRALI (Transfusion related acute lung injury) and pulmonary dysfunction.
  • Microaggregate filters are routinely used for transfusion in cardiovascular surgery e.g. CABG
  • Microaggregate filters are inappropriate to use in massive transfusion because it slows the rate of transfusion.
  • Microaggregate filters in pediatric cases can result in hemolysis.


  • For Pediatric transfusion, use 23 no scalp vein

If Blood Flow Rate Is Slow

  • Elevate blood container.
  • Check patency of needle and size.
  • Examine filter for excess debris.
  • Examine blood bag for presence of clot.
  • Add normal saline 50 to 100 cc

Blood Warming

  • For routine blood transfusion blood warming is NOT necessary.
  • As blood flows drop by drop, it attains body temperature quickly.
  • Infusion of blood without warming is NOT responsible for febrile reactions or any other transfusion reaction.
  • Blood warming results in increased metabolism, reduced 2,3 DPG and increased risk of bacterial overgrowth.

INDICATIONS for Blood warming:

  • Massive transfusion 100 ml/minute or 1 blood bag every 3 minute as the recipient may develop hypothermia and arrhythmias.
  • Exchange transfusion in a neonate.
  • Cold agglutinin disease


  • The whole blood bag should not be warmed.
  • Microwave should not be used for blood warming.
  • Blood warmers are available which warm the blood as it is flowing through the tubing.
  • While thawing FFP or warming blood the outlet port of the bag should be protected.

BLOOD WARMING occurs in clinical practice because of:

  • Delay in initiation of transfusion
  • Blood warming before initiation
  • Transfusion over prolonged duration.
  • Storage in unmonitored refrigerator.
  • Delay in completion.

*Addition of Drugs and Medications to Blood Bags is Prohibited:

  • Exception: Normal saline, 5% albumin.
  • Addition of drugs may cause a change in the blood e.g. Ringer's lactate results in clotting of blood and is contraindicated along with blood; 5% dextrose results in hemolysis.
  • Changes in drug can occur because of pH and ionic molecular constituent.
  • In case a reaction occurs it would be impossible to ascertain who was responsible for the reaction.

Don'ts For Blood Transfusion

  • Don't use blood from unlicensed blood bank.
  • Don't delay initiation of blood transfusion.
  • Don't warm blood.
  • Don't use routine pre-transfusion medication.
  • Don't infuse over more than 4 hrs.
  • Don't leave patients unmonitored.
  • Don't add any medication to blood bag.
  • Discard blood if not utilized.
  • Don't ask for all the blood bags at one time.
  • Don't use unmonitored refrigerator for storage.
  • Don't use the same transfusion set for more than one blood bag.
  • Do not wet outlet port of blood.
  • Don't store platelet in refrigerator.
  • Don't be complacent while checking identifying information.
  • Don't insist for immediate relative's blood and directed donation.

Adverse Reactions to Blood Transfusion

Any adverse reaction that occurs during the administration of blood and blood component must be considered as a transfusion reaction unless proved otherwise. Transfusion reactions occur in 7% to 10% of all recipients of blood or blood components. Fortunately, the majority of them are minor reactions. 10% of these reactions are hemolytic and 90% of these are non-hemolytic reactions. The incidence of ABO mismatch blood being infused is 1: 30,000 blood bag. 1 out of 10 ABO mismatch transfusion is fatal.

Transfusion reactions may be divided as follows:

Acute (<24 hrs):
Hemolytic transfusion reaction
Febrile non-hemolytic transfusion reaction
ABO incompatibility
Cytokines, anti-leukocyte antibodies
Antibodies to plasma proteins
Antibodies to IgA
Antibodies to leucocytes or complement
Marked fever with shock
Atypical reaction with hypotension
Congestive Heart failure
Air embolism
Hypokalemia and hyperkalemia.

Bacterial contamination
Associated with ACE inhibitors
Volume overload
Air infusion via line
Citrate toxicity
Rapid infusion of cold blood
Red cell storage

Delayed adverse reaction to transfusion (> 24 hrs): 

Alloimmunization to RBC, WBC, platelets
Post Transfusion Purpura
Exposure to antigen of donor origin-Plasma protein, HLA 
Anamnestic antibody to RBC antigen
Engraftment of transfused functional lymphocytes
Antiplatelet antibodies
not well understood

Iron overload
Transfusion transmitted diseases

multiple transfusion.
Hepatitis, HIV, cytomegalovirus, etc

Recognition of Acute Transfusion Reaction

Signs and symptoms of Acute hemolytic transfusion reaction:

  • Fever with or without chills
  • Rigors with or without fever
  • Pain at infusion site or in chest, abdomen or flanks.
  • Acute hypotension or hypertension.
  • Tachypnea and hypoxemia.
  • Nausea with or without vomiting.
  • Hemoglobinuria.
  • Urticaria, flushing, itching or edema.

