Lec Transfusion Medicine

                 Nina Ian John “G” Rachel Mark Jocelle Edo Gienah Jho Kath Aynz Je Glad Nickie Ricobear Teacher Dadang Niňa Arlene Vivs Paul F. Rico F. Ren Mai Revs Mavis  Jepay Yana Mayi Serge Hung Tope Ag Bien 

S2 L5: Transfusion Medicine by Dr. Ma. Mystica Flodalyn T. Bautista HIGLIGHTS OF TRANSFUSION MEDICINE  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

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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

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 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

O A B AB

O A B AB

O A,O B,O Any

Any A,AB B,AB AB

 

Single donor full volume platelets Any A,AB B,AB AB

Single donor reduced volume plt Any Any Any Any

Cryo ppt Irrel Irrel Irrel Irrel

The Formation of A, B and H Antigens 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 H A B

Transferase Fucosyltransferase Acetylgalactosaminyltransferase Galactosyltransferase

Sugar L-fucose N-acetylgalactosamine D-galactose

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

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

 

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

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5. Serologic test to syphilis

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

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)

o Acute HBV Infection with Recovery: Typical Serologic Course

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  Hepatitis B window period ~ HBV-DNA 31 days ~ HbsAg 56 days ~ ALT 78 days ~ Anti HBc 82 days Hepatitis B Markers Marker HBs Ag HBc Ag HBe Ag

~ HIV RNA ~ HIV p24 Ag ~ HIV Ab

Day 11 Day 16 Day 22

Anti-HBs Anti-HBc Anti-HBe

Significance Best indicator of early acute infection Found within the core of intact virus Found only in infected liver tissues Indicates chronic hepatitis Reliable marker for the presence of high levels of virus and high degree of infectivity Bestows lifetime immunity to further HBV infection Only marker seen during the window period First serologic evidence of convalescent phase

o Hepatitis C  Parenteral transmission, community acquired  Mean incubation time: 6 to 8 weeks  Hepatitis C markers during early infection

 Clinical course of HIV

           

~ HCV RNA ~ Anti-HCV

Day 12 Day 70

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INDICATIONS FOR TRANSFUSION STORAGE 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 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

INDICATIONS ADULT

PEDIATRIC

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

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

 When both oxygen-carrying capacity and volume expansion are required Hb < 8 mg/dL or Hct < 24%  Concomitant hemorrhage, COPD, CAD, sepsis, hemoglobinopathy  General anesthesia Hb < 10 mg/dL or Hct < 30%  Major operation

Hypovolemia from acute blood loss  Signs of shock  Anticipated blood loss of 1.5 times mid normal range within 8 hrs Significant congenital factor deficiency Anti thrombin III deficiency of transfusion (PT > 17 secs; PTT > 47 secs) Shelf life: 1 year Bleeding in exchange transfusion or massive Reversal of coumadin anticoagulation Contains all coagulation factors with transfusion Treatment of TTP complement Clinical coagulopathy associated with: Length of transfusion: 30 mins  Massive transfusion ≥ 10 U / 24 hours  within 4 hrs after leaving the blood bank  Late pregnancy  Abruptio placentae CRYOPRECIPITATE Approximate volume: 15 - 20 mL Preferred replacement for plasma exchange in TTP or HUS Significant hypofibrinogenemia (Factor XIII): < 100 mg/dL Storage temperature: ≤ -18 ⁰C Hemophilia A Shelf life: 1 year Von Willebrand’s Disease Thawing: 20 - 24 ⁰C Uremic bleeding with prolonged bleeding time Length of transfusion: 30 mins Burn or traumatic shock patients who lack fibronectin  w/in 4 hrs after leaving the BB

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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 Single whole blood Standard apheresis (in lbs) platelet concentrate 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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