INTRODUCTION — The appropriate use of blood products requires consideration of the benefits and risks. This topic provides a practical, accessible guide to transfusions in critically ill patients in the intensive care unit (ICU).
More detailed discussions and additional supporting evidence for appropriate use of blood products are presented separately:
●Red blood cells (RBCs) – (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult" and "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion".)
●Platelets – (See "Platelet transfusion: Indications, ordering, and associated risks".)
●Plasma and cryoprecipitate – (See "Clinical use of plasma components" and "Clinical use of Cryoprecipitate".)
●Massive transfusion – (See "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)
INSTITUTIONAL POLICY FOR TRANSFUSIONS — Hospitals have institutional policies and general guidelines for the care of individuals who may need transfusion support. Most institutions also have patient blood management programs.
Goals of these programs include:
●Optimizing hematopoiesis
●Minimizing blood loss
●Improving tolerance of anemia
●Minimizing unnecessary transfusion
●Reducing risks of transfusion-related events
●Optimizing the stewardship of the blood supply
The benefits of the patient blood management program include minimizing unnecessary transfusion, reducing risks of transfusion-related adverse events, and optimizing the blood supply for all patients.
The transfusion service determines policies and reviews transfusion orders to ensure that blood products are appropriately distributed. These are intended as recommendations to improve outcomes and should not supersede clinical judgement regarding the best approach for an individual patient. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Hospital-wide oversight programs/patient blood management' and "Perioperative blood management: Strategies to minimize transfusions", section on 'Goals of patient blood management'.)
Use of these principles is especially important in the intensive care unit (ICU), where a large proportion of patients receive transfusions [1-4].
RED BLOOD CELLS
RBC indications — Indications for red blood cell (RBC) transfusions in patients in the intensive care unit (ICU) include the following:
●Acute bleeding – Acute hemorrhage is an indication for RBC transfusion when either of the following are present:
•Massive blood loss and expected hemoglobin <7 g/dL
•Blood loss causing hemodynamic instability (hemorrhagic shock) (see "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Resuscitation and transfusion')
●Non-bleeding – In anemic patients who are not bleeding, transfusion is used for the following:
•Severe anemia with a hemoglobin <7 g/dL, but the threshold can vary depending on the clinical history (table 1) (see 'Restrictive strategy as the preferred approach' below)
•Anemia contributing to ongoing hemodynamic instability (eg, ischemia, poor tissue perfusion hypotension)
Restrictive strategy as the preferred approach — For patients in the ICU, we use a restrictive strategy (transfusing less blood; transfusing at a lower hemoglobin threshold) rather than a liberal strategy, consistent with the Association for the Advancement of Blood & Biotherapies (AABB) guidelines [5]. This includes individuals with sepsis, gastrointestinal bleeding, cardiac and noncardiac surgery. This practice is based on evidence from randomized trials in various populations demonstrating equivalent or superior outcomes with restrictive transfusions. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Summary of supporting evidence'.)
In most cases, a restrictive transfusion strategy involves transfusing for a hemoglobin of <7 g/dL rather than a higher threshold. However, the restrictive threshold of <8 g/dL is used for patients undergoing cardiac surgery and orthopedic surgery or those with pre-existing cardiovascular disease. For individuals with acute coronary syndromes, including acute myocardial infarction, the data do not clearly support a specific threshold, and the approach is individualized. The transfusion threshold used for a specific patient should generally match the value used in clinical trials that most closely match the patient’s condition, as summarized in the table (table 1 and algorithm 1). As an example, the Transfusion Requirements in Critical Care (TRICC) trial randomly assigned 838 critically ill adults to a restrictive transfusion strategy (transfusion for hemoglobin <7 g/dL) or a liberal strategy (transfusion for hemoglobin <10 g/dL) and found decreased hospital mortality in the restrictive arm [6]. Additional supporting evidence and meta-analyses are presented separately. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult", section on 'Thresholds for specific patient populations'.)
Ordering RBCs
Typing and crossmatching
Pretransfusion testing requires a patient blood sample taken within the previous three days to allow red blood cell (RBC) typing, antibody screening, and crossmatching. (See "Pretransfusion testing for red blood cell transfusion".)
Antibodies against ABO antigens develop in all individuals (A individuals develop anti-B, B individuals develop anti-A, and O individuals develop anti-A and anti-B). Type O, RhD-negative RBCs are considered the universal donor since they lack A, B, and RhD antigens on their surface.
In contrast to antibodies to the ABO blood group that are formed regardless to prior transfusions, other alloantibodies may develop following exposure to allogeneic blood (from transfusion, pregnancy, or sharing needles). These antibodies are detected as part of route antibody screening and the transfusion medicine service will determine the extent of testing needed to provide compatible blood. The turnaround time depends on whether the individual has a common or rare blood type and whether alloantibodies are present.
