Lec Transfusion Medicine

S2 L5:

by Dr. Ma. Mystica Flodalyn T. Bautista

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 1628- England

o William Harvey discovered blood circulation o Earliest known blood transfusion (BT) attempted  1665- England

o 1st recorded successful BT (dogs  other dogs)  1667

o Jean- Baptiste Denis (France) o Richard Lower (England)

 Sucessful transfusions from lambs to humans

 Law prohibited BT from animals to humans due to reactions

 James Blundell (England) o 1818

 Patient for the treatment of post partum hemorrhage

 Patient’s husband as a donor

o 1825-1830

 Performed 10 BT; 5/10 proved to be beneficial to his patients

 1873-1880

o US physicians transfused milk (from cows, goats and humans)  1884

o Saline infusion replaced milk as a blood substitute due to the increased frequency of adverse reactions to milk

 1900

o Karl Landsteiner (Austrian) discovered the 1st 3 human blood groups – A, B and O (formerly A, B and C)

o His colleagues added AB the 4th tyoe in 1902  1916

o World War I

 Problem with preservation and transport of blood

o Francis Rous and J.R. Turner

 Use of citrate-glucose solutionpermitted storage of blood for

several days after collection

 Establishment of the first blood depot by the British during WWI

 1940 (World War II)

o Use of preservative solutions

o US program for the collection of blood : “Plasma for Britain”

 American Red Cross collected 13 M blood units during WW II

 1947

o Blood banks established in major cities across the US and blood donation was promoted to the public as a way of fulfilling one’s civic responsibility

VOLUNTARY BLOOD DONATION Transfusion

 A multi-step process

1. Recruitment 4. Processing 7. Transportation

2. Collection 5. Prescribing 8. Transfusion

3. Testing 6. Issuing 9. Follow-up

 Purpose

1. Quickly restore blood volume post hemorrhage, burns or injuries

and combat shock

2. Treat severe anemia

3. Promote hemostasis

Criteria for Blood Donation

1. Medical History

o All donors are required to complete a health questionnaire and blood

safety form (Confidential interview)

2. Physical Health

3. Donor Information

a. Name

b. Date and time of donation

c. Address

d. Telephone number

e. Gender

f. Age and/or date of birth

 Less than 17 yo requires written consent from parent/ guardian

 No upper age limit – elderly donors may be accepted at the

discretion of the blood bank (BB) physician

4. Who is a potential donor?

o In good health and feeling well on the day of donation

o Not on prescribed medication that would cause the donor a problem

when donating or that would affect the recipient

o Normal hemoglobin (>12.5 mg/dL)

o Weight: at least 50 kg for 450 mL donations

o Pulse rate: regular rhtyhm, 60-100 bpm

o Blood pressure  Systole: 90-160 mmHg  Diastole: 70-100 mmHg Deferral  Permanent 1. Cancer 2. Cardiac diseases

 Arryhtmia, congestife heart failure, etc.

3. Severe lung diseas

 Complicated asthma, bronchiectasis, etc.

4. History of viral hepatitis

 (+) HBs Ag

 Reactive for Anti- HBc

 Past/present evidene of Hepatitis C infection

 Donor involved in post transfusion hepatitis

5. History of jaundice of unknown origin, or other liver diseases

6. Use of prohibited drugs (past or present)

7. Sexually transmitted disease (past or present)

8. Prolonged bleeding

 Hemophilia A or B

9. Unexplained weight loss of more than 5kg over 6 months

10. Chronic alcoholism

11. Prostitution

12. High risk sexual behavior or continuing exposure to persons with

hepatitis, HIV, and other STDs including inmates of mental institutions and prisons

13. Chronic eczema, dermatitis, recurring boils

14. Cardiovascular and kidney diseases

15. Convulsion, epilepsy or other mental diseases

 3 years 1. Malaria Nina  Ia n  John  “G ”  Ra ch el  Mar k  Jo ce lle  Edo  Gi enah  Jh o  Kat h  Aynz  Je  Gl ad  Nickie  Ricob ear  Te ac h er  Dadang  Ni ň a  Arlene  Vi vs  Paul  F.  Rico  F.  Re n  Ma i Revs  Mavis   Je pay  Ya n a  May i Se rg e  Hung  To p e  Ag  Bie n  

