Transfusion

Transfusion of whole blood or fractionated blood components is a widely used method for managing numerous conditions. Packed red blood cells (pRBCs), the most commonly transfused products, are primarily used for the treatment of acute and chronic blood loss. RBC transfusion elevates hemoglobin (Hb) levels and helps maintain organ perfusion and tissue oxygenation. The decision to transfuse RBCs is based on the patient's Hb level, hemodynamic status, and comorbidities (e.g., cardiovascular disease). Fresh frozen plasma (FFP), cryoprecipitate, platelet, and clotting factor transfusions are also available. Pretransfusion testing must be performed, unless in an emergency situation, to minimize the risk of transfusing incompatible RBCs and subsequent transfusion reactions. Testing involves blood typing (ABO and Rhesus) of the recipient's blood, RBC antibody screening of the recipient's serum or plasma, and compatibility testing (crossmatching recipient serum or plasma and donor RBCs).

See also “Transfusion reactions.”

There are more than 250 antigens on the RBC surface, which are classified into several antigen-antibody systems or blood groups. Blood type is most commonly communicated as a combination of ABO blood type and Rhesus blood type (e.g., O- for blood type O Rh-negative blood products and AB+ for blood type AB Rh-positive blood products). ^[1]

ABO blood type system ^[1]

• Consists of 2 antigens (A antigen and B antigen) that can be present in isolation or in combination, or be absent
• Anti-A and/or anti–B antibodies
  • Typically form spontaneously in antigen-negative individuals, i.e., without prior exposure to antigen-positive RBCs
  • Can trigger acute hemolytic transfusion reactions upon an individual's first contact with ABO-incompatible RBCs

Individuals with blood type O can only receive RBCs from other blood type O donors. RBCs from donors of any other type (e.g., A, B, or AB) can cause acute hemolytic transfusion reactions.

Rhesus blood type system ^[1]

• Consists of > 45 Rhesus (Rh) antigens of which Rh(D) antigen is the most immunogenic and clinically significant ^[2]
• In clinical practice, Rh status typically refers to the presence or absence of Rh(D) antigen, despite the existence of other Rh antigens (see “Extended RBC antigens”).
• Anti-Rh antibodies
  • Usually only form in antigen-negative individuals after exposure to antigen-positive RBCs, e.g., transfusion, fetomaternal hemorrhage
  • Can lead to hemolytic disease of the fetus and newborn (HDFN) and/or delayed hemolytic transfusion reactions (DHTR) in sensitized individuals

In Rh-negative women of childbearing age, exposure to Rh-positive RBCs (e.g., by transfusion or fetomaternal hemorrhage) can trigger maternal Rh alloimmunization, which can cause HDFN in subsequent pregnancies. Rh-negative donor blood is therefore preferred in these patients, however, Rh-positive blood is acceptable if an emergency transfusion is required.

FFP transfusions do not need to be Rh-compatible as the risk of transfusion reactions and/or subsequent alloimmunization is low. ^[3]

Extended RBC antigen systems ^[4]

Several other antigen groups can trigger antibody formation in antigen-negative individuals after exposure to antigen-positive RBCs. Only some cause clinically significant hemolytic anemias and/or transfusion reactions.

• Rhesus antigen system: Most non-D Rh antigens, e.g., Rh(C) and Rh(E), are less frequent and typically considered among the spectrum of extended RBC antigens. ^[2]
• Kell antigen system
  • A group of RBC antigens, which includes K (K1), k (K2), Kp(a), Kp(b), Js(a), and Js(b) antigens
  • A homozygote for the Ko allele expresses no Kell antigens
  • Responsible for up to 10% of severe HDFN cases
• Duffy antigen system ^[5]
  • A group of six glycoprotein receptors found on RBCs that are encoded on chromosome 1
  • Plasmodium vivax binds to Duffy antigens to invade RBCs and cause malaria.
  • Antibodies against Duffy antigen can also cause transfusion reactions and hemolytic disease of the newborn.
• Kidd antigen system ^[6]
  • A rare group of three RBC antigens: Jka (JK1), Jkb (JK2), and JK3
  • Also expressed in the epithelium of descending vasa recta, where they play an important role as urea transporters
• MNS antigen system ^[7]
  • A group of more than 40 RBC antigens, including M, N, S, s, and U antigens
  • MNS antigens are carried on glycophorin A and B and are fully developed at birth.
  • Less likely to be clinically significant than other antigen-antibody systems ^[1]