If there is life-threatening anemia and insufficient time to perform this testing, emergency release blood can be used. Emergency release RBCs are type O, RhD-negative (the universal donor), making the likelihood of a serious hemolytic transfusion reaction exceedingly low. Many institutions provide group O, RhD-positive RBC units for females who are beyond childbearing age and males. Using emergency release blood is always preferable to not transfusing in life-threatening anemia. In these situations, direct communication with the transfusion medicine service is essential, to confirm the need for emergency release blood and determine the likely number of units needed. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)
Whole blood versus RBCs — Red blood cell (RBC) transfusion is almost always performed using packed RBCs. Alternatives include whole blood or salvaged autologous blood. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Sources of RBC units' and "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Whole blood' and "Surgical blood conservation: Blood salvage".)
●RBCs – Each unit of RBCs has a total volume of 300 mL, of which RBCs constitute approximately 200 mL.
●Whole blood – Interest in using whole blood has been increasing, especially in trauma patients or massive transfusion settings, including cardiovascular surgery [7]. The rationale for use is that it provides RBCs, plasma, and platelets in an appropriate ratio in a single transfusion. Whole blood is not universally available. Local guidelines should be followed. (See "Massive blood transfusion", section on 'Trauma'.)
●Blood salvage – Blood salvage, also called cell salvage or autotransfusion, uses a device to collect, process, and return autologous blood to the bleeding patient. It can be used in a variety of surgical procedures when appropriate expertise is available. It may be lifesaving in certain cases of rare blood type or when crossmatch-compatible blood is not available. Specific indications, contraindications, and supporting evidence are presented separately. (See "Surgical blood conservation: Blood salvage".)
Number of RBC units — In most cases, one unit of red blood cells (RBCs) or whole blood is expected to raise the hemoglobin by approximately 1 g/dL and the hematocrit by approximately 3 percent.
General practice is to transfuse one unit of RBCs at a time and check a post-transfusion hemoglobin 15 minutes to 1 hour following transfusion to determine if additional units are needed. This avoids unnecessary transfusions, reduces the risk of transfusion complications, and preserves the blood supply for other patients. However, we occasionally transfuse more than one unit (eg, two to three units) sequentially before checking the hemoglobin when the initial hemoglobin and/or degree of continued bleeding warrant this approach.
In massive bleeding or massive hemolysis when it is not possible to obtain a post-transfusion hemoglobin rapidly enough to keep up with blood loss, bleeding is monitored clinically and RBC units are transfused based on the estimated blood loss, with periodic hemoglobin measurement to assist in monitoring.
Modifications — Certain patients may benefit from (or require) specialized modifications, such as the following:
●Leukoreduction – Leukoreduction (filtering out white blood cells [WBCs] using an in-line filter) is performed at the time of blood collection in virtually all blood collection facilities in the United States; this is referred to as pre-storage leukoreduction. The main advantages of leukoreduction include reducing febrile nonhemolytic transfusion reactions (FNHTRs; especially important in critically ill individuals) and decreasing the risk of cytomegalovirus (CMV) infection. There are no adverse complications. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Pre-storage leukoreduction' and "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)
●Irradiation – Irradiation is the principle means of preventing transfusion-associated graft-versus-host disease (ta-GVHD), a fatal complication that occurs when donor WBCs attack the recipient's bone marrow and other tissues as foreign. At-risk recipients include those who are partially HLA-matched with the donor (related family members, individuals from genetically homogenous populations) and those with immunocompromised states. The table summarizes indications for irradiation (table 2). The process slightly reduces the shelf-life of the unit. (See "Transfusion-associated graft-versus-host disease".)
●CMV-negative – Individuals who are CMV-negative and at risk for CMV infection (eg, solid organ or hematopoietic stem cell transplant recipients, pregnant individuals who are CMV-negative) can be transfused with either leukoreduced or CMV-negative units. As an alternative, some transfusion services substitute blood that has been treated with a pathogen inactivation method, provided that local guidelines permit this approach. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'CMV-seronegative red cells' and "Pathogen inactivation of blood products", section on 'RBCs and whole blood'.)
Other less-commonly used modifications including washing, volume reducing, and using frozen RBCs. Details are provided separately. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Specialized modifications and products'.)
There is no need to request "fresh" RBCs (RBCs stored for a shorter duration) or directed donations, as neither of these approaches improves outcomes [5]. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'RBC age/storage duration effect on clinical outcomes' and "Blood donor screening: Overview of recipient and donor protections", section on 'Directed donations'.)
Non-transfusion approaches to improve perfusion — The following may improve tissue perfusion and oxygenation in addition to (or as an alternative to) RBC transfusions:
●Hemodynamic support, attention to body temperature and pH, and oxygen therapy. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock".)
