The Osler Institute. Blood Bank II. D. Joe Chaffin, MD Cedars-Sinai Medical Center, Los Angeles, CA

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1 Blood Bank II D. Joe Chaffin, MD Cedars-Sinai Medical Center, Los Angeles, CA The Osler Institute Blood Donation & Pretransfusion Testing I. Blood Donation A. Allogeneic (homologous) whole blood donation 1. Process tightly regulated by FDA and AABB 2. Donor screening by history a. FDA-recognized AABB template called donor history questionnaire (DHQ); see end of this handout b. Necessary information 1) Full name (generally, formal ID required) 2) Home and/or work address 3) Date of birth/age to make sure over minimum age a) 17 unless age 16 donors approved by state 4) Reasons for previous deferral 5) Date of last donation a) > 8 weeks for whole blood b) > 16 weeks for double red cell collections c) > 4 weeks for infrequent plasmapheresis d) > 2 days for single platelet apheresis procedures e) > 7 days for double/triple platelet apheresis c. HIV information presented to donor 1) Signs/symptoms and risk factors for HIV 2) Statement: Do not to donate if have any risk factors or if just wanting HIV test d. Medication list; prevents donations from those taking: 1) Medications with teratogenic potential 2) Medications with infectious risk 3) Medications that damage platelets 4) See list on page 5 e. Informed consent must spell out risks 1) Not standardized; individual centers must develop 2) Notification that other agencies might be notified of results (e.g., state and/or local health departments) 3) Statement that blood might not be tested (lab accidents/errors, breakage, etc.) f. Donor questions 1) Version 1.3 of DHQ (recognized by FDA in May 2010) contains 48 standardized questions 2) May modify times only to make more restrictive 3) Most omit 2 HIV group O questions (see later) 4) May add additional questions at end only a) These can be more restrictive only; never less b) Commonly added questions are about medications/health issues not covered in DHQ P}Chaffin (2/26/2014) Blood Bank II page 1

2 Pathology Review Course g. Deferrals based on history 1) Permanent/indefinite deferrals Infectious Risks -High-risk behavior for AIDS (IVDA, male-male sexual contact since 1977) -Receiving money or drugs for sex -Serologic positive for HIV, HBV, HCV, HTLV -Viral hepatitis (any) after 11 th birthday -Transfusion of clotting factor concentrates (in hemophilia) -History of Babesiosis or Chagas disease -Growth hormone from human sources (pre-1985) -Insulin from bovine sources -Dura mater graft Malignancies (see below) -Leukemia or lymphoma Teratogens -Taking etretinate (Tegison) 2) Three year deferrals Infectious Risks -Recovered from malaria -Immigrants from malaria-endemic countries (after 5 consecutive years of living there) Teratogens -Taking acitretin (Soriatane) 3) One year deferrals Infectious Risks -Needle sticks or other contact with blood -Sex contact with person with HIV or hepatitis -Sex contact with person who used needles for drugs -Rape victims -Incarcerated > 72 consecutive hours -Paying money/drugs for sex -Blood transfusion (allogeneic); including plasma/clotting factors in nonhemophiliacs -Allogeneic transplant of organ/skin/bone -Living with person with active hepatitis (exception: Asymptomatic Hepatitis C) -Receiving Hepatitis B Immune Globulin (HBIG) -Tattoos/piercings (unless by regulated entity) -Travel to malaria-endemic areas for residents of non-endemic countries (>24 hrs, < 5 years) -Diagnosed with syphilis or gonorrhea -Non-prophylactic rabies vaccination - Travel to Iraq page 2 Blood Bank II P}Chaffin (2/26/2014)

3 4) Special situations a) Malaria (updated to 08/13 FDA Guidance) Endemic area means area that CDC recommends chemoprophylaxis to travelers Endemic country means any country with at least one endemic area Deferrals: Situation Deferral History of malaria 3 years (if asymptomatic) Living in endemic country for more than 5 3 years (if asymptomatic) consecutive years Travel by residents of non-endemic countries Travel to endemic area for more than 24 1 year (if asymptomatic) hours and less than 5 years Travel in endemic country but not endemic No deferral area for more than 24 hours Travel by previous residents of endemic countries Travel to endemic area (prior resident of 3 years (if asymptomatic) endemic country <3 years after leaving) Travel to endemic area (prior resident of 1 year (if asymptomatic) endemic country >3 years after leaving) b) Malignancy deferrals Medical director discretion (not mandated) Studies do not show that malignancy can be transmitted via transfusion Most defer leukemia/lymphoma permanently, but some accept cured childhood leukemics For solid tumors, most defer indefinitely and consider re-entry after 1-5 years disease-free BCC, localized skin SCC = no deferral. c) Heart and lung disease No specific mandated deferrals FDA: Donor free of acute lung disease AABB: Donor should be free of heart/lung disease unless determined suitable by medical director Medical directors determine acceptability (time since diagnosis, presence of limitations on activities, proper medical follow-up) d) Pregnant women: Defer until 6 wks postpartum. e) Non-routine dental work: Defer for 72 hours. f) Questions 46, 47: Africa questions These questions are omitted since all centers use anti-hiv test sensitive for HIV group O No reported US cases since 1996 Questions ask about being born, living in, traveling to, transfused in, or sexual contact with someone born or living in countries in Africa since 1977 The Osler Institute P}Chaffin (2/26/2014) Blood Bank II page 3