 12 months

1. Operation or blood transfusion

2. Ear piercing, tattooing, needle puncture

3. Exposure to a sexual partner or close household contact with HIV or

hepatitis

4. Rabies vaccine

 9 months

1. Child birth

 3 months

1. Whole blood donation

2. Weaning

 2 months

1. Anti- acne medication (retinoids, retinoic acid)

 1 month

1. Vaccine: German measles

 2 weeks

1. Acute febrile illness (2-3 weeks)

2. Vaccine: Measles, OPV, mumps

 12 hours

1. Alcohol intake

 Other conditions for temporary deferral

1. After skin lesion has completely healed

2. After full recovery from febrile illness

3. When TB is completely cured

No deferral

 Killed vaccines

1. Injectable polio vaccine

2. Hepatitis B vaccine

3. Influenza

4. DPT (diphtheria-pertussis-tetanus)

 Medications

1. Antibiotics other than anti-TB drugs (if medical condition is not severe)

2. Aspirin and piroxican – but not for platelets

3. Contraceptive pills, depoprovera

4. Other drugs for symptomatic treatment

Types of Donation

 Directed Donation

o Potential recipient of blood or blood products designates certain persons to donate specifically for his or her use

 Autologous Donation

o When a person donates his or her own blood for personal use o The blood is not to be used for anyone else

o If an autologous unit is collected but not used by the patient-donor, then it is destroyed.

Republic Act 7719: National Blood Services Act of 1994

 An act promoting voluntary blood donation, providing for an adequate supply of safe blood, regulating blood banks and providing penalties for violations thereof

o Philippines annual blood requirement = 700 000 to 750 000 units o Target = 1% of the population

 Commercial blood banks are prohibited because: o Blood sources may be contaminated o Limited means of crosschecking donors

 That may change names

 That conceal their medical history

 That supply blood repeatedly

Apharesis

 Involves removal of whole blood from a patient or donor

 One of the separated components is then withdrawn and the remaining components are re-transfused into the patient or donor

PRE-TRANSFUSION TESTING

Tests on All Units Collected for Transfusion

1. ABO typing

o Components to be transfused and permissible donor type

Px

type Whole blood RBC Plasma

Single donor full volume platelets Single donor reduced volume plt Cryo ppt

O O O Any Any Any Irrel

A A A,O A,AB A,AB Any Irrel

B B B,O B,AB B,AB Any Irrel

AB AB Any AB AB Any Irrel

2. Rh typing

o Rh considerations for blood and components

Px

type Whole blood RBC Plasma

Single donor full volume platelets Donor plt (Pheresed) Cryo ppt + +/- +/- +/- +/- +/- Irrel - - - +/- - - Irrel 3. Crossmatching o Types:

 Major crossmatch = Donor’s cells + Recipient’s serum

 Minor crossmatch = Donor’s serum + Recipient’s cells

o Purpose:

 Final check of ABO compatibility to prevent transfusionreaction

 Detect presence of antibody in patient’s serum that will react to

donor’s RBC that is not detected in antibody screen

4. Screening for blood group antibodies

o Purpose: to detect as many “clinically significant antibodies” as possible

 Clinically significant Abs

~ Reactive at 37⁰C and/or in the AHG test

~ Known to have caused a transfusion reaction or unacceptablyshort survival of the transfused red cell

ABO genes code not for the antigen themselves but for the production of glycosyl transferase that add immunodominant sugars that define the blood type

Gene Transferase Sugar

H Fucosyltransferase L-fucose

A Acetylgalactosaminyltransferase N-acetylgalactosamine

B Galactosyltransferase D-galactose

 Most clinically significant of all non-ABO antigens  Highly immunogenic

5. Serologic test to syphilis o Non treponemal methods

a. Venereal Disease Research Laboratory (VDRL) Test b. Rapid Plasma Reagin (RPR)

o Treponemal methods

a. T. Pallidum Immobilization Test (TPI)

b. Fluorescent Treponemal Antibody Absorption Test (FTA- ABS) c. T. Pallidum Hemagglutination Test (TPHA)

d. Microhemagglutination T. Pallidum Test (MHA-TP)

6. Serologic test for HIV: HIV antibody and HIV p24 antigen

o Human Immunodeficiency Virus (HIV)

 1982 = first cases od AIDS obtained from blood or blood products

were reported

 1983 = changes occurred in the donor criteria to exclude those at

high risk for transmission of HIV

 HIV markers during early infection

~ HIV RNA Day 11

~ HIV p24 Ag Day 16

~ HIV Ab Day 22

 Clinical course of HIV

7. Serologic tests for hepatitis: HbsAg, Hepatitis C antibody

o Acute HBV Infection with Recovery: Typical Serologic Course

 Hepatitis B window period

~ HBV-DNA 31 days

~ HbsAg 56 days

~ ALT 78 days

~ Anti HBc 82 days

o Hepatitis C

 Parenteral transmission, community acquired

 Mean incubation time: 6 to 8 weeks

 Hepatitis C markers during early infection

~ HCV RNA Day 12

~ Anti-HCV Day 70

Hepatitis B Markers

Marker Significance

HBs Ag Best indicator of early acute infection

HBc Ag Found within the core of intact virus

Found only in infected liver tissues

HBe Ag Indicates chronic hepatitis

Reliable marker for the presence of high levels of virus and high degree of infectivity

