blood components and component therapy22222

Compiled by: Victor Perlas Jr., RMT, AMT, IMT (ASCP, HAAD)This lecture handout will be utilized only by University of Saint Louis’ Medical Technology students for their Immunohematology class.

BLOOD COMPONENTS AND COMPONENT THERAPY

I. GeneralA. Basic concept of “component therapy”

1. More efficient use of products by giving patient what he needs and avoiding what he doesn’t need.

2. Made possible by advent of plastic bags around 1950.

3. Single unit may be made into numerous components (see figure below representing classical US method).

Figure 1: Basic component processing

B. Anticoagulant/preservative solutions 1. Allows blood to be stored for extended periods

without drastic effects on most metabolic and therapeutic qualities

2. Red cell storage defined by 75% survival of RBCs 24 hours after transfusion with <1% hemolysis (FDA)

3. Historic anticoagulant/preservatives: Acid Citrate Dextrose (ACD):

Used for apheresis platelets Formerly used for RBCs; 21 day

storage Citrate-phosphate-dextrose (CPD) and

citrate-phosphate-dextrose-dextrose (CP2D)

Allow 21 days of RBC/whole blood storage

Citrate-phosphate-dextrose-adenine (CPDA-1)

Very similar to CPD but with 17.3 mg of adenine (no adenine

in CPD) Allows 35 days of RBC/Whole

Blood storage 4. Additive solutions (“Adenine Saline” additives)

Increases shelf life of RBCs to 42 days Most common types

AS-1 (Adsol)

AS-3 (Nutricel) AS-5 (Optisol) AS-7 (SOLX)

Specifics vary, but all add more dextrose and adenine to increase blood shelf life.

AS-1, AS-5, AS-7 contain mannitol in varying quantities for RBC preservation

5. Preparation of additive solution RBCs: RBCs with additive solution process:

Blood collected in CPD or CP2D (NOT CPDA-1), spun, then mixed with 110 mL additive solution for 500 mL collections (100 mL for 450 mL bags)

This gives a product with more volume and less plasma (HCT usually 55-65%)

6. Know storage details for various products

WHOLE BLOODIndication Provide blood volume

expansion and RBC mass in acute blood loss

Storage 1-6oCTransport 1-10oCShelf-life 21 days (CPD/2D)

35 days (CPDA-1)42 days (AS)Open System – 24 hours

PACKED RBCsIndication Increase RBC mass of

symptomatic, normovolemic patients

Storage 1-6oCShelf-life 21 days (CPD/2D)


1


“For God did not give us a spirit of timidity, but a spirit of power, of love and of self-discipline.”2 Timothy 1:7

LEUKOCYTE-REDUCED RBCsIndication Increase RBC mass in

patients with severe and/or recurrent febrile transfusion reactions due to leukocyte antibodiesIncrease RBC mass in patients at risk for HLAAlloimmunization to HLA antigens or susceptible to CMV

Storage 1-6oCShelf-life 21 days (CPD/2D)


WASHED RBCsIndication Increase RBC mass of

symptomatic anemic patients with history of allergic, febrile, urticarial and anaphylactic reactions

Storage 1-6oCShelf-life Open System – 24 hours

FROZEN RBCsIndication Storage of rare and

autologous unitsStorage -65oC

Shelf-life 10 years24 hours @ 1-6oC after thaw

PLATELET CONCENTRATEIndication For bleeding due to

thrombocytopenia or thrombocytopathy

Storage 20-24oC / room temperature (with gentle

agitation)

Shelf-life Closed system – 5 daysOpen system – 4 hours

Nice to know:

CORRECTED COUNT INCREMENT

Absolute platelet increment/uL x body surface area (m 2 ) Number of platelet transfused (1011)

Minimum CCI is 10, 000/uL per m2

“Cast all your anxiety on Him for He cares for you.”1 Peter 5:7

PLATELET, PHERESISIndication For thrombocytopenic

patients alloimmunized to HLA or platelet antigen (donor should be HLA matched)Limit donor exposure in thrombocytopenic patients who acquire long term platelet transfusions

Storage 20-24oC / room temperature (with gentle

agitation)Shelf-life 5 days

FROZEN PLASMA (FFP or FP24)Indication Correct multiple

coagulation factor deficiencyReplace isolated factor deficiencies when specific component is not availableReverse affects of warfarin (Coumadin) anticoagulant drug

Storage -18oC or colderShelf-life 1 year @ –18oC

7 years @ -65oC24 hours at 1-6oC after thaw

FP24 not used within 24 hours after thawing can be relabeled as “Thawed

2


Plasma” and stored at 1-6oC for 5 days while adequate levels of Factors V and VIII are maintained.