4 Pathology Review Course 5) Defer permanently for vcjd risk all donors who: a) Lived over 3 months in UK, b) Lived Continental Europe > 5 years, 1980-now c) Were transfused in the UK, 1980-now d) Received dura mater transplant, pituitary growth hormone injections, or bovine insulin injection e) Have family history of CJD or vcjd f) Were military members/dependents: Stationed at Northern Europe bases (Germany, UK, Belgium, Netherlands) for 6 months from Stationed at other Europe bases (Greece, Turkey, Spain, Portugal, Italy) for 6 months from ) Immunizations a) General rule: no deferral for killed, toxoid, or recombinant/synthetic vaccines b) Live attenuated vaccines (either viral or bacterial) give deferrals of varying lengths Immunization Deferrals Four Weeks: Rubella Varicella Two Weeks: Measles Mumps Oral polio Yellow fever Oral typhoid No Deferral: Anthrax Cholera DPT Hepatitis A Hepatitis B Influenza Lyme disease Meningococcus Pneumococcus Polio (injection) RMSF Typhoid (injection) 12 Months: Unlicensed vaccines c) Smallpox vaccination i) Deferrals based on presence/ absence of vaccine scab and post-vaccination symptoms ii) No symptoms: defer until scab falls off or 21 days, whichever is longer iii) With symptoms: defer until 14 days after symptoms resolve page 4 Blood Bank II P}Chaffin (2/26/2014)

5 7) Drugs a) DHQ only requires questioning about a limited number of medications i) Some facilities add more to protect donor b) DHQ V 1.3 drug deferrals for teratogenicity: i) Etretinate (Tegison): Permanent deferral ii) Acitretin (Soriatane): Three year deferral iii) Isotretinoin (Accutaine, Absorica, Amnesteem, Claravis, Sotret): 30 day deferral iv) Finasteride (Proscar, Propecia): 30 days v) Dutasteride (Avodart, Jalyn): 6 months c) DHQ V 1.3 drug deferrals for infection risk: i) Human pituitary growth hormone: Permanent ii) Bovine insulin: Permanent iii) Hep B Immune Globulin (HBIG): 1 year iv) Unlicensed vaccine: 1 year d) Aspirin/aspirin like meds for platelets (48 hours) e) Platelet drug deferrals: i) Piroxicam (Feldene): 48 hours for platelet donors only ii) Clopidogrel (Plavix) and ticlopidine (Ticlid): 2 weeks for platelet donors only f) Warfarin is not addressed in DHQ, but most defer donors 7 days g) New drugs are fast arriving i) Antiplatelet and anticoagulant drugs seen in donors (e.g., Brilinta, Pradaxa, Xarelto) ii) Medical director discretion, but most are deferring like warfarin 3. Donor screening by physical criteria a. General appearance b. Arm check 1) Both arms for evidence of IVDA and venous access c. Physical requirements (weight, BP, pulse are not standards but most common practice): The Osler Institute Weight: > 110 lbs (50 Kg) Temperature: < 99.5 o F (37.5 C) Pulse: Blood pressure: < 180/ (unless athlete) HGB or HCT: > 12.5 g/dl or 38% 4. Donation specifics a. Amount drawn 1) Maximum of 10.5 ml/kg is allowed by AABB 2) 500 +/- 50 ml (+/ 10%) most common a) 450 ml bag also used; limit is 450 +/- 45 ml P}Chaffin (2/26/2014) Blood Bank II page 5

6 Pathology Review Course b. Time limit 1) < 10 minutes best, but no upper limit defined a) Beyond 15 minutes, plasma/plts not made 5. Testing donor blood (Collection center) a. ABO grouping b. RhD typing 1) Weak D required if D negative (see BBI) c. Antibody detection ( screen ) 1) Unexpected (non-abo) antibodies in donor serum 2) AABB Standards: If positive, may still use blood, but only to make products with minimal plasma (i.e., RBCs ok; can t make FFP, cryo, or platelets). 3) Label must reflect any positive results that are identified as clinically significant antibodies. 4) Reality: Most hospitals don t want this blood d. Infectious disease screening (as of 2/2014); see appendix and further details starting on page 13 1) Hepatitis B Tests a) HbsAg b) Anti-HBc c) HBV nucleic acid test (HBV NAT) 2) Hepatitis C Tests: a) Anti-HCV 4) HCV NAT 3) HIV tests: a) Anti-HIV-1/2 b) HIV-1 NAT 4) Other tests: a) Anti-HTLV-I/II b) West Nile virus NAT c) Anti-Trypanosoma cruzi (Chagas disease) d) Serologic test for syphilis 6. Testing donor blood (Transfusion Service) a. Requires confirmation of collection center s work b. Confirmatory tests: 1) ABO grouping (RBC grouping only) 2) RhD-negative confirmation a) Direct testing only of units labeled as D b) Weak D testing not required (done already) c) Units labeled as D+ do not require confirmation 3) Antibody screen and infectious disease screening on donor units do not require confirmation B. Donor reactions 1. Vasovagal reactions a. Most common reaction (2.5% of healthy donors) 1) Most common in young, first-time female donors 2) Can be seen in any donor, though 3) Can happen before, during, or after donation page 6 Blood Bank II P}Chaffin (2/26/2014)

