Blood Products and Transfusions


Blood Groups and Compatibility Testing

  1. Blood Groups
    • erythrocytes carry surface antigens for more than 30 different systems
    • leukocytes carry HLA antigens
    • platelets carry both HLA antigens and platelet-associated antigens
    • blood is typed and cross-matched only for RBC antigens
    • WBC and platelets that are incidentally infused with RBCs are usually well tolerated
    • clinically, the two most important RBC antigen systems are ABO and Rh

    1. ABO Group
      • of major importance in transfusion and transplantation
      • the four possible ABO types - O, A, B, AB - are the phenotypic expression of 2 co-dominantly inherited enzymes used to construct either A or B carbohydrate structures on red cells, endothelial cells, and secretory endothelia
      • group O patients have 2 alleles that produce an inactive protein
      • ABO carbohydrate structures are strongly immunogenic
      • owing to universal exposure to similar naturally occurring antigens, individuals who lack the A or B antigen will possess strong IgM antibodies to these antigens
      • because IgM antibodies fix complement, transfusion of ABO incompatible blood will cause immediate hemolysis and liberation of free Hg into the circulation
      • since type O is antigenically weak, most people can accept blood from an O-negative donor (universal donor)
      • in the United States, 47% are O, 41% are A, 9% are B, and 3% are AB

    2. Rh System
      • refers to the presence or absence of the D RBC antigen in the Rh blood group system
      • 15% of the population is Rh- negative
      • individuals who lack antigens to the Rh system do not generally possess strong preformed antibodies
      • prior exposure (by transfusion or during pregnancy) is necessary to sensitize the individual
      • anti-D antibodies cause hemolysis of Rh+ transfusions
      • most feared problem is hemolytic disease of the newborn, in which fetal Rh+ RBCs are destroyed by IgG anti-D antibodies crossing the placenta
      • fortunately, Rh immune globulin prevents nearly all Rh alloimmunizations in Rh- negative pregnant women bearing Rh+ children

  2. Compatibility Testing
    1. Type and Screen
      • ABO, Rh typing
      • screen for the most commonly found non-ABO antibodies
      • check blood bank records for previous transfusions

    2. Type and Crossmatching
      • type and screen
      • additional crossmatch of patient’s serum against the intended unit of PRBCs
      • blood can only be used for that specific patient
      • takes 30 – 60 minutes

    3. Emergency Transfusions
      • uncrossed type O, Rh-negative blood can be given in emergencies
      • type-specific blood (ABO and Rh matched) can also be used
        • antibody screen and final crossmatch have not been done
        • 1% risk of a hemolytic transfusion reaction
      • in a male who has never been transfused previously, the transfusion of Rh-positive blood is acceptable if Rh-negative blood is unavailable
      • in woman of child-bearing age, Rh-positive blood should never be transfused to Rh-negative patients

Blood Products

  1. Packed Red Blood Cells (PRBCs)
    • concentrated suspension of cells can be prepared by removing most of the supernatant plasma after centrifugation (~30 cc of plasma remains, which may cause hemolytic reactions)
    • a unit of PRBCs is preserved in a citrate-phosphate-dextrose-adenine-1 solution with a 300 mL volume and a 55 – 65% hematocrit
    • newer additive solutions allow a 42-day storage period
    • stored RBCs have a reduced capacity to transport oxygen (↓intracellular ADP, ↓ 2,3-diphosphoglycerate)
    • stored RBCs also progressively become more acidotic with elevated levels of lactate, potassium, and ammonia
    • one unit of PRBCs should raise the hemoglobin by 1 gram/dL and the hematocrit by 3%

  2. Leukocyte-Reduced/Washed Red Blood Cells
    • prepared by aspirating the buffy coat and supernatant plasma and passing them through a specific white-cell filter
    • removes 99.9% of WBCs and most of the platelets
    • red cells are then washed with a sterile isotonic solution
    • historically used in patients with demonstrated hypersensitivity to WBCs or platelets (fever, chills, urticaria)
    • may cause less post-op bacterial infections and multiorgan failure
    • has become the standard RBC transfusion product (some studies show decreased mortality and infections)

  3. Platelets
    • provided as units of 50 mL concentrates from pooled individual whole blood donations (6 – 10 donors per platelet transfusion)
    • a single donor apheresis concentrate is also available, but is more expensive
    • shelf-life is 120 hours from the time of donation
    • each unit of platelets should raise the platelet count by 5,000 - 10,000
    • ABO matching of donor and recipient is preferred but not essential
    • development of isoantibodies remains one of the most important factors limiting the usefulness of repeated platelet transfusions

  4. Fresh Frozen Plasma
    • prepared by centrifuging the cellular components of the whole blood donation and freezing the plasma within 6 hours of collection to preserve fully the labile coagulation factors V and VIII
    • each unit contains 225 mL
    • frozen shelf life is 12 months, and after thawing it is only 5 days
    • the plasma must be ABO-compatible to the patient’s blood type, but crossmatching and Rh-typing are not required
    • provides clotting factors
    • should not be used as a plasma expander
    • carries similar infection risks as other component therapies