CRYOPRECIPITATEIndication For treatment of fibrinogen

deficiency, haemophilia A, von Willebrand’s disease and factor XIII deficiency

Storage 1 year @ –18oCShelf-life 6 hours @ 20-24oC after

thaw (4 hours if pooled in open system)

GRANULOCYTES, PHERESISIndication Patients with granulocyte

dysfunction or myeloid hypoplasia who are unresponsive to antibiotics

Storage 20-24oC / room temperature (WITHOUT

agitation)Shelf-life 24 hours

C. Quality control of blood products 1. Blood is a controlled product that is tightly

regulated by the FDA (with more regulations from AABB & CAP).

2. Very specific, detailed requirements acceptability

Quality Control for Blood Products (US)Product QC

RBCs HCT < 80% (all);> 50 g HGB in 95% (apheresis RBCs)

RBCs Leukoreduced

≤ 5 x 106 WBCs in 95%, retain 85% of RBCs

Platelet Concentrate (PC)

≥ 5.5 x 1010 and pH ≥ 6.2 in 90%

PC Leukoreduced ≥ 5.5 x 1010 in 75%, pH≥ 6.2 in 90%, AND <8.3 x 105 WBCs in 95%

Apheresis Platelets

≥ 3.0 x 1011 and pH ≥ 6.2 in 90%

Apheresis Platelets Leukoreduced

Above + < 5.0 x 106 residual WBCs in 95%

CRYO Factor VIII ≥ 80 IU (all)

Fibrinogen ≥ 150 mg (all)Granulocyte concentrate ≥ 1.0 x 1010 in 75%

II. Blood and Components

A. Blood Components1. Red blood cells/additive solution red blood cells 2. Platelets

Whole blood-derived platelets (WBD-PLTs)

Apheresis-derived platelets (AD-PLTs) 3. Modified RBCs and Platelets

Leukocyte reduced products Irradiated products Frozen products Washed products

4. Plasma and derivatives Fresh frozen plasma (FFP) FFP alternatives (including PF24) Cryoprecipitate (“antihemophilic

factor”) Factor concentrates

Other plasma derivatives 5. Miscellaneous products

Granulocyte concentrate DDAVP Recombinant activated factor VII

(NovoSeven)

B. Whole Blood1. The original blood product!2. Minimal availability in most blood banks today

3. Potential indications: Massive blood loss (30-40% or more of

blood volume) Trauma/emergency transfusions

most commonly

3


This is popular in combat transfusions (“fresh whole blood”)

Occasional requests by trauma surgeons

Not commonly available in civilian settings

Use may lead to less exposure by providing coag factors (+/- functional PLTs), as well as volume

Whole blood must be ABO identical due to plasma; tougher to use in emergencies.

Exchange transfusions in neonates (more often “reconstituted” from separate RBCs and FFP)

Autologous transfusions4. Contraindications:

Transfusion Associated Circulatory Overload

5. Storage Time and Conditions Length depends on

anticoagulant/preservative used 1-6oC

C. Red Blood Cells (with and without additives)1. Most commonly used blood component (over

15 million units per year in the US as of 2008)

2. Prepared by centrifugation and removal of most of plasma layer of whole blood, or by apheresis collection.

May be transfused without modification after preparation or may use additive solution

3. Requirements: HCT < 80% for all RBCs (easy with

AS-RBCs)

Apheresis RBCs: 95% must have >50 g HGB or 150 mL of RBCs

4. Indications Oxygen delivery (DO2) insufficient

for oxygen consumption (VO2) Hemoglobin level and cardiac

output (CO) are most important factors in DO2

DO2 = CO x Arterial O2

content Arterial O2 made up of

hemoglobin-bound O2

(vast majority) and dissolved O2 (minority)

Oxygen consumption / demand (VO2)

VO2 is constant across a wide spectrum of DO2, so even with low hemoglobin, oxygen consumption is stable

So, transfusion is unnecessary and unhelpful in mild anemia without cardiac dysfunction despite a decreased DO2

HGB dissociation curve shift to right, incr. cardiac output, decr. blood viscosity, incr. respirations, etc. help compensate

Ischemia happens when DO2 drops so far that it can’t keep up with VO2 (“critical DO2”)

Once this point is reached, transfusion may be helpful, but defining critical DO2 is tough

Some suggestions:-Mixed venous O2 sat (SvO2) <60% -O2 extraction ratio >40-50% -VO2 decreased by >10%

Deciding if RBC transfusion is indicated:

Balance risks of anemia vs. risks of transfusion

HGB alone a very poor indicator for transfusion

All factors should be considered

4


Acute vs. Chronic loss Evidence of ischemia Comorbidities, age, medications, history

Situations that may require red cell transfusion:

Acute hemorrhage (> 30% acute blood vol loss)