7 b. Signs/symptoms 1) Bradycardia (or at least, non-tachycardia) with hypotension 2) Syncope 3) Nausea/vomiting 4) Incontinence (uncommon) c. Treatment is supportive 1) Distinguish from hypotensive shock 2) Elevate feet, cold compresses on neck 2. Hypovolemic shock a. Extremely uncommon b. Signs/symptoms 1) Tachycardia with hypotension 2) Loss of consciousness 3) Shock parameters c. Treatment 1) IV fluids, possibly return blood? 3. Hyperventilation a. Especially common in first-time donors and children b. Signs/symptoms 1) Shortness of breath 2) Facial twitching 3) Seizure activity (unusual) c. Treat with rebreathing (the paper bag thing) 4. Local injuries a. Hematomas: 0.35% (bruises almost 25%) b. Nerve injury: less common than bruises (0.9%); usually resolve on their own C. Apheresis procedures 1. Separation of blood into components using several technologies a. Centrifugation used for donor procedures (others for therapeutic procedures; see BB Practical section) b. Separation based on varying density of blood components c. Blood drawn into spinning bowl or chamber, separated, component harvested (all else returned). 2. Targets for donor collection a. Platelets b. Plasma c. Red blood cells d. Granulocytes e. Hematopoietic stem cells (after mobilization) 3. Multiple product collections in one procedure possible a. Common to get single/double/triple apheresis unit with concurrent plasma collection b. May also add an RBC collection c. Double RBC collections (no other products) The Osler Institute P}Chaffin (2/26/2014) Blood Bank II page 7

8 Pathology Review Course 4. Donor requirements a. Platelet donors 1) Same hemoglobin/hematocrit requirements as regular donors 2) Donation interval at least 2 days for single product (7 days for double/triple/quad) a) No more than 2 procedures per week b) No more than 24 procedures per year c) > 8 weeks after whole blood donation or if RBCs not returned (unless equipment has less than 100 ml extracorporeal volume) d) Physician may waive above if for a particular patient need (requires written certification). 3) Donation interval 7 days after double/triple products 4) No aspirin/aspirin-effect products in last 48 hrs 5) No clopidogrel or ticlopidine in last 14 days 6) Pre-procedure platelet count > 150,000/ L (may use previous count if not available) 7) Plasma volume loss as per manufacturer b. Plasma donors 1) Infrequent (> every 4 weeks): = whole blood 2) Serial (< every 4 weeks): a) Total protein and SPEP check every 4 months b) Interval > 48 hours; < 2 collections per 7 days c) Red cell loss < 25 ml/week, < 200 ml/8 weeks c. Double red cell donors 1) FDA: Assure donor safety 2) Equipment makers have donor requirements that are OK ed by FDA when machine is FDA-cleared 3) Double red cell donors are deferred for 16 weeks d. Multiple products collected at once 1) FDA-cleared equipment specific donor limits 5. Apheresis donor reactions a. Citrate effect 1) Citrate anticoagulant binds free calcium 2) Perioral tingling 3) Tetany and arrhythmias uncommon 4) Slow rate of infusion, give oral calcium b. Hypersensitivity reactions 1) Classic: Hydroxyethyl starch in WBC donors a) Given to facilitate better separation of WBCs from RBCs by inducing RBC aggregation b) Occasional hypersensitivity reactions seen II. Autologous Blood Collection A. Preoperative autologous blood donation (PAD) 1. Less screening stringency than allogeneic collections 2. AABB Standards: Don t cross over units into regular inventory unless exceptional circumstances page 8 Blood Bank II P}Chaffin (2/26/2014)

9 3. More lenient physical criteria (see table below) 4. Testing regulations a. Infectious disease screening not required unless units are to be shipped to another facility 1) Hospital centers collecting auto units for transfusion are not required to screen those units 2) If not tested, label units NOT TESTED b. Only first donation in a 30-day period MUST be tested 1) Others after that may be labeled DONOR TESTED WITHIN THE LAST 30 DAYS Parameter Allogeneic Autologous Donation Interval 8 weeks 72 hours HB/HCT > 12.5 or 38% > 11 or 33% Weight > 110 lbs (50 Kg) None Age > 16 or 17 (varies) None Infectious Disease Not required unless Required Screening shipped History of Disease or Positive Test Not eligible Potentially eligible 5. Potential issues with autologous donations a. Donor reactions 1) More complex donors with more health problems, so more likelihood of donor complications 2) Safety of donor during donation is responsibility of donor center medical director! b. Clerical errors/transfusion errors 1) Risk of wrong unit going to wrong patient still present with autologous donations 2) CAP survey (1992): about 1% of hospitals admitted making transfusion errors with autologous blood 3) Systems must be in place to prevent allogeneic units from being transfused before autologous units c. Bacterial contamination 1) Currently a greater risk than HIV or HCV 2) Risk of undetected infection leading to contamination of unit is not changed by PAD d. Cost 1) More costly to patients if transfused and hospitals if not transfused (wastage) e. Timing 1) Collections should be completed at least 72 hours before surgery (preferably sooner) 2) Surgery cancellations, etc, can lead to problems (freeze units? Let them expire?) f. Positive infectious disease testing 1) If donor has a reactive test, donor and the requesting physician must be notified The Osler Institute P}Chaffin (2/26/2014) Blood Bank II page 9

