Blood Transfusion and

ReactionsPresenter: Dr. Suresh Pradhan

Moderator: Dr. Upendra Krishna Regmi

Objectives• Blood: components, functions

• Blood Transfusion: Ten Commandments

• Different Blood Products: Brief discussion

• Transfusion Reactions

• is considered as river of life, fluid of life, growth & health • a specialized type of connective tissue

in which living blood cells (formed elements), are suspended in a non living fluid matrix called plasma

• cells-⌐ Red Blood Cells⌐ White Blood Cells⌐ Platelets

• normal blood volume = 65-80 ml/kg

• plasma = 40-50ml/kg

5blood and blood transfusions

• Hematocrit- the volume percentage (vol%) of red blood cells in blood

• is normally 45% (42-52) for men and 40% (37-47) for women

• PCV or Hct = 3 x Hb

• Hb = 13-18gm% (M); 11-16gm% (F)

Average blood volumes

Haemoglobin levels to diagnose anaemia at

sea level (g/l)

Functions of Blood• a vehicular organ that perfuses all other

organs • blood and interstitial fluid deliver nutrients

to cells and remove wastes• hemostatic governors are carried to and

from appropriate sites

Functions of Blood…• Transport

•Regulation

•Protection

Functions of Blood…Transport:• suspended cells include RBC that carry O2

• platelets contribute to the hemostatic process• chemicals dissolved in plasma (nutrients,

waste, hormones)•metabolic heat for disposal

Functions of Blood…Regulation: • plasma contains pH buffers• plasma water absorbs heat• plasma solutes maintain osmolality

Functions of Blood…Protection: • plasma precursor proteins form blood clot

when stimulated• suspended WBC attack bacteria and

viruses ( body’s defense )• plasma contains antibodies and opsonins

for immunity

Blood Groups• human red cell membranes are estimated to

contain at least 300 different antigenic determinants• at least 20 separate blood group antigen

systems are known• the ABO and the Rh systems are important in

the majority of blood transfusions

The ABO System• first described by Landsteiner in 1901 • ABO blood group typing is determined by the

presence or absence of A or B red blood cell (RBC) surface antigens: • type A blood has A RBC antigen,• type B blood has B RBC antigen,• type AB blood has both A and B RBC antigens, and • type O blood has neither A nor B RBC antigen present

• accidental transfusion of ABO-incompatible Blood- Rapid intravenous hemolysis

Blood Group

RBC Antigen

Serum Antibody %

A A Anti B 45B B Anti A 8

AB A & B - 4

O - Anti A Anti B 43

The Rh System• described in 1940 by Landsteiner & Wenier• approximately 46 Rhesus group red cell

surface antigens• patients with the D Rhesus antigen are

considered Rh-positive• individuals lacking this antigen are called Rh-

negative

• in contrast to the ABO groups, Rh-negative patients usually develop antibodies against the D antigen only after • an Rh-positive transfusion or• with pregnancy, in the situation of an Rh-negative

mother delivering an Rh-positive baby

Other Red Blood Cell Antigen Systems• Other red cell antigen systems include Lewis,

P, Ii, MNS, Kidd, Kell, Duffy, Lutheran, Xg, Sid, Cartright, YK, and Chido Rodgers• fortunately, with some exceptions (Kell, Kidd,

Duffy, and Ss), alloantibodies against these antigens rarely cause serious hemolytic reactions

Indications of blood transfusion

• Blood loss greater than 20% of blood volume • Hemoglobin level less than 8 g/dL• Hemoglobin level less than 10 g/dL with

major disease (e.g., emphysema, ischemic heart disease)• Hemoglobin level of less than 10 g/dL with

autologous blood • Hemoglobin level less than 12 g/dL and

ventilator dependence

•whole blood in case of surgical condition‐ during a major operation‐ severe blood loss or hemorrhage‐ post operatively in a severe debilitated and

anemic patient‐ as a prophylactic measure preoperatively in

hemorrhagic tendencies as in haemophilia, ITP

•Clinical judgement-• Cardiovascular status• nature of surgical/medical illness• age• anticipated additional blood loss• arterial O2 tension

• The Practice Guidelines for Blood component therapy developed by the ASA state that

“Red blood cell transfusion is rarely indicated when the haemoglobin concentration is greater than 10 gm/dl and is almost always indicated when it is less than 6 gm/dl”

Transfusion Ten Commandments • adapted from the NHS Blood and Transplant

‘Transfusion 10 commandments’• underpin safe and effective transfusion

practice1. Transfusion should only be used when the

benefits outweigh the risks and there are no appropriate alternatives.