Hemolysis Marrow failure

Thresholds

HGB 10 g/dL/HCT 30% trigger is bad practice

General guidelines from multiple specialties:

If HGB < 6 g/dL, transfusion usually needed

If HGB >10 g/dL, transfusion rarely needed

If HGB is between 6 and 10, clinical judgment, assessment of situation, etc, is required

It is reasonable to assess need for further transfusion after each unit given

AABB recommendations (Annals of IM, Mar 12):

Stable, ICU, hospital pts: 7 g/dL

Post-surgery patients: 8 g/dL or symptoms

Chronic cardiovascular disease: 8 g/dL

Acute coronary syndrome: No recommendation (no studies address this prospectively)

Other indication: Exchange transfusions

Sickle cell patients (esp. stroke or presurgery)

Hemolytic disease of the newborn/fetus (HDFN)

5. Contraindications Acute hemorrhage of < 20% of blood

volume Crystalloids are adequate in

most of these cases Chronic nutritional anemias (folate,

B12, iron)

6. Expected effect (per unit) HCT increases 3%, HGB 1 g/dL

(without acute bleeding or hemolysis) Effect can be measured 15 minutes

after transfusion

7. ABO compatibility

ABO type of transfused RBCs must be compatible with recipient plasma ABO antibodies

8. Storage and shipping Same as for whole blood if CPD, CP2D,

CPDA-1 42 days at 1-6 C if AS used Shipping temperature 1-10 C

9. Compatible fluids Normal saline (0.9%, not 0.45%) ABO-compatible plasma 5% albumin Normosol-R pH 7.4 and Plasma-Lyte

148 and –A Red cells should not contact lactated

Ringer’s (LR), D5W, 0.45% NS, antibiotics/other drugs, or TPN

5


Hypotonic solutions - red cells swell and burst; hypertonic solutions - red cell shrinkage

LR has enough calcium to counteract the citrate anticoagulant in blood (LR has 3 mEq Ca2+/L)

10. A couple of unusual RBC types Red Blood Cells, Low Volume

Prepared from whole blood collection 66-90% of the target volume (for 500 mL bags, 333-449 mL)

RBCs may still be used, but not plasma

Red Blood Cells, Rejuvenated RBCs may be “rejuvenated” up

to 3 days after expiration in CPD or CPDA-1, or up to the expiration date in AS-1 with “Rejuvesol.”

Restores ATP, 2,3-DPG levels to near-normal levels

Rejuvenated product is frozen (10 years for CPD, CPDA-1 RBCs; 3 years for AS-1) or transfused

Product must be washed, transfused within 24 hrs

D. Platelets1. Whole blood-derived platelets (platelet

concentrate, “random platelets”, WBD-PLTs) Prepared via centrifugation from one

whole blood unit The initial “soft” spin leaves

“platelet-rich plasma” on top, so the method is known as the PRP method

In Europe, order of spins is reversed; the initial “hard” spin creates a buffy coat

May be pre-pooled at blood center, or pooled in transfusion service before transfusion

Traditional dose 1 unit per 10 Kg body weight is

good estimate Commonly given 4-8 bags at a

time (6 most often) 10-15 mL/Kg in neonates

2. Apheresis platelets (“single donor”, “AD-PLTs”)

Made from one donor via apheresis procedure

Roughly 85% of platelets transfused in the US

“Double” or “triple” platelets products can come from 1 donor (each unit > 3.0 x 1011 PLTs)

Recent development: Platelet additive solutions

Dilutes proteins and may decrease allergic reactions and breakdown product accumulation

PAS-C and PAS-F currently approved

“Therefore, humble yourselves under the mighty hand of God, that He may exalt you at the proper time. Casting all your anxiety on Him, because He cares for you.”I Peter 5:6-7

6


Why choose AD-PLTs over WBD-PLTs?

Limiting exposure For potential decrease

in infectious disease transmission (viruses, parasites, bacteria, etc.)

1 unit for AD-PLTs vs. six for WBD-PLTs mathematically decreases potential exposure

AD-PLTs have less bacterial contamination

Platelet refractoriness Lack of response to

platelet transfusion (immune and nonimmune causes)

May be used as HLA-matched or crossmatched doses for immune refractoriness.

