Whole blood can provide improved oxygen-carrying capacity, volume expansion, and replacement of clotting factors and was previously recommended for rapid massive blood loss. However, because separating individual blood components is more efficient and cost-effective, whole blood transfusions have not been available in the United States for several decades. The low titer (for anti-A) whole blood type O is often used for trauma resuscitation as a universal blood type based on data suggesting improved survival when compared with component therapy (1).
Red blood cells (RBCs)
Packed RBCs are stored between 1 and 6° C for up to 42 days. Packed RBCs are the component of choice to increase hemoglobin (Hb) in a patient with anemia. Oxygen-carrying capacity may be adequate with Hb levels as low as 7 g/dL (70 g/L) in healthy patients, but transfusion may be indicated with higher Hb levels in patients with decreased cardiopulmonary reserve or ongoing bleeding. One unit of RBCs increases an average adult’s Hb by approximately 1 g/dL (10 g/L), and the hematocrit (Hct) by approximately 3%, above the pretransfusion value. When only volume expansion is required, other fluids can be used concurrently or separately. In patients with multiple blood group antibodies or with antibodies to high-frequency RBC antigens, RBCs with rare phenotypes of antigens are used; these are usually frozen for storage.
Washed RBCs are free of almost all traces of plasma, most white blood cells (WBCs), and platelets. They are generally given to patients who have severe reactions to plasma (eg, severe allergies, IgA immunization). In patients with IgA immunization, blood collected from IgA-deficient donors may be preferable for transfusion.
WBC-depleted RBCs (leukoreduced RBCs) are prepared with special filters that remove ≥ 99.99% of white blood cells. They are indicated for patients who have experienced nonhemolytic febrile transfusion reactions, for exchange transfusions, for patients who require cytomegalovirus-negative blood that is unavailable, and possibly for the prevention of human leukocyte antigen (HLA) alloimmunization to help prevent refractoriness to platelet transfusion (failure to achieve the target level of blood platelets after platelet transfusion).
Fresh frozen plasma
Fresh frozen plasma (FFP) is an unconcentrated source of all clotting factors without platelets. The FFP is stored at -18° C for up to 1 year. Indications include correction of coagulopathic bleeding secondary to clotting factor deficiencies for which specific factor replacements are unavailable or to multifactor deficiency states (eg, massive transfusion, disseminated intravascular coagulation [DIC], liver failure). FFP is used for urgent warfarin reversal only when a 4 factor-prothrombin complex concentrate (4F-PCC is the first choice) is unavailable. FFP is ineffective in managing bleeding due to direct reversal only when a 4 factor-prothrombin complex concentrate (4F-PCC is the first choice) is unavailable. FFP is ineffective in managing bleeding due to directfactor Xa inhibitors or direct thrombin inhibitors. FFP should not be used to treat patients who are bleeding due to unfractionated heparin overdose because its antithrombin content can potentiate the effect of inhibitors. FFP should not be used to treat patients who are bleeding due to unfractionated heparin overdose because its antithrombin content can potentiate the effect ofheparin and exacerbate bleeding. FFP can supplement RBCs when whole blood is unavailable for neonatal exchange transfusion. FFP should not be used for volume expansion or for correction of mild to moderate coagulopathy prior to procedures, particularly in patients with cirrhosis (their hemostasis is rebalanced) who are bleeding (often variceal bleed), because it rarely corrects laboratory coagulation abnormalities and the added plasma may increase portal pressure and precipitate further bleeding.
Pathogen-inactivated plasma, produced using solvent–detergent treatment, is available to reduce transmission of nearly all plasma-borne pathogens. Convalescent plasma has been used during outbreaks such as Ebola, influenza A (H1N1), and COVID-19.
Cryoprecipitate
Cryoprecipitate is a concentrate prepared from FFP and also stored at -18° C. Each concentrate usually contains approximately 80 units each of factor VIII and von Willebrand factor and approximately 250 mg of fibrinogen. It also contains ADAMTS13 (an enzyme that is deficient in thrombotic thrombocytopenic purpura [TTP]) and factor XIII. Although originally used for hemophilia and von Willebrand disease, cryoprecipitate is currently used as a source of fibrinogen in patients with hypofibrinogenemia with bleeding , and rare factor XIII deficiency when human coagulation factor XIII concentrate is unavailable.
A pathogen-inactivated pooled cryoprecipitate is available that can be used as a source of fibrinogen. It has the advantage that it can be thawed and stored at room temperature for up to 5 days unlike standard cryoprecipitate that needs to be thawed from -18° C and used within 4 hours.
White blood cells (WBCs)
Granulocytes may be transfused when sepsis occurs in a patient with profound persistent neutropenia (neutrophils < 500/mcL [0.5 × 109/L]) who is unresponsive to antibiotics. Granulocytes are stored at room temperature and must be given within 24 hours of collection; however, testing for HIV, hepatitis, human T-cell lymphotropic virus, and syphilis may not be completed before infusion. Because of improved antibiotic therapy and medications that stimulate granulocyte production during chemotherapy, granulocytes are seldom used.
