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Blood Bank II D. Joe Chaffin, MD Cedars-Sinai Medical Center, Los Angeles, CA
Blood Donation & Pretransfusion Testing I. Blood Donation A. Allogeneic (homologous) (homologous) whole whole blood donation donation 1. Process tightly regulated by FDA and AABB 2. Donor screening by history history a. FDA-recognized FDA-recognized AABB template called “donor history questionnaire” (DHQ); see end of this handout b. Necessary information 1) Full name (generally, formal ID required) required) 2) Home and/or work address 3) Date of birth/age birth/age to make sure over minimum age a) 17 unless state-approved age 16 donors allowed 4) Reasons for previous deferral 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 plasmapheresis d) > 2 days for single platelet platelet apheresis procedures e) > 7 days for double/triple platelet apheresis c. Not required, but often asked 1) Race 2) Social security number a) Identity theft concerns b) Alternative ID numbers (unique to donor) d. HIV information 1) Signs/symptoms and risk factors for HIV 2) Do not to donate if have any risk factors or if just wanting HIV test e. Medication list; list; prevents donations from those taking: 1) Medications with with teratogenic potential 2) Medications with with infectious risk 3) Medications that that damage platelets f. Informed consent must spell out risks 1) Informed consent is not standardized; individual centers must develop g. 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 restrictive 3) May omit HIV group group O questions if donor testing testing used is approved to detect group O (see later) 3) May add additional questions at end only a) These can be more restrictive only; never less less
Pathol Path ology ogy Review Review Cour se b) Commonly added questions are about medications/health issues not covered in DHQ h. Deferrals based on history 1) Permanent deferrals Infectious Risks -High-risk behavior for AIDS (including IVDA, male-male sex, exposure) -Receiving money money or drugs for sex -Serologic positive for HIV, HBV, HCV, HTLV -Viral hepatitis after 11 th birthday -Transfusion of clotting factor concentrates (in hemophilia) 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 © -Tegison
2) Three year deferrals Infectious Risks -Recovered from malaria -Immigrants from malaria-endemic areas ( after 5 consecutive years of living there ) Teratogens © -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); (Allogeneic); including plasma/clotting plasma/clotting factors factors in nonhemophiliacs nonhemophiliacs -Allogeneic transplant of organ/skin/bone -Living with person with active hepatitis -Receiving HBIG -Tattoos/piercings (unless by regulated entity) -Travel to malaria-endemic areas -Syphilis or gonorrhea -Non-prophylactic rabies vaccination -“Travel” to Iraq
4) Special situations a) Malignancy deferrals
Th e Os Osler ler I nstitu nstitu te i) Medical director discretion (not mandated) ii) Studies do not show that malignancy malignancy can be transmitted via transfusion iii) Most defer leukemia/lymphoma permanently, permanentl y, but some accept cured childhood leukemics iv) For solid tumors, most defer indefinitely and consider re-entry after 1-5 years disease-free v) BCC, localized skin skin SCC = no deferral. b) Heart and lung disease i) No specific mandated deferrals ii) FDA: Donor should be free of acute lung disease ii) AABB: Donor should be free free of heart/lung disease unless determined suitable by medical director iii) Medical directors determine acceptability (time since diagnosis, presence of limitations on activities, proper medical follow-up) c) Pregnant women: Defer until 6 wks postpartum. d) Non-routine dental work: Defer for 72 hours. e) Questions 46, 47: HIV group O Africa questions i) Rare in in US; no reported reported cases since 1996 ii) Being born in, living in, or having sexual contact with someone born or living in these countries in Africa since 1977 is a permanent deferral: Benin, Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, Gabon, Kenya, Niger, Nigeria, Senegal, Togo, or Zambia. iii) If traveled to these countries since 1977 and got a blood transfusion: Permanent deferral iv) HOWEVER, if an FDA-approved anti-HIV screening test that is sensitive for HIV group O is used, these questions may be omitted. 