●Correction of iron deficiency, vitamin B12 deficiency, or folate deficiency. (See "Treatment of iron deficiency anemia in adults" and "Treatment of vitamin B12 and folate deficiencies".)
●Alternatives to RBC transfusion that have been used in patients who decline transfusion are discussed separately. (See "Oxygen carriers as alternatives to red blood cell transfusion" and "The approach to the patient who declines blood transfusion", section on 'Supplemental and hyperbaric oxygen' and "Hyperbaric oxygen therapy".)
Not routinely used (eg, erythropoietin) — By contrast, routine use of iron or erythropoietin is not indicated for treatment of anemia in critically ill patients, as summarized in a 2013 guideline from the British Committee for Standards in Haematology [8]. These approaches carry risks, act slowly, and are not supported by high quality evidence showing that benefits outweigh the risks. Several randomized trials from the late 1990s and early 2000s evaluating erythropoietin in critically ill and trauma patients have shown mixed results in affecting the need for transfusion and possible survival benefit in trauma [9-12]. Further study is needed before this approach would be routinely adopted.
PLASMA — Plasma is the liquid portion of blood that contains clotting factors.
Plasma indications — There is a general consensus that plasma is often mis-used. (See 'Misuse of plasma' below.)
We limit plasma transfusion to situations in which there is a strong clinical rationale and demonstrated efficacy. Appropriate indications for plasma products in critically ill patients include the following:
●Massive transfusion – Plasma is included in massive transfusion protocols, to replace plasma proteins lost by bleeding that are not present in RBCs or platelet products. The ratio of 1:1:1 (one unit plasma and one unit of platelets for each unit of RBCs) is typically used in trauma. In this ratio, one unit of platelets refers to the platelets obtained from one unit of whole blood; platelets collected by apheresis are equivalent to six units, and the ratio of RBCs to plasma to platelets would be 6:6:1. In massively transfused patients, protocols with predefined ratios of blood products improves organ function and survival [13-15]. (See "Massive blood transfusion", section on 'Trauma'.)
●Severe liver disease or DIC with bleeding/invasive procedures – Severe liver disease and DIC may cause bleeding or thrombosis. Bleeding may be associated with multiple factor deficiencies that can be treated with plasma. Treatment of the underlying cause is critical to address the cause of factor deficiencies. If raising portal pressures due to increased intravascular volume is a concern with the administration of plasma, some experts use cryoprecipitate as a source of fibrinogen. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding' and "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Prevention/treatment of bleeding'.)
●Plasma exchange – In most uses of therapeutic plasma exchange, the patient's plasma is removed and an albumin solution is infused as replacement fluid. Use of plasma as a replacement fluid is restricted to patients at high risk of bleeding, such as those undergoing an invasive procedure, and individuals with certain disorders such as immune thrombotic thrombocytopenic purpura (TTP), where it is advisable to provide a missing plasma component. Plasma exchange using plasma as a replacement fluid is used in immune TTP to remove the autoantibody to ADAMTS13 and correct ADAMTS13 deficiency. Plasma infusion is used to replace the deficient ADAMTS13 in hereditary TTP. (See "Immune TTP: Initial treatment" and "Hereditary thrombotic thrombocytopenic purpura (TTP)".)
●Warfarin anticoagulation (or vitamin K deficiency) with bleeding/invasive procedures, PCC not available – All institutions that care for patients with possible anticoagulant-associated bleeding should stock a 4-factor prothrombin complex concentrate (PCC) to treat bleeding. If a PCC is not available, plasma may be an alternative, although large volumes are likely to be required. Vitamin K should also be administered, as clotting factors from plasma have a short half-life. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding' and "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of supratherapeutic INR without bleeding'.)
●Factor deficiency with bleeding or invasive procedure, specific factor concentrate not available – Certain rare clotting factor disorders may be treated with plasma when a specific factor concentrate is not available. (See "Rare inherited coagulation disorders", section on 'Management of specific deficiencies'.)
Misuse of plasma — Despite widespread use in the past, plasma is generally not appropriate in the following scenarios:
●Suspected clotting factor deficiency – When bleeding is associated with a specific clotting factor deficiency (hemophilia, von Willebrand disease, other deficiencies) and a factor concentrate is available, the concentrate is preferred because it delivers the needed factor in a smaller volume and carries lower risks of transfusion reactions, infections, and other complications. For fibrinogen, sources include cryoprecipitate and fibrinogen concentrates. (See 'Other approaches to treat or prevent bleeding' below.)
