GROUP A HS221 / 5AMLT 502

TRANSFUSION REACTION

INTRODUCTION

According to Medscape, Online Medical Dictionary, transfusion reaction can be define as reaction of the body to a transfusion of blood that is not compatible with its own blood during or within 24 hours of a blood transfusion.Transfusions are given:a)      To restore lost or depleted blood componentsb)      To improve clotting timec)      To improve the ability of the blood to deliver oxygen to the body’s tissues.

ACUTE HEMOLYTIC TRANSFUSION

REACTION

What is Acute Hemolytic Transfusion?

Types of transfusion reaction associated with hemolysis.

It occur as soon as possible after blood is being transfused.

AHTR also known as ‘Immediate Hemolytic Transfusion Reaction’.

Types of AHTR1)Immune Mediated2)Non-immune Mediated

• IMMUNE MEDIATED cause by :- Anti A, Anti B or both- Rh - Kell -Duffy

• This result in severe intravascular hemolysis and later cause extravascular. • NON IMMUNE MEDIATED occurs when there are

damage of RBC before transfusion which result in hemoglobinemia and hemoglobinuria. Patient shows asymptomatic or milder symptoms.

Sign and SymptomsFever HemoglobinemiahemoglobinuriaRed or dark urine Chills Hypotension Renal failure DIC (Disseminated intravascular

coagulation)Back pain

Management1)When reaction become more severe :

- stop transfusion and inform doctor for immediate patient review.

-check vital sign and respiratory status.- check patient ID and recheck again detail

on blood unit and compatibility label or tag.2) Inform transfusion service immediately.3)Administered low dose of dopamine for hypotension patient (1-5ug/kg/min)4) Monitor urine output commonly using catheterisation.

Complication Acute kidney failure. Anemia Lung problems Shock

Treatment Mild symptom can be treated with : - paint reliever and acetaminophen can reduce fever and discomfort. -intravenous

Prevention Prevent mislabeled Collect the correct sample. Must form bedside check before

administer blood product. Make sure correct bar coding of blood

component and patient ID. Transfusion practice should be done by

experience physician and nurse.

ALLERGIC TRANSFUSION REACTION

Definition : hypersensitivity reaction to a particular allergen

2 types of allergic reaction:• urticaria transfusion reaction• anaphylactic transfusion reaction

URTICARIA TRANSFUSION REACTION

• Simple allergic reaction

• Usually begin minutes after infusion

• The reaction is simple to diagnose and do not cause

significant problems to the patient.

• Patient are treated with an antihistamine such as

diphenhydramine (Benadryl).

Mechanism of urticaria transfusion reaction

• Urticaria transfusion reaction caused by soluble allergenic

substances in donor product

• The recipient IgE antibody will reacts against this allergenic

subtances, most commonly a donor plasma protein resulting in a

"type I hypersensitivity" reaction

• Histamine and other substances are released from mast cells and

basophils through interaction with IgE.

• The secretions result in the formation of pruritic (itchy) raised,

red-rimmed "wheals" on the skin of the recipient.

Sign & symptom of urticaria transfusion

reaction:

• No fever

•Erythema

• Cutaneous flushing

• Angioedema

• Nausea

• Vomiting

• Diarrhea http://upload.wikimedia.org/wikipedia/commons/6/63/EMminor2010.JPG

Treatment of urticaria transfusion reaction:

● Temporarily stop the transfusion

● Maintain intravenous access

● Give diphenhydramine 20–50 mg IV

● If the symptoms resolve, restart the transfusion slowly

● If the symptoms do NOT resolve, stop the transfusion

ANAPHYLACTIC TRANSFUSION REACTION

•Rapidly developing and serious allergic reaction

• This reaction affects a number of different body systems at one time.

• Severe anaphylactic reactions can be fatal

• Associated with IgA deficiency deficiency

•Patient treated with epinephrine

Mechanism of anaphylactic transfusion reaction

• Usually caused by exposure of an antigen to a sensitized patient.

