Principles of Transfusion

HospitalistsBrian Platz, MD AP/CP, BB/TM

September 4, 2014

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)

Ordering Blood in HealthConnect

Crossmatch of rbc units now automatedOrders for Type & Screen are ‘implied’ if

needed. (You do not need to order them separately)

For the NewbiesKaiser ‘Fresh Frozen Plasma’

In case no one has told you, Kaiser blood banks may give out

‘Plasma, thawed’ in lieu of

‘Fresh Frozen Plasma.’

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

Degradation of Coagulation Factors in FFP

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.

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.

For the Newbies from the East CoastPlatelet Pheresis

• Obtained by pheresis from a single donor• 1 unit from a whole blood donation contains

>5.5 × 1010 platelets and will raise platelet count of a 70-kg adult by 5000 to 10,000/µL

• 1 pheresis unit contains ≥3.0 × 1011 platelets (~6 single units) and should increase platelet count about 40,000/µL

For the NewbiesJW 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.

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.

Products and

Dosing

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%

Platelets• whole blood unit contains >5.5 × 1010 platelets in 40 to 70 mL of plasma. • apheresis platelets usually contains ≥3.0 × 1011 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).

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

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.

Transfusion Reactions

Transfusion ReactionsTYPE CAUSE FREQ NOTES

Febrile Transfused WBCs/cytokines 1:100 Cellular productsF>MGive Tylenol

Allergic Patient allergic to something transfused plasma (nuts, PCN).

1:333 Give antihistamines

Anaphylactic/Anaphylactoid

Severe allergic reaction orIgA deficient patients making anti-IgA. Circulatory collapse, laryngeal edema. Hypotension without fever.

1:20,000 to1:47,000

~1 death per yearSelf-limited, but may require intubation/ICU

Septic Platelets: StaphRBCs: Yersinia enterocolitica. Hypotension with high fever.

1:5000 Plt1:250,000 RBCs

Fatal in 1:50,000 platelet tx

Transfusion Reactions (Cont)TYPE CAUSE FREQ NOTES

Transfusion-AssociatedCirculatoryOverload(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 elevated5-15% mortality

Transfusion-RelatedAcuteLung 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.

1:12,000 ARC uses only MALE donors for plasma.BNP < 2505-10% mortality

Acute Hemolytic

Error in patient identification.Incompatible red cells given.

1:250,000 to1:600,000 fatal

Est 1:6,000 to1:33,000 non-fatal

Transfusion Reactions (Cont)TYPE CAUSE FREQ NOTES

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 A3- B27-Recip: HLA A3A24 B7B27

Disease is rare (0.1-1% in susceptible patients) due to irradiation. Transfusion-associated graft-versus-host disease. Dwyre DM, Holland PVVox 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 Pop37% Thalassemia Transfus Med 2006;16:200

18-47% SSD Transfusion 2002;42:37

“Antibody Formers”

TRALI TACODYSPNEA YES YES

ABG Hypoxemia Hypoxemia

BP Low to Normal Normal to High

TEMP Normal to Elevated Normal

CXR White out. Normal heart size. No vascularcongestion.

White out. Normal to increased heart size. Vascular congestion.Pleural effusions.

BNP Low (<250 pg/mL) High

Pulmonary artery occlusion pressure

Low to Normal High

Echocardiogram Normal heart function Abnormal heart function

Response to Diuretics Worsens Improves

Response to Fluids Improves Worsens

TRALI v TACO

Shealynn Harris, MD, Asst Med Dir., ARC, SoCal Div.

ID Risks

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)

Current ID Risks / Transfusion(12.9 million units transfused each year in US)

ID RISK / UNIT COMMENTS

HIV 1 : 2,300,000

HCV 1 : 2,000,000

HBV 1 : 350,000 LONG WINDOW PERIOD

HTLV I/II 1 : 2,000,000

WNV 1 : 350,000 11 CONFIRMED CASES BY A TRANSFUSION.USUALLY MILD DISEASE1 : 150-200 SEVERE/FATAL

BACTERIAL SEPSIS 1 : 1,000,000

GETTING STRUCK BY LIGHTNING IN A GIVEN YEAR

1 : 500,000 In Florida

GETTING STRUCK BY LIGHTNING IN A LIFETIME

1 : 6250

WINNING MEGAMILLIONS JACKPOT 1 : 175,711,536

Special Needs

Special NeedsCMV 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 <5 x 10^6/unit (>3-log reduction). Helps prevent febrile reactions and HLA alloimmunization.

Irradiation—Treating 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

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.

THUSWhen “CMV-negative” is requested, we will supply Leukocyte-reduced. If you really, really want CMV-seronegative units, you must call the blood bank.

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.

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.

Compatibility Testing

ANTIBODY SCREEN NEGATIVE ANTIBODY 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 SCREENTYPE—ABO and Rh (5 minutes).SCREEN—For “unexpected” antibodies, (30 minutes).

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.

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.

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.

Young BloodFountain 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.

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