Blood component therapy and transfucion reactions

BLOOD COMPONENT THERAPY

AND TRANSFUSION REACTIONS

Mercury Y. Lin, MD FCAP

LCDR MC USN

Staff Pathologist

16FEB2011

15JAN2014

Acknowledgement/References:

• D. Joe Chaffin, MD, “Blood Bank I-VII,” Osler Institute

• CDR Fahie, MSC, USN, “Blood Component Therapy”

• CDR Cox, MC, USN, “Blood Bank on-call”

• Marian Petrides, MD, “Practical Guide to Transfusion

Medicine.”

• AABB, “Standards for Blood Bank and Transfusion

Service, 26th Ed.”

• AABB, “Technical Manual, 15th Ed.”

• Naval Hospital Laboratory SOPs (depending on site of

lecture)

Disclosure Statement

• I have no financial interest with manufacturers or any

commercial products.

• Unlabeled / unapproved use of drugs or devices will not

be discussed during this presentation.

• Medicine is an evolving professional art that tries its best

to keep up with scientific discoveries. Always consult

updated medical references in your patient care.

Objectives

• 1. Describe common blood products (components) and

discuss indication for their usage.

• 2. Brief overview of transfusion reactions and other

complications of blood transfusion.

Blood Components

Covered in this presentation:

• Whole Blood

• Packed Red Blood Cells (PRBC)

• Platelets (Plt)

• Fresh Frozen Plasma (FFP)

• Cryoprecipitate (Cryo)

Not discussed:

• Granulocyte infusion

• Plasma derivatives

• Blood substitutes

(Hb based O2 carrier: Biopure, PolyHeme)

(Perfluorocarbon: Oxygent)

Whole Blood

Soft spin (2000 RPM x 3 min)

pRBC Platelet Rich Plasma

Hard spin (5000 RPM x 5 min)

Platelet (conc.) Fresh Frozen

Plasma

Cryo ppt. Plasma

derivatives

Apheresis

donor

screening

Whole Blood

• The “original blood product.”

• Not used in most healthcare facilities.

• Applications in operational setting, trauma, massive transfusion.

• Specs: 450-500 ml

• 200 ml pRBC

• 250 ml plasma

• WBCs

• Platelets

• Anticoagulants (70 ml).

• Whole blood transfusion needs to be ABO identical

Packed Red Blood Cells (PRBC)

• Spec: 250 ml (350ml w/ additives)

• Each unit of PRBC has 200-250mg of iron.

• Increase Hct by 3% and Hgb by 1g/dL

• In a pediatric patient, RBC transfusion of 8-10mL/kg will

raise will raise the hemoglobin level about 2 g/dL or the

HCT by about 6%.

• Depending on where you are stationed, it maybe available

different varieties.


• Leukocyte Reduced PRBC:

• Contains less than 5 x 106 leukocytes per unit [3 log

reduction (99.9%) (AABB standard)]

• The standard 170 micron filter does not remove leukocytes

• Best achieved after collection (prestorage)

• Prestorage leukoreduction results lower levels of cytokine

generation in the blood bag during storage and decreases risk

of febrile nonhemolytic transfusion reactions (FNHTR)

• Reduce HLA alloimmunization. Patients who receive frequent

transfusions and women who have had multiple pregnancies

may become alloimmunized to leukocyte antigens

• Reduce platelet refractoriness


• Leukocyte Reduced PRBC (con’t):

• Immunosuppressed, cytomegalovirus (CMV) sero-negative patients such as allogeneic stem cell hematopoietic or progenitor cell recipients who are susceptible to transfusion transmitted CMV

• Also reduces risk of other obligate intracellular virus (HTLV, EBV).

• Controversial: reduce risk of prion disease? (as practiced in UK and Canada).

• Reduce transfusion related immunomodulation (TRIM)– changes in the host immune function or immunosuppression

• Reduce risk of bacterial contamination?

• DOES NOT prevent transfusion associated graft versus host disease (TA-GVHDz).


