Blood Products

Packed RBCs are ordinarily the component of choice with which to increase hemoglobin (Hb). Indications depend on the patient. 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 about 1 g/dL (10 g/L), and the hematocrit (Hct) by about 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, and platelets. They are generally given to patients who have severe reactions to plasma (eg, severe allergies, paroxysmal nocturnal hemoglobinuria, IgA immunization). In IgA-immunized patients, blood collected from IgA-deficient donors may be preferable for transfusion.

WBC-depleted RBCs (leukoreduced) 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 Febrile nonhemolytic transfusion reaction The most common complications of transfusion are Febrile nonhemolytic reactions Chill-rigor reactions The most serious complications, which have very high mortality rates, are Acute hemolytic... read more , 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 (FFP) is an unconcentrated source of all clotting factors without platelets. Indications include correction of bleeding secondary to clotting factor deficiencies for which specific factor replacements are unavailable or to multifactor deficiency states (eg, massive transfusion, disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more [DIC], liver failure). FFP is used for urgent warfarin reversal only when prothrombin complex concentrate (PCC is the first choice) is unavailable. FFP is ineffective in managing bleeding due to direct factor Xa inhibitors. FFP can supplement RBCs when whole blood is unavailable for neonatal exchange transfusion. FFP should not be used simply for volume expansion or correction of mild to moderate coagulopathy before surgical procedures.

Pathogen-inactivated plasma obtained by treatment using the solvent detergent method is available to avoid transmission of almost all pathogens. During COVID-19 (SARS-CoV-2) pandemic, the convalescent plasma donated by a person who has fully recovered from this infection has been used as an option for treatment of COVID-19 with variable success. Convalescent plasma has been used in the past during Ebola and influenza H1N1 epidemics.

Cryoprecipitate is a concentrate prepared from fresh frozen plasma. Each concentrate usually contains about 80 units each of factor VIII and von Willebrand factor and about 250 mg of fibrinogen. It also contains ADAMTS13 (an enzyme that is deficient in congenital thrombotic thrombocytopenic purpura Thrombotic Thrombocytopenic Purpura (TTP) Thrombotic thrombocytopenic purpura (TTP) is an acute, fulminant disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia. Other manifestations may include alterations... read more ), and factor XIII. Although originally used for hemophilia Hemophilia Hemophilias are common hereditary bleeding disorders caused by deficiencies of either clotting factor VIII or IX. The extent of factor deficiency determines the probability and severity of bleeding... read more and von Willebrand disease Von Willebrand Disease Von Willebrand disease (VWD) is a hereditary quantitative deficiency or functional abnormality of von Willebrand factor (VWF), which causes platelet dysfunction. Bleeding tendency is usually... read more , cryoprecipitate is currently used as a source of fibrinogen in acute DIC with bleeding, treatment of uremic bleeding, cardiothoracic surgery (fibrin glue), obstetric emergencies such as abruptio placentae Placental Abruption (Abruptio Placentae) Placental abruption (abruptio placentae) is premature separation of the placenta from the uterus, usually after 20 weeks gestation. It can be an obstetric emergency. Manifestations may include... read more and HELLP syndrome Complications Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more (hemolysis, elevated liver enzymes, and low platelet count), and rare factor XIII deficiency when human coagulation factor XIII concentrate is unavailable. In general, it should not be used for other indications. A pathogen-inactivated pooled cryoprecipitate is now 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 has to be used within 4 hours.

Granulocytes may be transfused when sepsis occurs in a patient with profound persistent neutropenia Neutropenia Neutropenia is a reduction in the blood neutrophil count. If it is severe, the risk and severity of bacterial and fungal infections increase. Focal symptoms of infection may be muted, but fever... read more (neutrophils < 500/mcL [0.5 × 10⁹/L]) who is unresponsive to antibiotics. Granulocytes must be given within 24 hours of harvest; however, testing for HIV, hepatitis, human T-cell lymphotropic virus, and syphilis may not be completed before infusion. Because of improved antibiotic therapy and drugs that stimulate granulocyte production during chemotherapy, granulocytes are seldom used.

Rh immune globulin (RhIg), given IM or IV, prevents development of maternal Rh antibodies that can result from fetomaternal hemorrhage Pathophysiology Hemolytic disease of the fetus and neonate is hemolytic anemia in the fetus (or neonate, as erythroblastosis neonatorum) caused by transplacental transmission of maternal antibodies to fetal... read more . The standard dose of intramuscular RhIg (300 mcg) must be given to an Rh-negative mother immediately after abortion or delivery (live or stillborn) unless the infant is Rho(D) and Du negative or the mother’s serum already contains anti-Rho(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).

RhIg is also used to treat immune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more (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 Cytomegalovirus (CMV) Infection Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. A syndrome of infectious mononucleosis that lacks severe pharyngitis is common. Severe... read more , hepatitis A Hepatitis A Hepatitis A is caused by an enterically transmitted RNA virus that, in older children and adults, causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Young... read more , hepatitis B Hepatitis B, Acute Hepatitis B is caused by a DNA virus that is often parenterally transmitted. It causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and... read more , measles Measles Measles is a highly contagious viral infection that is most common among children. It is characterized by fever, cough, coryza, conjunctivitis, an enanthem (Koplik spots) on the oral mucosa... read more , rabies Rabies Rabies is a viral encephalitis transmitted by the saliva of infected bats and certain other infected mammals. Symptoms include depression and fever, followed by agitation, excessive salivation... read more , respiratory syncytial virus Respiratory Syncytial Virus (RSV) and Human Metapneumovirus Infections Respiratory syncytial virus and human metapneumovirus infections cause seasonal lower respiratory tract disease, particularly in infants and young children. Disease may be asymptomatic, mild... read more , rubella Rubella (See also Congenital Rubella.) Rubella is a viral infection that may cause adenopathy, rash, and sometimes constitutional symptoms, which are usually mild and brief. Infection during early pregnancy... read more , tetanus Tetanus Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani. Symptoms are intermittent tonic spasms of voluntary muscles. Spasm of the masseters accounts for the name... read more , smallpox Smallpox Smallpox is a highly contagious disease caused by the smallpox virus, an orthopoxvirus. Case fatality rate is about 30%. Natural infection has been eradicated. The main concern for outbreaks... read more , and chickenpox Chickenpox Chickenpox is an acute, systemic, usually childhood infection caused by the varicella-zoster virus (human herpesvirus type 3). It usually begins with mild constitutional symptoms that are followed... read more (for usage, see under specific disease).

Platelet concentrates are used

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 about 10,000/mcL, and adequate hemostasis is achieved with a platelet count of about 10,000/mcL (10 × 10⁹/L) in a patient without complicating conditions, and about 50,000/mcL (50 × 10⁹/L) for those undergoing surgery. Therefore, platelet concentrates derived from a pool of 4 to 5 units of whole blood are commonly used in adults.

Platelet concentrates are increasingly being prepared by automated devices that harvest the platelets (or other cells) and return unneeded components (eg, RBCs, plasma) to the donor. This procedure, called plateletpheresis Therapeutic cytapheresis Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more , 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. 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.

Irradiated blood products are used to prevent graft-vs-host disease Graft-vs-host disease (GVHD) The most common complications of transfusion are Febrile nonhemolytic reactions Chill-rigor reactions The most serious complications, which have very high mortality rates, are Acute hemolytic... read more in patients 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.

Hematopoietic stem cells Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more from autologous or allogenic donors can be transfused as a way of reconstituting hematopoietic function (particularly immune function) in patients undergoing myeloablative or myelotoxic therapy.