Transfusion

It is now accepted that a stable patient with hemoglobin readings in the range of 7-8 g/dL will not benefit from transfusion, and the transfusion to hemoglobin level above 7 g/dL can harm  a patient with gastrointestinal bleeding.

Transfusions with a hemoglobin concentration between 7-10 g/L may be indicated if there are significant underlying comorbidities such as heart disease, respiratory disease, bone marrow failure or other hematological diseases.

Single unit transfusions traditionally were not recommended, but as transfusion requirements have become more conservative transfusions of one unit can be effective and sufficient.

By using single unit versus 2 unit transfusion blood use can be reduced by as much as 25% with no adverse clinical consequences.

Each unit of blood transfused adds 200 hundred-250 mg of iron into the body’s iron burden.

Blood banking experts recommend transfusion hemoglobin concentration 7 grams per deciliter for hospitalized patients who are stable cardiovascular-wise, and 8 g/dL for those with cardiovascular disease, and the higher hemoglobin concentration for patients with acute coronary syndromes.

In general, RBC transfusions are used to treat tissue hypoxia, acute anemia due to trauma or surgical blood loss, anemia due to chemotherapy and cardiovascular decompensation of chronic anemia, to ensure optimal tissue oxygenation in patients undergoing radiation.

In general, red cell transfusions are not indicated for correction of anemia due to iron deficiency, as a source of nutritional supplementation for volume expansion.

Blood transfusion therapy complications include hemolysis, infection, fever, skin eruptions, pulmonary reactions.

Patients who receive perioperative RBC transfusions had significantly increased odds of developing VTE in the 30-day postoperative period.

Reactions or adverse events due to RBC transfusions occur in 1-3% of transfusion.

One to two percent of all patients who receive transfusions develop antibodies to RBC antigens.

The most common adverse events are febrile nonhemolytic transfusion reactions, due to human leukocyte antigen (HLA) antibodies in the recipient or due to allergic reaction to plasma proteins.

The most severe reaction to transfusion is acute hemolysis, usually due to ABO incompatibility from an administration error.

The main 3 causes of transfusion related fatalities are transfusion–related acute lung injury, transfusion associated circulatory overload and acute hemolytic transfusion reactions.

Acute hemolytic transfusion reactions may occur when receiving ABO-incompatible platelets with anti-A, and type B, or both in the plasma.

Rare transfusion related deaths are related to microbial contamination, anaphylaxis, transfusion associated graft versus host disease and hypotension.

Transfusion reactions are suspected when the patient experiences fever, chills, nausea, vomiting, pain, itching at the intravenous insertion site, variations in blood pressure, tachycardia, dyspnea, and restlessness.

Severity of transfusion reactions and consequences are proportional to the volume of incompatible product transfused so that early recognition and rapid intervention is essential to minimize harm.

Blood transfusions associated with the risk of transmissible diseases, the presence of immunoactive effectors Including antibodies, immunoglobulins, antigenic plasma proteins, biologic response modifiers such as cytokines and chemokines.

RBC transfusions may be associated with increased risk of postoperative infections, longer duration of hospitalization, and increased stays in the ICU.

Restricting blood transfusions for critically ill patients to maintain a hemoglobin level between 7.0 and 9.0 g/dL is equal if not superior to a transfusion strategy to maintain a hemoglobin level higher than 10.0-12.0 g/dL.

In critical and acute care setting a hemoglobin threshold of 7-8 gm/dL is associated with fewer red blood cell units transfused without adverse associations with mortality, cardiac morbidity, functional recovery, or length of hospital stay, compared with higher hemoglobin thresholds (Carson JL et al).

Restrictive transfusion strategy, where transfusions occur when a hemoglobin falls below either seven or 8 g/dL is safe in most clinical settings.

In trials that use 7 g/dL hemoglobin threshold as a restricted transfusion requirement in adult and pediatric intensive care unit patients and even patients with acute gastrointestinal bleeding, the mortality rate was 20% lower in the 7 g/dL group.

Many studies have shown that in some populations, nontransfusded patients have better outcomes than transfused patients and patients who receive fewer units do better than those who receive more RBC units.

Transfusions of RBCs in an ICU population increased a [atient’s chance of dying by a factor of 1.37 (Vincent JL et al).