• Leukocyte Reduced PRBC (con’t):

• Disadvantages:

• $$$

• Anaphylactoid reaction: with bedside leukoreduction, pts

taking ACE inhibitor Tx can develop severe hypotension

[due to ACE inhibitors blocking breakdown of bradykinin,

which are induced with interaction with filter surfaces].


• Irradiated pRBC:

• Serves to deactivate lymphocytes and prevent TA-GVHDz in at risk population.

• TA-GVHDz is rare but uniformly fatal!!!

At risk population for TA-GVHDz:

- Recipient of stem cell transplant

- Hematologic malignancies

- Selected solid tumors (neuroblastoma, rhabdomyosarcoma, glioblastoma).

- Intrauterine transfusion

- Premature infants

- Pts on purine analog chemoTx

- HLA match blood product

- Direct donor blood (from blood relatives).

Donor lymphocyte Host (recipient) lymphocyte

Source: Chaffin, Blood Bank III, Osler Inst.

Related Donor or HLA-matched blood products.

Source: Chaffin, Blood Bank III, Osler Inst.


• Washed pRBC:

• Red cells washed with 1 or 2L of normal saline to

removes all but traces of plasma, removes platelets, and

cellular debris.

• Indications:

• - pt with IgA deficiency (who makes anti-IgA Abs, so wash

pRBC to prevent anaphylaxis).

• Deglycs frozen pRBS is mostly equivalent to washed

pRBC


• Indications for pRBC:

• Increase oxygen carrying capacity

• Hgb < 7g/dL or HCT < 21% in a healthy person

• 7-9g/dL in symptomatic patients with cardiopulmonary or cerebrovascular risk

• Great for patients at risk for circulatory overload (neonates and CHF)

• Exchange transfusion for HDN or acute chest syndrome in sickle cell disease

• Hgb S <30% for stroke prevention in sickle cell disease.

• Not indicated for pRBC:

• Loss of <20% blood volume (crystalloids should be adequate in most cases, but may get pRBC)

• Chronic and nutritional anemia

• Competing in Tour de France


• If there is no other way around it and you must

concurrently infuse pRBC with another solution. Only

these fluids are compatible with pRBC

• 1) Normal saline (0.9%)

• 2) ABO compatible plasma

• 3) 5% albumin.

• NEVER give pRBC with D5W, 1/2NS, TPN, Antibiotics,

Lactate Ringer’s.

Platelets (Plt)

• Platelet Concentrates (Prepared from the plasma of whole

blood, not commonly used nowadays, “1 of 6 pack”)

• Apheresis Platelets (aka SDP: “single donor platelet”):

Collected from an individual donor during a 1-2 hour

apheresis procedure. 1 SDP = 6 plt concentrate.

• Spec of SDP: 100 ml

• > 3 x 1011 plts (in 90% tested units)

• minor amounts of plasma, WBC.

• Advantages of SDP: 1 donor vs. 6 donor exposure

• decrease risk of contamination.

Platelets (plt)

• Dosing of plt:

• 1 unit of platelet per 10kg body weight or 4 to 8 units for a 70kg adult

• A repeat failure to achieve hemostasis or achieve the expected increment count may signify refractoriness

• Refractoriness may be associated with bleeding, amphotericin, splenomegaly, DIC, fever, sepsis, or stem cell transplantation

• Refractoriness is suspected when there is a poor post-transfusion platelet count increment.

• 1 SDP expect 30,000 ~ 60,000 plt bump

Platelets (plt)

Corrected count increment (CCI):

CCI = (Post Tx plt ct) – (Pre Tx plt ct) x BSA

# Platelets transfused [in x 1011 ]

Pre-tx plt ct = pretransfusion platelet count

Post-tx plt ct = posttransfusion platelet count (10min – 1 hr

s/p transfusion)

BSA = Body surface area in m2

Each unit of concentrate: 6 x 1010 platelets

SPD platelets: 3 x 1011 platelets

• CCI of > 5000 is considered adequate response.