Blood bank measures

• Blood products for transfusion can be allogeneic (i.e., from a donor) or autologous.
• Systemic measures are taken by blood banks and blood donation services prior to release for transfusion to reduce risks associated with individual donor units.
  • Allogeneic donor blood is tested to determine blood type, screened for common infectious diseases, and then leukoreduced.
  • Some blood donations undergo additional processing to further reduce the risk of complications in high-risk groups.
  • Blood for autologous transfusion typically undergoes minimal processing intraoperatively prior to retransfusion. ^[8]
• All prospective blood donors in the United States undergo screening via a donor history questionnaire (DHQ), e.g., to identify infectious risk (see “Blood donation infection screening”) and high-risk medications (e.g., antiplatelet agents) and/or noninfectious conditions (e.g., cancer). ^[9][10][11]

Infection control

• Leukoreduction: filtration of leukocytes out of cellular blood products ^[12]
  • Reduces the risk of nonhemolytic febrile transfusion reactions; , HLA alloimmunization, and transmission of CMV, HTLV-1/2, and EBV via leukocytes
  • Prolongs the lifespan of pRBC in storage
• Blood donation infection screening
  • DHQ screening may exclude donors for a variable or indefinite period if they meet specific criteria, e.g., certain behavioral risk factors for bloodborne infections, history or active features of transmissible illnesses, and/or time spent in endemic areas for specific pathogens, e.g., vCJD, malaria. ^[13][14][15]
  • Laboratory screening: performed on all units received for blood donation
    • Routine screening in the United States ^[16]
      • HIV, hepatitis B, hepatitis C, and HTLV
      • West Nile virus
      • Zika virus
      • Syphilis (Treponema pallidum)
      • Chagas disease (Trypanosoma cruzi) ^[17]
    • Additional screening in endemic regions
      • Babesiosis (Babesia spp.)
      • Hepatitis A and hepatitis E
      • Malaria

Additional processing

Blood products for patients with certain preexisting conditions may require further processing to reduce the risk of complications.

• Irradiation ^[18]
  • Radiation exposure inactivates lymphocytes to reduce the risk of transfusion-associated graft-versus-host disease (ta-GvHD)
  • Indicated in patients at risk of ta-GvHD.
• Washing ^[19]
  • Replaces plasma in cellular blood products with an alternative solution to reduce the risk of an allergic reaction
  • Indicated in patients with a history of IgA deficiency or severe allergic reaction to blood products
• Volume reduction ^[20]
  • Decreases the amount of plasma and storage solution in cellular blood products to prevent volume overload during transfusion
  • Indicated in patients at risk of transfusion-associated circulatory overload (TACO)

Pretransfusion safety practices ^[17][21]

• Consider transfusion therapy when benefits outweigh the risks and alternatives to blood transfusion have been excluded.
• Choose condition-specific transfusion thresholds and indications tailored to individual patient needs, for example:
  • Preexisting conditions (e.g., heart disease, hematological malignancy)
  • Specific clinical circumstances (e.g., trauma, critical illness)
  • Functional status and desired level of care
• Whenever possible:
  • Obtain informed consent.
  • Complete pretransfusion testing.
  • Follow compatibility requirements for each blood product issued.
• Ensure that the right blood product is being transfused to the right patient at the right time.
• Do not delay life-saving transfusions.
• Only defer life-saving blood transfusions if a clear and valid advance directive prohibits their use or an individual with decision-making capacity declines transfusion after an informed discussion.

Emergency-issued blood products (e.g., uncrossmatched RBCs) can be given under implied consent and without pretransfusion testing in life-threatening situations.

Patients who do not wish to accept blood transfusions (e.g., Jehovah's witnesses) are advised to carry an advance directive card. However, in life-threatening situations, if the patient cannot be consulted and clear advance directives are not available, blood products should be given.