The Role of Trans fusionist In Case of an Acute Transfusion Reaction:

  • First is to suspect and then is to take action.
  • STOP Transfusion immediately.
  • NOTIFY responsible physician.
  • MAINTAIN IV LINE with normal saline drip.
  • CHECK for all identifying information for clerical error.
  • Notify Blood bank personnel and patient's physician immediately.
  • Conditions requiring aggressive management need to be ruled out immediately. A physician must evaluate to rule out Acute hemolytic transfusion reaction, Anaphylaxis, TRALI, transfusion-induced sepsis.
  • Initiate therapeutic actions. Collect blood samples for the blood bank as directed by them usually 3-cc EDTA blood and 5 cc in plain tube. Blood for coagulation profile in a 10 cc-citrate tube and plain tube for biochemistry, electrolytes and appropriate blood cultures.
  • Return discontinued blood bag along with IV administration set, attached IV solutions, all related forms and labels.
  • In case, the reaction is limited to urticaria or circulatory overload there is no need to evaluate post-reaction blood or urine samples.
  • Observe the post reaction urine sample for AIHTR.
  • Monitor hemodynamic status, urine output, ECG.

The Role of Blood Bank Laboratory

  • Check for identification error: Recheck all the steps of transfusion process. In case of misidentification, search for other patients at risk.
  • Visual check for hemolysis: Post reaction plasma for hemoglobinemia. Elevated bilirubin by 5-7 hrs. Post reaction urine sample for hemoglobinuria.
  • Serological check for incompatibility: DAT testing.

Febrile Non-Hemolytic Transfusion Reaction: (FNHTR)

  • Rise in temperature of 1 degree Celsius with or without rigors.
  • Common, 0.5 to 1%.
  • Higher incidence in multiple transfused and multiparous females.
  • Antibodies to leucocytes ; Cytokine release.
Clinical picture:
  • Fever with or without chills. Mild temperature rise early in transfusion or 1 to 2 hrs later which is responsive to antipyretic.
Warning sign:
  • Severe rigors, temperature more than 40 degree Celsius suggests bacterial sepsis.
  • 1 out of 7 with previous FNHTR.
  • Diagnosis of exclusion.
  • Stop transfusion till hemolytic transfusion reaction ruled out.
  • Restart blood transfusion slowly.
  • Supportive treatment with Chlorpheniramine 50 mg & paracetamol.
Diagnosis of exclusion.

Stop transfusion till hemolytic transfusion reaction ruled out.

Restart blood transfusion slowly.

Supportive treatment with Chlorpheniramine 50 mg & paracetamol.
  • Use leucodepletion filters if patient has more than 2 FNHTR.
  • Use saline washed RBCs.
  • Premedication with paracetamol.

Allergic Urticarial Reaction

Incidence:-1 to 3%
Etiology:-Antibodies to donor plasma proteins.
Clinical picture:-
Itching,urticaria, rash, flushing and rarely laryngeal edema & Bronchospasm. It occurs towards the end of transfusion or after transfusion.
No need to stop transfusion
IV Chlorpheniramine
IV Hydrocortisone
Subcutaneous adrenaline 1:1000 if there is laryngeal edema
Prophylactic Chlorpheniramine
Saline washed RBC.

Acute Immune Hemolytic Transfusion Reaction (AIHTR)

Definition:-Rise in temperature of 1 degree Celsius with or without rigors.

Common, 0.5 to 1%.
Higher incidence in multiple transfused and multiparous females.
Etiology:-Antibodies to leucocytes ; Cytokine release.
Clinical picture:-Fever with or without chills. Mild temperature rise early in transfusion or 1 to 2 hrs later which is responsive to antipyretic.
Warning sign:-Severe rigors, temperature more than 40 degree Celsius suggests bacterial sepsis.
Recurrence:-1 out of 7 with previous FNHTR.



Diagnosis of exclusion.
Stop transfusion till hemolytic transfusion reaction ruled out.
Restart blood transfusion slowly.
Supportive treatment with Chlorpheniramine 50 mg & paracetamol.
Use leucodepletion filters if patient has more than 2 FNHTR.
Use saline washed RBCs.
Premedication with paracetamol.