5) Defer permanently for for vCJD risk all donors who: a) Lived over 3 months in UK, 1980 to 1996 b) Lived in France over 5 years, 1980 to now c) Received dura mater transplant, pituitary growth growth hormone injections, or bovine insulin injection d) Were transfused transfused in the UK, 1980 to now e) Lived in Europe over 5 years, 1980 to now f) Have family history of CJD or vCJD g) Were military members/dependents: i) Stationed at Northern Europe bases (Germany, UK, Belgium, Netherlands) for 6 months from 1980 to 1990 ii) Stationed at other Europe bases (Greece, Turkey, Spain, Portugal, Italy) for 6 months from 1980 to 1996
Pathol Path ology ogy Review Review Cour se 6) Immunizations a) General rule: no deferral for for killed, toxoid, or recombinant/synthetic vaccines b) Live attenuated vaccines (either viral or bacterial) give deferrals of varying lengths
Immunization Deferrals Four Weeks: Two Weeks:
No Deferral:
12 Months:
Rubella Varicella Measles Mumps Oral polio Yellow fever Oral typhoid Anthrax Cholera DPT Hepatitis A Hepatitis B Influenza Lyme disease Meningococcus Pneumococcus Pneumococcus Polio (injection) (injection) RMSF Typhoid (injection) (injection) Unlicensed vaccines
c) Smallpox vaccination i) Deferrals based on presence/ absence of vaccine scab and post-vaccination symptoms ii) No symptoms: defer until scab scab falls off or 21 days, whichever is longer iii) With symptoms: defer until 14 days after after symptoms resolve 7) Drugs a) DHQ only requires questioning about a limited 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): (Soriatane): Three year deferral iii) Isotretinoin (Accutaine): 30 day deferral iv) Finasteride (Proscar, Propecia): 30 days v) Dutasteride (Avodart, (Avodart, Jalyn): 6 months c) DHQ V 1.3 drug deferrals for for infection risk: risk: i) Human pituitary growth hormone: Permanent ii) Bovine insulin: insulin: Permanent iii) HBIG: 1 year iv) Unlicensed vaccine: 1 year
Th e Os Osler ler I nstitu nstitu te d) Aspirin/aspirin like like meds for platelets (48 hours) hours) e) Platelet drug deferrals: i) Feldene: 48 hours for platelet donors only ii) Clopidogrel (Plavix) and ticlopidine (Ticlid): 2 weeks for platelet donors only f) Warfarin is not in DHQ, but most defer donors about 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 others above 3. Donor screening screening by physical criteria criteria a. General appearance b. Arm check 1) Both arms Both arms for evidence of IVDA and venous access c. Physical requirements: 1) Note that weight, pulse, and BP are are NO LONGER official standards defined by AABB or FDA, and the numbers listed below are most common practice Min. Weight:
> 110 lbs (50 Kg)
Temperature:
< 99.5o F (37.5 C)
Pulse:
50-100 (unless athlete)
Blood pressure: < 180/100 HGB or HCT:
> 12.5 g/dL or 38%
4. Donation specifics a. Amount drawn 1) 500 +/- 50 mL (+/ – – 10%) 10%) most common a) 450 mL bag also also used; limit is 450 +/- 45 mL 2) Maximum of 10.5 ml/Kg ml/Kg is allowed allowed by AABB b. Time limit 1) < 10 minutes best, but no upper limit defined defined a) Beyond 15 minutes, plasma/PLTs usually not made 5. Testing donor blood a. ABO grouping b. Rh typing 1) Weak D required if D negative (see BBI) c. Antibody detection (“screen (“screen”) ”) 1) Unexpected (non-ABO) antibodies antibodies in donor serum 2) AABB Standards: 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 reflect any positive results that are identified as clinically significant antibodies. 4) Reality: Most hos pitals don’t want this blood
Pathol Path ology ogy Review Review Cour se d. Infectious disease disease screening (as of 2/2013); 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; in 2013) 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 Anti-Trypanosoma cruzi (Chagas’ disease) d) Serologic test test for syphilis
