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Principles of Transfusion Hospitalists Brian Platz, MD AP/CP, BB/TM September 4, 2014.

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Presentation on theme: "Principles of Transfusion Hospitalists Brian Platz, MD AP/CP, BB/TM September 4, 2014."— Presentation transcript:

1 Principles of Transfusion Hospitalists Brian Platz, MD AP/CP, BB/TM September 4, 2014

2 Itinerary Ordering Blood in HealthConnect For the Newbies… ‘Dosing’ of Blood Products Transfusion Reactions ID risks from Blood Transfusion Special Needs (CMV neg, LR, Irradiated) (Compatibility Testing)

3 Ordering Blood in HealthConnect Crossmatch of rbc units now automated Orders for Type & Screen are ‘implied’ if needed. (You do not need to order them separately)

4 For the Newbies Kaiser ‘Fresh Frozen Plasma’ In case no one has told you, Kaiser blood banks may give out ‘Plasma, thawed’ in lieu of ‘Fresh Frozen Plasma.’

5 FFP Separated and frozen within 6 hours of donation. Prevents degradation of the “labile” factors (V, VIII). Must be used within 24 hours after being thawed. Plasma, thawed Can be stored and used for up to 5 days. After 24 hours, must be destroyed or relabeled as

6 Degradation of Coagulation Factors in FFP

7 For the Newbies ‘DoubleCheck’ 40% of ABO mismatched transfusions occur because of patient misidentification or specimen mislabeling at phlebotomy. Regulations require the BB to compare every blood type test to historical records for that patient, to confirm ABO type. If it is the patient’s first time here, we have no history, so we won’t recognize a drawing error.

8 For the Newbies ‘DoubleCheck’ We require a second (distinct) draw on patients without a prior typing on record. Should be behind the scene for inpatients (may be more problematic for outpatients). We catch about 2-3 of these ‘misdraws’ per year.

9 For the Newbies from the East Coast Platelet Pheresis Obtained by pheresis from a single donor 1 unit from a whole blood donation contains >5.5 × 10 10 platelets and will raise platelet count of a 70-kg adult by 5000 to 10,000/µL 1 pheresis unit contains ≥3.0 × 10 11 platelets (~6 single units) and should increase platelet count about 40,000/µL

10 For the Newbies JW Liaison ?? (but the operator has this number, too) Don’t assume you know what the patient will and won’t accept. JW are a diverse group.

11 FYI WLA is now using an ‘electronic crossmatch’ Computer compares the donor unit ABO type to the patient’s ABO type, and will not allow the tech to issue an incompatible unit. Faster (and more reliable) than the 3-5 minute ‘immediate spin’ crossmatch.

12 Products and Dosing

13 Red Blood Cells 400 ml donation, Hct at least 38% plasma (+/- platelets) removed: 250 ml, Hct 65-80% preservative added, Hct ~55-65% Dosage relies on patient blood volume, target Hct, volume and Hct of donor unit(s). Reality Check: 1 unit rbcs will raise Hb 1g or Hct 3%

14 Platelets whole blood unit contains >5.5 × 10 10 platelets in 40 to 70 mL of plasma. apheresis platelets usually contains ≥3.0 × 10 11 platelets and is the equivalent of 4 to 6 units of platelets. Use for low platelets (consumption, hemorrhage), dysfunctional platelets Thrombocytopenia is unlikely cause of bleeding with counts > 50,000/µL. prophylactic transfusions may be appropriate at <5000 to 10,000/µL not indicated in HIT or ITP, unless actively bleeding. contraindicated in TTP (beware of HELPP syndrome) Dosage: patient blood volume, target count, unit count. CCI = (postcount – precount) × BSA / platelets transfused Reality Check: 1 pheresis unit gives 20-60,000 increase in platelet count (I use 40,000) in chronic platelet transfusion, can make antibodies to the platelets (usually PLA1 or HLA-related).

15 Fresh Frozen Plasma Prepared from whole blood or apheresis, frozen at -18 C or colder 200-250 ml (whole blood), 400-600 (apheresis) Clotting factors, vWF, fibrinogen, fibronectin, albumin, ADAMTS13 Must be used within 24 hours of thawing (can then be relabeled as “Plasma, Thawed” which implies less of the labile clotting factors, V, VIII and Protein S) Uses: Pre-op for patients with multi-factor deficiencies (liver disease, DIC), patients undergoing massive transfusion, bleeding while on Warfarin (Vit K - II, VII, IX, X), Thrombotic Thrombocytopenic Purpura, (second line choice for specific factor deficiencies). Dosing: based on patient’s known factor level(s), desired levels, patient’s blood volume, volume of plasma units. Still variable, as different people have different levels of the clotting factors. Reality Check: give 2 units, re-evaluate

16 Cryoprecipitate aka Cryoprecipitated Antihemophilic factor (AHF), cryo Prepared from FFP (FFP produces cryo and CPP) fibrinogen*, Factor VIII, Factor XIII, vWF, and fibronectin. assume 80 IU of Factor VIII and 150 mg of fibrinogen for each unit Fibrinogen: one bag per 7 to 10 kg body weight to raise plasma fibrinogen by approximately 50 to 75 mg/dL (fibrinogen <100 mg/dL) VIII = (Desired increase in Factor VIII level in % × 40 × body weight in kg) / average units of Factor VIII per bag. von Willibrand Dz: vWF content of Cryoprecipitated AHF is not usually known; an empiric dose of 1 bag per 10 kg of body weight Reality Check: 8-12 bags. Usually ordered by surgeons to correct fibrinogen. They have their own ‘learning’ on AHF. I don’t argue.