Blood transfusions is a predictor of longer ICU stay, longer hospitalization length of stay and increases mortality rates (Corwin HL et al).

Risk of transmission of HIV 1/200,000-1/2,000,000.

Risk for Hepatitis C virus 1/30,000-1/150,000.

Current techniques to detect viral RNA of blood donors samples so sensitive that chances of any one blood unit transmitting hepatitis B, hepatitis C, and HIV are 1 in 205,000-288,000, 1 in 1,935,000 and 1 in 2,135,000, respectively.

Screening for the hepatitis B antigen may fail to prevent transmission early in the acute phase when the viral load is below the tests limit of detection and during a late chronic phase with hepatitis B antigen levels gradually become undetectable although infectivity remains.

Nuclear acid testing (NAT) decreases serological period of infectivity by decreasing the limit of detection for the presence of the viral genome, and testing to detect the presence of antibodies directed against the viral core protein to detect carriers have reduced risk of transfusion transmission of Hepatitis B virus infection to approximately 1 per 1 million donations.

Hepatitis C associated with a prolonged seroconversion period, lasting more than 50 days and approximately 1 230,000 donations with no demonstrable antibodies containing viral RNA.

Asymptomatic blood donors while viremic with West Nile virus, may transmit disease particularly to the immunosuppressed, elderly, and infants.

Increase risk of death with decreased preoperative hemoglobin level in patients with underlying cardiovascular disease compared with other patients.

Blood transfusions or a liberal blood transfusion strategy compared with no blood transfusions or a restricted blood transfusion strategy is associated with higher all cause mortality rates in patients with acute myocardial infarction (Chatterjee S et al).

Meta-analysis of 18 trials among 7593 patients, the absolute rates of hospital associated infection were 16.9% in the liberal transfusion group and 11.8% in the restrictive transfusion group (Rohde et al).

In the above study liberal transfusion policy was associated with increased risk of subsequent myocardial infarction.

Red blood cell transfusion in the setting of acute coronary syndromes and in hospitalized patients with a history of coronary artery disease is associated with increased risk of myocardial infarction and death.

Red cell transfusion during hospitalization for noncardiac surgery is associated with long-term mortality.

Observational studies show high-risk of infections associated with red blood cell transfusions.

A meta-analysis found significant reduction in mortality associated with a restrictive transfusion approach (Carson JL et al).

A trial of upper G.I. bleeding management found a significant lower risk of of death at 45 days in the restrictive transfusion group compared to a liberal transfusion group (Villanueva C et al).

With gastrointestinal tract bleeding patients may rebleed more frequently as a result of higher portal pressures from liberal transfusion policy.

Presently, there is insufficient evidence to establish appropriate transfusion threshold for patients with myocardial infarction.

The ideal transfusion threshold at which benefits outweigh risks differs depending on the predominant underlying pathophysiology of the disorder.

Hemoglobin levels of 10 g/dL threshold used is too high for most patients and is associated with increased rates of infection and other adverse effects.

Studies of patients with Jehovah witness faith suggest that mortality sharply increases when hemoglobin concentration declines to less than 5 g/dL, and it is suggested that 5-6 g/dL may be the optimal transfusion trigger. (Carson JL et al).

In patients with septic shock who underwent transfusion and hemoglobin threshold of 7 g/dL, as compared with those who underwent transfusion at hemoglobin threshold of 9 g/dL received fewer transfusions and had similar mortality at 90 days, use of life support, number of days alive and out of the hospital, and the numbers of patients with ischemic events and severe adverse reactions to blood were similar in the two groups (Holst LB et al).

Among patients undergoing PCI, the receipt of transfusion is associated with increased risk of in-hospital adverse cardiac events (Sherwood MW et al).

Can cause suppression of the immune system with increased mortality, increased postoperative bacterial infection, increased cancer recurrence and decreased rate of recurrence of Crohn’s disease.

In a study of adult intensive care unit patients there was a nonsignificant decrease in 30 day mortality with a restrictive transfusion strategy, as compared with the liberal strategy, 18.7% vs. 23.3% (Hebert PC et al).

Can be detrimental to tumor recurrence of colorectal cancer.

Can cause circulatory overload with pulmonary edema and congestive heart failure.

