Transfusion Therapy

General – How to Avoid Liability

Minimize donor exposure for the recipient

Give as specific a therapy as possible

Any incentive for blood donation other than altruism compromises the donor and puts the recipient at risk

Documentation of reason for transfusion and for the choice of blood component is mandatory for legal protection

Informed consent must be obtained; documentation is the best way to avoid transfusion-associated liability

Federal law prohibits dispensing blood and blood components without a prescription

"Circular of Information of the Use of Human Blood and Blood Components" serves a s a package insert for transfused blood

Autologous Blood – should be used when possible

preoperative autologous donations prior to elective surgery and/or intraoperative blood collection and reinfusion

pt should donate as far in advance as possible (6 wk max due to limitations of RBC storage

autologous donors can donate every 3 days as long as Hct ³ 33% with a 3 day interval before surgery

autologous salvage – collection of blood from a wound postoperatively

acute normovoluemic hemodilution – collected during induction of anesthesia and replaced by saline

directed donations – donations obtained from family members and friends; often less safe due to added pressure on family member to donate when they would not donate otherwise

Screening of Blood – rigorous screening procedure

2% of donated blood is rejected based on abnormal test results; 6% is wasted/outdated

eclipse phase – period between exposure and infectivity

window phase – period between infectivity and serologic detection

Current tests – RPR, HbsAg, Anti-HBc, Anti-HCV, Anti-HIV1/2 Anti-HTLV I/II and HIVAg

Nucleic Acid Testing (NAT) also known as Genomic Amplification Testing (GAT) – tests for viral RNA/DNA

Being developed for HIV and HCV; ß window phase and Ý sensitivity of viral detection

Window Period for HIV: 22 days currently, would be 7-12 days (ß 10-15 days) with NAT/GAT

Window Period for HCV: 70 days currently, would be 10-30 days (ß 41-60 days) with NAT/GAT

NAT/GAT is expected to detect < 10 additional HIV positive donations but more than > 100 HCV donations each year

NAT/GAT test is expected to replace the HIVag

Components of Blood

citrate is combined with citrate (ADSOL used today) to prevent coagulation; separated into blood components within 8 hours of collection

(1) Whole Blood – platelets and granulocytes are usually not viable; ß FV and VIII

Actions: restoration of oxygen carry capacity + blood volume

Indications: symptomatic anemia and large volume deficits (not used often today)

Risks: hemolytic anemia, fever, allergic infection and hypervolemia

(2) Red Blood Cells – cellular blood components made by removing, through light centrifugation, platelet-rich plasma

Hct @ 55-65% in a volume of about 300 ml after addition of the adenine additive solution

Storage: up to 42 days at 4° C

In 70 kg adult there is a 3% Ý in Hct per unit transfused

(3) Fresh Frozen Plasma (FFP) – non-cellular blood component

formed by heavy centrifugation of the platelet-rich plasma

Components: all plasma proteins including FV and FVIII; source of labile and nonlabile plasma factors

Storage: up to one year at -18° C

Once thawed and prepared for use it must be used within 4 hours if kept at room temp or 24 hours if refrigerated

(4) Thawed Frozen Plasma – FFP that has been thawed over 24 hours

most factors besides FVIII are still stable; UHC uses Thawed Frozen Plasma for up to 48 hours after thaw; ß wastage

FVIII is an acute phase reactant is not generally required

(5) Solvent Detergent Plasma (SD Plasma) – alternative to thawed frozen plasma; 3 X more expensive than FFP

produced from pools of 2,500 donors of like ABO type and then processed using a solvent and detergent to destroy/inactivate viral agents with a lipid envelope (HIV, HCV, HBV,HTLV-I/II)

ß factors of clotting/fibrinolytic process; in particular, anti-plasmin which down regulates the degradation of fibrinogen is absent in SD plasma compared to FFP)

(6) Platelets – non-cellular blood component; remains following removal of plasma from the platelet rich plasma

Random Donor – each unit of platelets is prepared from whole blood from many individuals;

Single Donor Platelet Phoresis – obtained by platelet aphoresis form a single donor; safer; able to do HLA histocompatability matching

Each unit contains 4-8 unit equivalents of platelets procured from individual blood units

Components: leukocytes; 7-8X10¹⁰ platelets suspended in 50 ml of residual plasma

Storage: stored for up to 5 days at room temp with continuous gentle agitation

Risks: bacterial growth during storage

Use: In 70 kg adult there is a 5,000-10,000/m l elevation in the platelet count per transfused unit; several units must be pooled to obtain an adequate dose (generally 1 unit/10kg)