B. Donor reactions 1. Vasovagal reactions a. Most common reaction (2.5% of healthy donors) 1) More common in young, first-time first-time donors b. Signs/symptoms 1) Bradycardia 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 consciousness 3) Shock parameters c. Treatment 1) IV fluids, possibly return return blood? 3. Hyperventilation a. Especially common in first-time first-time donors and children b. Signs/symptoms 1) Shortness of breath 2) Facial twitching 3) Seizure activity (unusual) c. Treat with 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
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C. Apheresis procedures 1. Separation of blood into components using several technologies a. Centrifugation used 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 (after mobilization) 3. Multiple product collections in one procedure possible a. One RBC unit and one platelet unit b. One RBC unit and one plasma unit c. One RBC unit, one platelet unit, one plasma plasma unit d. Two RBC units 4. Donor requirements a. Platelet donors 1) Same hemoglobin/hematocrit requirements as regular donors 2) Donation interval at least 2 days for single product a) No more than 2 procedures 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). certification). 3) Donation interval 7 days after double/triple double/triple products 4) No aspirin/aspirin-effect 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” Infrequent” (> every 4 weeks): = whole blood 2) “Serial” 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 FDA-cleared 3) Double red cell donors are deferred deferred for 16 weeks
Pathol Path ology ogy Review Review Cour se d. Multiple products collected at once 1) FDA-cleared equipment specific donor limits 5. Apheresis donor reactions a. “Citrate effect” 1) Citrate anticoagulant anticoagulant binds free calcium calcium 2) Perioral tingling 3) Tetany and arrhythmias uncommon 4) Slow rate of infusion, give oral oral calcium b. Hypersensitivity reactions 1) Classic: Hydroxyethyl Hydroxyethyl starch in WBC donors a) Given to facilitate better 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: Standards: Don’t cross over units into regular inventory unless exceptional circumstances. 3. More lenient physical criteria (see table below) 4. Testing regulations a. Infectious disease screening screening not required unless units are to be shipped to another ano ther facility 1) If not tested, label units “NOT TESTED” b. Only first donation in a 30-day period MUST be tested. 1) All others after that are labeled “DONOR TESTED WITHIN THE LAST 30 DAYS” Parameter Allogeneic Autologous 72 hours Donation Interval 8 weeks > 12.5 or 38% > 11 or 33% HB/HCT > 110 lbs (50 Kg) None Weight > 16 or 17 (varies) None Age Not required unless Infectious Disease Required shipped Screening History of Disease Not eligible Potentially eligible or Positive Test 5. Potential issues issues with with autologous autologous donations a. Donor reactions 1) More complex donors with more health 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/transfusion errors 1) Risk of wrong wrong unit going to wrong patient still still present with autologous donations. 2) CAP survey (1992): (1992): about 1% of hospitals admitted making transfusion errors with autologous blood.
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c.
d.
e.
f.
3) Systems must be in place to prevent allogeneic units from being transfused before autologous units. Bacterial contamination 1) Currently a greater greater risk than HIV or HCV 2) Risk of undetected infection leading leading to contamination of unit is not changed by PAD. Cost 1) More costly to patients if transfused and hospitals if not transfused (wastage). 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?) Positive infectious disease testing 1) If donor has a reactive reactive test, donor and the requesting physician must be notified. 2) Autologous collections Autologous collections with reactive testing can lead to deferral from future allogeneic donations. allogeneic donations.
