1 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
2 Icahn School of Medicine at Mount Sinai, New York, NY, USA
Blood products
Red blood cell preparations
The majority of RBC products are PRBCs produced from donated whole blood in an anticoagulant preservative solution; 11% are collected by RBC apheresis.
One unit typically contains 130–240 mL of RBCs, a total of 50–80 g of hemoglobin (Hb), and has a hematocrit (Hct) of 55–80%, with variation dependent upon the anticoagulant preservative solution used.
Higher volume and lower Hct are found in additive solution‐containing products.
Unmodified RBC preparations contain small amounts of plasma, platelets, and leukocytes.
In non‐bleeding patients each RBC unit will increase the Hb by 1 g/dL and the Hct by 3%.
Special preparations:
Leukocyte‐reduced concentrates (<5 × 106 leukocytes in the final component in the USA): for use with repeated febrile non‐hemolytic transfusion reactions, prevention of sensitization to HLAs for organ transplant patients, cytomegalovirus (CMV) and Epstein–Barr virus (EBV) transmission, and transfusion‐related immunomodulation.
Washed PRBCs: removes plasma proteins, some leukocytes, and remaining platelets. Used for recurrent severe allergic transfusion reactions not prevented by antihistamines and IgA‐deficient patients with anti‐IgA antibodies.
Irradiated PRBCs: inactivate immunocompetent lymphocytes for prevention of transfusion‐associated graft‐versus‐host disease (GVHD) in immunocompromised patients.
Frozen RBCs: long‐term storage of rare RBC phenotypes for use in patients with related alloantibodies.
Volume‐reduced RBCs: removal of plasma and supernatant for patients who are volume sensitive, have sensitivities to additive solution, and/or an increased potassium load.
Indications for PRBC transfusion
Hemorrhagic shock.
Acute hemorrhage and hemodynamic instability or inadequate oxygen delivery.
Symptomatic anemia.
Replacement of RBCs during exchange transfusion.
Stable anemia in critically ill patients: restrictive strategy is recommended; trigger of Hb <7 g/dL in most patients and ≤8 g/dL in patients with acute coronary syndrome.
Plasma products
Fresh frozen plasma (FFP): acellular fluid portion of blood which can be manufactured from whole blood or collected directly by apheresis.
Contains approximately 0.7–1 IU/mL of each clotting factor and 1–2 mg/mL of fibrinogen.
Frozen plasma (FP24): plasma frozen at –18°C or colder within 24 hours after phlebotomy.
Considered to be clinically equivalent to FFP.
Thawed plasma.
FFP or FP24 that has been thawed and stored for >24 hours.
Most clotting factors remain stable during the 5 days of storage. The activity of factors V, VII, and VIII declines significantly; however declines are not considered to be of clinical significance.
Cryoprecipitate‐reduced plasma: supernatant expressed during manufacture of cryoprecipitate from FFP.
Deficient in factors VIII, XIII, vWF, fibrinogen, cryoglobulin, and fibronectin.
Only used for transfusion or plasma exchange therapy in patients with thrombotic thrombocytopenic purpura.
The majority of plasma units have a volume of about 250 mL.
Estimated dosage is 10–15 mL/kg, which will increase factor activities by at least 30% in the absence of rapid ongoing consumption.
Should be given as close to the time needed for surgery or procedure to maximize hemostatic effect.
Indications for FFP transfusion
Multiple acquired coagulation factor deficiency.
Replacement of single plasma factor deficiency for which no factor concentrate exists.
Liver failure.
Disseminated intravascular coagulation (DIC).
Rapid reversal of warfarin.
Plasma infusion or exchange for thrombotic thrombocytopenic purpura, thrombotic microangiopathies, diffuse alveolar hemorrhage, and catastrophic antiphospholipid syndrome.
Cryoprecipitate
Cryoprecipitate is made from human plasma by refreezing the remains after the supernatant is removed from thawed FFP.
Main constituents are fibrinogen, fibronectin, factor VIII, vWF, and factor XIII.
One unit will increase fibrinogen concentration by approximately 50 mg/dL per 10 kg of body weight. Typical dose is 10 units.
Indications for cryoprecipitate transfusion
Acquired/congenital hypofibrinogenemia.
Recommended for fibrinogen <100 mg/dL in actively bleeding patients or prior to surgery.
Reversal of thrombolytic therapy with bleeding.
Factor deficiencies if factor concentrates are not available.
Platelet products
Can be manufactured from whole blood which usually requires pooling of multiple units (4–6 units) or from apheresis where one collection can usually provide multiple doses.
Typical dose is 3–4 × 1011 platelets for an adult.