3. Indications for platelet transfusion: Thrombocytopenia

Prophylactic (just in case)/therapeutic (bleeding)

Prophylactic transfusions Data supports

prophylactic threshold of <5,000 (but most use 10K)

20K threshold if patient has risk factor (Fever, sepsis, bleeding, thrombocytopathy)

50K if about to have major surgery

Therapeutic 50K if bleeding 100K reasonable for

patients with intracranial and pulmonary hemorrhage

Controversy in liver biopsy, endoscopy

Many use 50K or 100K prophylactic threshold

Not proven; count not predictive of bleeding

Thrombocytopathy Prophylactic transfusions not

indicated Therapeutic indications:

Congenital defects with bleeding

Drugs (Plavix, ASA most common)

Increased bleeding in emergency surgical patients, especially cardiac surgery

External agents (Cardiac bypass, ECMO)

Metabolic effects (e.g., chronic renal failure)

4. Contraindications to platelet transfusion Thrombotic thrombocytopenic

purpura (TTP) ADAMTS13 enzyme

deficiency most common leading to large vWF multimers and subsequent platelet microthrombi

More platelets could lead to more thrombi

May be overblown fear; many use PLTs in life- threatening situations without problems.

Hemolytic-uremic syndrome (HUS) similar to TTP without neurologic symptoms

Heparin-induced thrombocytopenia, type II

Antibody vs. heparin/platelet factor 4 complex

These patients are at great risk for thrombosis, and platelets should be avoided if possible

Immune/idiopathic thrombocytopenic purpura (relative)

Doesn’t help count, and patients don’t usually bleed

Use only if significant bleeding occurs

7


Post-transfusion Purpura (PTP) Uncommon antibody vs.

transfused PLTs Most transfused PLTs will be

antigen-positive

5. General comments about platelets Expected effect

Generally, if one hour post-count increases by >20,000-30,000, response is adequate (“eyeball”)

Minor value in assessing response adequacy, even if count doesn’t increase much

One-hour post-transfusion count is standard

10-minute post count has value as a screen

No increase on 10-minute post count strongly suggests alloimmunization

Storage and shipping 5 days at 20-24 C (with

gentle agitation) Shipping range “as close as

possible” to 20-24 C < 24 hours without agitation

during shipping 4 hours after transfusion

service pooling (in “open” system; “pre-pooled” PLTS have normal shelf life)

ABO and RhD PLTs do not require

pretransfusion crossmatches, and ABO-incompatible platelets commonly given

Platelet ABO incompatibilities

Major = platelet ABO antigens incompatible with recipient plasma (like A PLTs to O recip)

Cleared from circulation faster; less effect Some concern about effect of antibodies binding

to transfused soluble antigens Minor = donor AB

antibodies incompatible with recipient RBCs (like O PLTs to A recip)

A concern in children, neonates, and high- titer donors (“reverse” hemolytic reactions)

ABO-identical is best, but not always practical

RhD antigens are NOT present on platelets.

RBCs in PLTs have RhD (esp WBD PLTs)

Risk of making anti-D is low without prophylaxis (3.8% in recent ten-year study)

Consider Rh prophylaxis in premenopausal D-neg women (1 vial RhIG per 2-3 weeks; effective as long as anti-D is detectable)

Platelet sterility AABB Standards requires

centers to both limit and detect bacterial contamination of ALL platelets

Limiting contamination Careful skin

preparation Discarding initial 20-

30 cc of blood (done automatically with diversion pouches) Exclusive use of apheresis platelets

Detecting contamination Culture-based methods

Require 24 hour wait before taking sample BacT/ALERT (bioMerieux, Inc) Enhanced Bacterial Detection System (eBDS)

Pre-issue bacterial detection

Verax PGD (Verax Biomedical); approved for

8


leukoreduced AD-Platelets and pooled WBD-platelets

BacTx (immunetics); approved for transfusion service-pooled WBD-platelets

Old (no longer accepted) methods

Gram stain, swirling, glucose checks

E. Modifications to red cells and platelets Leukocyte reduction (LR)

Definitions (as of AABB Standards, 27th ed.)

In US: ≤ 5 x 106

residual WBCs In Europe: ≤ 1 x 106

residual WBCs US rules:

≤ 5 x 106 white cells in 95% of tested units defines leukocyte-reduced (RBCs, AD-PLTs, and whole blood)

≤ 8.3 x 105 WBCs in 95% of tested units defines leukocyte-reduced [WBD-PLTs (NOTE: 8.3 x 105 x 6 = 5 x 106)]

Each must also retain at least 85% of original component and meet all other QC standards.

Methods Leukocyte reduction

filters [At least 99.99% of WBCs (“4 log” reduction)]

Apheresis collection devices

“Universal” LR not mandated in the US, but vast majority of cellular components are leukoreduced

Types “Prestorage” leukocyte

reduction Usually < 72 hours after draw (always <5 days).

Inline filters at time of collection or post collection filters for red cells.

