ABO type
Rh type
Percentage
O
+
37
44
O
−
7
A
+
36
42
A
−
6
B
+
8
10
B
−
2
AB
+
3
4
AB
−
1
Table 8.2
Compatible donors’ blood types
Recipient blood type | PRBC donors | FFP donors |
|---|---|---|
O | O | AB |
A | A, O | A, AB |
B | B, O | B, AB |
AB | AB, A, B, O | AB |
Rh+ | Rh+, Rh− | Rh+ |
Rh− | Rh− | Rh+, Rh− |
Type and cross
In type and cross, the recipient’s blood is mixed with the donor RBCs. Crossmatching confirms compatibility between a donor unit of RBCs and the patient’s sera. Type and cross adds an additional 15 min to the type and screen. If unexpected RBC antibodies are identified on the type and screen, serologic crossmatching must be performed, which takes an additional 30 min.
Red Cells and Non-erythrocyte Blood Components
Control of ongoing blood loss not only requires impeccable surgical technique but also potentially the institution of red and non-red cell blood component therapy. An outline of the indications, risks, benefits, and complications of the different types of blood products available to transfuse follows.
Packed Red Blood Cells
Packed red blood cells (PRBCs) are ideal for transfusion in the presence of anemia (increase oxygen carrying capacity), but not volume replacement. The PRBCs red cells can be reconstituted with normal saline to provide volume, which also reduces the unit’s viscosity to facilitate rapid transfusion. Lactated Ringers solution should not be used because of the presence of calcium. Blood is transfused through a blood warmer (37 °C) to prevent hypothermia. Also, a transfusion tubing with a 170 μm filter is used to trap any clots or debris.
A unit of whole blood is collected from the donor (about 450 ml). To this unit 63 ml of a citrate phosphate dextrose (CPD) anticoagulant is added as preservative. The donated whole blood unit is processed to produce one unit each of the RBCs, platelet concentrate, and fresh frozen plasma (FFP). To generate a unit of RBCs, a whole blood unit is centrifuged to separate the RBCs from the plasma. Such a unit has a volume of about 250 ml and a hematocrit of about 70 % and may be stored for up to 21 days at 1–6 °C. To increase the shelf life for up to 35–42 days, about 100 ml of an additive solution [e.g., CPDA-1 (A is adenine), AS-1, AS-3, or AS-5] is added to CPD-RBC units. The final volume of a unit of PRBCs is about 350 ml with a hematocrit of 55–65 %.
Patients who have a history of nonhemolytic febrile transfusion reactions, and who require cytomegalovirus-negative blood, are transfused with leukocyte-reduced RBCs. These RBC units are prepared with special filters that remove ≥99.99 % of WBCs prior to storage. Leukoreduction does not prevent graft-versus-host disease, which requires irradiated RBC units. Cryoprecipitate and fresh frozen plasma do not contain significant numbers of viable leukocytes.
Fresh Frozen Plasma
Clinical scenarios facing the anesthesiologist necessitating the transfusion of plasma include major hemorrhage (after transfusion of one blood volume), postpartum hemorrhage, complex surgical procedures such as liver transplantation and major cardiothoracic surgeries, patients with advanced liver disease, and associated coagulopathies (clotting factor deficiencies, warfarin associated). Reversal of warfarin should be done by injections of vitamin K. FFP should be only transfused for warfarin reversal in case of emergencies (like before surgery).
FFP contains all clotting factors and plasma proteins, but no platelets. FFP is prepared by centrifuging a unit of whole blood. ABO-compatible FFP transfusion units are desirable, but not required. FFP units are stored at −18 to −30 °C and thawed to 37 °C prior to transfusion. The thawed units should be used within 24 h of thawing. Deficiency of clotting factors can be diagnosed by measuring PT (INR) and PTT. This is usually the case when PT > 1.5, INR > 2.0, or PTT > 2 times the normal.
FFP is administered in a dose of about 10–15 ml/kg. One ml of FFP/patient weight in kilogram will raise most clotting factors by 1 %. Since the volume of each FFP unit is about 200 ml, a 70 kg patient will have his/her clotting factors increase by about 3 % per unit of FFP transfused.
Platelets
The decision to transfuse platelets must be contextualized for a particular patient and surgery. Platelet transfusions are indicated to prevent or treat bleeding in patients with qualitative or quantitative platelet deficiencies. Generally, platelet counts greater than 50–80 k/mm3 are the acceptable standards for most procedures. In the case of neurosurgical operations, a number generally greater than 100 k/mm3 is the usual accepted practice. Although transfusion practices vary, a prophylactic transfusion trigger of 10 k/mm3 has been widely adopted in otherwise stable patients. In hemorrhaging patients, it is recommended that the transfusion trigger be 50 k/mm. Furthermore, a numeric trigger does not take into account platelet dysfunction, and clearly, without testing such as thromboelastogram interpretation, the platelet qualitative function is unknown. This issue is of particular importance when patients presenting for surgery have been receiving antiplatelet therapy such as aspirin or clopidogrel.