(7) Cryoprecipitate – non-cellular blood component

FFP is allowed to slowly thaw in a refrigerator and forms a white precipitate

Components: FVIII, fibrinogen, vWF, FXIII

Stored: -18° C

Use: declined with advent of monoclonal and recombinant FVIII preparations to treat hemophilia A; principally used to replace fibrinogen; 1bag (unit)/2-4 kg

Special Handling of Components

(1) Irradiation (Gamma) – irradiation of cellular blood components is performed anytime there is a risk for the development of transfusion-associated graft-versus host disease (TA-GVHD)

TA-GVHD is multisystem disorder which is almost uniformly fatal; multisystem disorder in which immuno-competent T cells in the donor blood are incompatible with recipient HLA type and attack the cells and tissues of the transfusion recipient

Lymphocytes remain viable for two weeks or more; irradiation irreversible damages the DNA and prevents T-cells from proliferating and engrafting

Immunocompromised patients are at most risk;

pts receiving blood from homozygous donors which is the same HLA type as one of the recipients alleles are also at risk Þ recipient will not recognize the donor’s leukocytes as foreign but the donor will recognize the recipient’s leukocytes as foreign setting up the usually fatal GVHD (often seen among family members)

HIV infected patients are paradoxically not susceptible to TA-GVHD Þ reason is unknown

(2) Filtration – can remove 99.99% of leukocytes

Prevent or delays alloimmunization to HLA antigens; not sufficient to reliably prevent TA-GVHD

alloimmunization occurs when a person’s immune system is expose to Ag not present in the host
HLA Ag present on leukocytes and platelets but not RBC

Effectively reduces or prevents transmission of viruses and bacteria found in leukocytes

CMV transmission can be virtually eliminated; HIV, HBV and HCV are not eliminated by filtration

Most effective when performed soon after collection Þ pre-storage leukocyte depletion

Removes leukocytes before they manufacture and secrete cytokines (platelets stored at room temp often store massive amounts of cytokines)

effective in preventing febrile transfusion reactions (³ 1° C Ý in temp often accompanied by chills and rigors)

febrile transfusion reactions – donor leukocytes interacting with HLA Ab in the transfusion recipient

(3) HLA Compatible Platelets – used in alloimmunized, refractory patients improve response to platelet transfusion therapy

may require several days for matching procedure

(4) Antigen Matched RBC – for patients who have developed irregular (non-AB)) blood group Abs

blood must be matched not only for AB) and Rh type bur for the Ag corresponding to the additional Ab
may require minutes to days in rare instances for matching procedure

(5) CMV-Screening/CMV Safe – used for CMV negative patients who are immunocompromised

Candidates:

Neonates
Bone marrow and solid organ transplant patients
Immunocompromised patients
Cancer patients receiving immunosuppressive chemotherapy

Transfusion Practice

Red Blood Cell Transfusions

given to Ý oxygen carrying capacity and tissue oxygenation

impaired tissue oxygenation manifested by Þ tachycardia with CHF · tachypnea · metabolic acidosis · locally impaired oxygen function

Indications: Hb < 8gm/dl or Hct < 24%; marrow suppression making spontaneous rise in Hb unlikely; evidence of impaired expected blood loss in surgery; administration of therapeutic irradiation

Iron and folic acid are safer than blood in a patient with acute, self limited blood loss and bone marrow function

Blood loss: up to 10 ml/kg Þ no replacement; up to 20 ml/kg Þ replace with colloid; > 25 ml/kg Þ colloid + RBC

Adult = 70 ml whole blood /kg (pregnant women + neonates have 80cc or more/kg)

Single unit of RBC will raise the Hb by 1 gm/dl and the Hct by 3%

Special Considerations in Sickle Cell Disease

RBC alloimmunization occurs in 35% of SS patients; always anemic

Raising the Hb > 12 gm/dl (Hct > 36%) Ý viscosity may impair perfusion

Acute Transfusion

Ý oxygen carrying capacity when there is a exacerbation of anemia (aplastic hyperhemolytic anemia and splenetic sequestration crisis)

ß veno-oclusive phenomena due to sickling when major complications are likely to ensue if blood flow is not restored (stroke, acute chest syndrome, priapism) and before major surgical procedures when post op hypoxia may occur

Chronic Transfusion

done to prevent sickling; suppresses production of HbS; leads to iron overload so chelation therapy must be used

Platelet Transfusion

Function: ß bleeding (therapeutic platelet transfusion therapy) and to prevent bleeding (prophylactic platelet transfusion therapy) in patients at due to thrombocytopenia

poor correlation between bleeding and platelet count due to age of platelets, drugs or diseases impairing platelet function

Indication: 10-40,000 platelets/m Þ no spontaneous bleeding but will bruise and have petechiae

pts with bone marrow failure and platelet counts < 10,000-20,000/m

actively bleeding patients undergoing invasive surgical procedures in should be transfused with platelets up to 70,000/m