Apheresis LR is prestorage by definition “Pretransfusion”

leukocyte reduction Immediately prior to transfusion (“bedside”)

• Least desirable• Lack of available QC, poor training• Many older studies done with this

method (especially CMV studies) Better done in

transfusion service before issuing

Established benefits: Prevention of febrile

nonhemolytic transfusion reactions

Generally benign, but mimic early hemolysis First type: WBCs secrete pyrogenic cytokines in

bag before transfusion: Common with PLTs Second type: Pyrogenic cytokines secreted after

transfusion• Seen more commonly with RBC

transfusions• Recipient antibodies against transfused

WBC antigens or immune complexes (donor WBCs and coating antibodies) binding to recipient macrophages

• Prestorage LR prevents both, pretransfusion only the second type

Prevention of HLA immunization

HLA antibody formation requires HLA class I antigens be presented by transfused lymphocytes

LR works well to prevent this interaction Use for multiple transfusion recipients UV-B treatment also works; not available in US.

Prevention of CMV transmission

Virus carried only in a small minority of donor WBCs (monocytes).

Blood. 1995;86,3598-3603; “The Bowden Study” – landmark LR study

• Filtered products equivalent to CMV

9

“For I know the plans I have for you, declares the Lord, plans to prosper you and not to harm you, plan

to give hope and a future.”Jeremiah 29:11


seronegative in preventing seroconversion.

Neither method is perfect; very early infection may escape testing and/or leukoreduction

Reduction of reperfusion injury post cardiac bypass

Potential benefits: Prevention of

transfusion-related immunomodulation (TRIM)

Controversial, not universally accepted Transfusion seems to immunosuppress

recipients• Increased post-op infections,cancer

recurrence, mortality in transfused patients

Donor WBCs may be the cause, but studies since LR widespread has not proven effect

Reduction of bacterial/parasitic contamination

Some studies suggest reduction in organisms like Yersinia or Leishmania with leukoreduction.

Probably not reliable enough to depend on! Reduction in the risk of

prion disease One of the reasons for universal LR in Europe Current: Prion known to be in plasma, too Prion-specific filters developed

Contraindications: Prevention of

transfusion-associated GVHD

Irradiation is only proven method (cases of TA-GVHD with leukoreduced blood reported)

Transfusion of granulocyte concentrate

Transfusion of previously frozen products (FFP, cryo, etc); most consider unnecessary

Washing 1-2 L of saline removes

about 99% of plasma Generally takes one to

several hours (automated)

Shelf life: Red cells: 24

hours post-wash Platelets: 4

hours post-wash Why bother?

a. Removal of plasma proteins for hypersensitivity (RBCs and platelets)

Classic example: IgA deficiency

A few IgA deficient patients develop anti-IgA; exposure leads to anaphylaxis.

Requires intense washing (3L or so) IgA-deficient donors are alternative

Haptoglobin deficiency

May be similar to IgA deficiency Especially common in Asians

Removal of unwanted antibodies

ABO antibodies (neonatal transfusions) T-activation (polyagglutination)

b. Neonatal alloimmune thrombocytopenia (NAT, NAIT, FNAIT)

Severe thrombocytopenia in neonate/fetus usually due to maternal anti-HPA-1A(80%); similar to HDFN in concept

Exposure to antigen via pregnancy or transfusion, antibody formed

IgG crosses placenta, attacks baby’s platelets 25% 1st pregnancy (rapid antibody formation) 10-30% get intracranial hemorrhage

Maternal IVIG used before birth (+/-intrauterine platelet transfusion)

Platelet choices: HPA-1A negative platelets given after birth Washed, irradiated maternal platelets may also

10


be used (lack antigen and antibody)

c. Removal of unwanted electrolytes (RBCs/PLTs)

Especially in neonatal transfusions

Large-volume or irradiated products

Freezing Cryopreservative agents protect

component while freezing and thawing

Most common: Glycerol at 40% concentration

Deglycerolization before transfusion = washing

DMSO for platelets, but recovery is very poor (1/3)

Why bother?a. Storage of rare, autologous, or O-

negative unitsb. Plasma hypersensitivities (as with

washed)c. Repeated febrile reactions (as with

washed) Storage

Before freezing: CPD, CPDA-1, or CP2D: Maximum 6 day shelf

life before glycerolization Additive solutions (AS-1, AS-3, AS-5): Up to

full 42 day shelf life before glycerolization Red Cells

10 years at –65 C (40% glycerol) 24 hours at 1-6 C after thawing/deglycerolizing

Platelets At least two years at -80 C

Irradiation of cellular components Irradiation dose deactivates T-

lymphocytes Prevent transfusion-associated

graft vs. host disease. Radiation dose:

2500 cGy (“rad”) dose required targeted to center of bag, with at least 1500 cGy in all parts of the bag

Indications for irradiation Immunosuppression

1.Congenital T-cell deficiencies (DiGeorge’s, SCID, Wiskott-Aldrich)

2.Stem cell or marrow transplant recipients3.Patients taking chemo agents that attack T-

cells (Fludarabine, other purine analogs)4.Aplastic anemia patients5.Patients with solid tumors getting intensive

chemotherapy/radiation

Intrauterine transfusions, premature neonatal transfusions, and neonatal exchange transfusions

Hematologic malignancies (esp. Hodgkin’s) Granulocyte transfusions Receiving blood from a first-degree relative

donor or receiving HLA-matched units

Patients probably NOT at risk (but often get irradiated products anyway).