"Any febrile reaction is treated as AIHTR unless proven otherwise."

TREATMENT and work up of AIHTR

  • Maintain IV access with crystalloid
  • Maintain Blood pressure, pulse
  • Maintain adequate ventilation
  • Give a diuretic and/or institute fluid diuresis
  • Monitor renal status (BUN, Creatinine)
  • Monitor coagulation status (PT, PTT, fibrinogen, FDP)
  • Monitor for signs of hemolysis (bilirubin, LDH, haptoglobulin)
  • If sepsis is suspected send appropriate cultures.
  • Delineation of every step from phlebotomist to medical technologist to Transfusionist.
  • Education of transfusionist as he has the last opportunity to prevent misidentification and the first one to identify transfusion reaction.

Non Immune Hemolysis: Bacterial Contamination









Healthy donor with transient bacteremia

Asymptomatic carrier of bacterial infection

Contamination of anticoagulant in blood bag

Defect in plastic bag

Improper handling of needles

Inadequate sterilization of skin

During component preparation

During storage: platelets stored at 20 to 22degree C.

Temperature fluctuations

Psychrophilic gram negative bacteria; pseudomonas, Citrobacter Freundii, E coli, Yersina enterocolitica, Bartonella, Brucella Staphylococci, Diphtheroids.

Due to endotoxin

Risk of bacterial contamination:
1:500 000 Red blood cells.
1:10,200 platelets.
1:19,500 platelet pheresis.







Risk is higher if there is improper storage condition for blood

Blood warming prior to transfusion

Keeping blood in unmonitored nursing station or nursing home refrigerator.

Giving blood over prolonged duration

Using blood transfusion set for more than one bag

Entry port contamination while thawing blood component

Insertion of medication

Fatality rate:

Clinical features:
Fever-40 degree C with rigors, shock, DIC, Renal failure, Hemoglobinuria, abdominal cramps, Diarrhea and vomiting.


  • Inspect blood bag for sign of bacterial overgrowth, Cells or plasma, brownish or purple color, Clots, opaque or muddy Plasma, Peculiar odor, Hemolysis.
  • Do Gram stain for organism.
  • Send cultures from blood bag at 4 degree Celsius, 20-24 degree Celsius, 35-37 degree Celsius.
  • Antibiotics
  • Treatment similar to AIHTR
  • Attention to storage conditions
  • Proper sterilization of phlebotomy site
  • Sterile connecting device while component preparation
  • Education of transfusionist regarding proper administration of blood
  • Open system to be infused with in 24 hrs and preferably before 6 hrs of preparation.

Anaphylactic Reaction:


-Antibody to donor plasma protein. 

-Most commonly Anti-IgA
Clinical features:
-Occurs after infusion of few ml of blood. Cough, bronchospasm, respiratory distress, Abdominal cramps, diarrhea, shock, loss of consciousness and absence of fever
-Stop transfusion

-Treat shock

-Epinephrine 0.3 to 0.5 mg C or IM 1:1000 solution. In severe cases 1:10 000 IV

-Steroid: IV hydrocortisone 100 mg

-Antihistaminic IV, B2 agonist

-Maintain donor file

-Deglycerolized RBC

-Extensively washed RBC

-Encourage autologous blood transfusion

-Plasma component prepared from IgA deficient individuals .

TRALI (Transfusion-related acute lung injury):

Anti HLA or Leucoagglutinin
Pathophysiology:-Migration of activated neutrophils to lung.

Microvascular occlusion. 

-Capillary leakage and pulmonary edema
Clinical presentation:
Idiosyncratic presentation with in 4 hrs of transfusion 

-Marked respiratory distress

-Hypoxia, hypotension, fever

-Bilateral pulmonary infiltrate
High dose steroids

-Supportive care

-Ventilator support.

Washed RBC

-Microaggregate filters

-Leucodepletion for blood and blood component

Transfusion Associated Graft Versus Host Disease

Very rare 

1:660 in Japan

Transfusion of viable lymphocytes which engraft in the recipient, proliferate and initiate GvHD 

-Immunocompromised host

-HLA compatible donor

-Blood relative

-HLA matched component

-Population with limited HLA diversity
Target organs:
Skin, Liver, Gastrointestinal tract, Bone marrow
Clinical features:

Begins by 10th to 12th day 


-Jaundice and liver enzyme abnormalities

-Diarrhea 3 to 4 liters of watery diarrhea


HLA typing

-Skin biopsy
Patient at risk:
Neonate, premature babies, Premature with Hemolytic disease of newborn 
(HDN), intrauterine transfusion, Full term and HDN requiring Exchange transfusion, Full term with neonatal alloimmune thrombocytopenia requiring mothers platelets.