●Reversal of anticoagulation – For bleeding in the setting of anticoagulation, specific reversal agents (or PCC) are a better option for reversal than plasma, as they can be administered faster, have better efficacy, and have lower risks of adverse events). (See "Management of bleeding in patients receiving direct oral anticoagulants" and "Management of warfarin-associated bleeding or supratherapeutic INR".)
●Bleeding of unclear etiology – When the cause of bleeding is unknown, a rapid evaluation is warranted, as administration of plasma for an unclear indication and may increase risks without treating the cause of the bleeding [16-19]. Involvement of the consulting specialist may be helpful if the cause is not readily apparent. (See 'Other approaches to treat or prevent bleeding' below and "Approach to the adult with a suspected bleeding disorder", section on 'Active bleeding'.)
●Unexplained abnormal clotting tests – As stated in a 2018 guideline from the British Society of Haematology, there is no evidence supporting the use of plasma to nonbleeding patients to "correct" abnormal coagulation tests of any cause (warfarin, liver disease, disseminated intravascular coagulation [DIC]) [20]. It is also not appropriate to use plasma to correct a minimally elevated INR (<2.0) prior to surgery. This practice exposes patients to risks of transfusion reactions without providing any benefit. (See "Clinical use of plasma components", section on 'Settings in which plasma is not appropriate'.)
Ordering plasma
Plasma dose — Plasma is ordered by the unit.
●When providing plasma for massive transfusion, dosing is typically matched to the number of units of RBCs and platelets (eg, 1:1:1). (See "Massive blood transfusion".)
●When replacing a deficient clotting factor (if the corresponding concentrate is not available), a typical dose is 15 to 20 mL/kg (table 3). (See "Rare inherited coagulation disorders", section on 'Management of specific deficiencies'.)
●When performing therapeutic plasma exchange such as for thrombotic thrombocytopenic purpura (TTP), typically 1 to 1.5 total body plasma volumes are replaced. (See "Immune TTP: Initial treatment", section on 'Therapeutic plasma exchange'.)
Types of plasma — Plasma can be prepared from whole blood or by apheresis.
There are several plasma products that differ mainly based on when they were frozen and thawed. They are considered interchangeable (functionally equivalent) for most indications, and the transfusion service will provide an appropriate product based on inventory and availability (see "Clinical use of plasma components", section on 'Plasma products'):
●FFP – Fresh Frozen Plasma (FFP) is frozen within 8 hours of collection.
●PF24 – Plasma Frozen within 24 Hours after phlebotomy (PF24, also called Frozen Plasma) is plasma that is frozen 8 to 24 hours after collection.
●Thawed Plasma – Thawed Plasma is FFP or PF24 that was thawed and kept at refrigerator temperature for up to 5 days.
●Liquid Plasma – Liquid Plasma has never been frozen. It is rarely used, often unavailable and may have reduced levels of factors V and VIII. (See "Clinical use of plasma components", section on 'Thawed Plasma'.)
Some centers use plasma that has been treated with a pathogen inactivation technology such as solvent/detergent (S/D) treatment or a DNA intercalating agent plus ultraviolet (UV) light. This reduces the risk of transmitting certain viruses. (See "Pathogen inactivation of blood products", section on 'Plasma/FFP'.)
PLATELETS
Platelet indications — Platelets are most commonly transfused to prevent or treat bleeding associated with severe thrombocytopenia or in the setting of invasive procedure.
●Treat bleeding – Increased postoperative bleeding generally occurs when the platelet count is <50,000/microL; spontaneous bleeding generally occurs at platelet counts <10,000/microL. If bleeding is present at higher platelet counts, other contributing factors besides thrombocytopenia are likely to be present (surgical, anatomic, or medication-related) and may require concurrent treatment. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Preparation for an invasive procedure'.)
●Invasive procedures – Platelets may be transfused to lower the risk of bleeding during invasive procedures. Thresholds for platelet transfusion before or during invasive procedures vary by the procedure (higher for central nervous system surgery, lower for central line placement or bone marrow biopsy). The Association for the Advancement of Blood & Biotherapies (AABB) guidelines recommend prophylactic platelet transfusion for central venous catheter placement if the platelet count is <20,000/microL, for lumbar puncture if the platelet count is <50,000/microL, and for major elective non-neuroaxial surgery if the platelet count is <50,000/microL [21]. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Prevention of spontaneous bleeding'.)
●Prevent bleeding – Spontaneous bleeding can occur at any platelet count, but prophylactic transfusions are generally reserved for platelet counts <10,000/microL (higher if other bleeding risk factors such as fever or sepsis are present) [21].
Supporting evidence and exceptions are presented separately. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion' and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Specific clinical scenarios'.)