Special preparations:
Leukoreduced: decreases febrile transfusion reactions, risk of CMV transmission, and HLA alloimmunization and resultant risk for platelet refractoriness.
Irradiated: prevents transfusion‐associated GVHD.
Washed or volume reduced: removes antibodies contained within the plasma. Can lead to reduction of number of available platelets by 5–30% as well as decrease in platelet function.
Indications for platelet transfusion
Therapeutic transfusion:
Actively bleeding patients with platelet count <50 000/μL or dysfunctional platelets.
Prophylactic transfusion triggers:
For most patients <10 000/μL without active bleeding.
Consider <20 000/μL for bleeding, febrile, or septic patients.
Consider <50 000/μL for planned lumbar puncture, indwelling catheter insertion, or most invasive procedures.
Consider <100 000/μL for major surgery or procedures involving the eye or brain.
Platelet dysfunction:
If underlying cause of platelet dysfunction cannot be corrected, if there is no improvement with RBC transfusion to Hct >30%, and if the use of desmospressin is inappropriate or does not prove effective.
Treatment protocols
Blood products for transfusion
Obtain informed consent in non‐emergent situations.
Order appropriate blood product(s).
Inform nursing staff.
Obtain vascular access.
Confirm patient identity and receipt of appropriate blood products.
Monitor patient for complications during and after transfusion.
Check follow‐up labs.
Massive transfusion protocol (MTP)
Typically defined as transfusion of 10 or more RBC products within 24 hours, but also defined as replacement of 50% of total blood volume within 3 hours, or blood loss exceeding 150 mL/min.
As PRBCs and crystalloid volume expanders are infused, concentrations of platelets and clotting factors will decline.
Depletion of approximately 35% of coagulation factors after replacement of one blood volume.
Platelet concentration will decrease to approximately 50 000/μL and fibrinogen to approximately 100 g/dL after two blood volumes.
Optimal ratios of blood products are unknown, however it is important to provide plasma and platelet products along with RBC products.
Better outcomes have been shown with equal ratio 1:1:1 dosing of PRBCs, plasma, and platelets.
MTP can be managed by component therapy‐based approaches, with transfusion triggers such as Hb <8 g/dL, PT >1.5 times normal, platelets <50 000/μL, and fibrinogen <100 g/dL.
Frequent monitoring of platelets, PT, aPTT, and fibrinogen should be performed.
Potential complications of MTP:
Coagulopathy.
Hypothermia.
Hyperkalemia.
Hypocalcemia.
Acid–base disorders.
Acute respiratory distress syndrome.
Adverse transfusion reactions
Potentially severe acute reactions
Allergic, urticarial, or anaphylactic reactions
Onset: 0–4 hours; anaphylaxis onset is seconds to 45 minutes.
Presentation: depending on severity, can have urticarial rash, generalized pruritis, erythema, angioedema, hoarseness, stridor, wheezing, hypotension, tachycardia, and even cardiac arrest.
Incidence:
Platelets: 0.3–6%.
RBCs: 0.03–0.61%.
Plasma: 1–3%.
The majority of reactions are mild; anaphylaxis occurs in 1:20 000 components transfused.
Prevention:
Leukoreduction is not beneficial.
Premedication is probably not beneficial, but may reduce symptoms in patients at high risk for reactions (prior history of reaction).
Plasma reduction of platelets may be beneficial.
Slower transfusion rates may help.
IgA deficient products for patients with IgA deficiency and anti‐IgA antibodies.
Treatment of severe reactions:
Discontinue transfusion.
Epinephrine 0.01 mg/kg with maximum of 0.5 mg intramuscularly to the thigh every 5 minutes.
Additional vasopressors as needed.
Intubation and mechanical ventilation if necessary.
Antihistamines.
Glucocorticoids.
H2 antagonists.
Treatment of mild reactions:
Temporarily stop transfusion.
Diphenhydramine or other antihistamine.
If symptoms resolve quickly can restart transfusion, otherwise discontinue.
Acute hemolytic reactions
Onset: 0–24 hours after transfusion.
Presentation: signs and symptoms include fever, chills, rigors, back and flank pain, hypotension, epistaxis, hemoglobinuria, oliguria or anuria, renal failure, DIC.
Incidence:
True incidence is unknown.
In 2008 it was estimated to be 1:38 000 to 1:100 000 transfusions.
Risk of death is 1:1 500 000 transfusions.
Prevention:
Strict adherence to pre‐transfusion patient identification.
Administration of ABO‐compatible blood products.
Treatment:
Discontinue transfusion.
Fluid support with 10–20 mL/kg of isotonic fluids.
Diuretic to maintain urine output between 30 and 100 mL/h or more.
Vasopressor support as needed.