B. Acute Normovolemic Normovolemic (isovolemic) hemodilution hemodilution 1. Primary goal: goal: reduce RBC volume during surgery. surgery. 2. Added benefit: Reduces plasma and platelet needs even more 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 (Hi-Hf )/Hav (source: Waters JH, “Perioperative Blood Sequestration”, AABB 2008) 2) Key: i) V = volume to remove ii) EBV = estimated estimated blood volume iii) Hi = initial hematocrit iv) Hf = = final hematocrit v) Hav = 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 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 first
Pathol Path ology ogy Review Review Cour se 6. Indications (not standardized) a. At least 1 L blood loss anticipated in surgery surgery b. Hemoglobin at least 12 g/dL c. No active cardiac or other serious serious medical disease d. No infection or bacteremia 7. Potential advantages a. Better monitoring monitoring than PAD, use for riskier patients? patients? b. Bleeding more dilute blood leads to less overall hemoglobin loss (not as huge a benefit b enefit as predicted). c. Decreased blood viscosity increases cardiac output and may improve oxygenation. d. Coag factors and platelets survive well well for short short periods and help hemostasis. e. May be used in future with blood supplements (“substitutes”): “Augm “Augmented ented hemodilution” 8. Potential disadvantages a. Requires training training of phlebotomist (most (most commonly done by anesthesiologist) b. Units should be labeled with full name, date/time, medical record number, and “FOR AUTOLOGOUS USE ONLY.” 8. 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 procedures with large expected blood losses (cardiac, orthopedics, vascular surgeries) 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 embolus risk b. Hemolysis of processed blood from excessive suction in the operative field c. Coagulation factor activation 5. Historical contraindications; used by some, ignored by others a. Bacterial contamination of operative field b. Malignant cells in field c. Other contaminants contaminants in field (cement, irrigation, amniotic fluid, etc)
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D. Postoperative blood salvage 1. Blood reinfused from from operative drains with or without without processing (I’m (I’m sorry, that is just gross!) a. Microaggregate filters used during re-infusion 2. Shelf life: 6 hours at room temperature
III. Pretransfusion Testing A. Basic outline 1. Requires actions by supplier, phlebotomists, phlebotomists, transfusion transfusion services, and infusing staff 2. Crossmatch is final check of everyone’s work . a. Main reason reason for crossmatch: ABO ABO compatibility!
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 1997 Transfusion 1997 37; 1169-72: Mislabeled specimens 40X more likely to have a blood grouping discrepancy! c. Should tell what’s needed 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 hold sample,, not units. c. Uncommonly used or even offered 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 determine current ABO/Rh, but should be compared to to current results. 2) ABO testing
Pathol Path ology ogy Review Review Cour se a) Forward and reverse 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) (non-ABO) antibody check b) Panel of 2, 3, or 4 RBC-phenotyped donors i) Always group O ii) Most common combination: 1 1 • Cell I: R R 2 2 • Cell II: R R • Cell III: rr c) Antigens represented required by FDA: a b a b a b i) D, C, c, E, e, Fy , Fy , Jk , Jk , K, k, Le , Le , M, N, P1, S, s d) IAT phase is is required, IS/37 C are not required. e) If positive, positive, identify antibody (see BB Practical) 5. Type and crossmatch (T&C) a. Everything in T&S + crossmatch b. Crossmatch types 1) Major crossmatch (or just “crossmatch”) a) Recipient serum vs donor RBCs b) Final check of ABO compatibility c) IAT/AHG IAT/AHG phase (“full crossmatch”) not crossmatch”) not required if antibody screen is negative d) Required Required if ≥ 2 ml of RBCs in product . 2) Minor crossmatch a) Donor serum serum vs. recipient RBCs b) Not required 3) Units go back into inventory if 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 RBCs/recipient serum centrifuged at room temp 2) Computer crossmatch crossmatch (see (see below) 7. Variations to the above a. Infants less less than four months of age (neonatal period) 1) Baby’s antibodies = mom’s IgG antibodies. 2) Initial testing: a) Infant’s Infant’s ABO (red 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 crossmatch not needed in same hospital stay up until age 4 months 4) Serum grouping not required unless non-group O baby receives non-group O RBCs