In certain thrombocytopenic conditions, the risk of thrombosis is also increased. Examples include heparin-induced thrombocytopenia (HIT), thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP) and complement-mediated hemolytic uremic syndrome (CM-HUS), disseminated intravascular coagulation (DIC), and antiphospholipid syndrome (APS). There is a theoretical concern, mostly based on small observational reports, that platelet transfusions in individuals with these disorders may further increase the risk of thrombosis. Observational studies and systematic reviews have reported mixed findings regarding whether the risk of thrombosis (and what types of thrombosis, venous or arterial) are increased, as discussed separately [22-24]. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'TTP or HIT'.)
HIT, TTP, CM-TMA, DIC, and APS are potentially life-threatening conditions in which both over-use and under-use of platelet transfusions are to be avoided; involvement of the consulting expert is important to ensure the optimal approach. If an individual with any of these conditions has critical or severe bleeding associated with severe thrombocytopenia, platelet transfusion can be life-saving while the underlying condition is being treated. However, prophylactic platelet transfusions should not be given to a non-bleeding patient merely to increase the platelet count or prior to an invasive procedure such as central linen placement, due to the possible increased risk of thrombosis.
Early consultation by a clinician with expertise in these disorders is prudent; details of management are discussed separately:
●HIT – (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia (HIT) during cardiac or vascular surgery".)
●TTP – (See "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)" and "Diagnosis of immune TTP" and "Immune TTP: Initial treatment".)
●CM-HUS – (See "Thrombotic microangiopathies (TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS".)
●DIC – (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)
●APS – (See "Clinical manifestations of antiphospholipid syndrome" and "Management of antiphospholipid syndrome".)
Ordering platelets — Platelets can be prepared from donated units of whole blood by centrifugation that are pooled together (referred to as random donor platelets) or obtained by apheresis (single donor). One apheresis unit is approximately equivalent to six pooled random donor units and raises the platelet count by approximately 30,000/microL in an adult of average size.
Platelets are generally ABO and RhD compatible; further crossmatching is not required. The small amount of immune globulins in the plasma generally does not cause hemolysis, although the direct antiglobulin (Coombs) test may become positive. One exception is that RhD-negative individuals of childbearing potential should receive RhD-negative platelets if possible, to reduce the risk of sensitization and hemolytic disease of the fetus and newborn (HDFN) if they become pregnant. If this is not possible, a dose of RhD-immune globulin can be administered.
Platelet refractoriness — When the platelet count does not increase by the expected amount, documented by a post-transfusion platelet count, on at least two or more occasions, the individual may be considered to have refractoriness to platelet transfusion. Platelet refractoriness can be non-immune or immune.
●Non-immune refractoriness can be due to pooling of platelets in an enlarged spleen or rapid consumption or destruction of platelets.
●Immune refractoriness may occur in individuals who have received multiple platelet transfusions and have developed alloantibodies to platelet HLA antigens.
The transfusion medicine service can be very helpful in determining the cause of platelet refractoriness. The approach to distinguishing between the two types of refractoriness and to overcoming them are discussed separately. (See "Refractoriness to platelet transfusion".)
OTHER APPROACHES TO TREAT OR PREVENT BLEEDING — Several other therapies are available to treat critical or severe bleeding, depending on the perceived cause:
Cryoprecipitate — Cryoprecipitate consists of the insoluble coagulation factors fibrinogen, factor VIII, factor XIII, von Willebrand factor (VWF), and fibronectin. It is primarily used as a concentrated source of fibrinogen for patients with fibrinogen deficiency due to DIC or other hypofibrinogenemic states. One dose of 5 to 10 units will raise the fibrinogen concentration by approximately 70 to 100 mg/dL in a 70 kg adult. (See "Clinical use of Cryoprecipitate", section on 'Dose'.)
Fibrinogen concentrates are available in some regions and can also be used. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)
Plasma derivatives and recombinant clotting factors — Clotting factors are especially useful for treating bleeding with specific factor deficiencies and oral anticoagulants (vitamin K antagonists and direct oral anticoagulants [DOACs]). For some clotting factors, plasma-derived and recombinant forms are available. (See "Plasma derivatives and recombinant DNA-produced coagulation factors".)
●Specific clotting factor concentrates – Factor concentrates are used to treat specific factor deficiencies. (See "Treatment of bleeding and perioperative management in hemophilia A and B" and "von Willebrand disease (VWD): Treatment of major bleeding and major surgery".)
●PCCs – 3- or 4-factor PCCs (table 4) (along with vitamin K) are used to treat bleeding associated with vitamin K deficiency or vitamin K antagonist (warfarin) anticoagulation. (See "Management of warfarin-associated bleeding or supratherapeutic INR".)
A PCC may also be a good option for bleeding associated with a direct oral anticoagulant. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'PCCs and aPCCs'.)
Activated clotting factors can be used for bleeding for several indications.
