Blood Components Therapy Brian Poirier, M.D.

University of California, Davis Medical Center

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Topics

• Whole Blood

• Packed Red Blood Cells

• Plasma

• Platelets

• Special Transfusions/Modifications

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Modern Hemotherapy

• Administer that component of blood that the patient needs to prevent morbidity or mortality.

• The need may be due to lack of production, increased destruction or blood loss.

Whole Blood Donation

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Transfusion criteria for whole blood (Hct ~ 40% if

available)

Overt bleeding with clinical signs of hypovolemia

Exchange transfusion of a neonate (if RBCs reconstituted with FFP not available)

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Bristol, England, 1941

Packed Red Blood Cells

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Transfuse red blood cells

• …to increase oxygen-carrying capacity in anemic patients

Do NOT transfuse red blood cells• For volume expansion• In place of a hematinic• To enhance wound healing• To improve general “well-being”

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RBC concentrates to raise Hgb level of average-size adult 1g/dL

Anticoag/Anticoag/preservativepreservative

HctHct Flow rateFlow rate DatingDating

CPDA-1CPDA-1 70-80%70-80% SlowSlow 35 days35 days

AS-5 (Optisol -AS-5 (Optisol -mannitol)mannitol)

45-59%45-59% RapidRapid 42 days42 days

AS-3 (Nutricel AS-3 (Nutricel -no mannitol)-no mannitol)

45-59%45-59% RapidRapid 42 days42 days

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RBC transfusion trigger: 7 vs. 9.5 or 10 g/dL

• 7 g/dL is as effective as 10 g/dL in adults*• 9.5 g/dL or 10 g/dL in PICU patients without

cardiovascular disease (similar morbidity and mortality)**

*Hebert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-17.

**Lacroix J et al. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007;365:1609-19.

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Properties of Stored RBC’s

• Supernatant– Citrate– Potassium – free hemoglobin– pH low

• RBC– 2,3 DPG low– spherocytic change

UCDMC Massive Transfusion Guideline (MTG)

Pack

6 units of pRBC

3 FFP Jumbo (or 6 regular)*

1 Plateletpheresis

*Kept thawed at 4°C for up to 5 days

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Washed Red Cells

• All Plasma and 85% of White Blood Cells are removed by washing.

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Indications for Washed Red Cells

• Urticarial transfusion reaction to several consecutive red cells transfusions.

• Anaphylactoid reaction to packed red cell transfusion (suspect IgA antibodies in an IgA deficient patient).

Frozen, Thawed Deglyceralized

Red Cells• White cells and plasma are removed from

the product

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Indication for Frozen, Thawed Deglyceralized Red Cells

• Predeposition of autologous blood for elective surgery to occur >42 days after donation.

• Patient with rare or multiple antibodies that need antigenically rare blood from the local blood bank or the “rare donor file”.

• Patients with HLA antibodies where febrile reaction occurred with transfusion of washed red cells.

• History of anaphylaxis to packed red cells or washed red cells.

Irradiated Blood Products• Recommended dose is between 1,500 and

5,000 cGy.• 3,000 rads destroy the spindle apparatus of

the lymphocytes so that they cannot divide. No functional impairments develop in the cells including phagocytosis by granulocytes.

• Leukemic patients, all lymphoma patients, immature infants, children with neuroblastoma receive irradiated products

Indications for Irradiated Blood Products

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Autologous Blood• Encourage physicians to use this

product.

• The patient cannot develop diseases from it.

• If multiple units will be needed the patient will be placed on iron therapy.

• Criteria for transfusion remain the same.

Fresh Frozen Plasma

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Male Donors

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Plasma

• Contains all the coagulation factors, albumin and fibrinogen.

• FFP (and FP24): Stored at -18°C for up to 1 year.

• Once thawed, must be used within 24 hours, or may be stored at 1-6°C for 5 days (as thawed plasma).