Solid organ transplant recipients Term neonates AIDS patients Patients receiving previously frozen blood

products (FFP, CRYO)

Maximum storage: 28 days after irradiation or regular expiration date, whichever comes first

K+ triples and free hemoglobin increases in plasma, indicative of mild RBC membrane damage

F. Plasma Group

Fresh Frozen Plasma (FFP) Widely used but not well-

studied prospectively Whole blood-derived or from

apheresis (AD-FFP can have much higher volume)

Specifics for WBD-FFP:

11


General notes about coagulation and FFP transfusion:

30-40% of coag factors required for hemostasis. “Adequate” factor levels don’t necessarily give

normal coag tests (mild elevations common) Most FFP transfusions are given for elevated

PT/INR levels (Factor VII most responsible)• Factor VII in-vivo half-life is only about

4 hours• The INR of FFP is roughly 1.2-1.5!

Prophylactic FFP use with mild lab elevations is usually a mistake, even before procedures

• No evidence of bleeding prevention or lab value correction when these patients are transfused

No universal threshold exists, but many use INR of 2.0 as indicator of serious factor deficiency

Indications: Bleeding patients with coagulopathy due to

multiple factor deficiencies• Hepatic Failure• Dilution from massive transfusion• Consumptive processes (DIC)

Bleeding patients requiring urgent reversal of vitamin K deficiency from warfarin effect

• Warfarin affects factors II, VII, IX, X• Vitamin K (even IV) takes hours

(between 6 and 12) to result in replenishment of these factors

• For non-bleeding patients, correct without FFP administration (hold dose and give vitamin K)

• In bleeding patients, Prothrombin Complex Concentrate (PCC, containing II/VII/IX/X) may be better choice than FFP

• In general, need at least 10-20 ml/Kg of FFP to attain hemostasis in these patients (usually more)

• Chest 2008;133:160S-198S; guidelines on correction of warfarin-related coagulopathy

Trauma transfusion• Recent literature suggesting that trauma

patients given plasma in close to 1:1

ratio with RBCs have better survival (first reported in military)

• Many trauma centers have established “trauma/massive transfusion protocols” that attempt to make 1:1 ratio automatic

• Concerns about plasma transfusion complications (TRALI) and AB plasma wastage

Dilutional coagulopathy• Transfusion of multiple coag factor poor

products (RBCs and crystalloids in massive transfusion) dilutes coag factors.

• Usually not apparent until after at least 10-15 or more units of RBCs (with accompanying fluid) in a 24 hour time span

• May be less of an issue with massive transfusion protocols and 1:1 ratios mentioned above

Transfusion or plasma exchange for TTP/HUS

• Acquired or congenital ADAMTS13 deficiency; large vWF multimers lead to platelet thrombi

• FFP has normal amounts of ADAMTS13

• Plasma exchange standard treatment• Treatment until PLT count is at least

100K with near normal LDH Other factor-specific coagulopathies without

an available factor concentrate (V, X, XI in US)

C1-esterase inhibitor deficiency

Contraindications: Volume expansion

• Albumin, crystalloids are safer. Heparin reversal

• Antithrombin, which potentiates heparin!

• Use protamine sulfate or just stop the heparin.

Factor deficiencies with available concentrates Prophylactic or pre-procedure treatment of mild

elevations of PT/PTT “Nutrition,” “Wound healing,” or “well-being”

Preparation/storage Pre-storage

• Separated and placed at -18 C within 8

12


hours• NOTE: FFP does not have to be

completely frozen at 8 hours, just in -18C environment

Pre-transfusion• Stored at -18C up to 1 year (or -65C for

7 yrs)• Thawed at 30-37C (water bath/approved

device)• Stored after thawing at 1-6 C for 24

hours*** FDA historically allowed 6 hours; now allows 24 hrs as specified in Circular of Info; May extend beyond 24 hours per AABB (see“thawed plasma” below)

Dosage Commonly given two bags at a time in adults 10-20 mL/Kg more appropriate (3-7 bags if 70

Kg) 10-15 mL/Kg appropriate dose in neonates.

Effect Standard dose increases factor levels by about

20-30% in a 70 Kg person. Transient due to short half-lives (FVII) Greatly elevated PT/PTT more affected than

mild Will not help if INR is <1.5-1.6!