10 Pathology Review Course 2) Autologous collections with reactive testing should lead to deferral from future allogeneic donations B. Acute Normovolemic Hemodilution (ANH) 1. Primary goal: Reduce RBC volume during surgery in order to prevent exposure to allogeneic blood a. Studies to date: May work ok, but only with aggressive hemodilution b. Can save exposure, but isn t very cost effective 2. Added benefit: Reduce plasma and platelet needs 3. Remove 1 L or more of blood immediately before surgery a. Collection is done into multiple standard blood bags and each bag should be monitored for overfill b. Standard formulae exist for collection amount; typically take patients down to HCT 25-28% or so 1) V = EBV x (H i -H f )/H av (source: Waters JH, Perioperative Blood Sequestration, AABB 2008) 2) Key: i) V = volume to remove ii) EBV = estimated blood volume iii) H i = initial hematocrit iv) H f = final hematocrit v) H av = average hematocrit during process c. Shelf life: 1) 8 hours at room temperature 2) 24 hours in monitored refrigerator 4. Replace volume with saline/crystalloid (3 ml per 1 ml of blood removed) or colloid (1 ml per ml of blood removed) a. Replace the volume unit by unit; i.e., when a unit is withdrawn, immediately replace volume (don t remove a bunch of blood and THEN correct the volume) 5. Re-infuse blood near end of surgery. a. Units usually re-infused in reverse order to how drawn (i.e., last drawn is first re-infused) b. If using intraoperative salvage, infuse those units first 6. Indications (not standardized) a. At least 1 L blood loss anticipated in surgery b. Hemoglobin at least 12 g/dl c. No active cardiac or other serious medical disease d. No infection or bacteremia 7. Potential advantages a. Bleeding more dilute blood leads to less overall hemoglobin loss (not as huge a benefit as predicted). b. Decreased blood viscosity increases cardiac output and may improve oxygenation. c. Coag factors and platelets survive well for short periods and help hemostasis. 8. Potential disadvantages a. Requires training of phlebotomist (most commonly done by anesthesiologist) page 10 Blood Bank II P}Chaffin (2/26/2014)

11 b. Units should be labeled with full name, date/time, medical record number, and FOR AUTOLOGOUS USE ONLY. 9. Component sequestration: a. Similar in thought to ANH, but involves harvesting specific components (platelets, plasma, RBCs) for targeted transfusion depending on patient needs b. More complex and requires lots of expertise C. Intraoperative blood salvage ( Cell Saver ) 1. Semi-automated process; usually involves processing and concentrating shed blood from suction apparatus 2. Generally indicated for major surgeries with large expected blood losses (cardiac, orthopedics, vascular) a. Requires coordination with team performing recovery b. Trend: More aggressive use in lower-risk cases 3. Shelf life: a. 4 hours at room temperature b. 24 hours in monitored refrigerator 4. Potential problems a. Air or amniotic fluid embolus risk b. Hemolysis of processed blood from excessive suction in the operative field c. Coagulation factor activation 5. Historical contraindications; Not uniformly used a. Bacterial contamination of operative field b. Malignant cells in field c. Other contaminants in field (cement, irrigation, amniotic fluid, etc) D. Postoperative blood salvage 1. Blood reinfused from operative drains with or without processing (Editorial comment: That is just gross!) a. Microaggregate filters used during re-infusion 2. Shelf life: 6 hours at room temperature III. Pretransfusion Testing The Osler Institute A. Basic outline (see figure above) 1. Requires actions by supplier, phlebotomists, transfusion services, and infusing staff 2. Crossmatch is final check of everyone s work a. Main reason for crossmatch: ABO compatibility! P}Chaffin (2/26/2014) Blood Bank II page 11

12 Pathology Review Course B. Testing recipient blood 1. Request forms a. Identification critical 1) Number one cause of fatal HTR s: clerical error! b. No identification labeling errors are acceptable. 1) Transfusion ; : Mislabeled specimens 40X more likely to have a blood grouping discrepancy! c. Should tell what s needed and when needed, ordering provider, and any modifications (washing, irradiation, etc.) needed 2. Specimen a. Serum or plasma (red top vs lavender top) 1) Either ok, but non-tube technologies prefer plasma. b. Required q 3 days with transfusion or pregnancy in the last three months c. Retained 7 days after transfusion in the blood bank. 3. Type and hold (T&H) a. ABO/Rh check only b. Hold means to hold sample, not units. c. Uncommonly used or even offered now 4. Type and screen (T&S) a. Includes: 1) Records check a) Previous antibodies or compatibility problems b) Not to be used to determine current ABO/Rh, but should be compared to current results. 2) ABO testing a) Forward and reverse grouping b) Resolve any discrepancies 3) Rh typing a) No weak D test required if D negative. Common exception: obstetric patients 4) Antibody screen a) Unexpected (non-abo) antibody check b) Panel of 2, 3, or 4 RBC-phenotyped donors i) Always group O ii) Most common combination: Cell I: R 1 R 1 Cell II: R 2 R 2 Cell III: rr (cell III not used with gel) c) Antigens represented required by FDA: i) D, C, c, E, e, Fy a, Fy b, Jk a, Jk b, K, k, Le a, Le b, M, N, P1, S, s d) IAT phase is required, IS/37 C are not required. e) If positive, identify antibody (see BB Practical) 5. Type and crossmatch (T&C) a. Everything in T&S + crossmatch page 12 Blood Bank II P}Chaffin (2/26/2014)