Anti-HBs Bestows lifetime immunity to further HBV infection

Anti-HBc Only marker seen during the window period

INDICATIONS FOR TRANSFUSION

STORAGE _ADULT INDICATIONS _PEDIATRIC

WHOLE BLOOD

Approximate volume: 500 mL Storage temperature: 1 - 6 ⁰C Shelf life: 35- 42 days

Components: RBCs and plasma Length of transfusion: 2-4hrs  within 4 hrs after leaving the

blood bank

Active bleeding with at least one of the following:  >15% blood volume loss

 Hb < 9 mg/dL

 Blood pressure decrease > 20% Systolic pressure < 90 mmHg

 When both oxygen-carrying capacity and volume

expansion are required

For exchange transfusion

 Hyperbilirubinemia – Direct bilirubin of 20 mg/dL during the 1st week of life

 Hyperbilirubinemia with prematurity or other concomitant illness:

o Prenatal asphyxia ᴏ Hypothermia

o Acidosis ᴏ Sepsis

o Prolonged hypoxemia ᴏ Hemolysis

PACKED RED BLOOD CELLS

Approx volume: 225 - 250 mL Storage temperature: 1 - 6 ⁰C Shelf life: 35- 42 days Length of transfusion: 2-4hrs  within 4 hrs after leaving the

blood bank

Hb < 8 mg/dL or Hct < 24%

 Concomitant hemorrhage, COPD, CAD, sepsis, hemoglobinopathy

 General anesthesia Hb < 10 mg/dL or Hct < 30%  Major operation

 Normovolemic patients (chronic anemia/ bleeding)

who require an increase in oxygen-carrying capacity and red cell mass regardless of Hb level

Hypovolemia from acute blood loss  Signs of shock

 Anticipated blood loss of <10% Hct < 30% (Nocturnal Hct < 35%)  Major surgery

Anemia

 Chronic hemolytic anemia

 Anemia with Hb < 8 mg/dL or Hct < 25%  Signs and symptoms of anemia

WASHED RBC / LEUKOCYTE-POOR RBC

Approximate volume: 180mL Storage temperature: 1 - 6 ⁰C Shelf life: 24 hours after wash  Wash= removes 70-80% of WBC  Ffilter = removes 99% of WBC

Anemia with history of febrile reactions Multiple transfusions

O blood for emergencies

Paroxysmal Nocturnal Hemoglobinuria (PNH)

IRRADIATED RBC

Shelf life: 28 days or the normal dating period of blood (whichever comes first) Irradiation: Cs 137 or Co 60

Gravt versus host reactions Congenital immunodeficiency syndrome

Bone marrow transplant Fetus receiving intrauterine transfusion

Direct donation from a blood relative Exchange transfusion

 Prevents CMV reactions

PLATELET CONCENTRATE

Approximate volume: 50 mL Storage temperature: 20 - 24 ⁰C Shelf life: 5 days

 Requires continuous agitation Length of transfusion: 30 mins  within 4 hrs after leaving the

blood bank

Prophylaxis with platelet count ≤ 20 000/L Hemolytic Uremic Syndrome (HUS) Plt count ≤ 50 000/L

 Active bleeding

 Invasive procedure within 8 hrs Plt count ≤ 100 000/L

 Surgery in critical area (eye, brain) Massive transfusion with diffuse microvascular

bleeding and no time to obtain platelet count

Active thrombocytopenia  Platelet count < 50 000/L  Risk for intracranial hemorrhage

Active bleeding and qualitative platelet defect

FRESH FROZEN PLASMA

Approx volume: 200 - 250 mL Storage temperature: ≤ -18 ⁰C Shelf life: 1 year

Contains all coagulation factors with complement

Length of transfusion: 30 mins  within 4 hrs after leaving the

blood bank

Multiple coagulation deficiencies or acquired factor deficiency (Eg. Dengue shock syndrome) PT or PTT > 1.5 times mid normal range within 8 hrs

of transfusion (PT > 17 secs; PTT > 47 secs) Reversal of coumadin anticoagulation Treatment of TTP

Clinical coagulopathy associated with:  Massive transfusion ≥ 10 U / 24 hours  Late pregnancy

 Abruptio placentae

Significant congenital factor deficiency Anti thrombin III deficiency

Bleeding in exchange transfusion or massive transfusion

CRYOPRECIPITATE

Approximate volume: 15 - 20 mL Storage temperature: ≤ -18 ⁰C Shelf life: 1 year

Thawing: 20 - 24 ⁰C

Length of transfusion: 30 mins  w/in 4 hrs after leaving the BB

Preferred replacement for plasma exchange in TTP or HUS Significant hypofibrinogenemia (Factor XIII): < 100 mg/dL Hemophilia A