Use of packed RBC’s associated with circulatory overload in one in 700 transfusions.

Each unit of red blood cells contains 200-250 mg of iron and can lead to iron overload after only 10-20 transfusions.

Packed red cells referred to as the red cell mass after most of the plasma is removed with the hematocrit about 70-80%.

A preservative is added to the packed red cells to improve flow of blood and to provide nutrients for red cells and reduces the hematocrit to approximately 60%.

The volume of the red cell unit is approximately 340 mL.

In the average result when 1 unit rbc transfusion raises the hematocrit by 3%. 

Single RBC unit transfusions the present standard for hospitalized patients without bleeding.

Patients with G.I. bleeding may benefit by the use of fewer blood transfusions, because this results in lower portal blood pressure and less recurrent bleeding: perhaps due to a thrombus plug that is not disrupted by higher blood pressures.

Blood plasma can be collected by apheresis.

Blood and blood components should be used only in critical situations.

Whole blood is rarely used today., as most patients require only one blood component.

Whole blood can be fractionated into one unit of red blood cells, 1 unit of platelets, and one unit of fresh frozen plasma.

Whole blood is used as autologous blood donations, and increasingly used in massive transfusion for trauma patients, with the rationale being that all essential components are being transfused at once.

Whole blood is the product of one unit of donating blood plus anticoagulant/preservative and by definition contains one unit of plasma and red cells.

Most patients require only one particular component of whole blood.

Utilizing normal storage techniques, blood components have a greater shelf life than whole blood.

Blood products can often be infused regardless of ABO Blood group.

Products made from donated Blood include:

Whole Blood

Red Blood Cells

Washed Red Blood Cells

Leuko reduced Red Blood Cells

Pediatric/Divided RBC Units

Platelets

Granulocytes (Neutrophils)

Fresh Frozen Plasma (FFP)

Cryoprecipitate (CRYO)

Factor VIII Concentrates

Factor IX Concentrates

Antithrombin III

CMV Negative blood and Components

Irradiated blood and Components

Leuko reduced blood and Components

Whole blood product of one unit of donated and unadulterated Blood plus ACD (anticoagulant/preservative) and contains one unit of plasma and cells.

Whole blood can be stored for 5 weeks, and its Factors V and VIII are labile and are significantly decreased after 7 days.

Whole blood is still utilized in resuscitation of a patient who has severe blood loss.

A unit of red blood cells contains approximately 180ml (range 150 to 210 ml) of red cells, 100ml of Optisol, and approximately 30ml (range 10 to 50 ml) of plasma, and a total volume of a RBC unit is 310 ml (range 270 to 350 ml).

A unit of RBC is prepared from whole blood collection using a closed sterile system with the drawing of the blood into a bag containing the anticoagulant CPD.

Most of the platelet rich plasma is separated from the whole blood using a centrifuge and separated into an attached container.

RBC must be stored between 1° to 6°C.

Optisol is a crystalloid solution containing sodium, dextrose, adenine and mannitol is added to the red blood cells, and it extends the shelf life of the cells to 42 days.

The crystalloid additive also increases the fluid volume of the unit decreasing its hematocrit to approximately 57%, improving the flow characterisitic of the unit.

All RBC transfusions must be ABO/Rh compatible with the recipient.

Red blood cell transfusions do not provide viable platelets or neutrophils, or clinically significant amounts of coagulation factors.

Indication for blood transfusios of packed red blood cells it is symptomatic anemia that is not treatable with specific therapy such as iron, vitamin B12 or with folic acid.

In an average sized adult one unit of RBCs can be expected to increase the hematocrit by approximately 3% or the hemoglobin by 1 gm/dl.

Washed red blood cells refers to the use of normal saline to remove most of the plasma, and are not to be considered leuko reduced.

Washed red blood cells must be given within 24 hours of their preparation.

Washed red cells are considered for patients who have had repeated hypersensitivity reactions to blood or components despite prophylactic antihistamines.

Washed red blood cells may not reduce proteins enough to prevent hypersensitivity reactions.

Controversial indications for washed red blood cells include complement mediated immune hemolysis and paroxysmal nocturnal hemoglobinuria.

A unit of washed red blood cells will raise the hematocrit less than will a unit of packed red blood cells because of an approximate 20% loss of red cells from the unit during the washing process.