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Plasma: usual dose to increase clotting factor levels is 15-20

mL/kg body weight

ComponentComponent VolumeVolume

FFP (single donor)FFP (single donor) 180-250 mL180-250 mL

FP24FP24 180-250 mL180-250 mL

Jumbo FFP (single Jumbo FFP (single donor)donor)

400 mL400 mL

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Indications for Plasma

• Prolonged PT and/or PTT ( 1.5x ULN or INR >2) or coagulation factor assay 25% with active bleeding or impending surgery

• Bleeding with coagulopathy and specific concentrate unavailable

• Plasma exchange for TTP/HUS• Emergency reversal of Coumadin (Warfarin)

effect

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(Adapted from NIH Consensus conference)

Plasma Transfusion

Do NOT transfuse plasma

• For volume expansion

• As a nutritional supplement

• Prophylactically following cardiopulmonary bypass

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Plasma for TTP

ADAMTS13 is present in similar amounts in FFP, Cryo-poor plasma, and Plasma 24h and storage at 1-6°C for up to 5 days does not significantly diminish its activity, e.g., for TTP.

Scott EA et al. Comparison and stability of ADAMTS13 activity in therapeutic plasma products. Transfusion 2007;47:120-5.

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Properties of Stored Plasma

• Citrate Anticoagulant

• Coagulation Factors – Degradation of V and VII with prolonged

storage (4°C), 10 & 7 days respectively

Cryoprecipitate

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Cryoprecipitate unit (bag)

Volume: 10-25 mLIncreased levels of:- Factor VIII ( 100 U)- Fibrinogen (200-300 mg)- Von Willebrand’s factor- Factor XIII- ADAMTS13

Usual dose – 10 bags/adult

N.B. – once thawed, keep at room temp

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Indications for Cryoprecipitate

• No longer recommended for mild hemophilia A.• It is better to use heat treated factor VIII since HIV is

destroyed by heat.

– D.I.C– Von Willebrand’s disease– Massive intra-abdominal clotting in liver

lacerations– Fibrin glue (cryoprecipitate is mixed with

thrombin and applied directly to blood vessels)

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Platelets

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PLATELET AGITATION AT ROOM TEMPARATURE

Platelets

• A platelet pack contains 5.5 x 1010 platelets and can raise the platelet count 10,000 mm3 maximally.

• A plateletpheresis contains 3 x 1011 platelets and can raise the platelet count 30,000 mm3.

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Properties of Stored Platelets

• Citrate

• Cytokines/Vasoactive Substances

Indications for Platelets

• Prevention or arrest of bleeding in thrombocytopenic patients

• Maintain a platelet count 10,000 – 20,000 mm3 in medical cases

• Maintain a platelet count 50,000 – 100,000 mm3 in surgical cases

• GI bleeder who has taken aspirin

Indications for Platelets

• Non-bleeding patient with count of <10,000/mm3 or 1x109/L

• Platelet count < 50,000/mm3 or 5x109/L and - Bleeding due to thrombocytopenia and/or - Surgical/invasive procedure imminent

• Documented abnormal platelet function with bleeding or surgical/invasive procedure imminent

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Platelet transfusion

Do NOT transfuse platelets• To patients with immune

thrombocytopenic purpura (unless there is life-threatening bleeding)

• Prophylactically following cardiopulmonary bypass

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ABO Compatible Blood Components

Blood Compatible Compatible

Type RBCs FFPs A A, O A, AB

B B, O B, AB

AB AB, A, B, O AB

O O A, B, AB, O

4104/18/23

Editorial: Platelet ABO matters. RM Kaufman Transfusion

2009;49:5-7.PLT recovery is not the only problem

with ABO-incompatible PLTs• In ABO minor-incompatible PLTs, anti-A/B

is passively transfused and, rarely, causes acute hemolysis

• PLT ABO incompatibility – major or minor – should be avoided whenever possible

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ABO Compatibility Study

Julmy F, Amman RA, Taleghani BM, et al. Transfusion efficacy of ABO major-mismatched platelets (PLTs) in children is inferior to that of ABO-identical PLTs. Transfusion 2009;49: 21-33.

