Physiology of Transfusion Therapy

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    Physiology of Transfusion

    Therapy

    Vithal V. Vernenkar, D.O.Dept. of Surgery

    St. Barnabas Hospital

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    Indications for Transfusion Enhance oxygen carrying capacity of blood

    by expanding red call mass.

    Replace clotting factors, either lost,

    consumed, or not produced.

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    Enhancement of Oxygen

    Carrying Capacity Majority of arterial blood oxygen binds

    with hemoglobin reversibly.

    Release of O2 to tissues depend on many

    factors, the oxygen saturation being the

    most important.

    The saturation of hemoglobin molecules

    with O2 determines the binding affinity.

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    Enhancement of Oxygen

    Carrying Capacity As saturation increases, affinity decreases, release

    of O2 to tissues is then enhanced.

    The partial pressure of O2 required to saturate50% of the Hb molecules is called P-50.

    P-50 value is increased with fever, acidosis,increased 2,3 DPG, thus O2 is released to tissues

    with greater ease under these circumstances. However with hypothermia, alkalosis, and

    decreased 2,3 DPG affinity is increased, releasedecreased.

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    O2 Carrying Capacity Tissue oxygenation also depends on tissue

    oxygen demands.

    Under normal circumstances, there is aphysiologic reserve between O2 delivery

    (1000cc/min) and consumption (250cc/min).

    Despite this large reserve, clinical circumstances,such as massive MOSF, can have consumption

    outstripping delivery.

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    O2 Carrying Capacity Hb normally ranges between 12-18g/dL

    depending on race, age, sex, medical condition.

    Old tradition of keeping Hb at 10 is not valid. A Hb of 7-8 has been demonstrated to be

    adequate except in patients with CAD, COPD.

    It is clear that the rate and magnitude of blood

    loss, state of tissue perfusion, pre-existingcardiopulmonary disease all affect the ability ofthe patient to tolerate lower concentrations of Hb.

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    O2 Carrying Capacity Decreased levels of 2,3 DPG increase O2-

    Hb binding affinity.

    2,3 DPG levels may decrease by 30% inblood stored for greater than 2 weeks, by60-70% in 3 weeks.

    When transfused, this old blood has asignificantly diminished ability to releaseO2 to tissues.

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    Enhancement of Hemostasis Replacement products should be used only

    in preparation for elective surgery, or with

    clinically significant abnormalities in

    hemostasis.

    These include disorders of consumption or

    production of fibrinogen, intrinsic orextrinsic factor defects, platelet

    dysfunction.

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    Packed Red Blood Cells Prepared by removing 200 cc of plasma

    from fresh whole blood, to achieve a final

    HCT of 70-80%. They are kept anticoagulated with CPD

    (citrate, phosphate, dextrose), stored in

    liquid state at 4 degrees or frozen at80C. The longer the storage, the lower the rate of

    survival. Immediate (90%), 6 weeks (65%).

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    Cryopreserved RBC This technique utilizes rapid cooling of

    PRBC to80C in 40% glycerol, post

    transfusion survival is 80-90%, 2,3 DPGlevels are normal, antigenic reactionsminimized.

    Large quantities of red cells can be storedfor many years.

    Kind of expensive!

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    Autotransfusion Involves collection and immediate reinfusion of

    patients own blood for volume replacement an d

    to increase red cell mass. Massive exsanguination from either blunt or

    penetrating trauma without gross enteric

    contamination best candidates.

    Eliminates risk of histocompatability reactions,

    infectious disease.

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    Autotransfusion Not without risk, most common

    complication is thrombocytopenia.

    When patients receive more than 4L ofblood, platelet count may drop to less than50,000, risk of ATN increased from debris

    of plasma-free Hb. Also risk of air embolism, particulate

    microemboli, DIC.

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    Pre-Donation Increased with public awareness of

    transmission of infection with blood

    transfusion. Blood storage in pre-donation is similar to

    PRBC (42 day maximum).

    Contraindications include significant CAD,COPD, existence of a hematologicdisorder.

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    Products That Enhance

    Hemostasis Fresh Frozen Plasma-Single donor, same

    risk of HIV, Hepatitis as PRBC.

    Frozen at 8C, this temperature protects

    Factor V and VII in particular.

    FFP contains components of the

    coagulation, fibrinolytic, and complement

    systems.

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    Products That Enhance

    Hemostasis Useful in treating deficiencies in

    2,5,7,8,9,10,11. Also in Coumadin reversal,

    ATIII deficiency.

    Type and Rh specific plasma should be

    used.

    Urticaria, fatal pulmonary edema.

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    Cryoprecipitate Used to replenish Factor VIII or fibrinogen.