•Reaction commonly occur when recipient has no IgA antibody and

transfusion was elicits anti-IgA response of recipient

• The "classic" type of anaphylaxis involves IgE antibodies on the surface of

a mast cell targeted against an offending antigen. When the patient is

exposed to the antigen a second time, the IgE stimulates the mast cells,

leading to an outpouring of histamine.

Sign and symptoms of anaphylactic transfusion reaction:

• Hypotension• Tachycardia• Chest pain• Loss of consciousness• Arrhythmia• Wheezing• No fever• Patient can have upper and lower airway obstruction such as hoarseness and dypsnea

http://www.cambrianfirstaid.co.uk/mediafiles/anaphylaxis%20baby%20gif.gif

Treatment of anaphylactic transfusion reaction:

● Stop the transfusion

● Maintain IV access with normal saline

● Administer oxygen

● Intubation may be needed

● Epinephrine is most effective medication for treatment of anaphylaxis

● Steroid and H1-receptor antagonists have been used

● Observe the patient closely

● Report the reaction to the transfusion medicine service

TRALITRANSFUSION RELATED

ACUTE LUNG INJURY

• TRALI=Transfusion Related Acute Lung Injury

• TRALI is a complication of allogenic blood transfusion that typically manifested by shortness of breath due to noncardiogenic pulmonary edema,fever and hypotension.

• It can cause transfusion-associated mortality.

What is TRALI?

•There are two types of mechanisms that involve with the TRALI which are:▫ A) Immunologic Mechanism▫ B) Nonimmunologic Mechanism

•Mechanism of TRALI pathogenesis is differ among patients.

Pathophysiology of TRALI

A)Immunologic mechanism

Principle • Involve antibody-mediated

event.• Alloantibodies are

responsible for TRALI.

Types of Alloatibodies

involve

• Anti-human leukocyte antigen(anti-HLA) class I or class II antibody

• Also associated with antilymphocyte,antimonocyte

• Specific neutrophil alloantigen:HNA-1a,HNA-1b,HNA-3a and HNA-2a

Donor alloantibody interact with

recipient leukocyte antigen

Activation of complement

cascade,cytokines

Initiate antigen-antibody

interacion

Produce inflammatory

mediators.

Activation of complement

components and neutrophils

Increased vascular permeability lead to

capillary leak and pulmonary tissue damage

B) Nonimmunologic Mechanism• It involve soluble mediator-mediated not antibody mediated event.• In this mechanism, antigranulocyte or anti-HLA antibodies are not

detected in either recipient or donor • It is suggested that the granulocyte activation is mediated by a

soluble lipid substance that will accumulate during the storage of the products

• It also postulated that, biologically active lipids or interleukins is generated and present in increased concentration in stored blood products.

•All this event cause pathogenesis of TRALI due to non-antibody mediated.

Biologically active lipids that

accumulate during the storage

Alveolar damage

Increase in permeability of

pulmonary circulation

Pulmonary edema

Sign and Symptoms• Acute hypoxemia and

noncardiogenic pulmonary edema (NPE).

• Acute onset of respiratory compromise.

• Severe hypoxemia within 6 hours of beginning transfusion caused by a decrease in pH and pO2 and an increase in pCO2 levels in arterial blood gas analysis.

• Progressive dyspnea• Cyanosis• Fever (increase of 1-2˚C)• Tachycardia• Hypotension (may not respond to

IV fluid resuscitation)• Frothy sputum (yellow or pink in

color)

TERMS MEANING

Hypoxemia Low blood oxygen

(NPE) Acute respiratory distress

Dyspnea Shortness of breath

Cyanosis Appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen.

Tachycardia Heart rate exceeds the normal range

Frothy Full of or covered with a mass of small bubbles

BILATERAL LUNG INFILTRATES ON THE CHEST RADIOGRAPH

www.ssm.gov.mo/cts/Download/6thEdE.pdf

TREATMENT AND PREVENTION

• Mild TRALI needs supplemental oxygen therapy.• Severe TRALI may require mechanical ventilation and

ICU support.• Upgrade blood transfusion guidelines which will be

minimize the unnecessary transfusions are occurred.• Advocate temporary disqualification of donors

implicated in TRALI reactions until leukocyte antibody testing can be completed.