●rFVIIa – Certain disorders including hemophilia with an inhibitor, Glanzmann thrombasthenia, and intractable bleeding of other causes may be treated with recombinant activated factor VII (rFVIIa). (See "Recombinant factor VIIa: Administration and adverse effects".)
●FEIBA – Factor Eight Inhibitor Bypassing Agent (FEIBA) is a PCC in which factor VII is in the active form (an activated PCC [aPCC]). It may be used to treat bleeding in hemophilia with an inhibitor, life-threatening dabigatran-associated bleeding if idarucizumab is not available, and intractable bleeding of other causes. (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Bypassing products (rFVIIa products or FEIBA)' and "Management of bleeding in patients receiving direct oral anticoagulants", section on 'PCCs and aPCCs'.)
Hemostatic medications
●TXA or EACA – Antifibrinolytic agents including tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are especially valuable for treating mucosal bleeding. Randomized trials in trauma-associated bleeding have demonstrated a survival benefit with TXA (initial dose, 1 gram intravenously), and clinical experience in other bleeding disorders is also encouraging; supporting evidence is discussed separately. (See "Coagulopathy in trauma patients", section on 'Management of fibrinolysis' and "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Antifibrinolytic agents'.)
Antifibrinolytic agents should not be used in DIC. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Avoid antifibrinolytic agents and PCCs'.)
●DDAVP – Uremic bleeding and some case of mild bleeding in VWD are treated with DDAVP (desmopressin). (See "Uremic platelet dysfunction".)
●Antidotes – Reversal agents are available for certain anticoagulants to treat severe anticoagulant-associated bleeding (table 5). (See "Management of bleeding in patients receiving direct oral anticoagulants".)
COMPLICATIONS
Transfusion reactions (any blood product) — Transfusion reactions are summarized here and discussed in detail in the linked topic reviews. An approach to evaluating an individual with a suspected acute transfusion reaction is summarized in the flowchart (algorithm 2) and discussed separately. (See "Approach to the patient with a suspected acute transfusion reaction".)
Transfusion reactions can be categorized by their likelihood (see "Approach to the patient with a suspected acute transfusion reaction", section on 'Frequency of reactions') and the timing in which they present (within a few hours of transfusion or days to months later (table 6)). Most reactions occur within six hours of transfusion and with any product (red blood cells [RBCs], plasma, or platelets) (table 7).
●Hemolytic reactions – Hemolysis is caused by alloantibodies generated by the recipient that lyse donor RBCs. They can be acute or delayed, depending on whether antibodies are in the circulation or induced by triggering of immune memory following exposure to a RBC antigen in the more distant past (anamnestic response). (See "Hemolytic transfusion reactions".)
•ABO incompatibility reactions are extremely rare but potentially life-threatening acute hemolytic reactions. They can present with fever, chills, back or chest pain, mental status changes, hypotension, and diffuse bleeding due to disseminated intravascular coagulation (DIC); in an anesthetized individual, diffuse bleeding, hypotension, or hematuria may be the only clues. In suspected cases of ABO incompatibility, it is essential to stop the transfusion immediately and contact the transfusion service. Hydration should be used to prevent acute kidney injury from heme pigment. (See "Hemolytic transfusion reactions", section on 'Acute hemolytic transfusion reactions'.)
•Delayed hemolytic transfusion reactions or delayed serologic transfusion reactions can occur one to two weeks (up to four weeks) after transfusion. Delayed hemolytic reactions present with symptoms, while delayed serologic reactions are only diagnosed when a new alloantibody is identified on the subsequent type and screen sample.
•Hyperhemolysis can occur in individuals with sickle cell disease (SCD). This should be suspected if an individual with SCD has a rapid drop in hemoglobin following transfusion. (See "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Hyperhemolysis'.)
●Allergic and anaphylactic reactions – Allergic reactions can range from mild, requiring only temporary cessation of the transfusion, to severe anaphylaxis.
•Allergic transfusion reactions refer to isolated urticaria (hives) with transfusion; these reactions are common (1 to 3 percent of all transfusions). They can be caused by both donor and recipient factors. As an example, an allergic reaction may occur when a recipient with pre-existing IgE antibodies reacts to a soluble substance in the donor plasma. This is the only transfusion reaction in which the remainder of the product can be administered, after temporarily stopping the transfusion and allowing the hives to resolve, with or without an antihistamine. (See "Immunologic transfusion reactions", section on 'Allergic reactions'.)
•True anaphylactic transfusion reactions are rare (1 per 30,000 transfusions). Anaphylaxis involves sudden release of histamine and tryptase and causes a spectrum of symptoms including hypotension, angioedema, respiratory distress, and/or wheezing. Emergency management is summarized in the table (table 8). Possible causes and their evaluation are discussed separately. (See "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions'.)