Th e Os Osler ler I nstitu nstitu te b. Electronic (computer) crossmatch 1) Computer system verifies ABO compatibility between donor and recipient (replaces immediate spin crossmatch) 2) Requires a patient patient with a negative antibody screen both now and in the past 3) Requires two separate ABO determinations 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 crossmatch a. With positive antibody screen 1) Alloantibodies 2) Autoantibodies 3) Reagent antibodies 4) Rouleaux and other false false positives b. With negative antibody screen 1) ABO incompatibility 2) Antibodies vs low-incidence antigens 3) Positive donor DAT 9. Routine blood order order templates a. Maximum Surgical Blood Ordering Schedule (MSBOS), or just “routine surgical blood orders” b. Multidisciplinary and institution-specific institution-specific c. Gives surgeons / blood bankers a guide to how many RBC units to crossmatch (or not) for a given proce dure
IV. Transfusion-transmitted Diseases (See April 2011 Podcast) A. Current risk of disease transmission 1. For perspective, risk risk of acute hemolytic reaction stated stated as 1 in 25,000 transfusions 2. Risk of dying dying in the hospital hospital from something something other than transfusion problem: 6 per 1000! Organism
Current Risk Estimate
HIV-1 Hepatitis B Hepatitis C HTLV-I HIV-2 WNV Syphilis
1 in 1,467,000 (2010) 1 in 355,000-357,000 (2009) 1 in 1,149,000 (2010) 1 in 3,000,000 Remote Remote Remote Unknown, likely remote 1 in 75,000 platelet transfusions 1 in 500,000 RBC transfusions
T. cruzi
Bacteria
B. Hepatitis viruses 1. Hepatitis A virus a. Fecal-oral transmission (30 day incubation) b. Generally not a big blood banking problem (not tested)
Pathol Path ology ogy Review Review Cour se c. Some concern concern in pooled products 1) Solvent-detergent Solvent-detergent treatment doesn’t deactivate HAV (nonenveloped). 2) Transmission possible possible in pooled factor concentrates d. Not prone to chronicity like HBV and especially HCV 2. Hepatitis B virus a. DNA virus ( Hepadnavirus) 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%) (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 f. Current testing (see appendix) 1) Anti-HBc EIA/ChLIA EIA/ChLIA and HBsAg HBsAg EIA/ChLIA a) Confirmatory test for HBsAg: neutralization b) No confirmatory test for anti-HBc 2) No anti-HBsAg testing (vaccinated donors positive) 3) HBV NAT required in 2013 4) HBV is currently the most likely of the major viruses to be transmitted via transfusion! g. Serology patterns below HBV DNA
HBsAg
ANTI-HBc (TOTAL)
ANTI-HBc (IGM)
ANTIHBsAg
– + – +/ – – –
– + – + –
– + + + –
– + – – –
– – + – +
–
–
+
–
–
INTERPRETATION
Incubation Acute infection Recovered infection Carrier Vaccinated Probable false pos.,possible early or chronic infection
3. Hepatitis C virus a. RNA virus b. 0.5-1.0% of US blood donors c. Both cellular and plasma components transmit. d. Strong association with chronic hepatitis (75%), (75%), cirrhosis, and hepatocellular carcinoma (>HBV) 1) Currently #1 reason reason for hepatic transplant transplant in the US. 2) Initial presentation presentation mild or asymptomatic asymptomatic e. Donor testing (see appendix) 1) Antibody test is anti-HCV (EIA/ChLIA)
Th e Os Osler ler I nstitu nstitu te a) Reactive anti-HCV confirmed confirmed by Recombinant ImmunoBlot Assay (RIBA); current US shortage 2) Window period with antibody test: 70-80 days a) During some of this time, HCV RNA is detectable by PCR testing, and the virus is transmissible by transfusion (see below). 3) Also must use use nucleic acid testing testing (HCV NAT) a) Window period from 70-80 days to 10-30 days 4) See appendix for deferral deferral guidelines 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 India and Asia; rare rare transfusion transmission
C. Retroviruses 1. HIV-1 and HIV-2 a. RNA retrovirus identified in 1984 1) Hemophiliacs and homosexual men first first 2) Transfusion, sexual sexual contact, breast-feeding, breast-feeding, blood b. Clinical/pathophysiology 1) Symptoms in acute infection: “flu“flu-like” 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 = 20-22 days 2) Organism testing a) HIV-1 antigen (p24) testing March March 1996 • Reduced window period to about 16 days b) p24 testing replaced in 1999-2000 by nucleic acid testing for HIV RNA (HIV NAT) • Reduction of window period period to to 9-10 days d. Both cellular and plasma products products can transmit HIV-1 HIV-1 e. See appendix for deferral guidelines f. HIV-2 1) Related virus found found originally in West Africa 2) Really, really rare 3) Less readily transmitted transmitted vs HIV-1, with less AIDS 4) No licensed confirmatory test