Platelet concentrates are derived from donated whole blood. Most platelet units used in the United States are actually obtained via plateletpheresis from a single donor. Platelet units usually contain some RBCs and the Rh antigen; hence, type-specific and crossmatched platelets should be transfused, whenever possible. Platelet concentrates are stored at room temperature (20–24 °C) with continuous gentle agitation (facilitates gas exchange and enhances survival) for up to 5 days. Because platelets are stored at room temperature, bacterial growth can occur during storage. Septic transfusion reactions may be observed, especially in immunocompromised patients.
Typically, one unit of platelets contains between 5 and 10 k/mm3 cells. By convention the usual dose of platelets is 4–6 units (6 pack), which will characteristically raise the platelet count 40–60 k/mm3 in the average-sized adult (70 kg). If lower than expected posttransfusion platelet count results, it may indicate a refractory state, either due to immune or nonimmune causes. The causes for the latter include fever, sepsis, certain medications, DIC, splenomegaly, hepatic veno-occlusive disease, and graft-versus-host disease (GVHD).
Cryoprecipitate
Cryoprecipitate is typically administered in hemorrhaging patients with presumed fibrinogen deficiency (<150 mg/dl). Examples of hypofibrinogenemic states encountered by the anesthesiologist include patients receiving massive transfusions and patients with disseminated intravascular coagulopathy (DIC). Cryoprecipitate is obtained from slow thawing of plasma (1–6 °C) into a cryoglobulin fraction.
Cryoprecipitate is rich in factor VIII and hence can be used for the treatment of hemophilia A. Each unit of cryoprecipitate contains about 80 units each of factor VIII and von Willebrand factor, about 200 mg of fibrinogen, and lesser quantities of fibronectin and factor XIII. Ten units of cryoprecipitate will typically raise the fibrinogen level to 80–100 mg/dl. Cryoprecipitate is administered in pooled units, which are administered within 4 h of thawing. ABO compatibility testing is not required before administration.
Erythropoietin
Erythropoietin is secreted by the kidney in the body to increase red cell mass. Manufactured recombinant human erythropoietin can be administered to increase red cell mass. It is administered in patients with anemia and chronic renal failure. It can also be used in patients who refuse blood transfusions. Its effect starts in about 2 weeks (therefore, not useful in acute situations) and it is expensive.
Recombinant Activated Factor VII
Recombinant activated factor VII (RVII) is administered in life-threatening hemorrhage and coagulopathy when other measures have failed. It is used to control bleeding in patients with hemophilia A or B. RVII binds to tissue factor to augment thrombin formation via the intrinsic clotting pathway and directly activating factors IX and X. Its dose is 50–100 mg/kg IV, which can be repeated in 2 h, though only one dose is usually administered. The administration of RVII is not associated with a risk of transfusion-transmitted diseases. However, it is expensive to use and is associated with thrombotic events (cerebrovascular accidents, myocardial infarction, pulmonary embolism, clotting of indwelling catheters).
Strategies for Perioperative Blood Conservation
It has been well established that the transfusion of allogeneic blood can potentially lead to a range of clinically significant complications, which can vary from mild to life-threatening. Therefore, conserving and reinfusing autologous blood in an attempt to minimize exposure to allogeneic blood appears to be an attractive option. Strategies for perioperative blood conservation include autologous pre-donation of blood, acute normovolemic hemodilution (ANH), which is initiated before the beginning of the surgical procedure, or cell salvage (utilized intraoperatively).
(i)
Autologous blood donation
The decision for autologous donation is made by the surgeon in consultation with the anesthesiologist. The donation of blood should be made by the patient at 1-week intervals (maximum 2–3 units) and not within 72 h of the anticipated surgery. Autologous blood should not be collected if the likelihood of transfusion is low or the patient is at risk of developing perioperative anemia. The patient must meet certain criteria for autologous donation, which include a hemoglobin of 11 g/dl and absence of bacterial infection and severe cardiopulmonary, cerebrovascular (epilepsy), renal, or liver diseases.
The advantages of autologous blood donation include prevention of transfusion-transmitted diseases, reassurance to patients who are concerned of blood transfusion risks, and supplementation of blood supply to the patient (in addition to allogeneic units). Disadvantages of autologous blood donation include risks of bacterial contamination, error in storage leading to ABO incompatibility, more cost than allogeneic blood, and wastage of blood if not transfused.