Transfusions of plasma, platelets, and/or cryoprecipitate as needed for bleeding and DIC.
Immediately notify transfusion service:
Clerical check of patient and blood product.
Return blood product for testing.
Sepsis
Onset: 0–6 hours after transfusion.
Presentation: symptomatic to fevers, rigors, hypotension, tachycardia, dyspnea.
Incidence:
RBCs: approximately 1:30 000 units are contaminated with infectious organisms, with septic reactions occurring in approximately 1:250 000 units transfused. Infectious agents typically are gram‐negative bacteria, most commonly Yersinia enterocolitica.
Platelets: approximately 1:1000 units of whole blood‐derived and 1:5000 units of apheresis‐derived platelets are contaminated with infectious organisms, with septic reactions occurring in approximately 1:250 000 whole blood‐derived and about 1:108 000 apheresis‐derived units transfused. Infectious agents typically are gram‐positive bacteria such as staphylococci, streptococci, and gram‐positive bacilli.
Plasma and cryoprecipitate: rare reports of endocarditis and mediastinal wound infections. Infectious agents typically are Burkholderia cepacia and Pseudomonas aeruginosa.
Treatment:
Broad spectrum antibiotics covering suspected organisms, narrowed based on susceptibilities if available.
Supportive care and vasopressors as needed.
Transfusion‐related acute lung injury (TRALI)
Onset: 0–6 hours after transfusion.
Presentation: sudden onset of respiratory distress with hypoxemia, dyspnea, tachypnea, and bilateral lung infiltrates, typically with fever, tachycardia, or hypotension.
Incidence:
Unknown incidence.
Associated with all blood products, but increased risk in plasma‐containing products (plasma and platelets).
Mortality rate of 15–20%.
Prevention: dependent on preparation of blood product.
Treatment:
Immediately stop transfusion.
Report to transfusion service.
Supportive care with intubation, mechanical ventilation, fluids, and vasopressors as needed.
Clinical improvement typically occurs after 48–96 hours.
Estimated up to 1% of transfusions, but likely under‐reported.
Prevention:
Volume‐reduced blood products.
Slow transfusion of blood products.
Treatment:
Stop transfusion.
Diuresis.
Phlebotomy in rare cases.
Potentially moderate acute reactions
Hypotension
Onset: 0–15 minutes after start of transfusion.
Presentation: sudden drop in systolic blood pressure (SBP) by ≥30 mmHg and SBP ≤80 mmHg.
Treatment:
Discontinue transfusion.
Supportive care with IV fluids as needed.
Avoid use of bedside leukoreduction filters.
Metabolic derangements
Onset: typically occurs after transfusion of large volumes of blood products.
Hyperkalemia: treat with dextrose, insulin, calcium, sodium polystyrene.
Hypocalcemia: treat with calcium infusion.
Hypothermia: prevent by using blood warmers prior to infusion; can treat using a heating blanket.
Mild acute reactions
Fever
Onset: typically 0–4 hours after transfusion.
Presentation: fever and/or chills without hemolysis; severe reactions include increase in temperature by >2°C, headache, nausea, and vomiting.
Diagnosis: made by exclusion of other causes of fever.
Incidence:
Platelets: 0.4–2.2% in non‐leukoreduced, 0.1–1.5% with leukoreduced platelets.
RBCs: up to 6.8% with non‐leukoreduced, reduced with leukoreduced RBCs.
Plasma: approximately 0.02%.
Prevention:
Use of leukoreduced blood products.
Removal of plasma from platelet products.
Unclear if premedication with acetaminophen and diphenhydramine is beneficial.
Treatment:
Discontinue transfusion.
Antipyretics (acetaminophen 325–650 mg is preferred agent).
Meperidine 25–50 mg IV for rigors (avoid with renal failure and MAOI therapy).
Transfusion‐associated dyspnea (TAD)
Onset: 0–24 hours after transfusion.
Presentation: respiratory distress that does not meet criteria for TRALI, TACO, or allergic reaction and is not explained by another medical condition.
Treatment:
Discontinue transfusion.
Delayed post‐transfusion complications
Onset within days:
Delayed hemolytic reactions.
Alloimmunization.
Transfusion‐transmitted diseases.
Onset within weeks:
Transfusion‐associated graft‐versus‐host disease.
Post‐transfusion purpura, moderate to severe.
Transfusion‐related immunomodulation.
Onset within years:
Iron overload.
Reading list
Carson JL, et al. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med 2012; 157:49–58.
Retter A, et al.; British Committee for Standards in Haematology. Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. Br J Haematol 2013; 160(4):445–64.
Shaz BH, Hillyer CD, Roshal M, Abrams CS. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects, 2nd edition. Philadelphia: Elsevier Science, 2013.
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