17 Transfusion Reactions

18 TYPECAUSEFREQNOTES FebrileTransfused WBCs/cytokines1:100Cellular products F>M Give Tylenol AllergicPatient allergic to something transfused plasma (nuts, PCN). 1:333Give antihistamines Anaphylactic/ Anaphylactoid Severe allergic reaction or IgA deficient patients making anti-IgA. Circulatory collapse, laryngeal edema. Hypotension without fever. 1:20,000 to 1:47,000 ~1 death per year Self-limited, but may require intubation/ICU SepticPlatelets: Staph RBCs: Yersinia enterocolitica. Hypotension with high fever. 1:5000 Plt 1:250,000 RBCs Fatal in 1:50,000 platelet tx

19 Transfusion Reactions (Cont) TYPECAUSEFREQNOTES Transfusion- Associated Circulatory Overload (TACO) Too much volume given. Cardiogenic edema. NL to high BP Varies with the underlying dz. Up to 10% in elderly and ICU. (less frequent since advent of pRBCs) BNP elevated 5-15% mortality Transfusion- Related Acute Lung Injury (TRALI) Anti-HLA antibodies + patient’s PMNs. Get caught up in pulmonary bed and cause non- cardiogenic edema. NL to low BP, +/- fever. Usually within 6 hours of transfusion. 1:12,000ARC uses only MALE donors for plasma. BNP < 250 5-10% mortality Acute Hemolytic Error in patient identification. Incompatible red cells given. 1:250,000 to 1:600,000 fatal Est 1:6,000 to 1:33,000 non-fatal

20 Transfusion Reactions (Cont) TYPECAUSEFREQNOTES Iron Overload Chronic transfusion (in our hospital, sickle cell and thalassemia patients) 50% of patients transfused with 75 or more units have increased Fe in myocardium Chelation with e.g. deferoxamine (IM, IV). Trials on oral medications. Graft-vs- Host disease Host is ‘blind’ to transfused lymphocytes, but transfused lymphocytes can recognize ‘host’ as foreign. E.g. Donor: HLA A 3 - B 27 - Recip: HLA A 3 A 24 B 7 B 27 Disease is rare (0.1- 1% in susceptible patients) due to irradiation. Transfusion- associated graft-versus-host disease. Dwyre DM, Holland PV Vox Sang. 2008 Aug; 95(2):85-93. Prevented by irradiation (2500 cGy of gamma radiation). Fatal in 87-100% Brubaker D. Transfusion-associated graft- versus-host disease. Hum Pathol. 1986;17:1085–1088 Alloimmuni - zation Due to immunization by red cell antigens in the donor unit. 0.5-3% Gen Pop 37% Thalassemia Transfus Med 2006;16:200 18-47% SSD Transfusion 2002;42:37 “Antibody Formers”

21 TRALITACO DYSPNEAYES ABGHypoxemia BPLow to NormalNormal to High TEMPNormal to ElevatedNormal CXRWhite out. Normal heart size. No vascular congestion. White out. Normal to increased heart size. Vascular congestion. Pleural effusions. BNPLow (<250 pg/mL)High Pulmonary artery occlusion pressure Low to NormalHigh EchocardiogramNormal heart functionAbnormal heart function Response to DiureticsWorsensImproves Response to FluidsImprovesWorsens TRALI v TACO Shealynn Harris, MD, Asst Med Dir., ARC, SoCal Div.

22 ID Risks

23 How Safe is the Blood Supply? Donor Testing HBsAg, anti-HBcAb anti-HCV anti-HTLV I/II anti-HIV 1/2 NAT testing for HCV, HBC, HIV, WNV anti-Trypanosoma cruzi Ab (Chagas Disease) Serologic test for syphilis (in addition, all platelet donations are tested for bacteria) (perhaps anti-CMV, if not known to be positive)

24 Current ID Risks / Transfusion (12.9 million units transfused each year in US) IDRISK / UNITCOMMENTS HIV1 : 2,300,000 HCV1 : 2,000,000 HBV1 : 350,000LONG WINDOW PERIOD HTLV I/II1 : 2,000,000 WNV1 : 350,00011 CONFIRMED CASES BY A TRANSFUSION. USUALLY MILD DISEASE 1 : 150-200 SEVERE/FATAL BACTERIAL SEPSIS1 : 1,000,000 GETTING STRUCK BY LIGHTNING IN A GIVEN YEAR 1 : 500,000In Florida GETTING STRUCK BY LIGHTNING IN A LIFETIME 1 : 6250 WINNING MEGAMILLIONS JACKPOT1 : 175,711,536