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Julmy F et al. (cont.)

• ABO major-mismatched PLTs, (e.g., A1 to O or B), result in lower 1 hr post counts (21% vs. 32%)

• ABO major-mismatched PLTs more often unsuccessful

• Platelets expressing A1 on their surface are cleared in O or B recipients

• A2 PLTs, expressing no detectable A, were as successful as ABO identical PLTs

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Julmy et al. (cont.)

Conclusions

• In children, ABO major-mismatched PLT transfusions result in inferior efficacy, except for A2 PLTs

• ABO minor-mismatched PLTs showed comparable efficacy to identical PLTs

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Other Products andSpecial Considerations

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Granulocyte Transfusions

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Granulocyte Transfusions

• Severely neutropenic patients (Absolute Neutrophil count <500/mm3) with sepsis (especially if Gram negative bacteria)

- Unresponsive to 24-48 hrs. of appropriate antibiotics

- Reasonable chance of marrow recovery soon

- Progressive cellulitis

• Neonatal sepsis with transient granulocytopenia

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Leukocyte-Depleted Components: Advantages

Sensitization to wbc

Febrile reactions (and some TRALI)

Risk of cell-associated viruses, e.g., CMV (and bacteria)

Response to platelet transfusions49

No benefit of leukocyte reduction for HIV-infected

patients

“Specifically, there was no difference in survival…in HIV-1 related serious events, nor…in the rate of transfusion reactions.”

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Collier AC et al. Leukocyte-reduced red blood cell transfusions in patientswith anemia and human immunodeficiency virus infection. The ViralActivation Transfusion Study: A randomized controlled trial. JAMA 2001;285:1592-1601.

CMV seronegative (cellular) components

• Intrauterine transfusions.

• Premature infants (<1200 g) born to CMV seronegative mothers.

• CMV seronegative transplant candidates receiving CMV negative tissues/organs.

• CMV seronegative pregnant women.

• CMV seronegative, HIV-infected patients.

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Alternatives to standard allogeneic transfusions

• Hemodilution

• Intraoperative autologous transfusion

• Perioperative blood salvage

• Lower transfusion trigger

• Pharmacologic therapies

• Pathogen inactivated components

• Red cell substitutes

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The ideal red cell substitute

• Delivers oxygen (and maybe enhances delivery)

• Does not transmit disease

• Does not have immunosuppresive effects

• Available in abundant supply

• Universally compatible

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Characteristics of HBOC(Hemoglobin-based Oxygen

Carriers)ProductProduct PolyHemePolyHeme HemopureHemopure HemospanHemospan

CompanyCompany NorthfieldNorthfield BiopureBiopure SangartSangart

Volume (mL)Volume (mL) 500500 250250 250 or 500250 or 500

Hb ConcHb Conc 10 g/dL10 g/dL 13 g/dL13 g/dL 4.2 g/dL4.2 g/dL

Hb Mass (g)Hb Mass (g) 5050 ~30~30 ~10 or 20~10 or 20

PP5050 (mmHg) (mmHg) 26-3226-32 3838 66

Met [Hb]Met [Hb] <8.0%<8.0% <15.0%<15.0% <0.5%<0.5%

TetramerTetramer 1.0%1.0% 3.0%3.0% 1.0%1.0%

Shelf-lifeShelf-life >1 year>1 year 3 years3 years >1 year>1 year

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Blood substitutes increase risk of death

• 16 trials of hemoglobin-based blood substitutes – 3,711 patients

• 30% increase in risk of death

• ~ 3 fold chance of heart attack

Natanson C et al. JAMA May 21, 2008

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Scientists take step toward converting A and B Red Blood Cells to Universal O

Bacterial enzymes can remove A & B antigens at room temperature in neutral pH: B. fragilis enzyme removes B antigen E. meningosepticum enzyme targets A antigen

Liu QP et al. Bacterial glycosidases for the production of universal red blood cells. Nat Biotechnol 2007;25:1-11.

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Thank You!

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