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 saturate
  50 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, release
  decreased.

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O2 Carrying Capacity

• Tissue oxygenation also depends on tissue oxygen
  demands.
• Under normal circumstances, there is a
  physiologic 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-existing
  cardiopulmonary disease all affect the ability of
  the 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 in blood
  stored for greater than 2 weeks, by 60-70 in 3
  weeks.
• When transfused, this old blood has a
  significantly diminished ability to release O2 to
  tissues.

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Enhancement of Hemostasis

• The second most common indication for transfusion
  is repletion of hemostatic agents.
• It is not safe to simply correct abnormal lab
  values, or to blindly adhere to old unproven
  surgical dictums.

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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 or extrinsic
  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 at 80C.
• 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 to
  80C in 40 glycerol, post transfusion survival
  is 80-90, 2,3 DPG levels are normal, antigenic
  reactions minimized.
• Large quantities of red cells can be stored for
  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 of blood,
  platelet count may drop to less than 50,000, 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 hematologic disorder.

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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
  of hemolytic 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 lose
  ability 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 is then 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 and
  vasoconstriction cause a reduction in GFR,
  thrombi form in renal tubules.
• Circulating antibody complexes released in to
  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 indirect bilirubin.
• 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 anaphylactic shock.

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Febrile Reactions

• Most common transfusion reaction (7 of
  transfusions.).
• Due to antileukocyte antibodies that develop as a
  result 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 of
  bacteria in the blood product confirms diagnosis.
• Mortality 50-80.
• Most common blood product cause of contamination
  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 of
  more 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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