13 b. Crossmatch types 1) Major crossmatch (or just crossmatch ) a) Recipient serum vs donor RBCs b) Final check of ABO compatibility c) IAT/AHG phase ( full crossmatch ) not required if antibody screen is negative d) Required if 2 ml of RBCs in product. 2) Minor crossmatch (not required or routinely done) a) Donor serum vs. recipient RBCs 3) Units go back into inventory if not used 6. Converting a T&S to a T&C a. ABO check only required (if antibody screen negative) 1) Immediate spin crossmatch a) Donor RBCs/recipient serum centrifuged at room temp 2) Computer crossmatch (see below) 7. Variations to the above a. Infants less than four months of age (neonatal period) 1) Baby s antibodies = mom s IgG antibodies. 2) Initial testing: a) Infant s ABO (red cell grouping only) b) Infant Rh type c) Antibody screen on mom s or baby s serum. 3) If screen neg, repeat initial testing and crossmatch not needed in same hospital stay up until age 4 months 4) Serum grouping not required unless giving nongroup O RBCs b. Electronic (computer) crossmatch 1) Computer system verifies ABO compatibility between donor and recipient (replaces immediate spin crossmatch) 2) Requires a patient with a negative antibody screen both now and in the past 3) Requires two separate ABO determinations of the patient (either on different specimens or repeated on the same specimen with different reagents) 4) Requires a properly validated computer system 8. Reasons for positive major crossmatch a. With positive antibody screen 1) Alloantibodies 2) Autoantibodies 3) Reagent antibodies 4) Rouleaux and other false positives b. With negative antibody screen 1) ABO incompatibility 2) Antibodies vs low-incidence antigens 3) Positive donor DAT The Osler Institute P}Chaffin (2/26/2014) Blood Bank II page 13

14 Pathology Review Course 9. Routine blood order templates a. Maximum Surgical Blood Ordering Schedule (MSBOS), or just routine surgical blood orders b. Multidisciplinary and institution-specific c. Gives surgeons / blood bankers a guide to how many RBC units to crossmatch (or not) for a given procedure IV. Transfusion-transmitted Diseases (See April 2011 Podcast) A. Current risk of disease transmission 1. For perspective, risk of acute hemolytic reaction stated as 1 in 25,000 transfusions 2. Risk of dying in the hospital from something other than transfusion problem: 6 per 1000! Organism Current Risk Estimate HIV-1 1 in 1,467,000 Hepatitis B 1 in 765,000-1,000,000 Hepatitis C 1 in 1,149,000 HTLV-I 1 in 4,364,000 HIV-2 Remote WNV Remote Syphilis Remote T. cruzi Unknown, likely remote Bacteria 1 in 75,000 platelet transfusions 1 in 500,000 RBC transfusions B. Hepatitis viruses 1. Hepatitis A virus a. Fecal-oral transmission (30 day incubation) b. Generally not a big blood banking problem (not tested) c. Some concern in pooled products 1) Solvent-detergent treatment doesn t deactivate HAV (nonenveloped). 2) Transmission possible in pooled factor concentrates d. Not prone to chronicity like HBV and especially HCV 2. Hepatitis B virus a. DNA virus (Hepadnavirus) b. Blood transmission, intimate contact less likely c. Both cellular and plasma components transmit. d. Incubation period: approximately 8-12 weeks e. Clinical 1) Primary infection may be subclinical (65%) or only mild (jaundice, nausea, fatigue, dark urine). 2) Fulminant presentation rare 3) Chronic infection ( carrier state ) much less likely than with HCV (< 5% of adult infections) a) Greatly decreased carriers since routine vaccination b) 400 million worldwide carriers, per WHO page 14 Blood Bank II P}Chaffin (2/26/2014)

15 HBV DNA f. Current testing (see appendix) 1) Anti-HBc EIA/ChLIA and HBsAg EIA/ChLIA a) Confirmatory test for HBsAg: neutralization b) No confirmatory test for anti-hbc 2) HBV NAT now required (done in combination with HIV and HCV) 3) No anti-hbsag testing (vaccinated donors positive) 4) HBV is currently the most likely of the major viruses to be transmitted via transfusion! g. Serology patterns below ANTI-HBc ANTI-HBc ANTI- HBsAg INTERPRETATION (TOTAL) (IGM) HBsAg Incubation Acute infection + + Recovered infection +/ + + Carrier + Vaccinated Probable false pos.,possible early or chronic infection h. Deferrals with HBV NAT (source: FDA Guidance 2012): + The Osler Institute 3. Hepatitis C virus a. RNA virus b % of US blood donors c. Both cellular and plasma components transmit. d. Strong association with chronic hepatitis (75%), cirrhosis, and hepatocellular carcinoma (>HBV) 1) Currently #1 reason for hepatic transplant in the US. 2) Initial presentation mild or asymptomatic e. Donor testing (see appendix) 1) Antibody test is anti-hcv (EIA/ChLIA) a) Window period with antibody test: days P}Chaffin (2/26/2014) Blood Bank II page 15