• Rejected all multiparous females from plasma donation.

• No administration of diuretics

GRAFT VERSUS HOST DISEASE

What is GVHD??

• Graft-versus-host disease or GVHD is a term used to describe a battle between the transplanted stem cells and the patient’s body. This is a complication that occurs when the new stem cells (the graft) reject or assume body (the host) as foreign.

• GVHD is rare in autologous transplants (stem cells come from own blood or bone marrow), it occurs in approximately 50% of patients who have an allogeneic (donor) transplant.

• GVHD is less likely to occur if the donor and recipient are matched – have identical tissue or “HLA (human leukocyte antigen)” types.

How GVHD develops?• GVDH occur when the transplant affects recipient immune system. T cells from

donor’s bone marrow or stem cells will contain some T cells. T cells are a type of white blood cells that function to attack and destroy cells that recognize as foreign and can be harmful to the host.

• T cells don’t attack body own cells, because they recognize proteins on the cells called HLA (human leukocyte antigens). HLA is inherited protein. Apart from identical twins HLA is unique to each person.

• Tissue typing is a blood test to check how closely recipient and donor HLA matches. . If recipient and donor have very similar HLA, the chances of GVDH are lower. The more differences there are between recipient HLA and donor, the more likely recipient are to get GVHD.

• After a transplant recipient bone marrow starts making new blood cells from the donor stem cells. These new blood cells have the donor's HLA pattern. They recognize the HLA pattern on recipient body cells as different (foreign) and may begin to attack some of them. The GVHD may affect different areas of body. Most commonly it affects the skin, digestive system (including the bowel and stomach) and liver.

Types of GVHDTwo types of GVHD:

Acute GvHD: occur early when the bone marrow starts to engraft around two to four weeks after the transplant▫ It often causes an itchy red skin rash. If the bowel, stomach or liver

are affected, nausea and vomiting, diarrhea and a jaundice may be develop.

▫ Acute GvHD is more likely to affect recipient if: Recipient have a transplant at an older age the donor is unrelated or not such a close match to recipient

Chronic GvHD: occurs after day 100 after transplant. It may develop as a continuation of acute GVHD or occur without any prior history of acute GVHD. Chronic GVHD is usually less serious.

Signs and Symptoms of GVHD

Acute GVHDInvolve three main body systems:

1. Skin • a rash on the skin surface but it is mostly seen on the hands, feet, abdomen and

face. • itching, redness on areas of the skin that initially looks sun-burnt. 2. Liver• Jaundice (yellow coloring of the skin or eyes)3. Gastrointestinal Tract• Abdominal pain or cramps, nausea, vomiting, and diarrhea

Chronic GVHD

• soreness or dryness of the mouth or eyes• lung and liver complications• changes in skin pigmentation •hair loss•weight loss•vaginal dryness•Cough• shortness of breath • joint problems

Possible benefits of GVHD

•  Although GVDH may have a serious even life threatening problem, it may give a benefit too. In case of transplant for leukaemia, having mild GVHD may be a good thing.

• As well as attacking recipient body cells, the donor T cells will also attack any remaining leukaemia or cancer cells. Doctors call this the graft versus disease effect, or graft versus leukaemia effect (GVL).

• The graft means "the donor T cells". There may also be graft versus disease effect after a transplant for lymphoma or myeloma.

Risk factors for GVHD

• Unrelated donor transplantsRisk of developing GVDH is greater if donor and recipient is not related

• Mismatched donorsIf you have a mismatched transplant your donor will be as close an HLA match as possible. But sometimes the best available bone marrow donor is still a slight mismatch. This increases the risk of GVHD.

• High numbers of T cells in the donated stem cells or bone marrowDonated stem cells or bone marrow that contain high numbers of T cells are more likely to cause GVHD. This is called a T cell replete stem cell transplant. Whilst this type of transplant may cause more GVHD, it may also lower the chance of relapse.

• AgeThe older recipient and donor are, the greater recipient risk of developing GVHD.