ABO and Rh Donor antibodies compatible with recipient

RBCs. Give without regard to Rh.

ABO compatibility for plasma transfusion

Plasma Variants Plasma frozen within 24 hours

of phlebotomy (PF24 or “FP24”)

Not frozen in 8 hours like FFP, but 24 hours

Factor V levels essentially equal to those in FFP, while factor VIII levels decline 20-25% vs. FFP

Stored and managed just like FFP Except for DIC patients, can be used identically

to FFP (low FV and/or FVIII is uncommon) Can’t be used to make CRYO May be from whole blood or from apheresis

plasma collection

Plasma frozen within 24 hours of phlebotomy held at room temperature up to 24 hours after phlebotomy (PF24RT24)

Horribly named product (HAHAHAHA! I’m sorry for this guys!); only from apheresis plasma collections

As per the name, held up to 24 hrs at RT before freezing

As expected, decreased FV, FVIII (also protein S) vs. FFP

Store and use just like FFP/FP24

“Thawed Plasma” FFP/PF24/PF24RT24, once thawed, is only

good for 24 hours Thawed FFP/FP24/PF24RT24 may be relabeled

as “Thawed Plasma” and kept at 1-6 C for up to 5 days

Indications are essentially identical to FFP, despite a decrease in FV and FVIII to ~50% by 5 days

Plasma, cryoprecipitate reduced (“CRYO- reduced plasma”, “cryosupernatant”)

Residual plasma that remains after cryoprecipitate harvested from FFP.

Decreased levels of stuff that is in CRYO (FVIII, fibrinogen, vWF, FXIII)

Sole indication: TTP patients (due to less vWF), used in plasma exchanges if regular FFP doesn’t work (literature shows mixed results on this).

Storage and transfusion just like FFP.

Source plasma Apheresis collection, usually paid donors Used for manufacture, not transfusion Licensed product

Recovered plasma

13


Plasma from volunteer whole blood donation Unused units of frozen plasma may be relabeled

as recovered and sold for further manufacture (albumin, etc) under short supply agreement

Unlicensed product, blood center revenue source

Liquid plasma/plasma

Plasma separated from whole blood up to 5 days after expiration

Liquid plasma: stored at 1-6 C, not frozen (Can be transfused up to 5 days after whole blood expiration date, but rarely used)

Plasma: stored at -18 C or below; rarely used

Cryoprecipitate Also has seen increased use in

recent years

QC Requirements: > 80 IU FVIII per bag > 150 mg fibrinogen per bag (easy! Most

contain at least 250-300 mg)

Indications Fibrinogen deficiency (congenital or

acquired)• General threshold: 100 mg/dl for

adequate hemostasis post-surgery.• Many use 10-20 bags per dose in adults,

more if fibrinogen is less than 50 mg/dl.• 10 bags deliver about 2500 mg of

fibrinogen in about 150 ml of volume (> 1 liter FFP needed for same amount!)

• Fibrinogen concentrate may decrease future use

Treatment of uremic thrombocytopathy• Acquired adhesion defect (probably)

which may respond to vWF supplementation

• Generally seen with creatinine levels > 3

mg/dL• Second line of defense (after DDAVP,

dialysis)• Also: Conjug. estrogens, inc. HCT to

~30%• Am J Med. 1994;96:168-79 describes

treatment of uremic thrombocytopathy.

Factor XIII deficiency (if concentrate unavailable)

Topical “glue”• Historically mixed with bovine

thrombin and applied directly to raw surfaces

• Currently available fibrin sealants (treated, virus-free) have made this less common.

Treatment of von Willebrand’s disease• Use only if FVIII concentrates are not

available [Some FVIII concentrates (e.g., “Humate- P”) contain vWF]

• Cryo may be used for severe forms. • DDAVP can be used for milder forms

Treatment of hemophilia A• Use only if emergency and no factor

VIII concentrate available.

Manufacture Made from a single unit of FFP (not PF24 or

PF24RT24) Thaw FFP at 1-6 C, spin and remove liquid, re-

freeze slushy precipitate within 24 hours Commonly “pre-pooled” (before storage) under

sterile conditions at blood centers (variants: 4, 5, 8, 10 bags most common)

Storage and preparation for transfusion

-18 C for 1 year After thawing (at 30-37 C, like FFP), store up to

6 hours at 20-24 C (unlike FFP) (Pre-pooled CRYO has a 6 hour shelf life after thawing)

If units are pooled without sterile docking equipment, transfuse within 4 hours.

No compatibility testing required ABO-compatible is preferred by some, but

paucity of anti-A/B makes it really not important Can give without regard to Rh status

14


Factor concentrates Factor VIII concentrate

Used for moderate to severe hemophilia A Virus inactivated or recombinant May contain vWF and be used in vWD.