Pretransfusion checklist

Ensure the following whenever possible:

• Check patient records to identify any special transfusion requirements.
• Discuss transfusion risks, benefits, and alternatives to blood transfusion in detail with patients or surrogate decision-makers.
• Document informed consent.
• Order pretransfusion testing as indicated by transfusion product: e.g., type and screen, crossmatching.
• Transfuse blood products within normal working hours for all nonurgent transfusions. ^[22]
• Use fully crossmatched blood products as soon as they are available.

Requests and prescriptions

Ensure the following are appropriately labeled, documented, and communicated:

• Two independent patient identifiers (e.g., full name and unique medical record number)
• Reasons for transfusion
• Type and number of units of the blood product to be transfused
• Rate or duration of transfusion
• Special requirements (e.g., washed or irritated products)
• Name and contact details of the requesting clinician

Safety check prior to administration ^[17]

• Confirm the patient's identity.
• Check if the correct blood products have been issued.
• Ensure blood product containers are undamaged and contents appear normal.

Compare patient and blood product identifiers immediately prior to transfusion. Do not transfuse if there is any discrepancy!

Transfusion administration ^[17]

See “Fractionated blood components” for component-specific administration instructions.

• Equipment
  • Give blood component transfusions through a standard blood infusion set.
  • Use blood-warming devices in patients with cold agglutinins or those requiring multiple transfusions.
• Rate of administration
  • When possible, transfuse at a slower rate for the first 15 minutes.
  • Complete all transfusions within 4 hours of removing the blood product from temperature-controlled storage. ^[23]
• Cautions
  • Do not administer any other medication or solution (except normal saline) through the same tubing.
  • Do not routinely use antipyretics, antihistamines, or steroids to prevent transfusion reactions. ^[24]

Diuretics are often used in clinical practice to help maintain a normal volume status in patients requiring multiple transfusions but have not been shown to reduce the risk of transfusion-associated circulatory overload. ^[24]

Monitoring ^[17][22]

• Check clinical status and vital signs for every unit transfused:
  • Before initiation
  • 15 minutes after starting the transfusion
  • Within 60 minutes of completion
  • If any symptoms or signs of a possible transfusion reaction (e.g., dyspnea, chills, pruritus) develop
• Monitor for signs of fluid overload, especially in patients requiring multiple transfusions.
• Observe inpatients for 24 hours after transfusion.

Follow the initial management of acute transfusion reactions for any patient who has a change in vital signs or becomes acutely unwell during or in the hours following a transfusion.

• Goal: Ensure compatibility between recipient and donor blood products and avoid hemolytic transfusion reactions.
• Methods: A variety of test strategies that mostly rely on hemagglutination (i.e., clumping of erythrocytes) induced by antibodies binding to RBC antigens (see “Overview of pretransfusion testing” for more specific methods.)
• Standard testing requirements: vary by blood product and institutional policy
  • RBC: Blood typing, RBC antibody screen, and crossmatching are typically required.
  • FFP: Blood typing is typically required.
  • Platelet and/or cryoprecipitate: Blood typing may be required.
• Turnaround times ^[1][25][26]
  • Blood typing alone: up to 25 minutes
  • Type and screen: up to 75 minutes
  • Type and screen and crossmatch: up to 120 minutes
• Routine testing: Order advance pretransfusion testing based on anticipated transfusion requirements. ^[1][25][26]
  • High probability during admission: Consider type and screen on arrival.
  • High probability within the next few hours (e.g., need for major surgery): Consider immediate type and screen PLUS crossmatch.
• Extended RBC phenotype matching: matches donor units to the recipient based on their extended RBC antigens profile ^[22][27]
  • Involves detailed serological and genetic profiling of extended RBC antigens to select compatible donor units followed by serologic crossmatching (turnaround time can be several days)
  • Performed early in patients with anticipated long-term or recurrent transfusion needs (e.g., due to sickle cell disease, thalassemia) to prevent alloimmunization and transfusion reactions.

Transfuse blood products with complete pretransfusion testing whenever possible. If life-saving transfusion is required before pretransfusion testing is complete, use emergency-issued blood products until fully tested blood products are available.