• Having a donor of a different sex to youIf donor is a different sex to recipient, the risk of GVHD is slightly increased. This is particularly true if a male has a female donor who has had children or been pregnant in the past.

•Several lab and imaging tests that can be done to diagnose and monitor problems caused by GVHD :▫Liver function tests

Elevation of the alkaline phosphatase concentration an early sign of liver involvement by GVHD

Hypoalbuminemia is usually due to GVHD-associated intestinal protein leak and a negative nitrogen balance

▫Serum electrolytes and chemistries Potassium, magnesium, bicarbonate levels can be altered Massive diarrhoea and diminished oral intake can lead to serious

electrolyte abnormalities

•A biopsy of the skin, mucus membranes in the mouth, or other parts of the body can help to confirm the diagnosis.

LABORATORY DIAGNOSIS

Prevention and treatment • Way to prevent GVDH

▫ Tissue typing. Tissue typing is a process to match the transplanted donor cells as closely

as possible to the host or patient cells. Of all the proteins in the body, it is crucial to try to match up the proteins

called HLA antigens that are found on the surface of all the cells. The mixture of HLA proteins belonging to each of us is inherited equally from our parents. The closer the HLA match between the donor and host tissues, the less likely the outcome of GVHD for the host (patient).

▫ Intake of drug before transplant (esp. Stem cell transfusion) Drug given such as cyclosporine and methotrexate, tacrolimus (Prograf®)

and methotrexate, tacrolimus and mycophenolate mofetil (CellCept®) and Prograf and sirolimus (Rapamune®).

• Treatment ▫ Intravenously administered glucocorticoids, such as prednisone.

But this medicines have side effects, including kidney and liver damage so close monitoring is needed.

BACTERIAL CONTAMINATION OF

BLOOD COMPONENTS

DEFINITIONBacterial contamination of blood component is the second

most common caused of death in transfusion reactionPlatelet contamination is the most common blood

component that easily contaminated due to the storage temperature (room temperature) may facilitate bacterial growth

Infusion of contaminated component may be asymptomatic or cause fever with evidence of sepsis or septic shock and death

Bacterial psychrophilic gram negative bacteria (pseudomonas, coliforms and achromobacters) are common contaminants

TYPES OF BACTERIABLOOD COMPONENTS ORGANISMS

PACKED RBC Yersinia enteroloticaPseudomonas fluorescnesSerratia liquefaciens

PLATELETS Stahplycoccus epedermidisStaphylococcus aureusBacilus cereusPropionibacterium spp.Micrococcus spp. Group C Streptococcus

Sources of bacterial contamination

External▫Venipuncture site▫Contaminated needle▫Collecting set

Internal▫Blood collected from donor suffers mild bacterimia or

infection

ETIOLOGYETIOLOGY FOR PLATELET CONTAMINATION

Platelets is contaminated with bacteria because the storage for platelets is at room temperature with gently agitation which facilitate the bacterial growth

The most common organism contaminating platelets are rapidly growing aerobic organisms

Organism may contaminate the platelet from the skin of donor venipuncture site or from equipments that is used during collection and processing

ETIOLOGY FOR PACKED RBC CONTAMINATION Being stored at 4 oC, most common organism that associated with packed

RBC contamination are psychrophilic bacteria which can withstand cold temperature such as Yersinia enterolotica

Donor infected with Yersinia enterolotica may have bacteremia during donation of blood because infection may be asymptomatic

Transfusion of packed RBC with Yersinia spp. Contaminated unit may caused rapid development of life-threatening gram negative sepsis in recipient

SIGN AND SYMTOMPS

HypertensionNauseaVomitingDiarrhea feverOliguriaShockDyspnoea, wheezing and/or coughRespiratory distressBleeding: endotoxin induce DIC