2. Results of laboratory tests are not the sole deciding factor for transfusion.

3. Transfusion decisions should be based on clinical assessment underpinned by evidence-based clinical guidelines.

4. Not all anaemic patients need transfusion. (there is no universal ‘transfusion trigger’)

5. Discuss the risks, benefits and alternatives to transfusion with the patient and gain their consent.

6. The reason for transfusion should be documented in the patient’s clinical record.

7. Timely provision of blood component support in major haemorrhage can improve outcome – good communication and team work are essential.

8. Failure to check patient identity can be fatal. Patients must wear an ID band (or equivalent) with name, date of birth and unique ID number. Confirm identity at every stage of the transfusion process. Patient identifiers on the ID band and blood pack must be identical. Any discrepancy, DO NOT TRANSFUSE.

9. The patient must be monitored during the transfusion.

10.Education and training underpin safe transfusion practice.

Blood Products• any therapeutic substances that are prepared

from human blood

Blood Components - red cell concentrates - platelet concentrates - fresh plasma - cryoprecipitate

Plasma Derivatives - albumin - coagulation factors - immunoglobulins

Blood Component Therapy• process of transfusing only that portion of

the blood needed by the patient• allows a single unit of donated blood to

benefit more than one patient• Red blood cells and Platelets are the most

frequently transfused blood components

Blood Components

Banked Whole blood• no components have been removed• consists of red blood cells, white blood

cells and platelets in plasma • can be stored for 5 weeks• stored in the refrigerator, the platelets

are useless and factors V & VIII are greatly reduced

Banked Whole blood…

• 49 ml of CPDA preservative solution is added to 301 ml blood• transfusion of whole blood may be necessary • certain types of major surgery • Acute blood loss > 15%

• major trauma such as a car accident or gunshot wound requiring emergency surgery

Fresh whole blood• blood that is administered within 24 hours of

its donation• rarely indicated• poor source of platelets and factor VIII

Packed Red Cells• the red cells from a donor unit, diluted

with plasma to a hematocrit of about 75% • volume is about 200 mL• storing red cells (just above freezing)

allows survival for 42 days• decreases 2,3-DPG• ruins the platelets and neutrophil

Packed Red Cells…• Red blood cells contain hemoglobin• carries oxygen throughout the body• essentially provides oxygen-carrying capacity

• product of choice for most clinical situations• Indications• acute trauma before surgery • people with anemia who are having surgery

Packed Red Cells…• fastest way to increase the oxygen-delivering

capacity of the blood• a unit of packed red cells will raise the

hematocrit by 3% and the hemoglobin by 1-1.5 gm/dL

Frozen Red Cells• reduces the risk of infusing antigens, or

foreign bodies, that the body might regard as potentially dangerous• Previously sensitized patients

• not available for use in emergency situations• RBC viability is improved• ADP and 2,3 DPG maintained

Frozen Red Cells…• stored in the frozen state in a hypertonic

glycerol solution for up to 10 years• indicated for prolonged storage of rare red

cells• expensive but the chance of reaction &

diseases transmission is less • Glycerol must be separated from RBC before

transfusion

Microaggregate-Free Blood• used to prevent reactions to leucocyte

and platelet antigens• specially designed machines are used to

wash the red blood cells (RBCs), which are then suspended in sterile saline

Microaggregate-Free Blood…

• haematocrit of 70-80% and a volume of about 180ml • saline washing removes residual plasma

(98%), and reduces the concentration of leucocytes, platelets and cellular debris• Stored for 24 hr at 1-6 ˚C

Irradiated Red Cells • gamma radiation is used to destroy the

lymphocytes in a unit of packed red cells that are responsible for transfusion related graft versus host disease• Uses:

⌐ severely immunocompromised recipients⌐ lymphoma⌐ stem cell and marrow transplants⌐ unborn children undergoing intrauterine

transfusion

Leucocyte Depleted Red Cells

• 99.9% of the white cells removed by freezing or microfiltration • reduces, but does not eliminate the risk of

cytomegalovirus (CMV), Epstein-Barr, HTLV infections and febrile reactions

Granulocytes

• indicated for life-threatening infections in neutropenic cancer patients who are unresponsive to antibiotics • prepared by separating white blood cells

from blood donated by volunteers whose leucocyte count has been increased by pre-treatment with corticosteroids, or those with chronic granulocytic leukaemia

Granulocytes…• donations must be cross-matched because

they contain large numbers of red blood cells• irradiated to remove the lymphocytes• collected either by apheresis or derived from

whole blood• stored for 24 hours at 20-24 ˚C

Platelet Concentrates• collection and storage of platelets 1. Pooled platelets 2. Apheresis platelets• platelets last for 3-5 days if stored on an

agitator at 22˚C and at a pH of between 6.2 and 7.8• each bag has a volume of 250-350ml

Platelet Concentrates…• are not usually cross-matched with the

recipient, but where possible ABO specific platelets should be used• risk of transmission of bacterial infection is

higher with platelet transfusions than red cells, particularly if they have been stored for 3 days or more

Platelet Concentrates…• bacterial contamination may occur at the time

of collection, and the storage bags are made of special plastic, which allows gas exchange (oxygen and carbon dioxide) to occur across its walls at 22˚C• this helps preserve platelet function but

promotes bacterial growth• the longer the platelets are kept prior to

transfusion, the higher the risk of bacteremia

Platelet Concentrates…• indications• in platelet disorders• in massive blood loss

• one unit will usually raise the platelet count 5-10k/microliter• check one hour after transfusion

Indications For Platelet Transfusion

Fresh Frozen Plasma• used to provide replacement coagulation

factors in cases of excessive bleeding• from freshly donated blood• contains all the coagulation factors and

albumin• source of plasma cholinesterase• only source of factor V

• 1 unit FFP = 3% increase in CF levels• at least 30% to ensure adequate coagulation• Indicated for coagulopathy and deficient

clotting factors

Indications For The Use Of Fresh Frozen Plasma

Collection And Storage Of FFP

• FFP is collected as the supernatant after centrifuging a donation of whole blood• is frozen within 8 hours and may be stored

for up to 1 year at -30 ˚C• under these conditions, the loss of Factors V

and VIII is kept to a minimum• frozen packs are brittle and should be

handled with care

• frozen plasma can be thawed using a dry oven (10 minutes), microwave (2-3 minutes) or a water bath (20 minutes)• thawed FFP is best used immediately, but

may be stored at 4˚C and infused within 24 hours, provided it is kept at this temperature or returned to the blood bank for storage within 30 minutes of being removed from a 4˚C fridge or transport box

Cryoprecipitated antihemophilic factor• an antihemophilic concentrate• prepared from plasma• is rich in clotting factors • used in people with hemophilia, von

Willebrand's disease or other major coagulation abnormalities to prevent or control bleeding

• contents are the major portion of the Factor VIII, von Willebrand factor, fibrinogen, Factor XIII and fibronectin present in freshly drawn and separated plasma• one unit of plasma typically generates 10 to

20 mL of cryoprecipitate• these small concentrates are combined for a

single adult dose of five bags and frozen at –20°C

Indications For The Use Of Cryoprecipitate

Plasma Derivatives• proteins processed from plasma for therapeutic

infusions• Albumin• Immunoglobulin• Clotting factors

• derivatives are purified from plasma using physicochemical fractionation methods developed by Edwin J. Cohn in the 1930s

Albumin•when all the cellular material and coagulation

factors have been removed from plasma, it contains mostly albumin• available as 5% and 25% (salt poor albumin)

solution• Albumin is heat-treated to kill viruses• Shelf life of 2 years and should be stored at

room temperature.• used to restore intravascular volume

Immunoglobulins• IgGs are given for immune support or for

immunomodulation to suppress native antibody production• Hyperimmune globulins are fractionated from

the plasma of donors with high levels of antibody to specific antigens of interest, such as viruses (HBV, CMV, varicella zoster) or the Rh blood group D antigen (RhIG to prevent anti-D formation in RhD-negative women)