●TRALI and TACO – Transfusion-related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) are both transfusion reactions that can occur with any product; they both present with dyspnea and hypoxemia, but their mechanisms (immune in TRALI, hemodynamic/volume-related in TACO) and their management differ. The table summarizes distinguishing features (table 9). Consultation with the blood bank or transfusion service is important to make the correct diagnosis and facilitate accurate reporting to the blood supplier, which may prevent complications in other patients. Donors implicated in a TRALI reaction are permanently deferred from all types of blood donation in the future. (See "Transfusion-related acute lung injury (TRALI)" and "Transfusion-associated circulatory overload (TACO)".)
●FNHTRs – Febrile nonhemolytic transfusion reactions (FNHTRs) are among the most common and least serious of transfusion reactions. They are thought to be related to cytokines in the transfused product, including cytokines released by leukocytes during storage. Pre-storage leukoreduction reduces the risk of FNHTRs. These reactions are evaluated primarily to exclude an acute hemolytic transfusion reaction. Other transfusion reactions in the differential diagnosis include TRALI, septic transfusion reaction, and fever unrelated to the transfusion. The transfusion is stopped immediately and the patient's blood sample submitted to the transfusion service to evaluate for more serious causes of fever. (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)
●ta-GVHD and PTP – Transfusion-associated graft-versus-host disease (ta-GVHD) and post-transfusion purpura (PTP) are extremely rare reactions considered in individuals who develop concerning symptoms several days following transfusion, including the following:
•ta-GVHD is an extremely rare cause of rash, diarrhea, and typically fatal pancytopenia caused when donor lymphocytes mount an immune response against recipient tissues. It is prevented in susceptible individuals by using irradiated cellular blood products (RBCs and platelets) or products treated with a licensed pathogen inactivation technology. If ta-GVHD occurs, management options are limited and include hematopoietic cell transplantation and immunosuppression. (See "Transfusion-associated graft-versus-host disease".)
•PTP is an extremely rare (case reports) cause of thrombocytopenia that occurs when recipient antibodies to a previously encountered platelet antigen cause delayed destruction of platelets (donor as well as recipient), causing severe thrombocytopenia one to two weeks following transfusion of any platelet-containing product (RBCs, platelets, granulocytes). The pathophysiology is similar to a delayed hemolytic transfusion reaction. Treatment includes intravenous immune globulin (IVIG), and future transfusions must avoid the implicated antigen. (See "Immunologic transfusion reactions", section on 'Post-transfusion purpura'.)
Infection — Infection risk is minimized by screening of the donor via a questionnaire and testing the donated product for selected pathogens. However, infections can occur, and there is always a theoretical risk of a previously unidentified infectious organism for which screening has yet to be instituted.
●Bacterial – The risk of bacterial infection is greatest with platelets; platelets are stored at room temperature, which can allow bacterial growth. (See "Transfusion-transmitted bacterial infection".)
●Viral – Risks of viral infections are summarized in the table (table 10). Viruses for which blood is tested are listed separately. (See "Blood donor screening: Laboratory testing", section on 'Viruses'.)
●Other – Transmission of certain protozoal parasites (Chagas disease, Babesia and Malaria species, leishmaniasis) and prion disorders is extremely rare in the United States and Europe but can occur. (See "Blood donor screening: Medical history", section on 'Parasitic diseases' and "Blood donor screening: Medical history", section on 'Prion disorders'.)
Complications of large-volume transfusion — Large-volume transfusion can cause additional complications including the following:
●Hypothermia – RBCs are stored at refrigerator temperature, and plasma is refrigerated prior to transfusion. If these products are infused rapidly, the core body temperature can decrease to <32 to 35°C (<90 to 95°F), leading to cardiac irritability and coagulation abnormalities. Peripheral vasoconstriction and reduced tissue perfusion can occur. Hypothermia can be prevented by using an external blood warmer. It can be treated with rewarming measures while maintaining an ambient temperature of 27ºC (80ºF) or greater. (See "Accidental hypothermia in adults", section on 'Rewarming interventions based on severity of hypothermia'.)
●Coagulopathy – Massive transfusion without plasma can lead to a dilutional coagulopathy. Acidosis from tissue hypoxia can further worsen hemostasis. This is prevented by using a fixed ratio of blood products (1:1:1) and providing hemodynamic support as needed. (See "Massive blood transfusion", section on 'Trauma'.)