    Formed as a plasma concentrate that consists

    primary as Factor VIII and fibrinogen. In addition it contains Factor XIII, vWF,

    fibronectin.

    Stored at 37C. Above this Factor VIII destroyed.

    Disadvantage is multiple donors, increased risk ofhemolytic reactions due to small amts of anti-A,anti-B, and Rh antibodies left over in preparation.

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    Platelets Collected by repeated centrifugation of fresh

    whole blood, and suspension in 30-50 cc of

    plasma at 22C. Remain viable up to 5 days, most efficacious if

    used within 24-48h of pooling. After that loseability to produce thromboxane A-2, a potent

    vasoconstrictor and platelet aggregator. Risk of infectious complications equal to number

    of donors, must be ABO and Rh compatible,since donor plasma is present.

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    Complications of Transfusion Immunologic reactions

    Metabolic reactions

    Infectious complications

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    Immediate Hemolytic Reactions ABO incompatibility most commonly

    caused by sample labeling,

    misidentification.

    Reaction soon after transfusion started.

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    Immediate Hemolytic Reactions Change in mental status, SOB,

    hypotension, back pain, chest pain, facial

    flushing, cyanosis, tachycardia, profound

    shock. Can end in DIC, acute renal failure,

    death. Normally haptoglobin is capable of

    binding free Hb in plasma. The complex isthen cleared by reticuloendothelial system.

    If this clearance mech is exceeded.

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    Immediate Hemolytic Reactions Renal failure produced by free hemoglobin

    bound to albumin to form methalbumin.

    Hemoglobinuria occurs, hypotension andvasoconstriction cause a reduction in GFR,thrombi form in renal tubules.

    Circulating antibody complexes released into circulation make renal failure worse.

    In OR may present as diffuse bleeding.

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    Delayed Hemolysis Infrequent, related to red cell antigens other

    than A or B.

    Can occur 3-21 days after blood is infused.

    Symptoms include malaise and fever.

    Labs show low Hb, elevated indirectbilirubin.

    Usually observe if stable.

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    Allergic Reactions Transfusion of antibodies or antigens to

    which the recipient is sensitive.

    Urticaria, chills, itching, fever.

    Occurs frequently, 2% of transfusions.

    In rare occasions, can cause anaphylacticshock.

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    Febrile Reactions Most common transfusion reaction (7% of

    transfusions.).

    Due to antileukocyte antibodies that develop as aresult of prior transfusions.

    Fever, chills, flushing, tachycardia.

    May progress to hypertension, cyanosis, collapse. Rule out bacterial contamination and ABO

    incompatibility when it occurs.

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    Anaphylactoid Reactions When recipient is sensitized to IgA, a

    common immunoglobulin.

    Fever, chills, bronchospasm, diarrhea,

    abdominal pain, vascular collapse.

    Transfusion related acute lung injury- Rare,

    caused by antibodies to recipients WBC,

    clot in pulmonary circulation.

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    Bacterial Contamination All blood products except albumin and

    serum globulins carry HIV and Hepatitis

    risk. Thats because they are heat treated.

    19% of all fatal reactions involve blood

    products with contamination.

    1-2% of all blood products may be

    contaminated with bacteria.

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    Bacterial Contamination Most common cold growing, endotoxin-

    producing, gram negative organisms are

    klebsiella, pseudomonas, identified in 68%

    of the reported reactions. Gram positive

    organisms responsible usually staph.

    Contamination arises from donor. Hypotension, fever, abd pain, extremity

    pain,sepsis.

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    Bacterial Contamination Onset shortly after transfusion begins, temp

    spikes at 12 h intervals.

    Absence of hemoglobin in urine and presence ofbacteria in the blood product confirms diagnosis.

    Mortality 50-80%.

    Most common blood product cause ofcontamination is plateletsnot refrigerated.

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    Viral Contamination Hepatitis most common. 2.5-8% risk per unit.

    Most common is Hepatitis C (85-98%),

    incubation 8 weeks, chronic in 50% of patients.

    HIV risk 1: 1,000,000- 2,000,000 per unit blood.

    CMV, EBV especially in premature infants,

    transplant patients.

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    Other Problems Citrate- causes hypocalcemia, also direct

    cardiac depressant. From massive rapid

    transfusions of PRBC.

    Replace calcium 1 gram for each 6 units

    transfused, since in a trauma scenario,

    checking ionized Ca not practical

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    Other Problems Hypothermia, coagulopathy, leftward shift in O2

    dissociation curve, less release.

    Dilutional thrombocytopenia, after transfusion ofmore than 10 units blood.

    Hyperkalemia- as a result of ADP pump

    inactivation in stored blood, potassium levels can

    reach 70 meq/L. Watch out in renal patientsNot

    really a problem though.

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