-Congenital immune deficiency: SCID, Wiskcott Aldrich syndrome, Purine nucleotide phosphorylase deficiency, and Nezloff syndrome.

-Fresh maternal and paternal plasma

-Leukemia estimated risk 0.1 to 1%

-Lyphoma estimated risk 2%

-Post BMT

-HLA matched allogenic BMT

-Transfusion from blood relative

-HLA matched blood component

-Donor of the same ethnic back ground with limited HLA diversity

-Solid tumours on intensive chemotherapy.
Components implicated in TAGvHD:

Whole blood
Packed cells
Granulocyte pack
Fresh plasma
Components not implicated
in TAGvHD:


Comparison of TAGvHD and GvHD in BMT

0.1 to 1.0%30 to 70%;
2-47 days35 to 70 days
Hypocellularnot affected
Duration of illness
<54 days5 months
87- 100%5-10%
Irradiation of blood and blood component for patients at risk. Dose: 2500
Irradiation of:
  •  Cellular component intrauterine transfusion
  •  Patients identified at risk for TAGvHD
  •  Transfusion of cellular component between blood relatives
  •  Transfusion of HLA selected products
  • MORTALITY:87 TO 100%

    Anaphylactoid reaction to ACE inhibition

    Reaction: flushing and hypotension in patients on ACE inhibitors

    Mechanism: Prekallikrein present in blood and blood product is converted to vasoactive bradykinin whose metabolism is inhibited by ACE inhibitors resulting in hypotension.

    Procedures associated:

    • Therapeutic plasma exchange with albumin replacement

    • Contact of plasma with dialysis membrane

    Delayed Hemolytic Transfusion Reaction

    Two types:
    Anamnestic response to transfused RBCs
     -Primary alloimmunisation
    1:11000 to 1:5000 
      0.05% to 0.07% of transfusion recipient
    Clinical presentation:
    More common in multiply transfused & Multiparous women 
     -Occurs 3-7 days post transfusion
     -Extravascular hemolysis
     -Absence of anticipated Hb or HCT rise following blood
     -Rarely hemoglobinuria
    Antibodies implicated:

    Common antibodies
    Uncommon antibodies

    Anti jka
    Anti A1

    Anti E
    Anti P1

    Anti D 
    Anti C 
    Anti K 
    Anti Fya 
    Rarely Anti HLA antibodies

    Freshly draw blood to test for alloantibodies,
      Compare with previous sample.
    Rarely necessary
     -Observe urine output
     -Blood Transfusion that lack the corresponding antigen.
    Prevention: Blood that lack the responsible antigen.
      Issue medical alert card to these patients

    Maintain record of the offending antibodies.

    Post Transfusion Purpura

    Acute severe thrombocytopenia 5-10 days after transfusion in a previously pregnant female or multiple-transfused individual.
     -Typically perimenopausal or menopausal women
     -Rare in males.
    Patients platelet lack HPA -1a (PLA1) 
     -2% of population
     -Antibodies destroy both HPA-A1 positive and HPA -A1negative platelet..
    Self-limited, recovery in 21 days
    Steroids controversial 
     -Plasma exchange
     -IV IgG
     -HPA-A1 antigen negative platelet of benefit but difficult to arrange.
      Recurrence rare.
    Prevention: Washed PC

    Blood from HPA-A1 negative patients.

    Platelet Refractoriness

     20 to 70% requiring multiple platelet transfusion
     Lack of accepted CCI of two platelet transfusion
      Poor response to three platelets in 2 weeks
     Platelet alloimmunization
      Non-immune causes
    Immune causes:
     ABO mismatch
      Anti HLA antibodies
      Platelet specific allo and autoantibodies
      Drug dependent antibodies
    Most common cause:
     Anti HLA antibodies
      Produced by passenger lymphocytes
      May disappear
    Strategies for prevention:
     ABO matched Single donor apheresis platelets
     -Leucodepletion using leukocyte filters
     -HLA matched platelets difficult-Need a donor pool of 2000 to 3000 donor
     -Irradiation of HLA matched platelets must

    Blood Transfusion Blood Transfusion 2005-05-01
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