Fibrin Glue• fibrin glue and fibrin gel are blood derivatives

rather than pharmacologic agents• is derived from a source of fibrinogen and

factor XIII (fibrin-stabilizing factor), in which a solution of fibrinogen is mixed with a solution of thrombin and applied to a surgical field• applied directly to wounds that display diffuse

microvascular bleeding or can be used to seal vascular grafts

Things To Be Considered Before Transfusion

• checked by two individuals• identification with patients name and bag

number• blood grouping and cross matching• date of collection and expiry• inspected for bacterial contamination such as

discoloration, bubbles, or any suspended particles and clots inside the bag

Things To Be Considered Before

Transfusion…•warming up of blood to 37oC• rapid transfusion• pediatric patients• warming may not be necessary if 1 or 2 units of

blood are slowly transfused to normothermic adult patients

• secure IV access• preparation of transfusion set• a standard blood transfusion set with a pore size

of 170 m to trap any clots or debris

• initial transfusion (about 15 minutes) should be slow• the IV line should be free from calcium

containing drugs/fluids

Transfusion Reactions

1. Immune Complications

2. Infectious Complications

3. Complications related to massive blood transfusion

Immune Complications• are due to sensitization of the recipient to the

donori. red cellsii. white cellsiii. plateletsiv. plasma proteins

• less commonly- the transfused cells or serum may mount an immune response against the recipient

• Immune Reactions can be divided into:

Haemolytic Reactions

Non-haemolytic Reactions

1.Haemolytic Reactions• involves specific destruction of the transfused

red cells by the recipient’s antibodies

• can be classified intoI. Acute Haemolytic Reactions

II. Delayed Haemolytic Reactions

I.Acute Haemolytic Reactions

• due to ABO incompatibility•most common cause- misidentification of • patient• blood specimen• transfusion unit

• symptoms vary depending upon patient’s conditions

• in awake patients- chills, fever, nausea, chest and flank pain• in anesthetized patients- • rise in temperature• unexplained tachycardia• hypotension• hemoglobinuria• diffuse oozing from the surgical site• rapid development of- DIC, Shock, Renal failure

Management Of Acute Hemolytic Reaction

i. stop transfusionii. recheck unit against blood slip and patient

identityiii. send blood sample for Hb, repeat

compatibility test, coagulation study and platelets count

iv. urinary catheterization and send urine for Hb

v. osmotic diuresis- mannitol/ IV fluids

II.Delayed Haemolytic Reactions

• also known as extravascular hemolysis• usually mild• caused by antibodies to non-D antigens of Rh

system or to foreign alleles in other systems such as Kell, Duffy, Kidd antigens• hemolytic reactions are delayed 2-21 days

after the blood transfusion

• symptoms- usually mild• malaise• jaundice• fever• patients’ Hematocrit fails to rise or rises only

transiently inspite of blood transfusion and absence of bleeding• serum conjugated bilirubin increases due Hb

breakdown

• diagnosis- Direct Coombs’ test

• treatment- primarily supportive

2. Non-haemolytic Reactions

• occur due to sensitization of the recipient to the donor’s white cells, platelets or plasma proteins

• risk of these reactions can be reduced by use of leukoreduced blood products

Different Non-hemolytic Reactions

• Febrile Reactions• Urticarial Reactions• Anaphylactic Reactions• Transfusion Related Lung Injury (TRALI)• Graft Versus Host Disease• Post Transfusion Purpura• Transfusion Related Immunomodulation

Febrile Reactions•white blood cells or platelet sensitization is

manifested as febrile reactions• relatively common• characterized by increase in temperature

without evidence of hemolysis• patients with history of repeated febrile

reactions should receive leukoreduced transfusions only

Urticarial Reactions• characterized by

‐ erythema‐ hives‐ itching without fever

• relatively common• due to sensitization of the patient to

transfused plasma proteins• treatment- antihistaminics and steroids

Anaphylactic Reactions• relatively rare (1:150,000)• are severe reactions•may occur after transfusion of only a few ml of

blood• treatment-epinephrine, fluids, corticosteroids,

H1 & H2 blockers• patients with IgA deficiency should receive

thoroughly washed packed red cells, deglycerolized frozen red cells or IgA free blood.