●Metabolic alkalosis and hypocalcemia due to citrate toxicity – Citrate is a preservative in blood products that is metabolized upon infusion. If tissue perfusion is limited, liver function is impaired, and if transfusion volumes are large, excess citrate can cause metabolic alkalosis and hypocalcemia (citrate chelates calcium). If citrate toxicity is suspected or the risk of citrate toxicity is considered high, a calcium solution can be administered (10 percent calcium gluconate, 10 to 20 mL per 500 mL of blood, or 10 percent calcium chloride, 2 to 5 mL per 500 mL of blood); this must be given by a separate vein from the blood products and ionized calcium should be monitored. Details are presented separately. (See "Massive blood transfusion", section on 'Complications'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)
SUMMARY AND RECOMMENDATIONS
●Scope – Transfusion is common in critically ill individuals. Institutional policies can ensure appropriate use of products and reduce unnecessary transfusions. (See 'Institutional policy for transfusions' above.)
●RBCs
•Indications – Red blood cell (RBC) transfusions are required for massive bleeding or anemia contributing to hemodynamic instability (ischemia, hypotension, poor perfusion). (See 'RBC indications' above.)
They may also be appropriate for hemodynamically stable ICU patients with hemoglobin ≤7 g/dL. A threshold of ≤8 g/dL is used for those with pre-existing cardiovascular disease or undergoing cardiovascular or orthopedic surgery. Thresholds are summarized in the table (table 1) and algorithm (algorithm 1) and discussed separately. (See "Indications and hemoglobin thresholds for red blood cell transfusion in the adult".)
•Ordering – Most experts administer RBCs one unit at a time, unless bleeding is severe or for massive transfusion. Emergency release units (type O, RhD-negative) can be used if time is insufficient for typing and crossmatching. Many institutions provide group O, RhD-positive emergency release RBC units for females beyond childbearing age and males. (See 'Ordering RBCs' above.)
•Other approaches – Supportive care should optimize tissue perfusion. (See 'Non-transfusion approaches to improve perfusion' above.)
Management in patients who decline transfusion is discussed separately. (See "The approach to the patient who declines blood transfusion", section on 'The actively bleeding patient'.)
●Plasma
•Indications – Plasma is often misused. It should be reserved for:
-Massive transfusion (see "Massive blood transfusion")
-Severe liver disease with bleeding (see "Hemostatic abnormalities in patients with liver disease", section on 'General approach to managing bleeding')
-Disseminated intravascular coagulation (DIC) with bleeding (see "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Prevention/treatment of bleeding')
-Plasma exchange in thrombotic thrombocytopenic purpura (TTP) (see "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology" and "Immune TTP: Initial treatment")
Plasma is not used to replace specific clotting factors or to reverse anticoagulation in severe bleeding or invasive procedures unless a specific clotting factor concentrate, prothrombin complex concentrate, or reversal agent is unavailable. (See 'Plasma indications' above and 'Misuse of plasma' above.)
•Ordering – A fixed ratio of plasma to RBC and platelet units is used in massive transfusion. To replace a clotting factor when a concentrate is unavailable, a plasma dose of 15 to 20 mL/kg is reasonable. Fresh Frozen Plasma (FFP), PF24, and Thawed plasma are considered functionally equivalent. (See 'Ordering plasma' above.)
●Platelets
•Indications – Platelets are usually transfused to treat perioperative bleeding with platelet count <50,000/microL or before an invasive procedure when the platelet count is below the recommended threshold for that procedure (eg, <20,000/microL for catheter placement). Transfusions to prevent spontaneous bleeding are used when the platelet count is <10,000/microL. (See 'Platelet indications' above.)
Supporting evidence and exceptions are presented separately. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion' and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Specific clinical scenarios'.)
•Ordering – One apheresis platelet unit is approximately equivalent to six random donor units and raises the platelet count by approximately 30,000/microL. If the platelet count does not increase, the blood bank, transfusion service, or hematology consultant can help determine the likely cause(s). (See 'Ordering platelets' above and 'Platelet refractoriness' above.)
●Other approaches for bleeding – Cryoprecipitate, plasma derivatives, recombinant clotting factors, and hemostatic medications are tailored to the bleeding cause(s) and severity. Antifibrinolytic agents (tranexamic acid, aminocaproic acid) are useful for mucosal bleeding and trauma-associated bleeding but should not be administered in DIC. (See 'Other approaches to treat or prevent bleeding' above.)
●Complications – Transfusion risks include acute and delayed reactions, infection, and others (see 'Complications' above). Allergic and febrile nonhemolytic reactions are most common. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Frequency of reactions'.)
The figures summarize:
•Timing (table 6)
•Presenting findings (table 7)
•Infectious risks (table 10)
•Evaluation (algorithm 2)
Large-volumes transfusions carry additional risks (hypothermia, citrate toxicity). (See 'Complications of large-volume transfusion' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Nilam Mangalmurti, MD, and Addison May, MD who contributed to earlier versions of this topic review.
The UpToDate editorial staff also gratefully acknowledges the extensive contributions of Arthur J. Silvergleid, MD, to earlier versions of this and many other topic reviews.