Recommendations in this article are consistent with the American Association of Blood Banks (AABB) guidelines for transfusing red blood cells (2016), platelets (2015), and plasma (2010). ^[29][30][31]

Whole blood ^[32]

• Content: all blood components
• Indications
  • Planned surgery (autologous blood)
  • Management of traumatic massive hemorrhage, as an alternative to fixed transfusion ratios

Whole blood is rarely used, as most patients require just one blood component, e.g., pRBCs to treat anemia.

Fractionated blood components

Fractionated blood components are prepared by separating whole blood into its constituent elements and storing each under ideal conditions.

• Packed red blood cells
• Platelet transfusion
• Fresh frozen plasma (FFP)
• Cryoprecipitate
• Plasma derivatives

Recommendations in this section are consistent with the 2015 AABB guideline for red cell transfusion. ^{[17][24][30][33]}

Content

• RBCs
• A preservative, typically citrate-based ^[34]
• Unit volume: ∼200–350 mL ^[22]

Compatibility requirements

See “ABO blood type system” and “Rhesus blood type system.”

• Must be ABO compatible
• Give Rh(D)-negative recipients Rh(D)-negative pRBCs if possible.
• See also “Type and screen” and “Crossmatching.”

Common indications for pRBC transfusion

The decision to transfuse should be made on a case-by-case basis. ^[17][24][30]

• Hemorrhagic shock or ongoing rapid blood loss
• Exchange transfusion: e.g., in severe sickle cell disease or methemoglobinemia
• Severe anemia (even if asymptomatic)
  • Hb ≤ 7 g/dL even if no additional factors are present
  • Hb ≤ 8 g/dL with preexisiting cardiovascular disease; or if the patient is due to undergo cardiac or orthopedic surgery
• Moderate anemia, in any of the following situations:
  • Symptoms of anemia ^[26]
  • Increased risk of complications, e.g., acute onset , significant comorbidities, older age
  • Signs of hypoxia
  • Planned surgery

Indications for RBC transfusion are not determined solely by Hb value, but rather by an assessment of the clinical circumstances and the patient's overall condition.

Restrictive transfusion thresholds (i.e., Hb 7–8 g/dL) in hemodynamically stable patients are associated with similar clinical outcomes and less blood use and adverse effects compared to liberal thresholds (9–10 g/dL) ^[30]

Administration

• Dose ^[24]
  • Give the minimum number of units required to relieve symptoms and/or restore Hb to above transfusion thresholds.
  • In the absence of active bleeding, reassess the patient clinically after each unit and check their CBC.
• Usual rate: 90–120 minutes per unit ^[33]

Effect

• ↑ Hb and oxygen-carrying capacity of the blood
• 1 unit of pRBCs increases Hb value by ∼ 1 g/dL.
• Intravascular volume expansion roughly equivalent to unit volume

Complications

• Repeated transfusions can lead to iron overload.
• See also “Transfusion reactions.”

Recommendations in this section are consistent with the 2015 AABB guideline for platelet transfusion. ^{[17][24][29][33]}

Content ^[22][35]

• Platelets suspended in plasma or platelet additive solution ^[35]
• Typically provided as either of the following: ^[35]
  • Single donor apheresis platelets (SDAP) unit: derived from 1 unit of whole blood from a single donor and contains ∼ 310 X 10⁹ platelets in ∼300 mL
  • Random donor pooled platelets (RDP) pack: derived from 4–6 units of whole blood from various donors and contains ∼ 280 X 10⁹ platelets in ∼200 mL

Compatibility requirements ^[17][35]

Compatible donor platelets may not be available due to limited supply. The risks of incompatible platelet transfusion are lower than those of incompatible pRBCs. ^[36]

• ABO compatibility: preferred but not required for routine transfusions ^[1][36]
• Rh(D) matching: Rh(D)-negative platelets are preferred in Rh(D)-negative recipients to prevent alloimmunization. ^[22]
• Consider donor plasma compatibility when transfusing multiple units. ^[37]

Indications for platelet transfusion ^[24][29][35]