Leuko reduced red blood cell units contain reduced numbers of leukocytes by utilizing filtration techniques.

Leuko reduced red blood cells is indicated for patients who have experienced two or more non-hemolytic febrile transfusion reactions.

Leuko reduced red cells are usuful in preventing non-hemolytic febrile transfusion reactions for most patients, and are effective in prevention of CMV transmission or HLA alloimmunization.

Leukocyte reduced red blood cells associated with a 10 to 15% loss of red cells due to filtration.

Pediatric red packed cells contain approximately 45 to 50 ml of red blood cells and approximately 15 ml of plasma.

Platelet products also contain plasma, some red cells and some white cells.

Platelet transfusions are usually cloudy and yellowish in color, but may occasionally have a pink tone because of the presence of residual red cells.

Platelets are stored at 68° to 75° Fahrenheit, require continuous gentle agitation, and can be stored up to five days.

When received for transfusion, pooled and apheresis platelets expire in less than four hours to avoid bacterial growth, since preparation for transfusion involves pooling, volume reduction and leuko reduction which require entry into the component.

Bacterial contamination of blood components is a significant challenge, especially for platelets because they cannot be stored at sufficiently low temperatures that have a bacteriostatic effect.

Bacterial contamination of blood components may be a result of endogenous bacteria with donors that might Have subclinical infections to include endocarditis, osteomyelitis dental disease or, more commonly related to skin contamination.

During the storage of blood/components bacteria present in the container may increase significantly in numbers up until the time of transfusion.

A whole blood platelet concentrate is prepared from whole blood by centrifugation to separate the red cells from the platelet rich plasma.

A second harder centrifugation is used to concentrate the platelets that are then resuspended in 60 ml of residual plasma.

A clinically adequate dose of platelets for an adult consists of four to six platelet concentrates.

Pooled platelets are ABO type compatible, but other types may be substituted.

Avoiding giving type A platelets to an O recipient who may have a high titer of anti-A, as the post transfusion platelet count increment will be reduced.

Platelets products contain an insufficient number of red cells to cause incompatibility reactions but there are sufficient numbers of red cells for an Rh negative person to be sensitized (develop Rh antibodies) if they receive Rh positive blood.

Platelet concentrates are pooled so that the plasma present is from a number of different donors so that the risk of an incompatibility reaction is very small.

Apheresis platelets are obtained from the donor with the use of an apheresis machine, and the platelets are separated from the red cells, leukocytes and most of the plasma by centrifugation.

With apheresis the red cells, leukocytes and plasma are returned to the donor and the platelets are retained in a collection bag for later transfusion.

The apheresis procedure takes approximately 60 to 90 minutes.

The majority of apheresis platelets collected are considered leukocyte reduced.

One apheresis collection of platelets generally contains 200 to 400 ml of plasma, and the unit is volume reduced in cases of minor ABO incompatibility.

Apheresis platelet concentrates can be collected from unselected community donors and is known as a random spheresis platelets.

Platelets may be drawn from a family or donor specifically matched to the patient on the basis of HLA typing, and is referred to as a matched apheresis platelets.

Standard dose random donor apheresis contains a smaller average count of platelets equivalent to four units of pooled platelets.

Large dose random apheresis contains the approximate equivalent to six units of pooled platelets.

Platelet transfusions are indicated for patients with bleeding due to thrombocytopenia or platelet dysfunction or both.

A bleeding time twice the upper normal limit may be an indication for a platelet transfusion in a bleeding patient.

HLA Matched platelets are indicated for patients who are refractory to random donor platelets due to alloimmunization.

Patients with ITP should not receive platelet transfusions unless bleeding is significant or life threatening.

Platelet transfusions in patients with ITP will be rapidly removed from circulation by anti-platelet antibodies and thus will be only of transient benefit.

Failure to achieve hemostasis or the expected increment in the platelet count after platelet transfusion may signify a refractory state.

Platelet refractoriness after transfusion may be caused by fever, sepsis, splenomegaly or to platelet alloimmunization.

With platelet alloimmunization, HLA matched platelets may be necessary to control bleeding.

Granulocytes are obtained by an apheresis procedure after G-CSF stimulation of an ABO-Rh compatible donor.