16 Pathology Review Course b) During some of this time, HCV RNA is detectable by PCR testing, and the virus is transmissible by transfusion (see below). c) Confirmation: i) Reactive anti-hcv historically confirmed by Recombinant ImmunoBlot Assay (RIBA); NOT AVAILABLE ii) Instead, confirm either with a different EIA (requires FDA variance) OR with a specific HCV NAT licensed for supplemental testing 2) Nucleic acid testing (HCV NAT) a) Window period from days to about 7 days b) Typically done in combination with HBV and HIV NAT 3) See appendix for deferral guidelines 4. Other hepatitis viruses we don t test for: a. Hepatitis D virus 1) Formerly known as delta agent 2) Blood transmission 3) Defective virus (requires coating with HBsAg in order to cause disease). b. Hepatitis E virus 1) Fecal-oral transmission 2) Epidemics in India and Asia; rare transfusion transmission C. Retroviruses 1. HIV-1 and HIV-2 a. RNA retrovirus identified in ) Hemophiliacs and homosexual men first 2) Transfusion, sexual contact, breast-feeding, blood b. Clinical/pathophysiology 1) Symptoms in acute infection: flu-like 2) LONG asymptomatic period (often over ten years), then rapid immune compromise 3) Damage caused by attack on CD4+ lymphocytes 4) Death secondary to opportunistic infections or malignancies like Kaposi s or CNS lymphoma c. Testing 1) Antibody testing a) Required since 1985 b) Window period = days 2) Organism testing a) HIV-1 antigen (p24) testing March 1996 Reduced window period to about 16 days b) p24 testing replaced in by nucleic acid testing for HIV RNA (HIV NAT) Reduction of window period to 9-10 days d. Both cellular and plasma products can transmit HIV-1 e. See appendix for deferral guidelines page 16 Blood Bank II P}Chaffin (2/26/2014)

17 f. HIV-2 1) Related virus found originally in West Africa 2) Really, really rare 3) Less readily transmitted vs HIV-1, with less AIDS 4) No licensed confirmatory test 2. HTLV I/II a. Transmission through cellular products only b. HTLV-I disease associations 1) Adult T-cell leukemia/lymphoma (ATLL) 2) HTLV-associated myelopathy (HAM; formerly called tropical spastic paraparesis ) c. HTLV-II: no clear-cut disease associations d. Both transmitted readily, but actual post-transfusion disease is very unlikely (~99% of infected no disease) e. See testing discussion in appendix D. Other organisms for which we test: 1. West Nile virus (WNV) a. RNA virus causing disease in birds; humans incidental (most flu-like, some meningitis/encephalitis) b large increase in cases in US c. Testing done via pooled NAT (until high risk of disease in area, then single donor) d. Deferrals: 1) Confirmed/suspected WNV infection: 28 days from symptom onset or 14 days after symptoms resolved 2) Positive test only: 120 days from test date 2. Trypanosoma cruzii (Chagas disease) a. Transmitted through bite of reduviid bug ( kissing bug ) in Central/South America b. Potentially growing problem with immigration (roughly 1 in 20,000 donors, higher in immigrants) c. Specific question on donor questionnaire (permanent deferral for history of Chagas disease); the problem is that many are asymptomatic. d. Screening test (EIA) required as of ) Testing allowed to be one time per lifetime of donor 3. Treponema pallidum a. Organism doesn t survive well in refrigerated storage (48-96 hours); not considered a large problem b. Surrogate marker for high-risk behavior c. See testing discussion in appendix 4. Cytomegalovirus (CMV) a. Extremely common DNA virus (> 50% are exposed) that lives in WBCs only (monocytes). b. Causes severe infections in immunocompromised adults and neonates, but minimal disease in healthy people (may have cold-like symptoms) c. Prevent with seronegative donors and leukocyte reduced products (see discussion in BB III) The Osler Institute P}Chaffin (2/26/2014) Blood Bank II page 17

18 Pathology Review Course d. Testing not required but available 5. Parvovirus B19 a. Primarily infects RBCs 1) Entry through P antigen receptor b. Fifth disease in children, red cell aplasia in adults c. Nonenveloped, so not destroyed by solvent-detergent treatment (concern in pooled treated products) d. Source and recovered plasma for plasma derivative manufacture are tested for Parvovirus via NAT E. Other organisms for which we don t test: 1. Prion disease a. Prion: probably an infectious protein particle b. Creutzfeldt-Jakob Disease (CJD) 1) Mostly sporadic (occasionally familial) spongiform encephalopathy, nearly universally fatal 2) Found in older patients 3) Long disease course 4) Transmission via transfusion theoretical only c. Variant CJD (vcjd) 1) Emerging syndrome in the United Kingdom 2) Caused by prion that causes bovine spongiform encephalopathy ( mad cow disease) 3) Distinct from CJD (younger, more rapid course) 4) Transfusion transmission proven 5) US deferral of many donors who lived in UK or Europe since 1980 (see earlier) 6) Led to universal leukoreduction in many countries (but current research suggests prion may also be found in plasma) 2. Plasmodium species a. Malaria is readily transmissible through transfusion. b. No effective screening except by history. c. See earlier for deferral guidelines 3. Babesia species a. Tick-borne intraerythrocytic parasite infection b. Huge concern in endemic areas in East currently; pilot studies to test donors c. Caused 10 cases of transfusion fatality from d. Screen via history (permanent deferral) page 18 Blood Bank II P}Chaffin (2/26/2014)