• Treatment of active bleeding in patients with any of the following:
  • Platelets < 50,000/mm³
  • Platelets < 100,000/mm³ and brain injury or multiple trauma ^[38]
  • Qualitative platelet disorders (e.g., Bernard-Soulier syndrome) ^[24]
  • Massive hemorrhage as part of balanced resuscitation
• Prevention of bleeding in any of the following situations:
  • Severe thrombocytopenia (platelets < 10,000/mm³ ) secondary to active treatment-induced myelosuppression ^[29][39]
  • Patients with thrombocytopenia who are due to undergo invasive procedures ; ^[29][35][39]
    • Elective central venous catheter placement or bone marrow aspirate in patients with platelets < 20,000/mm³
    • Neurosurgery in patients with platelets < 100,000/mm³
    • Other invasive procedures in patients with platelets < 50,000/mm³
  • Childbirth, if maternal platelets are < 50,000/mm³

Cautions ^[24][35]

Platelet transfusion is usually not recommended to treat idiopathic or autoimmune thrombocytopenia in nonbleeding patients, e.g.:

• Thrombocytopenia due to chronic bone marrow failure not associated with myelosuppressive therapy (e.g., chemotherapy, radiation) ^[35][40]
• HIT
• TTP/HUS
• ITP
• Vaccine-induced immune thrombotic thrombocytopenia (VITT) ^[41]

Platelet transfusion in patients with HIT or TTP is associated with higher rates of arterial thrombosis and mortality compared to no transfusion. ^[42]

Administration

• Dose
  • Transfuse 1 unit of apheresis platelets or 1 pack of pooled platelets to prevent bleeding due to severe thrombocytopenia (platelets < 10,000/mm³ ). ^[29]
  • In massive hemorrhage, follow the ratio recommended in the massive transfusion protocol.
  • For other indications, use the minimum dose required to restore platelets to the recommended transfusion thresholds.
• Usual rate: 30–60 minutes per apheresis platelets unit/pooled platelets pack ^[22][33]

Effect

• 1 unit of apheresis platelets or 1 pack of pooled platelets increases the platelet count by 20–60,000/mm³. ^[17]
• Intravascular volume expansion roughly equivalent to unit/pack volume

Complications ^[24]

• Multiple platelet transfusions may lead to platelet transfusion refractoriness. ^[35]
• See also “Transfusion reactions.”

Do not use platelet transfusions to treat severe thrombocytopenia due to ITP, TTP, HUS, or HIT unless there is major bleeding.

Fresh frozen plasma ^{[17][24][31][33]}

Recommendations in this section are consistent with the 2010 AABB guideline for plasma transfusion. ^[31]

• Content
  • Plasma, including all coagulation factors and plasma proteins
  • All cellular components are removed from the transfusion product.
  • Unit volume: ∼200–300 mL ^[17][22]
• Compatibility requirements: See “ABO blood type system.”
  • ABO compatibility must be considered. ^[1]
  • Rh(D) matching: not required ^[22]
• Indications ^[17][24]
  • Management of coagulopathy in patients with multiple clotting factor deficiencies (e.g., due to liver cirrhosis, DIC)
    • Usually considered for patients with INR ≥ 2.0 who have active bleeding or require invasive procedures.
    • Not recommended for correction of mild INR elevations (i.e., INR = 1.1–1.9) ^[43]
  • Prevention of dilutional coagulopathy in massive transfusion
  • Plasma exchange transfusion, e.g., in TTP ^[44]
  • Management of some coagulation factor deficiencies if no specific concentrate for treatment exists
  • Alternative therapy for:
    • Management of plasma protein deficiencies if recombinant products are unavailable
    • Immediate reversal of warfarin in patients with life-threatening bleeding or intracranial hemorrhage if 4-factor PCC is unavailable ^[24]
• Administration
  • Dose: 10–20 mL/kg ^[43]
  • Usual rate: 10–20 mL/kg/hour ^[33]
• Effect
  • Correction of both isolated and multiple coagulation factor deficiencies
  • Intravascular volume expansion roughly equivalent to unit volume
• Complications: See “Transfusion reactions.”