  5. Cryoprecipitate
    • collected by thawing FFP and collecting the white precipitate
    • often pooled like platelets from multiple donors
    • each unit is 15 mL
    • rich in factor VIII, fibrinogen, factor XIII, and von Willebrand’s factor
    • used in von Willebrand’s disease, DIC, and to reverse tPA

  6. Factor Concentrates
    • recombinant factor VIII and factor IX concentrates are used in patients with congenital hemophilias
    • prothrombin complex concentrate:
      • contains the 4 vitamin K-dependent factors (II, VII, IX, X) and the 2 vitamin K-dependent anticoagulants (proteins C and S)
      • requires 85% less volume and contains 25X higher clotting factor concentrations than FFP
      • can be stored at room temperature
      • FDA-approved for emergency warfarin reversal

Indications for Transfusion

  1. Red Blood Cells
    1. Oxygen Delivery
      • blood delivers oxygen to the tissues, and most of the delivered oxygen is bound to hemoglobin
      • anemia, therefore, has the potential to reduce oxygen delivery
      • oxygen delivery DO2  =  cardiac output  x  arterial oxygen content
      • many patients are able to compensate for anemia by increasing cardiac output (↑ heart rate, ↑ stroke volume)
      • at rest, there is a large reserve in oxygen delivery, since delivery exceeds consumption by a factor of 4
      • all of this suggests that patients with normal cardiovascular status can tolerate very low hemoglobin levels
      • however, critically ill patients have impaired compensatory mechanisms and likely require higher hemoglobin levels

    2. Impact of Anemia on Morbidity and Mortality
      • severe postoperative anemia has an adverse effect on mortality
      • hemoglobin < 7 g/dL appears to be the critical value where mortality greatly increases
      • it hasn’t been demonstrated that correction of severe anemia improves mortality (correlation vs. causation)

    3. Red Cell Transfusion Guidelines
      1. Massive Hemorrhage
        • PRBCs, FFP, and platelets are transfused in a 1:1:1 ratio
        • indications for transfusion are ongoing hemorrhage and hemodynamic instability, not a specific hemoglobin level
        • permissive hypotension (SBP > 60 – 70 mm Hg) and minimizing crystalloids are additional components of damage control resuscitation

      2. Symptomatic Patients
        • symptoms of anemia include tachycardia, dyspnea, myocardial ischemia, mental status changes, oliguria or anuria, lactic acidosis
        • symptomatic patients with a hemoglobin < 10 g/dL should be transfused

      3. Hemoglobin < 7 – 8 g/dL
        • for hemodynamically stable patients, transfusion should be considered at a hemoglobin of 7 – 8 g/dL
        • this threshold hemoglobin level has been validated in multiple studies, and balances the benefits of treating anemia with avoiding the risks and costs of transfusions

  2. Fresh Frozen Plasma
    1. Indications
      • active bleeding in the setting of known or suspected coagulation abnormalities
      • as part of a massive transfusion protocol
      • preoperatively for any procedure with a high risk of bleeding complications, if the patient has a significant abnormality in their coagulation tests
      • DIC
      • reoperatively for any procedure with a high risk of bleeding complications, if the patient has a significant abnormality in their coagulation tests

  3. Platelets
    1. Indications
      • platelet count < 10,000, to prevent spontaneous hemorrhage
      • platelet count < 50,000, in patients who are actively bleeding, or who are scheduled for an invasive procedure
      • platelet count < 100,000, in patients who have a CNS injury or multisystem trauma
      • as part of a massive transfusion protocol
      • normal platelet count in uremic patients or patients on antiplatelet therapy, who are actively bleeding or who require an invasive procedure

Complications of Transfusions

  1. Hemolytic Reactions
    1. Acute Hemolytic Reactions
      • incidence of nonfatal hemolytic transfusion reactions is 0.016%
      • fatal hemolytic reactions occur in 0.003% of RBC transfusions and are due to administration of ABO and Rh incompatible blood, resulting from clerical, laboratory, or technical error
      • characterized by intravascular destruction of RBCs and consequent hemoglobinemia and hemoglobinuria
      • renal consequences include acute tubular necrosis and precipitation of hemoglobin within the tubules
      • DIC may occur from antigen-antibody complexes activating factor XII and complement, leading to activation of the coagulation cascade

      1. Clinical Manifestations
        • symptoms may include:
          • heat or pain along the vein into which blood is being transfused
          • flushing of the face
          • pain in the lumbar region
          • chest pain
          • fever, chills, respiratory distress
          • hypotension
        • in anesthetized patients, diffuse bleeding and hypotension are the hallmarks
        • laboratory criteria:
          • hemoglobinuria > 5 mg/dL
          • serum haptoglobin below 50 mg/dL
        • positive Coombs’ test indicates transfused cells coated with patient antibody
        • simple clinical test is insertion of a Foley catheter and evaluation of the color and volume of the excreted urine, since hemoglobinuria and oliguria are the most characteristic signs