Pathol Path ology ogy Review Review Cour se 2. HTLV I/II a. Transmission through cellular products only b. HTLV-I disease associations 1) Adult T-cell T-cell leukemia/lymphoma (ATLL) 2) HTLV-associated myelopathy (HAM; formerly called “t “tropical spastic paraparesis”) c. HTLV-II: no clear-cut disease associations d. Both transmitted readily, readily, but actual post-transfusion disease is 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. 2012 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: only: 120 days from test date 2. Tr ypanos ypanosoma oma cr cr uzii (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, dono rs, 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 2011 1) Testing allowed to to be one time per lifetime of donor 3. Tr eponema ponema pall pall idum a. Organism doesn’t survive 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 seronegative donors and leukocyte reduced products (see discussion in BB III) d. Testing not required but available 5. Parvovirus B19 a. Primarily infects RBCs 1) Entry through through P antigen receptor b. “Fifth disease” in children, red cell aplasia in adults
Th e Os Osler ler I nstitu nstitu te c. Nonenveloped, so not destroyed 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: don’t test: 1. Prion disease a. Prion: probably an an infectious protein particle b. Creutzfeldt-Jakob Disease (CJD) 1) Mostly sporadic (occasionally familial) spongiform encephalopathy, nearly universally fatal 2) Found in older patients patients 3) Long disease course 4) Transmission via 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 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 species a. Malaria is readily transmissible through through transfusion. transfusion. b. No effective screening except by history. c. See earlier for deferral guidelines 3. Babesia species 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 fatality from 2007-11 d. Screen via history (permanent deferral) deferral)
Pathol Path ology ogy Review Review Cour se APPENDIX I Blood Donor Infectious Disease Screening Tests Agent
Screening Test(s)
HIV
Anti-HIV 1/2 (EIA/ChLIA) HIV-1 NAT (PCR, TMA)
Confirmatory Test(s)
HCV
HBV
HTLV-I/II
Syphilis (T. (T. pallidum) pallidum)
West Nile Virus Chagas Disease (T. cruzi) cruzi)
Anti-HCV (EIA/ChLIA) HCV NAT (PCR/TMA)
HBsAg (EIA/ChLIA) Anti-HBc (EIA/ChLIA) NAT HBV (Required in 2013)
Western blot (WB) or IFA for HIV-1 HIV-2 EIA required after reactive antiHIV-1/2 Individual donor NAT (if not done)
RIBA for anti-HCV Individual donor NAT (if not done)
Neutralization for HBsAg None for anti-HBc Individual donor NAT (if not done)
Anti-HTLV-I/II (EIA/ChLIA/mic roEIA) Many (hemagglutination, EIA, RPR)
Usually FTA or TPPA
WNV NAT (PCR) T. cruzi EIA/ChLIA
Individual donor NAT (if not done) Enzyme Strip Assay (ESA); FDA approved Many use RIPA (not FDA approved)
None licensed
Discussion 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 + NR HCV NAT = indefinite deferral (may try to reenter in 6 months) RR anti-HCV + positive RIBA = 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 = 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
RR: Repeat reactive EIA/ChLIA: Enzyme immunoassay or chemiluminescent chemiluminescent immunoassay PCR/TMA: Polymerase chain reaction or transcription-mediated transcription-mediated amplification IFA: Immunofluoresence assay RIBA: Recombinant immunoblot assay FTA: Fluorescent treponemal antibody TP-PA: Treponema pallidum particle agglutination RIPA: Radioimmunoprecipitation assay RPR: Rapid plasma reagin Sources: AABB Sources: AABB Technical Manual, Manual, 17 th ed , www.fda.gov
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APPENDIX 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? 3. Currently taking any other medication for an infection? Please read the Medication Deferral List 4. Are you now taking or have you ever taken any medications on the Medication Deferral List? 5. Have you read the educational materials? 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.”)