4-factor PCC is preferred over FFP for the immediate reversal of vitamin K antagonists. ^[24]

Cryoprecipitate ^[17][24]

• Content: clotting factors (fibrinogen, factor VIII, factor XIII), vWF, and fibronectin
• Compatibility requirements
  • ABO compatibility: preferred but not required ^[17]
  • Rh(D) matching: not required ^[22]
• Indications
  • Bleeding associated with fibrinogen deficiency (e.g., due to DIC, liver disease): typically performed if serum fibrinogen is < 100–150 mg/dL ^[24]
  • Alternative therapy for deficiencies in clotting factors; , including vWF, factor VIII, and factor XIII
  • Treatment of uremic bleeding syndrome
• Administration
  • Dose: typically 1 unit per 7–10 kg of the patient's body weight ^[17]
  • Usual rate: 10–20 mL/kg/hour ^[33]
• Effect: 1 unit of cryoprecipitate per 7–10 kg of the patient's body weight increases serum fibrinogen by ∼ 50–75 mg/dL. ^[17]
• Complications
  • Rarely, transfusion of large volumes of ABO-incompatible cryoprecipitate may lead to a mild hemolytic transfusion reaction.
  • See also “Transfusion reactions.”

Cryoprecipitate is primarily used to treat bleeding associated with fibrinogen deficiency.

Only consider cryoprecipitate in the management of vWD, hemophilia A, or factor XIII deficiency if single-factor concentrates and recombinant synthetic factors are unavailable. ^[17]

Clotting factors

Prothrombin complex concentrate (PCC) ^[45]

• Composition
  • Vitamin K-dependent clotting factors: factors II, VII, IX, and X ^[45]
  • Anticoagulants: protein C, protein S, antithrombin, and/or heparin
• Indications
  • Vitamin K antagonist-associated major bleeding: 4-factor PCC is given with IV vitamin K (see “Warfarin reversal” for further information). ^[46]
  • Treatment and prevention of bleeding in patients with rare clotting factor deficiencies if specific factor preparations are not available ^[47][48]
  • Consider for the reversal of DOACs in life-threatening bleeding. ^[49][50]
• Adverse effects
  • Thrombotic complications (e.g., VTE, myocardial infarction)
  • HIT
  • Hypersensitivity reactions (e.g., anaphylaxis)

Do not use PCC or FFP to reverse vitamin K antagonists unless there is an emergency indication (e.g., life-threatening bleeding, emergency surgery). ^[24]

Single-factor concentrates ^[22]

• Composition: specific clotting factors that have been pooled from multiple donors
• Indications: specific clotting factor deficiencies (e.g., factor VIII and factor IX are used for the treatment of hemophilia A and hemophilia B) if recombinant factors are not available

When possible, use recombinant synthetic factors over blood-derived clotting factors, as they are not associated with any risk of infection transmission. ^[22]

Antithrombin III

• Composition: : human antithrombin III; , which is synthesized in the liver and inhibits coagulation factors IXa, Xa, XIa, and XIIa, and thrombin
• Indications
  • Patients with hereditary antithrombin III deficiency to optimize thrombosis prophylaxis with heparin
  • Patients on cardiopulmonary bypass who are experiencing heparin resistance ^[51]
  • DIC, in select cases ^[52]
• Effect: increases the effects of heparin

Albumin

• Composition: human albumin, which is produced exclusively in the liver
• Indications: after paracentesis or in the setting of therapeutic plasmapheresis
• Effect
  • Maintains colloid osmotic pressure
  • Increases intravascular volume
  • Functions as transport protein for various substances (e.g., drugs, hormones, enzymes)

General principles ^[1]

• Emergency-release blood components can be issued from the blood bank in < 5 minutes but are associated with an increased risk of hemolytic transfusion reactions. ^[1][53]
• Unknown recipient blood type: Give universal donor blood products (blood products that could potentially be safely transfused to any recipient regardless of their ABO blood type, including blood type O negative packed RBCs, blood type AB plasma, and blood type AB platelets)
• Known recipient ABO type and Rhesus status: Give type-specific blood products.