Develop within minutes to up to 2 hours from start of transfusion

PATHOGENESIS AND CLINICAL MANIFESTATION

PATHOGENESIS OF BACTERIAL CONTAMINATION: The psychrophilic organisms multiples at 4oC These organism pseudomonas, coliform and achromobacter are all gram negative bacilli

produces endotoxin that present in the cell wall of these organisms These organisms metabolises citrate and produces endotoxins consisting of lipid polysaccharide

and amino acids Endotoxins are pyrogenic and causes granulocytosis and thrombocytopenia, gram negative

septicimia, endotoximic shock Fall in cardiac output leads to endotoximic shock that triggers disseminated intravascular

coagulation (DIC) which is responsible for the fatal outcome rather than bacterimia

CLINICAL MANIFESTATION OF BACTERIAL CONTAMINATION: Clinical manifestation may be observed after introduction of contaminated blood in the form of

circulatory collapse At the beginning, there may be fall in body temperature subsequently it rises It then effects the brain, the respiratory system and gastrointestinal tract resulting in

conciousness or semiconciousness, dyspnea, vomitting and loose motion Treatment consists of immediate discontinuation of blood transfusion, vigrous management of

endotoximic shock to avoid occurrence of DIC through suitable antibiotics

PREVENTIONGENERAL Written procedure for all aspects of procuring, issuing, and administering transfusion must be

prepared. Improve the technique for proper use of equipment, intravenous solutions, and drugs used

during the administration of blood and blood component. Equipment must be properly maintained and records kept of how and when items are used. Medications that can be given intravenously must never be injected into blood bags which only

use intravenous access devices.

BACTERIAL CONTAMINATION FOR PLATELETS The storage time of platelets must be shorten as logically possible Order platelet concentrated for transfusion only when the patient is ready to receive them After platelet concentrates are pooled, it must be use within 4 hours Once platelets have been delivered to the appropriate location, hang the bag and start

transfusion immediately No platelet concentrates can be leaved unattended in an uncontrolled, unmonitored

environment If platelet concentrates are ordered for a patient but then not transfused, it must be return as

soon as possible to the transfusion service for the appropriate storage.

MANAGEMENT Send all the blood sample

to the microbiology laboratory for gram stain as soon as possible

Reactions are potentially fatal and they must be detected and treated immediately if suspected with bacterial contamination

Start with aggressive broad-spectrum antibiotic therapy and give supportive care such as corcticosteroids.

The patient`s intravascular volume should be maintained with crystalloid solution and possible vasopressor drugs such as dopamine

Blood culture from the recipient must be done

Save and collect all blood component units transfused within 90 minutes of the reaction diagnosis

Obtain recipient`s post transfusion blood sample for transfusion reaction investigation

Management for Post-transfusion sample and blood

component

IRON OVERLOAD/ HEMOSIDEROSIS

IRON OVERLOAD/ HEMOSIDEROSIS

•Each unit of blood contains 250mg of iron as iron can be found in Hb molecule.

• Iron is released when RBCs is destroyed.•Human lack major mechanisms for iron excretion,

thus iron is accumulated in liver, spleen, heart and endocrine organ as hemosiderin.

•Frequent blood transfusion has high risk of iron overload.

•The diseases that require frequent transfusion include:• Thalassemia• Sickle cell disease• Aplastic anemia

•Signs and symptoms of hemosiderosis:• Muscle weakness• Fatigue• Weight loss• Mild jaundice• Anemia• Cardiac arrhythmias

•Complications that may occur:• Tissue damage• Heart failure• Liver failure• Diabetes• Hypothyroidism

•Treatment: chelating agent desferrioxamine, deferiprone, desferasirox binds to iron and helps remove it through the

urine or feces.

Picture of kidney under the microscope. The brown area contains hemosiderin.

Retrieved from:http://www.medialabinc.net/spg404281/iron_overload.aspx

References• Borton, D. C. (2011, April 20). Patient.Co.UK. Retrieved from

Blood Transfusion Reactions: http://www.patient.co.uk/doctor/blood- transfusion-reaction

• http://www.pathologyoutlines.com/topic/transfusionmedallergic.html

• http://www.transfusionmedicine.ca/articles/transfusion-related-acute-lung-injury-trali

• http://health.nytimes.com/health/guides/disease/graft-versus-host-disease

• http://www.patient.co.uk/doctor/iron-overload