Platelets (plt)

• Corrected count increment (CCI):

• pt (BSA of 1.7 m2 ) received 1 SDP and plt count increased from 10,000/ul to 30,000/ul (1hr post)

• CCI = (30,000 – 10,000) x 1.7 m2 / 3

• CCI = 11,333 m2 /ul

• So response is adequate. If CCI is below 5000 on 2 consecutive plt transfusion is presumptive evidence of plt refractoriness.

• Patient who are refractory should receive HLA matched or platelet crossmatched platelets

Platelets (plt)

• Indications for Platelets

• Count of 10,000 or less in non bleeding patients

• Count of 50,000 or less in acute hemorrhage

• 100,000 or less if bleeding into a critical space such as the lung, eye, or CNS

• Plt dysfxn (Aspirin, cardiopulmonary bypass)

• Contraindications for platelets

• Thrombotic thrombocytopenia purpura (TTP) [↑plt =↑thrombi]

• HIT type II [↑plt =↑thrombi]

• ITP [just doesn’t help]

• Post transfusion purpura.

Platelets (plt)

• Q: plt have to be ABO Rh compatible?

• A: general answer is NO*(for adults). Plts express some

ABO antigen but not Rh. ABO incompatible platelets may

get cleared from the recipient's circulation more rapidly,

thus less effective…but you use what you have.

• *may consider Rhogram when RH+ plt is being transfused

to a Rh- reproductive age female (b/c plt preparation may

contain few RBC contaminates). Neonates should also

get type specific plt.

Fresh Frozen Plasma (FFP)

• Spec: 200-250 ml

• contains all coagulation factors.

• Use/don’t abuse

• Not necessary to restore 100% of patient’s coag factors to

achieve hemostasis. (generally 20-30% should be good).

• Half-life for factor VII is only 4 hrs.

• Plasma should be compatible with the patient’s red blood

cells ( AB blood group is universal FFP donor and O blood

group is universal FFP recipient).


• Dosage for Fresh Frozen Plasma

• 10-20mL/kg for initial dosing

• 20mL/kg for patients with liver disease

• These doses should raise factor levels by about 25%

unless the patient is bleeding or in DIC

• Further guidance by clinical response and PT/PTT

measurements.

• Don’t administer FFP with a goal of brining INR to 1. Not

a realistic goal.


• Common Indication for FFP

• Multiple coagulation factor deficiencies

• Urgent reversal Vitamin K dependent Factors (II, VII, IX,

X) due to Coumadin and pt is bleeding.

• Trauma (some advocate 1:1 pRBC:FFP ratio).

• Dilution coagulopathy (s/p transfusion of 10+ pRBCs).

• TTP/HUS (supplement ADAMTS13 level)

• Contraindication for FFP:

• Volume expansion

• Heparin reversal

• If specific factor concentrates are available (factor VIII and IX).

Cryoprecipitate (Cryo)

• Cryo is prepared by thawing FFP at 1-6oC and refreezing

the precipitate within 1 hr.

• Spec: 15 ml

> 150 mg fibrinogen (usually 250mg)

> 80 IU factor VIII.

80-120 IU of vWF

40-60 IU of factor XIII

• Cryo has only 4 hr shelf life.

• Rich in Factor VIII, but seldom used for hemophilia

because of commercial products


• Indication for Cryo:

• Fibrinogenemia (< 80-100mg/dL) in bleeding patient*

• Disseminated Intravascular Coagulation (DIC)

• Hemophilia A (rich in factor VIII)

• VonWillibrand’s Factor deficiency

• Fibrinogen replacement in massive transfusion.

Unit vs unit, FFP (400mg) actually has more fibrinogen than Cryo (250mg). But main reason to use Cryo is volume.

e.g. to give approx 2500 mg of fibrinogen:

1) 10 units Cryo = 150 ml

2) 6 ¼ units FFP = approx 1.5 liters!