Pretransfusion testing takes up to 120 minutes; emergency transfusion can occur prior to pretransfusion testing using uncrossmatched products. ^[1]

Blood product selection ^[1][26][35]

• Unknown recipient blood type
  • pRBCs: Uncrossmatched blood type O; (universal RBC donor) pRBCs (Rhesus D negative if possible)
  • FFP: Blood type AB (universal plasma donor) FFP
  • Platelets: Ideally use blood type AB platelets (preferably Rh(D)-negative) but platelets of any blood type may be used.
• Known recipient blood type
  • pRBCs: Uncrossmatched ABO and RhD-compatible pRBCs
  • FFP: ABO-compatible FFP
  • Platelets
    • ABO-compatible platelets are preferred but platelets of any blood type may be used.
    • Rh(D)-negative platelets are preferred for Rh(D)-negative recipients. ^[22][35]

Definition

• The replacement of a large volume of blood in response to massive hemorrhage
• There is no universal threshold for a massive transfusion; proposed values include: ^[54][55]
  • Complete replacement of a patient's blood volume (∼ 10 units of RBCs) within 24 hours
  • Replacement of ≥ 50% of a patient's blood volume (∼ 5 units of RBCs) within 3 hours
  • Blood loss replacement at a rate of > 150 mL/minute
  • Transfusion of ≥ 3 units of pRBCs within 1 hour

Risks ^[56]

Giving patients large volumes of blood products, especially if unbalanced or given rapidly, risks the following massive transfusion-associated complications:

• Acidosis
• Hypothermia
• Coagulopathy ^[57]
• Electrolyte imbalances
• Citrate toxicity
• Transfusion-related lung injury
• Transfusion-associated circulatory overload

Judicious use of blood products to avoid overtransfusion is the best way to prevent massive transfusion-associated complications!

Massive transfusion protocols (MTP) ^[58]

• Goal: mitigate the risks of massive transfusion ^[59][60]
• Clinical application: activated for patients with large volume transfusion requirements, e.g., due to trauma, major surgery, obstetric complications, GI bleeding
• Protocol components
  • Multidisciplinary instructions to expedite transfusion
  • A series of laboratory studies to perform on the patient's blood
  • A set ratio of blood products to be given
  • May include antifibrinolytics, e.g., tranexamic acid, in patients with ongoing bleeding
• Initial approaches: Consider a fixed ratio approach or whole blood approach for patients with ongoing hemorrhage prior to laboratory results.
• Subsequent approach: Consider targeted transfusion regimen once laboratory results become available and/or hemostatic control is achieved.

The optimal approach to blood component transfusion for massive hemorrhage remains unknown. Follow local hospital protocol under specialist guidance.

Fixed ratio approach ^[22][59]

• Transfusion of RBCs, FFP, and platelets at predefined ratios
• Intended for prophylaxis and empiric treatment of coagulopathy
• Ratios vary by local protocols. Examples include:
  • RBC, FFP, and platelet units in a 1:1:1 ratio
  • RBC, FFP, and platelet units in a 6:4:1 ratio

Whole blood approach ^[32]

• Initial transfusion of whole blood (limited availability).
• Used as an alternative to the fixed ratio approach in the treatment of massive traumatic hemorrhage
• Type O blood with low anti-A and anti-B antibody titers is used in emergency transfusions to minimize the risk of hemolytic transfusion reactions.

Targeted transfusion regimen ^[59][61]

• Requires frequent laboratory monitoring (e.g., every 1–2 hours)
• Thresholds and dosing vary by local protocols
• Consult transfusion services if available.

Massive transfusion protocol checklist ^[59]

• Activate the MTP, following local hospital guidance.
• Start monitoring, including continuous telemetry.
• Place 2 large-bore peripheral IV catheters.
• Obtain routine baseline massive transfusion studies, including CBC, PT, aPTT, serum fibrinogen, ionized calcium, BMP, and blood gases.
• Consider using point-of-care thromboelastography if available.
• Start transfusing blood through blood-warming equipment.
• Regularly reassess the patient to assess for signs of fluid overload and/or respiratory distress.
• Repeat massive transfusion studies, including arterial blood gases, at regular intervals.

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