Factor IX concentrate Used for hemophilia B Virus inactivated or recombinant NOT the same as Factor IX Complex

Concentrate

Prothrombin Complex Concentrate (PCC)

Or, “Factor IX Complex Concentrate” Approved only for bleeding hemophilia B

patients, but USED in warfarin overdose correction

Not “activated” as in the past; much less thrombosis

All U.S. versions except one lack Factor VII, which limits utility

Albumin and plasma protein fraction

Virus inactivated, expensive volume expanders

Differ only in composition Albumin: 96% albumin, 4% globulins/others PPF: 83% albumin, 17% globulins/others.

G. Granulocyte concentrate Increasing use due to off-label use of

donor stimulation with G-CSF and/or steroids

Effect not definitively proven Indications

Consider in premature neonates with sepsis or infections, transplant patients with infections, patients with chronic granulomatous disease

Aside from above, a clinical situation including:

Fever for 24-48 hours, Proven bacterial or fungal infection No response to antibiotic therapy Neutropenia (<500/uL; <3000/uL in neonates) Reversible bone marrow hypoplasia

Not currently indicated for: Prophylactic use Patients with no hope of marrow

recovery 1.0 x 1010 is minimum yield (required in

75%), but stimulation gives much greater yield; not FDA-approved

Cans and Cant’s! Can (and must) irradiate to

prevent TA-GVHD. (Irradiation deactivates T-lymphs but not PMNs)

Can’t leukoreduce to prevent CMV transmission.

Storage conditions 24 hours from collection at 20-

24 C, without agitation Cautions

Must be ABO, Rh, and crossmatch compatible

Most are transfused before inf. disease testing is done; recently tested apheresis PLT donors commonly used

H. DDAVP (Desmopressin) Synthetic ADH used for treatment of

diabetes insipidus. Causes release of vWF from endothelial

cells; functionally increases FVIII, as well.

Potential indications: Uremic thrombocytopathy

15

Cast your cares on the Lord and He will sustain you; He will never let the righteous fall.Psalm 55:22


0.3-0.4 g/Kg IV x 1; repeat with caution Should be considered before platelets or CRYO.

Mild hemophilia A (>5% FVIII levels) and von Willebrand’s disease (type I)

0.3 g/Kg IV x over 30 min (30 min before surgery); repeat with caution

Effect decreases with doses >q 48 hrs (“tachyphylaxis”)

I. Recombinant activated factor VII (NovoSeven) Non-human-plasma-derived product that

is currently FDA-approved for use in: Hemophiliacs (A or B) with

inhibitors (bleeding prevention and bleeding treatment)

Patients with congenital factor VII deficiency (bleeding prevention and bleeding treatment)

Widespread “off-label” use has occurred, as NovoSeven gained traction as a “magical” hemostatic agent!

Estimated 1-2% risk of thrombosis is concerning

JAMA. 2006;295:293-298 (O’Connell, et al) article reported that most serious thromboembolic complications from NovoSeven followed off-label use

Thrombotic stroke, acute MI, and pulmonary emboli; NOTE that these were not definitely caused by NovoSeven, just associated with its use.

Off-label use may be considered for: Treat/prevent surgical bleeding

in trauma patients Reversal of anticoagulant

therapy (warfarin and factor Xa inhibitors)

Treat/prevent surgical bleeding in advanced liver failure

patients. Perioperative blood loss

prevention (after failed clotting factor replacement therapy) in cardiac surgery, neurosurgery, OB/GYN surgery, and urologic surgery

Not indicated for routine pre-procedure prophylaxis

Typical doses: 20 to 40 mcg/Kg in non-emergencies, 41 to 90 mcg/Kg otherwise

Roughly 2-hour half-life, repeat dose often

"Don't Quit" From an internet source

When things go wrong, as they sometimes will,when the road you’re retrudging seems all up hill,when the funds are low and the debts are high,and you want to smile, but you have to sigh,when care is pressing you down a bit,rest, if you must-but don’t you quit.

Life is queer with its twists and turns,as every one of us sometimes learns, and many a failure turns abut,when we might have won had we stuck it out,don’t give up, though the pace seems slow-you might succeed with another blow.

Often the goal is nearer than it seems to a faint faltering man,often the struggler has given upwhen he might have captured the victor’s cup,and he learned too late, when the night slipped down, how close he was to the golden crown.

Succeed is failure turned inside out-the silver tint of the clouds of doubt-and you never can tell how close you are,it may be near when it seems afar;

16


so stick to the fight when you’re hardest hit-it’s when things seem worst that you ’t quit.

17

blood components and component therapy22222

Health & Medicine