Large numbers of red cells in granulocyte concentrates require ABO-Rh matching for granulocyte transfusions.

Granulocyte concentrates are irradiated to prevent graft versus host disease, and administered as soon as possible after collection as there is a four hour expiration time once issued from the blood center.

Granulocyte transfusions are considered for patients with severe neutropenia and documented life-threatening bacterial or fungal infection not responsive to appropriate antibiotic therapy.

Granulocyte transfusions are continued daily until the infection clears or the neutrophil count recovers.

Fresh frozen plasma (FFP) is the plasma removed from a unit of whole blood and frozen at or below 55° Fahrenheit within eight hours of collection.

FFP contains all coagulation factors in normal amounts and is free of red cells, leukocytes and platelets.

One unit is approximately 225 ml and must be ABO compatible with the recipient’s red cells, Rh need not be considered.

FFP is indicated for patients with documented coagulation factor deficiencies who are actively bleeding and for those about to undergo an invasive procedure.

FFP beneficial for congenital factor deficiencies, liver disease, anticoagulation with warfarin or massive transfusion with red cells and crystalloid/colloid solutions.

FFP is also indicated in treatment of thrombotic thrombocytopenic purpura, usually in conjunction with plasma exchange.

One ml of FFP per kg of patient weight will raise most clotting factors by approximately 1%.

FFP should be used as soon as possible after it is thawed and always within 24 hours after thawing.

The amount of FFP needed depends on the patient’s clotting factor levels, the bleeding status and the patient’s blood volume status.

Cryoprecipitate is a low purity concentrate from donated whole blood and contains an average of 100 units of factor VIII and von Willebrand factor and 150 to 250 mg of fibrinogen with some factor XIII and fibronectin.

Administration requires no compatibility testing and ABO-Rh type is not relevant.

Units are thawed, suspended in sterile normal saline and pooled.

Pooled cryoprecipitate is not be chilled or refrigerated as the protein will precipitate.

Cryoprecipitate is the only component therapy for fibrinogen.

Cryoprecipitate is indicated for bleeding or for imminent invasive procedures for patients with significant hypofibrinogenemia of less than 100 mg/dl.

Cryoptecipitate can be used for the preparation of fibrin glue used in neurosurgery, orthopedic and ENT surgery.

Ten bags of cryoprecipitate provides enough fibrinogen to raise the fibrinogen 60 to 70 mg/dl in an adult.

Factor VIII concentrates are prepared as a lyophilized powder purified from human plasma to treat patients with hemophilia A or von Willebrand’s disease.

Recombinant Factor VIII protein is purified from genetically engineered non-human cells grown in tissue culture.

One factor VIII concentrate unit equals the clotting activity in 1 ml of fresh plasma.

Factor VIII concentrate is cell free, and is heat treated and/or solvent detergent treated to reduce the risk of virus transmission, and had eliminated the risk of HIV, HBV and HCV transmission.

Risk of HIV transmission associated with transfusion 1 in 2.135 million and detection limitation approximately 22 days.

Factor VIII is administered without regard to patient or donor ABO or Rh type.

Highly purified factor VIII, or current recombinant factor VIII concentrates, are stabilized by adding 98% of pasteurized human albumin.

Porcine factor VIII concentrate is available for patients with high titer anti-human factor VIII antibody inhibitors.

Factor VIII concentrates are stored refrigerated at 35° to 45° Fahrenheit for up to two years and once reconstituted, it should not be refrigerated.

To reduce risk of bacterial infection Factor VIII concentrate should be infused within four hours of preparation.

Factor VIII concentrate is indicated for: the treatment of bleeding or imminent invasive procedures in patients with hemophilia A, and for patients with low titer factor VIII inhibitors.

The half life of circulating factor VIII is eight to twelve hours.

To maintain hemostatic levels in Factor VIII deficient patients transfusions may need to be repeated every 12 to 24 hours.

After a surgucal procedure it is necessary to maintain hemostatic levels for up to two weeks to prevent delayed bleeding and promote wound healing in Factor VIII deficient patients.

The amount of Factor VIII concentrate required is dependent on the nature of the injury, the degree of factor deficiency, the weight of the patient and the presence and level or absence of factor VIII inhibitors.