• Dosage for Cryo

• 1 unit of cryo increases the fibrinogen count by about

7mg/dL ( in a 70kg adult)

• Calculate blood volume = Weight in (kg) x 70 mL/kg

• Blood volume (mL) x (1.0 – hematocrit) = plasma volume (mL)

• Mg of fibrinogen required = (desired fibrinogen level in mg/dL – initial fibrinogen level mg/dL) x plasma volume (mL)/100 mL/dL

• Bags of Cryo required = mg of fibrinogen required/250 mg/bag of Cryo

Summary of Blood Products

Massive Transfusion

• Replacement of one or more blood volumes in less than

24 hours (around 10-12 units) or 5000mL in 70-kg adult

• Associated with dilutional coagulopathy

• Hypothermia

• Hypocalcemia (due to citrate in the blood units)

Massive Transfusion

• Administer RBCs to maintain oxygen carrying capacity

when HCT is less 21-24% (or symptomatic) or Loss of

25% or greater of blood volume

• Administer 2-4 units of FFP after administering 4-6 units

of RBCs and continuing blood loss

• Administer 10 bags cryo if fibrinogen is less than 100.

• Administer platelets if platelet count is less than 100,000

and head trauma.

Massive Transfusion

1 unit of FFP ≈ 2 units of cryo

1 unit of FFP for every 2-3 units of RBCs (or even 1:1 as

some may advocate)

14 units of cryo raise the fibrinogen by 100mg/dL

Transfusion Reactions

Transfusion Reactions With Fever

Without Fever

Acute (usually within 24hr).

Acute

Delayed

Delayed

Acute hemolytic

Febrile nonhemolytic

Bacterial contamination (septic)

TRALI

Delayed hemolytic

TA-GVHDz

Urticarial RXN

Anaphylactic

TACO (overload)

(medicated) febrile

Post-transfusion purpura

Iron overload

Source: Joe Chaffin, MD


• General rule: assume all reactions are hemolytic, until proven otherwise.

• 1st thing: STOP THE TRANSFUSION!!!!!!!!!

• Amount of incompatible blood administered is the main indicator of patient survival from acute hemolytic transfusion reaction

Workup:

• Clerical check

• Visible hemoglobinemia check (spin post-transfusion sample and look for hemolysis).

• DAT (Coomb’s test)

• Repeat ABO testing

• Others: repeat Ab screen, indirect bili, Haptoglobin, UA(urine hemoglobin)

• Selected types of transfusion reaction will be discussed further.

Transfusion Reactions (USNHJ)

Transfusion Reactions (NHCP)

• Notify NHCP Laboratory.

• Refer to SOP NO: 6.201/002

• SOP Title: Suspected Transfusion Reaction Work-up


• Acute hemolytic transfusion reaction:

• Maybe fatal, usually ABO related

• Symptoms/findings: fever/chill, back pain, hypotension, DIC,

hemoglobinuria, Schistocytes.

• Ag-Ab complex activates coag factors DIC

bradykinins systemic hypotension

• Treatment: (obviously stop the transfusion 1st).

• Support volume and blood pressure

• Maintain urine output (>100 ml/hr)

• Monitor for DIC.


• Febrile nonhemolytic transfusion reaction:

• Symptoms: +fever/chills, no laboratory findings of

hemolysis.

• Mechanisms:

• Due to release of pyogenic cytokines. (TNF, IL-1beta)

• Prevention: leukoreduction (prestorage)

• Treatment: acetaminophen (premedicate).


• Bacterial Contamination (Septic)

• bacterial contamination is the #1 infectious risk of blood

transfusion

• RBC (cold): gram =, Yersinia enterocolitica, citrobacter, E.

coli, Pseudomonas

• Platelet (room temp): gram + cocci.

• Clinical findings: high fever/ rigor/ N/V.

• Lab: +/- hemoglobinemia/uria, neg DAT, positive gram

stain (in only 50% of cases), Blood culture positive.

• Tx: IV Abx, pressure support.