19 APPENDIX I Blood Donor Infectious Disease Screening Tests Agent Screening Test(s) Confirmatory Test(s) Discussion HIV Anti-HIV 1/2 (EIA/ChLIA) HIV-1 NAT (PCR, TMA) HCV HBV HTLV-I/II Syphilis (T. pallidum) Anti-HCV (EIA/ChLIA) HCV NAT (PCR/TMA) HBsAg (EIA/ChLIA) Anti-HBc (EIA/ChLIA) NAT HBV (Required 2013) Anti-HTLV-I/II (EIA/ChLIA) Many (hemagglutination, EIA, RPR) EIA/ChLIA: Western blot (WB) or IFA for HIV-1 EIA/ChLIA: HIV-2 EIA required after reactive anti-hiv-1/2 NAT: Individual donor NAT (if not done) EIA/ChLIA: Repeat EIA with another EIA (under FDA variance) or approved supplemental NAT versions RIBA for anti-hcv EIA (not currently available) NAT: Individual donor NAT (if not done) EIA/ChLIA: Neutralization for HBsAg, none for anti-hbc NAT: Individual donor NAT (if not done) None licensed Usually FTA or TP-PA West Nile Virus WNV NAT (PCR/TMA) Individual donor NAT (if not done) Chagas T. cruzi Enzyme Strip Assay Disease (T. EIA/ChLIA (ESA); FDA approved cruzi) Many use RIPA (not FDA approved) RR: Repeat reactive EIA/ChLIA: Enzyme immunoassay or chemiluminescent immunoassay PCR/TMA: Polymerase chain reaction or transcription-mediated amplification (available US NAT platforms) IFA: Immunofluoresence assay RIBA: Recombinant immunoblot assay (NOTE: RIBA has been discontinued by manufacturer, and all protocols using it are unavailable; see strikethrough text above) FTA: Fluorescent treponemal antibody TP-PA: Treponema pallidum particle agglutination RIPA: Radioimmunoprecipitation assay RPR: Rapid plasma reagin Sources: AABB Technical Manual, 17 th ed, The Osler Institute RR anti-hiv + Reactive HIV NAT = permanent deferral RR anti-hiv + WB neg/indeterm + NR HIV NAT = indefinite deferral (may try to re-enter in 8 weeks) RR anti-hiv + positive WB = permanent deferral NR anti-hiv + reactive HIV NAT = indefinite deferral (may try to re-enter in 8 weeks) RR anti-hcv + reactive HCV NAT = permanent deferral RR anti-hcv + RIBA neg/indeterm (unconfirmed supplement) + NR HCV NAT = indefinite deferral (may try to re-enter in 6 months) RR anti-hcv + positive RIBA (confirmed supplement) = permanent deferral RR anti-hcv + RR anti-hcv (different platform) OR positive supplemental NAT = permanent deferral NR anti-hcv + reactive HCV NAT = indefinite deferral (may try to re-enter in 6 months) RR anti-hbc x 1 = no deferral RR anti-hbc x 2 = permanent deferral RR anti-hbc + RR HBsAg = permanent deferral RR HBsAg + confirmed neutralization = permanent deferral RR HBsAg + nonconfirmed neutralization = retest in > 8 weeks NAT HBV reactive + RR HBsAg (confirmed neutralization) = permanent deferral Reactive anti-htlv-i/ii x 1 = no deferral Reactive anti-htlv-i/ii x 2 = permanent deferral Reactive screen + negative confirm = no definite deferral (though many will defer) Reactive screen + reactive confirm = at least 1 year deferral (after treatment) Reactive NAT = 120 day deferral (if asymptomatic) Reactive EIA = permanent deferral ESA and RIPA results only for counseling No re-entry currently Testing may be once per lifetime only P}Chaffin (2/26/2014) Blood Bank II page 19