Factor IX concentrates are a commercially prepared, lyophilized powder purified from human plasma to treat patients with hemophilia B.

Factor IX concentrates are heated to reduce the risk of disease transmission, particularly HIV and hepatitis.

Factor IX concentrates may be refrigerated at 35° to 45° Fahrenheit, but should not be frozen.

Factor IX concentrates are indicated for patients with hemophilia B, Factor IX deficiency, also called Christmas Disease, who are requiring treatment of bleeding or about to undergo invasive procedures.

Factor IX concentrates should not be used for patients with acquired combined deficiency of factor(s) II, VII, IX and/or X.

Treatment for bleeding generally requires Factor IX concentrates every 12-hour or daily infusions until symptoms resolve.

Antithrombin III concentrates are commercially purified from human plasma pools and lyophilized, and are approved for and indicated in reducing an acute increased risk of venous thrombo-embolic disorders in patients with symptomatic, congenital antithrombin III deficiency.

Antithrombin III concentrates can beused prophylactic therapy to correct levels from half-normal to around 100% during surgical procedures or periods of increased risk.

CMV Negative blood Components

Description – CMV is a herpes virus that resides in the white blood cells of persons who have been infected with the virus. There is a high prevalence of CMV positive persons worldwide. Most persons that are CMV positive have no history of illness.

CMV transmission to susceptible patients is effectively prevented by use of either CMV seronegative, a donor determined to be negative for antibody to CMV, or leuko reduced, containing less than a certain range of leukocytes.

Cryoprecipitate and Fresh Frozen Plasma are cell free and have not been implicated in CMV transmission.

Indications – CMV negative Bbood products are indicated for patients in the following categories, regardless of CMV status of the mother:

Premature infants;

Infants under four weeks of age; and,

Patients requiring intrauterine transfusion.>

CMV negative blood products are indicated for CMV negative patients in the following categories: Bone marrow or organ transplant recipients (if the marrow or the organ donor is also CMV negative); Potential candidates for transplant;

AIDS or HIV infected patients;

Patients who have congenital immune deficiency;

Patients undergoing splenectomy; and,

Pregnant women.

If CMV status is pending in these patients, CMV negative components are indicated. CMV negative components are not considered necessary for patients receiving chemotherapy.

Therapeutic Effect – In patients with compromised immune systems, a CMV infection could result in a serious complication. CMV negative or leuko reduced blood products reduce this hazard.

Patients at risk for circulatory overload often have preexisting circulatory overload before transfusion, are older, have severe anemia, renal insufficiency and underlying cardiac disease.

In patients having suffered an acute myocardial infarction the risk of death estimated to be 3.94 times higher in patients undergoing a transfusion compare the those who did not, adjusting for other variables.

In patients over the age of 65 treated for an acute myocardial infarction the 30-day mortality was lowered for those patients with an admission hematocrit less than 33% and received at least 1 unit of packed red blood cells, whereas the 30-day mortality was increased for those transfused with an admitting hematocrit value of 36% or higher.

Blood transfusion in patients with anemia and acute coronary artery syndromes associated with an increased 30-day mortality with a hematocrit nadir above 25%, indicating stable ischemic heart patients can tolerate such low levels of blood.

Randomized controlled trials reveal that better outcomes are associated with a restrictive transfusion policy with hemoglobin levels ≤ 7 g/dL compared with a liberal transfusion policy of ≤ 10 gm/dL in most patients, possibly excepting those patients with severe cardiac disease.

In a study of 2016 patients over the age of 50 with a history of or risk factors for cardiovascular disease, and whose hemoglobin was less than 10 g/dL after hip fracture surgery randomized to liberal transfusion or transfusion restricted to symptomatic patients with a hemoglobin of less than 8 g/dL: primary outcome was death or inability to walk across a room on pay 60 of follow-up-there was no reduction in rates of death, the inability to walk independently on day 60 or reduction in in-hospital mortality in elderly patients at high cardiovascular risk (FOCUS Investigators).

Transfusion of short termed storage RBCs versus long term storaged RBCs revealed no difference in mortality rate (McQuilten ZK).

Synthetic anti-fibrinolytic agents such as epsilon amino caproic acid or tranexamic acid reduce blood loss and transfusion during cardiac surgical procedures and should be routinely used perioperatively for blood conservation.