Bacterial contamination of platelet products has been acknowledged

as the most frequent infectious risk from transfusion occurring in

approximately 1 of 2,000 - 3,000 whole-blood derived, random donor

platelets, and apheresis-derived, single donor platelets. -Hillyer, “Bacterial Contamination of Blood Components: Risks, Strategies, and Regulation.”

Hematology 2003

Source: Chaffin, Blood Bank IV, Osler Inst.


• TRALI (transfusion related acute lung injury):

#1 cause of transfusion-related fatality in the U.S. (morality 5 -25%)

• NHLBI definition:

• 1) new acute lung injury < 6hr after completing blood transfusion.

• 2) hypoxia

• 3) bilateral infiltrate on CXR

• 4) no other risk factor for pulmonary edema.

• Most commonly associated with platelets and FFP.

• Not been reported with plasma derivatives (IVIG, Albumin)

• Initially, TRALI is indistinguishable from ARDS. Don’t wait/need for lab results for management of TRALI. (test takes weeks).

• Will know in a few days. (TRALI usually resolves in a few days).

• That being said, TRALI should be a dx of exclusion.


• TRALI (con’t)

• 2 possible mechanisms:

• A) Donor Ab hypothesis: Donor’s anti-HLA or anti-neutrophil Ab attack recipient's WBC. immune complex deposit in pulmonary vasculature.

• B) Non-immune(2-event) hypothesis:

1) preexisting stress that “primes” recipient's

neutrophils.

2) BRMs (lipids) in stored blood product activates

primed neutrophils and deposit in pulmonary

vasculature

Treatment: same as ARDS (Vent, O2, Pressers)

Donor selection: implicated donors are deferred, utilize plasma product form males donors (women have higher incidence of Abs due to pregnancy).


• TACO (transfusion-associated circulatory overload).

• Risk: CHF pts, very young or very old, CRF, chronic

anemia pts.

• TACO vs. TRALI:

• TACO responds to diuretics and usually no fever

• TRALI does not respond to diuretics and is associated

with fever.

• Prevention of TACO:

• Slow infusion rate, consider split units.


• Delayed hemolytic transfusion reaction:

• Hemolysis that occurs days~weeks after transfusion, due

to:

• 1) Anamnestic response (previous formed Ab comes

roaring back after re-exposure; Kidd [Jk])

• 2) Primary response (new Ab formed while foreign RBC

are still circulating)

• Findings: +/- fever, mild jaundice, anemia, +“mixed-field”

DAT, previous neg now pos antibody screen.

• Tx: treat as AHTR if symptomatic, otherwise monitor.


• Urticarial transfusion reaction:

• Symptoms: localized hives ONLY, no fever, no perioral swelling.

• Due to hypersensitivity to donor’s plasma proteins (even minute amounts).

• If rash appears rate-dependent, then may be safe to restart transfusion (at a slower rate), once the rash has resolved.

• DDx: harbinger of anaphylactic reaction.

• Tx: Benadryl.

• using washed pRBC or deglyc’ed pRBC can lower incidence of urticarial transfusion reaction.


• Anaphylactic/anaphylactoid reactions:

• Towards the opposite spectrum of the allergy spectrum, compared to urticarial reaction.

• Distinction between anaphylactic vs. anaphylactoid rest of if the reaction is IgE mediated.

• Symptoms: rash, dyspnea, circulatory collapse.

• Examples include:

IgA deficient pt receives a “normal” donor’s blood.

Donor is on a medication for which the recipient is allergic to.

• Tx: Epi, IV steroids, pressors (if severe)


• Post Transfusion Purpura:

• Marked thrombocytopenia approx 1 week s/p transfusion.

• Multiparous female especially at risk.

• Mechanism:

• PLA1 neg patient is exposed to PLA1 pos platelet

• Abs are formed which now destroys both PLA1 pos and to

PLA1 neg platelets*.

• Tx: IVIG.

• *due to passive reabsorption of Ag-Ab complex or autoAb.

The End

Health & Medicine

Blood component therapy and transfucion reactions