Guidelines for Dose Calculation: 1 unit of random donor platelets will raise the platelet count by 5000-10,000m in a 70kg recipient and 35-70,000m in a 10 kg recipient

Usual Dose in Adults Þ 5 pooled random donor units or one single donor apheresis unit

Usual Dose in Children Þ 1 random donor unit/10kg

When post transfusion platelet count increment is poor, alloimmunization is the usual cause and the use of single donor HLA matched platelets, platelets donated by family members or cross-matched platelets may result in a better response

Plasma Transfusion

FFP is most abuse blood component; often used when colloid (albumin) or saline are equally efficacious

All viruses present in blood are present in blood are transmitted in plasma except HTLV-I/II and CMV

Indications:

Documented coagulation factor deficiencies, liver disease, DIC and patients receiving l-asparignase for leukemia
Thrombotic thrombocytopenic purpura (TTP) with plasma exchange
Rapid reversal of warfarin effect
C-1 esterase inhibitor deficiency (edema)

Guidelines: make sure you give enough; when PT and PTT are prolonged and fibrinogen is ß 10-20ml/kg is needed

Cryoprecipitate

Indications: Appropriate for some patients with von Willebrand’s Disease, dysfrinogenemia and afibrinogenemia and to prepare fibrin glue for topical surgical use

used today to replace fibrinogen and sometime FVIII

Transfusion Therapy Process

Indications/Appropriateness Þ 1. Defining the transfusion trigger (how much is needed); 2. Transfusion guidelines

Pretransfusion Compatibility Testing

No testing - Emergency Transfusion Þ when transfusion is so urgent that any delay will threaten the clinical outcome

O neg is a universal donor and can be used; O neg unmatched is safer statistically than matched

Erroneous ABO incompatible transfusions occur approximately 1/33,000 transfusions Þ usually clinical error

1/250,000-1/1,000,000 chance of a clinically significant incompatibility to a minor blood group Ag on O neg transfusion

In emergency situations, incompatible blood is better than no blood at all.

ABO/Rh Testing – Urgent Transfusion; Type specific Blood Þ when you have 10 minutes to type blood

Antibody Screen Þ test for non-ABO RBC Ab resulting from prior transfusion or pregnancy

requires test to known red cell Ag type to a recipients serum; traditional test tube method or Gel technique which uses a column of negatively charged beads

Antibody Identification Þ if the Ab screen is positive a more detailed RBC Ab panel is used to identify the Ab

Crossmatching

Full Þ patients with a history of RBC alloimmunization mush undergo a major, full serologic crossmatch

Antiglobulin phase – detects non-ABO Ab (so called irregular Ab; usually IgG) present in the intended transfusion recipient, specific for RBC Ag that might be clinically significant following transfusion with a potentially incompatible unit of blood; requires 30 minutes

Immediate Spin Þ patients without a history of red cell alloimmunization is a candidate for the immediate spin crossmatch

variation of the full crossmatch and consists of the addition of red cells from the donor units with serum from the intended recipient; instead of the extended incubation phase, the sample mixture is centrifuged and viewed immediately at room temperature
tests ABO compatibility but not non-ABO red cell Ab

Electronic or Computer – substitute for the immediate spin crossmatch

pts without a history of red cell alloimmunization and has two or more ABO and Rh types on file is a candidate

Transfusion Efficacy

Documentation of post-transfusion benefit

Recognition and Therapy of Transfusion Complications

Transfusion Reaction – any adverse reaction of the patient associated with a transfusion

Fatal Transfusion Reactions – must be reported to the FDA by telephone within 24 hrs and written report – 7d

General Classification

Hemolytic Transfusion Reactions

Workup of Suspected Hemolytic Transfusion Reactions

Transmission of Infectious Disease

Alloimmunization of the recipient

Nonhemolytic Febrile Transfusion Reactions (FNHTR) – Definition: Temperature rise ³ 1° C in association with transfusion; Relieved with antipyretic; chills, rigors, cold and discomfort are not relieved by antipyretic

Factors Not Associated with FNHTR: previous transfusion, history of pregnancy, febrile status before transfusion, history of previous adverse reaction, pretransfusion medication or antibiotic therapy at time of transfusion

Factors Associated with FNHTR: component type (platelets > > > RBC), component WBC quantity, component age (most significant factor)

Other Transfusion Reactions: Transfusion-Associated Acute Lung Injury, Graft vs Host Disease, Allergic Reaction, Circulatory Overload, Iron Overload, Microaggregates, Depletion of coagulation proteins and platelets, Metabolic complications (Hypothermia, Citrate toxicity, Acidosis/alkalosis, Alteration in potassium), immune suppressive effects

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