Transfusion Related Lung Injury (TRALI)

• presents as acute hypoxia and non cardiac pulmonary edema occurring within 6 hours of blood product transfusion• frequency- 1:5000• can occur with transfusion of any blood

components but specially platelets and FFP• transfusion of antileukocytic or anti HLA

antibodies results in damage to the alveolar-capillary membrane

• treatment: similar to ARDS• but response to treatment varies • TRALI may resolve within a few days with

supportive therapy

Graft Versus Host Disease• seen in immunocompromised patients• cellular blood products contain lymphocytes

capable of mounting an immune response against the compromised (recipient) host• irradiation of red cell, granulocyte, and

platelet transfusions effectively eliminates lymphocytes without altering the efficacy of such transfusions

Post Transfusion Purpura• rarely, profound thrombocytopenia may occur

after blood transfusion• results due to development of platelet

alloantibodes• these antibodies destroy the patient’s own

platelets• platelet count drop precipitously 5-10 days

following blood transfusion• treatment- IV IgG and Plasmapheresis

Transfusion-Related Immunomodulation

• diminishes immune responsiveness and promote inflammation• recent studies show perioperative

transfusion may increase the risk of post operative bacterial infection, cancer recurrence and mortality• so unnecessary blood transfusions should be

avoided

Infectious Complications

• viral infections• hepatitis- B (1:200,000) , C (1:190,000)• AIDS (1:190,000)• other viral infections- CMV, EBV,

Parvovirus, West Nile Virus

•parasitic infections•malaria• toxoplasmosis• Chagas disease

• bacterial infections• second leading cause of transfusion associated

mortality• gram positive- Staphylococcus and gram

negative- yerisina, citrobacter• to avoid possibility if significant bacterial

contamination, blood products should be administered over a period shorter than 4 hrs

• specific bacterial diseases which are rarely transmitted are:

⌐syphilis⌐brucellosis⌐salmonellosis⌐yersiniosis⌐rickettsioses

Massive Blood Transfusion•Massive transfusion is defined, in adults, as

replacement of • total blood volume in 24 hours• half of total blood volume in 6 hours• one unit blood in 5 mins• 5 units blood in 60 mins

• in children, it is defined as transfusion of >40 mL/kg

•Massive transfusion occurs in settings such as • severe trauma• ruptured aortic aneurysm• surgery and obstetrics complications

• the goals to the management of massive transfusion include:• early recognition of blood loss• maintenance of tissue perfusion & oxygenation

by restoration of blood volume & haemoglobin• arrest of bleeding including with early surgical or

radiological intervention, and• judicious use of blood component therapy to

correct coagulopathy

• coagulopathy• Dilutional thrombocytopenia • Lack of coagulation factors V & VIII• DIC associated with hypoperfusion or hemolytic

reaction

• citrate toxicity• calcium binding by citrate- hypocalcemia• citrate metabolism is primarily hepatic-patients

with hepatic disease or dysfunction (and possibly hypothermic patients) may demonstrate hypocalcemia and require calcium infusion during massive transfusion, as may small children and others with relatively impaired parathyroid–vitamin function

• hypothermia• all blood products should be warmed to normal

body temperature• ventricular arrhythmias progressing to

fibrillation may occur at 30oC• hypothermia hampers cardiac resuscitation

• acid-base balance:• metabolic acidosis----as normal tissue perfusion

occurs---metabolic acidosis resolves and metabolic alkalosis occurs due to citrate/lactate

• Serum Potassium concentration:• extracellular concentration of potassium in

stored blood increases with time• the amount of extracellular potassium

transfused with each unit is typically less than 4 mEq per unit• Hyperkalemia can develop regardless of the age

of the blood when transfusion rates exceed 100 mL/min