20 The Osler Institute APPENDIX II AABB Uniform Donor History Questionnaire (V 1.3, AABB 2008) Question Comment Are you: 1. Feeling healthy and well today? 2. Currently taking an antibiotic? Medical director discretion 3. Currently taking any other medication for an Same infection? Please read the Medication Deferral List 4. Are you now taking or have you ever taken any See deferrals listed medications on the Medication Deferral List? previously in notes 5. Have you read the educational materials? Includes HIV risk info In the past 48 hours 6. Have you taken aspirin or anything that has aspirin in it? In the past 6 weeks 7. Female donors: Have you been pregnant or are you pregnant now? (Males: check I am male. ) 48 hour deferral as sole source of platelets per FDA This question (as well as #24 and #34) serves as a check to make sure donors are paying attention In the past 8 weeks have you 8. Donated blood, platelets or plasma? See details in notes 9. Had any vaccinations or other shots? See notes 10. Had contact with someone who had a smallpox vaccination? In the past 16 weeks 11. Have you donated a double unit of red cells using an apheresis machine? In the past 12 months have you No deferral unless symptomatic. If so, defer at least 14 days. 16 week donation interval 12. Had a blood transfusion? 1-year deferral 13. Had a transplant such as organ, tissue, or bone 1-year deferral marrow? 14. Had a graft such as bone or skin? 1-year deferral (unless dura mater, then permanent) 15. Come into contact with someone else s blood? 1-year deferral 16. Had an accidental needle-stick? 1-year deferral 17. Had sexual contact with anyone who has are all 1-year HIV/AIDS or has had a positive test for the deferrals from the time of HIV/AIDS virus? last contact 18. Had sexual contact with a prostitute or anyone else who takes money or drugs or other payment for sex? 19. Had sexual contact with anyone who has ever used needles to take drugs or steroids, or anything not prescribed by their doctor? 20. Had sexual contact with anyone who has hemophilia or has used clotting factor concentrates? P}Chaffin (2/26/2014) Blood Bank II page 20

21 The Osler Institute 21. Female donors: Had sexual contact with a male who has ever had sexual contact with another male? (Males: check I am male. ) 22. Had sexual contact with a person who has hepatitis? 23. Lived with a person who has hepatitis? 1 year deferral, unless asymptomatic Hepatitis C 24. Had a tattoo? For 24-25, these can be allowed if certified that procedure was done by state-certified entity using sterile, one-time use needles 25. Had ear or body piercing? 26. Had or been treated for syphilis or gonorrhea? 1 year following treatment completion (or from time of positive test if no symptoms) 27. Been in juvenile detention, lockup, jail, or 72 hours is consecutive prison for more than 72 hours? In the past three years have you 28. Been outside the United States or Canada? Primarily for malaria exposure or vcjd risk From 1980 through 1996, 29. Did you spend time that adds up to three (3) months or more in the United Kingdom? (Review list of countries in the UK) 30. Were you a member of the U.S. military, a civilian military employee, or a dependent of a member of the U.S. military? From 1980 to the present, did you 31. Spend time that adds up to five (5) years or more in Europe? (Review list of countries in Europe.) 32. Receive a blood transfusion in the United Kingdom or France? (Review list of countries in the UK.) From 1977 to the present, have you 33. Received money, drugs, or other payment for sex? 34. Male donors: had sexual contact with another male, even once? (Females: check I am For 29-32, see vcjd discussion in notes; permanent deferral Permanent deferral Currently controversial, but permanent deferral female. ) Have you EVER 35. Had a positive test for the HIV/AIDS virus? May require investigation to determine if true positive. If so, permanent deferral 36. Used needles to take drugs, steroids, or anything not prescribed by your doctor? Permanent deferral. Includes obvious physical stigmata of IVDA (needle tracks) 37. Used clotting factor concentrates? Permanent if for hemophilia, otherwise 1 year deferral P}Chaffin (2/26/2014) Blood Bank II page 21

22 The Osler Institute 38. Had hepatitis? Permanent deferral after 11 th birthday 39. Had malaria? 3 year deferral 40. Had Chagas disease? Permanent deferral 41. Had babesiosis? Permanent deferral 42. Received a dura mater (or brain covering) graft? Permanent deferral for vcjd possibility 43. Had any type of cancer, including leukemia? Medical director discretion (see discussion in notes) 44. Had any problems with your heart or lungs? Medical director discretion (see discussion in notes) 45. Had a bleeding condition or a blood disease? If hemophilia, permanent deferral. Otherwise, medical director discretion. 46. Had sexual contact with anyone who was born See HIV group O discussion in or lived in Africa? in notes. Can be omitted if anti-hiv test used detects group O. 47. Been in Africa? HIV group O discusssion 48. Have any of your relatives had Creutzfeldt- Jakob disease? Permanent deferral Medication Deferral List (Source: Please tell us if you are now taking or if you have EVER taken any of these medications: Proscar (finasteride) usually given for prostate gland enlargement Avodart, Jalyn (dutasteride) usually given for prostate enlargement Propecia (finasteride) usually given for baldness Accutane, Absorica (Amnesteem, Claravis, Sotret, isotretinoin) usually given for severe acne Soriatane (acitretin) usually given for severe psoriasis Tegison (etretinate) usually given for severe psoriasis Growth Hormone from Human Pituitary Glands used usually for children with delayed or impaired growth Insulin from Cows (Bovine, or Beef, Insulin) used to treat diabetes Hepatitis B Immune Globulin given following an exposure to hepatitis B. NOTE: This is different from the hepatitis B vaccine which is a series of 3 injections given over a 6 month period to prevent future infection from exposures to hepatitis B. Plavix (clopidogrel) and Ticlid (ticlopidine) inhibits platelet function; used to reduce the chance for heart attack and stroke. Feldene given for mild to moderate arthritis pain Experimental Medication or Unlicensed (Experimental) Vaccine usually associated with a research protocol P}Chaffin (2/26/2014) Blood Bank II page 22