25 Special Needs

26 CMV Negative— Historically, based on Serology of donor, but Prestorage Leukocyte reduction is equivalent, for most situations. Used for pregnant women, intrauterine transfusion, low birth weight or premature infants, BM/solid organ transplant patients, and severely immunocompromised patients (including HIV infection). Not indicated if patient is CMV positive, (50-80% of population is positive). Leukocyte-Reduction (LR)— Prestorage LR reduces the number of white cells to 3-log reduction). Helps prevent febrile reactions and HLA alloimmunization. Irradiation—T reating a unit with 2500 cGy of gamma radiation destroys the lymphocytes ability to divide. The ONLY purpose is to prevent GVHD. Used for Directed donations to family members, HLA- matched platelet tx, intrauterine tx, organ transplant patients

27 CMV Negative Serologic test not 100% reliable — A “negative” unit can actually be positive either because of the window period, or because the antibody titer becomes undetectable. Leukoreduction — Appears to be as effective. Some Suppliers (ARC)— No longer supply them. THUS When “CMV-negative” is requested, we will supply Leukocyte-reduced. If you really, really want CMV- seronegative units, you must call the blood bank.

28 Leukocyte Reduction “Pre-storage” Performed under controlled conditions, over a specified period of time, at a cooled temperature. Greater than 3-log reduction in lymphocytes. “Before-issue” Run through a LR filter in the lab, before being picked up. (We don’t do this here. I’ve never worked anywhere that did this) “At the Bedside” Run through a LR filter while being transfused to the patient. NOTE: this is NOT equivalent to “CMV-Negative”. NOTE: a Leukocyte-reduction filter is different from the “microaggregate” filter that is used for all cellular products.

29 Special Needs (cont) IgG-deficient donors– Used only for IgA-deficient recipients who are making igG anti-IgA antibodies (1 in 333 people, but many don’t make the anti-IgA) Washed RBCs — Rarely necessary. Use special donors if IgA- deficient units are needed. Used for, eg, washing the mothers red cells when she is a directed donor for a newborn child with HDN Frozen — We use mostly with Sickle Cell Disease patients (multiply-transfused, multiple antibodies) or if an unlucky patient is making antibodies to a high-frequency antigen.

30 Compatibility Testing

31 ANTIBODY SCREEN NEGATIVEANTIBODY SCREEN POSITIVE Can Use “Immediate-spin crossmatch” (5 minutes) or “electronic crossmatch” (1 second) First, must perform a “Panel” to identify which antibody is being made (45 minutes) Must use units that lack the identified antibody (takes 5-30 minutes to type the unit) Must use “Coombs Phase Crossmatch” 30 minutes) Total time: 35 minutes.Total time: 2 hours + As long as the sample is valid (72 hours), additional units will take about 5 minutes. Additional units will take 45 minutes to an hour to get ready. TYPE AND SCREEN TYPE—ABO and Rh (5 minutes). SCREEN—For “unexpected” antibodies, (30 minutes).

32 Please!!!! Do not hesitate to call me!! Any time, day or night. I would MUCH rather be awoken at 3am to help coordinate the best care for a patient than to get to work the next day to find the little red light on my phone blinking and a bunch of messages from irate clinicians about poor quality of care.

33 MSM Donors Still not in the US (Lifetime deferral) Canada has reduced deferral to 5 years UK has 1 year deferral South Africa has 6 month deferral Chile and China are among countries that now allows gay men to donate The American Red Cross and the AABB both advocate changing the U.S. policy on donations by gay men to a one-year ban -- on par with donation policies for other high-risk groups.

34 Synthetic Blood Hemoglobin-based Perfluorocarbon-based Many have been tested, but they tend to show an increase in death and often increase in heart attacks in trials on trauma patients Produced by stem cells (Pharming) Arteriocyte contracted by DARPA (Defense and Research Projects Agency). Produce rbcs from umbilical stem cells. Studies going on. The major advantage is the natural rbc shape and near-normal life span. Cost has been reduced to $1000/unit. Each cord can produce 20 units.

35 Young Blood Fountain of Youth? the Studies joining the vascular systems of young mice and old mice show REVERSED signs of aging in the older mice: age- related decline in cognitive function, muscle atrophy, and the sense of smell. This might explain vampires I anticipate a resurgence in Goth culture In light of the above, for the first time in my life I’m glad I’m over 50 and no longer have young blood. Katsimpardi et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344(6184): 630-4. Sinha, et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science 2014; 344(6184): 649-52. Villeda, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine 2014.

36 ? blood bank stuff x4350 310-594-2269

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