WBC collection is logistically challenging, as granulocyte donors typically require glucocorticoid pretreatment to mobilize neutrophils, which limits donor availability and acceptance; granulocyte-colony stimulating factor (G-CSF)–stimulated granulocyte collection is not routinely used, further constraining access to this product.
Immune globulins
Rh immune globulin, given IM or IV, prevents development of maternal Rh-D antibodies that can result from fetomaternal hemorrhage. The standard dose of intramuscular Rh immune globulin (300 mcg) must be given to an Rh-negative mother immediately after abortion or delivery (live or stillborn) unless the infant is Rh(D) and weak D negative or the mother’s serum already contains anti-Rh(D). If fetomaternal hemorrhage is > 30 mL, a larger dose is needed. If hemorrhage of this amount is suspected, testing of the volume of fetomaternal hemorrhage begins with the screening rosette test, which, if positive, is followed by a quantitative test (eg, Kleihauer-Betke test or flow cytometry).
Rh immune globulin is also used to treat immune thrombocytopenia (ITP), in which case it is given IV.
Other immune globulins are available for postexposure prophylaxis for patients exposed to a number of infectious diseases, including cytomegalovirus, hepatitis A, hepatitis B, measles, rabies, respiratory syncytial virus, rubella, tetanus, smallpox, and chickenpox (for usage, see under specific disease).
Platelets
Platelet concentrates are used:
To prevent bleeding in asymptomatic severe thrombocytopenia (platelet count < 5,000 to 10,000/mcL [<5 × 109/L to 10 × 109/L])
For bleeding patients with less severe thrombocytopenia (platelet count < 50,000/mcL [< 50 × 109/L])
For bleeding patients with platelet dysfunction due to antiplatelet medications (other than aspirin) but with a normal platelet count
For patients receiving massive transfusion that causes dilutional thrombocytopenia
Platelet concentrates are also sometimes used before invasive surgery, particularly with extracorporeal circulation for > 2 hours (which often makes platelets dysfunctional). One platelet concentrate unit increases the platelet count by approximately 10,000/mcL (10 × 109/L), and adequate hemostasis is achieved with a platelet count of approximately 10,000/mcL (10 × 109/L) in a patient without complicating conditions, and approximately 50,000/mcL (50 × 109/L) for those undergoing major surgery. Therefore, platelet concentrates derived from a pool of 4 to 5 units of whole blood are commonly used in adults.
Platelet concentrates are usually prepared by automated devices that harvest the platelets and return unneeded components (eg, RBCs, plasma) to the donor. This procedure, called plateletpheresis, provides enough platelets from a single donation (equivalent to 4 to 5 whole blood platelet units) for transfusion to an adult, which, because it minimizes infectious and immunogenic risks, is preferred to multiple donor transfusions in certain conditions.
Certain patients may not respond to platelet transfusions (called refractoriness), possibly because of splenic sequestration, platelet consumption due to disseminated intravascular coagulation, or destruction due to HLA or platelet-specific antigen alloimmunization (and immune-mediated destruction). If patients are refractory to transfusion, they are tested for alloimmunization, if possible. Patients with immune-mediated destruction may respond to pooled whole blood platelets (because of greater likelihood that some units are HLA compatible), platelets from family members, or ABO- or HLA-matched platelets. Since some HLA antigens are present in high concentration on WBCs, HLA alloimmunization may be mitigated by transfusing WBC-depleted RBCs and WBC-depleted platelet concentrates.
Pathogen-inactivated platelets, inactivated by using a chemical (amotosalen), are also available for clinical use. Most platelets are stored at 20 to 22° C for up to 5 to 7 days. Platelets can also be stored at 1 to 6° C for up to 14 days. During cold storage, platelets are partially activated and thus, hemostatically more functional than platelets stored at room temperature; therefore, cold storage platelets are used during surgery or in a patient who is bleeding.
Other products
Irradiated blood products are used to prevent transfusion-related graft-versus-host disease in patients who are at risk.
Many attempts have been made to develop blood substitutes using inert chemicals (eg, perfluorocarbons) or hemoglobin solutions to carry and deliver oxygen to tissues. Although these hemoglobin substitutes had promising ability to deliver oxygen to tissues during an emergency, several clinical trials have failed due to increased mortality and severe adverse cardiovascular toxicities (eg, hypotension). Attempts to regenerate platelets and RBCs from various stem cell sources are underway (2).
Hematopoietic stem cells from autologous or allogenic donors can be transfused as a way of reconstituting hematopoietic function (particularly immune function) in patients undergoing myeloablative therapy.
References
1. McCoy CC, Brenner M, Duchesne J, et al. Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient. Shock. 2021;56(1S):9-15. doi:10.1097/SHK.0000000000001685
2. Kim KM, Albaira KI, Kang J, et al. Cell-based artificial platelet production: historical milestones, emerging trends, and future directions. Blood Res. 2025;60(1):32. doi:10.1007/s44313-025-00071-9
Drugs Mentioned In This Article