Von Willebrand’s Disease

Uremic bleeding with prolonged bleeding time Burn or traumatic shock patients who lack fibronectin

Administration Considerations

1. Platelets

o Contraindications:

a. Prophylactic transfusion in a stable patient with platelet refractoriness of a known cause

b. Thrombotic Thrombocytopenic Purpura (TTP) c. Idiopathic Thrombocytopenic Purpura (ITP) d. Heparin-induced Thrombocytopenia

o Effect of platelet product and patient weight on platelet increment Patient wt

(in lbs)

Single whole blood platelet concentrate Standard apheresis 50 17 600 70 400 100 8 800 35 200 150 5 900 23 500 200 4 400 17 600 o Administration

a. Must not be refrigerated b. Require immediate transfusion c. Rate of infusion (10mL/min in adults)

2. Fresh Frozen Plasma

o General guidelines

a. Document PT/PTT pre and post transfusion within 4 hours b. Dose: 10 mL/kg BW or initial loading dose of 15 mL/kg BW c. Correction of significant coagulopathy:

~ Prolonged PT and aPTT required > 2 units of FFP o Administration

a. Must not be refrigerated

b. If transfusion cannot proceed immediately, return the unit to the BB for proper storage within 1 hour from release

3. General

o Medications

a. Do not add medications directly to a unit of blood during transfusion b. Medications by IV push

~ Stop transfusion prior to administration of meds via IV ~ Clear the line at the medical injection site with 5-10 mL NSS ~ Administer the medication

~ Re-flush the line with saline ~ Restart the transfusion o Suspected transfusion reaction

a. Stop the transfusion immediately b. Disconnect the IV line from the needle.

c. Attach a new IV set and prime with saline. Flush the line with NSS used to initiate the transfusion and reconnect the line.

d. Open the line to slow drip.

e. It may be possible to restart transfusion after evaluation and treatment of the patient.

COMPLICATIONS OF TRANSFUSION

 Hemolytic Transfusion Reactions

1. Intravascular

 Due to immune mechanism; mediated by IgM and complement

 Signs and symptoms:

a. Anxiety e. Tachypnea

b. Restlessness f. Tachycardia

c. Nausea and vomiting g. Chills followed by fever

d. Chest or lumbar pain h. Cyanosis

 Causes:

a. ABO incompatibility (misID of patient or blood) b. Antibodies other than anti-A or anti-B c. Exposure of red cells to hypertonic solutions d. Improper storage of blood

2. Extravascular

 Occurs outside the circulatory system (reticuloendothelial cells)

 Most commonly involves the antibodies of the Rh system

 May not occur until a week or more after the transfusion

 Much milder than those of intravascular hemolysis

~ Include malaise, fever, decreased hemoglobin

 Coomb’s test and hyperbilirubinemia

 Febrile Non-hemolytic Reactions

o Most common type of transfusion reaction

o Caused by sensitization to white cell, platelet or plasma antigens,

especially in people who have received multiple transfusions

o Signs and symptoms:

1. Chills followed by fever within an hour after starting the transfusion

2. Headache

3. Nausea and vomiting

4. Back or leg pain

o Mgt: Use of leukocyte filters during transfusion; Anti pyretics

 Allergic Reactions

o Mediated by IgE

o Sx: Hives, rash and pruritus that may progress to laryngeal edema and

bronchial spasm

o Mgt: Administration of antihistamine before transfusion

 Anaphylactic Reactions

o Potentially fatal

o Usually occur in people with antibodies against IgA immunoglobulins

o Signs and symptoms:

1. Generalized flushing

2. Dyspnea

3. Bronchospasm

4. Substernal pain

5. Laryngeal edema and collapse

6. Gastrointestinal distress (nausea and vomiting)

 Circulatory Overload

o Develops in people with cardiac or renal impairment

o Overload capacity of heart  circulatory failure  pulmonary edema

o Signs and symptoms:

1. Dry cough  Productive cough

2. Precordial and back pain

3. Dyspnea

4. Cyanosis

 Infectious Diseases

o Transmission of diseases such as hepatitis, malaria, syphilis,

toxoplasmosis and AIDS  Graft vs Host Disease

o Occurs when immunocompetent donor lymphocytes (commonly found

in PRBC and granulocytes) are transfused and multiply in severely immunodeficient recipients

 Bacterial Contamination (Eg. Pseudomonas and coliforms)

o Cause: improper preparation of donor phlebotomy site or inadequate

refrigeration  Air Embolism

o Introduction of air into the circulation

o Sx: cyanosis and circulatory collapse

 Citrate Intoxication

o When toxic levels of citrate is reached  Depression of blood calcium

 Muscle twitching and spasm  Possible cardiac arrest  Hemorrhagic Reaction

o Since refrigeration destroys platelets, stored blood is low in viable

platelts

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