      2. Treatment
        • stop the transfusion
        • send a sample of the recipient’s blood along with the suspected unit to the blood bank for comparison with the pretransfusion samples
        • insert Foley catheter and begin aggressive fluid resuscitation
        • initiate diuresis with mannitol and lasix
        • consider alkalinizing the urine with bicarbonate to prevent precipitation of hemoglobin within the tubules
        • if marked oliguria or anuria occurs, then fluid intake and potassium intake are restricted
        • dialysis may be necessary

    2. Delayed Hemolytic Reactions
      • occur 2 – 10 days after transfusion, and are characterized by extravascular hemolysis, mild anemia, and indirect hyperbilirubinemia (mild jaundice)
      • many patients are asymptomatic
      • results from non-ABO incompatibilities

  2. Febrile Non-Hemolytic Reactions
    • most common complication and occurs in 7% of RBC transfusions
    • results from patient’s antibodies against donor WBCs
    • treatment is tylenol, and the transfusion does not have to be stopped
    • repeated febrile reactions may require premedication with tylenol, a slower transfusion rate, or the use of leukocyte-poor RBCs

  3. Allergic Reactions
    • occur in 1% of transfusions
    • most commonly associated with FFP and platelet transfusions
    • reactions usually are mild – hives, rash, or flushing
    • rarely the reaction may be severe enough to cause anaphylactic shock
    • caused by the transfusion of antigens to which the recipient has preexisting antibodies
    • treatment consists of the administration of antihistamines, epinephrine, and steroids, depending on the severity of the reaction

  4. Transmission of Disease
    • malaria, Chagas’ disease, brucellosis, syphilis can be transmitted by transfusion
    • cytomegalovirus can be transmitted in immunosuppressed patients
    • hepatitis C and HIV have been dramatically minimized by better testing (risk now < 1 per 1,000,000 units)
    • risk of hepatitis B is 1 per 300,000 units
    • new pathogens are a continuous threat (West Nile virus, Zika virus, etc)

  5. Transfusion Related Acute Lung Injury (TRALI)
    • defined as “new acute lung injury occurring during or within 6 hours of a transfusion”
    • manifested by noncardiogenic pulmonary edema, diffuse bilateral pulmonary infiltrates, fever
    • HLA antibodies and neutrophil-specific antibodies in the plasma of both donors and recipients have been implicated as the cause of TRALI
    • treatment consists of stopping the transfusion and pulmonary support

  6. Volume Overload
    • expansion of intravascular volume has the potential to cause pulmonary edema
    • high risk groups include older patients and small children, and patients with poor cardiac and renal function

  7. Immunomodulation
    • ↑ susceptibility to bacterial infection
    • ↑ cancer-related mortality and shortened disease-free interval
    • ↑ post-op morbidity/mortality
    • improved outcome in kidney transplants
    • donor WBCs and cytokine release likely responsible

  8. Storage Defects
    • massive transfusions can cause hypocalcemia and metabolic alkalosis
      • citrate binds ionized calcium
      • citrate is converted into bicarbonate in the liver
    • since potassium and lactate can leak from RBCs during storage, hyperkalemia and/or acidosis may occur during rapid blood transfusion/li>

Transfusion Alternatives

  1. Autologous Predonation
    • useful in planned elective surgery with long lead times like hip replacements
    • contraindications include Hg < 11, significant cardiac disease
    • does not prevent identification errors at the collection site or at bedside

  2. Intraoperative Cell Salvage
    • RBCs shed during surgery are collected, filtered, washed, and reinfused
    • most frequently used in cardiac and open vascular surgery
    • relative contraindications include bacterial and enteric contamination, ascites, tumor
    • systems that wash blood may be safer than systems without washing capability

  3. Autotransfusion Devices
    • most common use is with a chest tube placed for massive hemothorax
    • an optional autotransfusion cannister can be connected to the collection device
    • once filled, the cannister can be hung like a unit of PRBCs

  4. Pharmacological Measures to Limit Transfusions
    1. Tranexamic Acid
      • inhibits fibrinolysis
      • chemically similar to, but more potent than, aminocaproic acid (Amicar)
      • CRASH-2 trial demonstrated a significant reduction in mortality in patients with major traumatic hemorrhage who received the drug within 3 hours of injury

    2. Erythropoietin
      • increases RBC production in the bone marrow
      • acceptable to most Jehovah’s Witnesses

    3. Iron
      • oral iron is used for chronic iron-deficiency anemia
      • IV iron may be used to rapidly increase the hemoglobin level, but its use is limited by a significant risk of severe allergic reactions

    4. DDAVP
      • causes release of factor VIII and von Willebrand factor from endothelial cells
      • useful in patients with mild hemophilia A (type 1) or von Willebrand’s disease
      • also valuable in patients with platelet dysfunction from uremia







References

  1. Simmons and Steed, Pgs 425 - 433
  2. O’Leary, 4th ed. Pgs 554 – 567
  3. Schwartz, 10th ed. Pgs 96 – 104
  4. UpToDate, Use of Blood Products in the Critically Ill. Pgs 1 -21
  5. UpToDate, Indications and Hemoglobin Thresholds for Red Blood Cell Transfusion in the Adult. Pgs 1 -21
  6. UpToDate, Massive Blood Transfusion. Pgs 1 - 17