Medical director director discretion discretion Same
See deferrals listed previously in notes Includes HIV risk info 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? 9. Had any vaccinations or other shots? 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 12. Had a blood transfusion? 13. Had a transplant such as organ, tissue, or bone marrow? 14. Had a graft such as bone or skin? 15. Come into contact with someone else’s blood? 16. Had an accidental needle-stick? 17. Had sexual contact with anyone who has HIV/AIDS or has had a positive test for the HIV/AIDS virus? 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?
See details in notes See notes No deferral deferral unless symptomatic. symptomatic. If so, defer defer at least 14 days. 16 week donation interval
1-year deferral 1-year deferral 1-year deferral (unless dura mater, then permanent) 1-year deferral 1-year deferral 17-23 are all 1-year deferrals from the time of last contact
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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? 24. Had a tattoo?
25. Had ear or body piercing? 26. Had or been treated for syphilis or gonorrhea?
27. Been in juvenile detention, lockup, jail, or prison for more more than 72 hours? In the past three years have you 28. Been outside the United States or Canada? 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, male, even once? (Females: check “I am female.”) Have you EVER 35. Had a positive test for the HIV/AIDS virus?
1 year deferral, unless asymptomatic Hepatitis C For 24-25, these these can be be allowed if certified that procedure was was done by state-certified state-certified entity entity using sterile, one-time one-time use needles needles 1 year following treatment completion (or from time of positive test test if no symptoms) 72 hours is consecutive
Primarily for for malaria exposure or vCJD risk For 29-32, see see vCJD discussion in notes; permanent deferral deferral
Permanent deferral deferral Currently controversial, but permanent deferral deferral
May require require investigation investigation to determine if true positive. If so, permanent permanent deferral deferral 36. Used needles to take drugs, steroids, or anything Permanent deferral. deferral. not prescribed by your doctor? Includes obvious obvious physical physical stigmata of IVDA (needle (needle tracks) 37. Used clotting factor concentrates? Permanent if if for hemophilia, hemophilia, otherwise 1 year deferral
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38. Had hepatitis? 39. 40. 41. 42.
Had malaria? Had Chagas’ disease? Had babesiosis? Received a dura mater (or brain covering) graft?
43. Had any type of cancer, including leukemia? 44. Had any problems with your heart or lungs? 45. Had a bleeding condition or a blood disease?
46. Had sexual contact with anyone who was born in or lived in Africa?
47. Been in Africa? 48. Have any of your relatives had CreutzfeldtJakob disease?
Permanent deferral deferral after after th 11 birthday 3 year deferral Permanent deferral deferral Permanent deferral deferral Permanent deferral deferral for vCJD possibility Medical director director discretion discretion (see discussion in notes) Medical director director discretion discretion (see discussion in notes) If hemophilia, hemophilia, permanent permanent deferral. Otherwise, medical director discretion. See HIV group O discussion discussion in notes. Can be omitted if anti-HIV test used detects group O. HIV group O discusssion discusssion Permanent deferral deferral
Medication Deferral List (Source: http://www.aabb.org/resources/donation/questionnaires/Pages/dhqaabb.aspx) 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© (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 f uture infection from exposures to hepatitis B. inhibits platelet function; used to reduce the Plavix (clopidogrel) and Ticlid (ticlopidine) – inhibits chance for heart attack and stroke. given for mild to moderate arthritis pain Feldene – given Experimental Medication or Unlicensed (Experimental) Vaccine – usually associated with a research protocol