Oral iron supplementation should be started prior to initial unit donation. Erythropoietin can be used in autologous donation programs to increase red cell production. The blood units are collected in standard collection bags with added preservative solution. The collected units are usually stored as whole blood, with a refrigerated shelf life of 35 days.
(ii)
Acute normovolemic hemodilution
ANH can be utilized in patients who have a high likelihood of blood transfusion or an estimated blood loss of at least 1.5 l. The aim of ANH is that the removal of blood decreases then concentration of RBCs, leading to decreased blood loss during the surgical procedure. For ANH, patients should have a hemoglobin of at least 12 g/dl and absence of infection, coagulation abnormalities, and severe coronary, pulmonary, kidney, or liver disease. Advantages of ANH include decreased risk of human error, as no compatibility testing is required, and lower cost than banked blood. The disadvantages of ANH include its cost and decreased oxygen delivery to the tissues if hemoglobin is reduced drastically.
For ANH, blood is collected from the patient (usually via a large-bore IV) before the anticipated blood loss, which is usually before the surgical incision. The allowable blood loss is calculated by the formula
Where
Hct(i) = the initial hematocrit before the start of the procedureHct(f) = the final hematocrit after hemodilutionHct(avg) = the hematocrit average during the hemodilution process
The volume of blood removed is replaced with crystalloids/colloids just prior to the surgical process, such that the patient remains normovolemic with a minimum hematocrit of about 25 %. Crystalloids are replaced in a ratio of 3:1 (crystalloid/blood) and colloids in a ratio of 1:1. Though ANH will decrease the total oxygen carrying capacity of blood, compensatory mechanisms for oxygen delivery include an increase in cardiac output and oxygen extraction by the tissues. The removed blood is stored in CPD bags at room temperature for up to 6 h and then given back to the patient, when desired.
(iii)
Cell salvage
An effective method of blood conservation is intraoperative collection of blood from the surgical field, called as cell salvage. Cell salvage is utilized when a high degree of intraoperative blood loss is anticipated (>1.5–2 l) and includes procedures such as surgery for trauma and vascular, cardiac, orthopedic, transplantation, urologic, and gynecologic surgery. The advantages of using cell salvage are that blood compatibility is not required, with little risk of human error, and the cost is lower. Cell salvage, however, is contraindicated in patients with malignancy (risk of cancer dissemination), infection, clotting abnormalities, or contamination with urine, fat, or bowel contents. Studies of cell saver use show minimal bacterial load in the returned blood, which is further reduced or eliminated altogether by antibiotic prophylaxis and by the use of the leukoreduction filter. The disadvantages of using cell salvage include availability of trained personnel, specialized equipment, and associated costs.
Blood is suctioned by the surgeon into the container of the cell salvage device. Heparin is then added to the blood by the perfusionist or a specially trained nurse to provide anticoagulation. Typically after approximately 500 ml of blood has been collected, the cell salvage machine is activated, which centrifuges the blood to separate out the RBCs. The RBCs are then washed, suspended in saline, and reinfused to the patient, when desired, in a packaging very similar to that of a blood bank unit of blood. The reinfusate has a hematocrit of 50–70 %.
Excessive use of cell salvage blood has its own complications. These include dilution of clotting factors and platelets, causing coagulopathy, since only the RBCs are reinfused to the patient. Moreover, the salvaged blood can be contaminated with bacteria and debris from the surgical field.
Perioperative Transfusion Criteria
Quantification of the blood loss
Quantification of blood loss is done by visual inspection. Blood loss is calculated by measuring the blood collected in the suction canister, sponges, and pads and by visual inspection of the surgical field. A 4 × 4 sponge holds about 10 ml of blood, while a pad holds about 100–150 ml of blood. Serial estimation of hematocrit reflects the ratio of the blood cells to the plasma and is affected by sudden fluid shifts; therefore, do not reliably estimate the actual blood loss.
Monitoring the vital signs
The parameters utilized to measure fluid status and blood loss include urine output, arterial blood pressure, and heart rate. Additional parameters include analysis of arterial blood gases, central venous pressure, mixed venous saturation, and echocardiography. Significant fluid or blood loss may be indicated by a decrease in urine output, hypotension, tachycardia, acidosis, low CVP (<6 mmHg), and low mixed venous saturation and cardiac output. The patient, if not adequately resuscitated, progresses from normovolemia to hypovolemia and finally to hypovolemic shock (hypoperfusion of the organs and tissues).
Transfusion triggers
Morbidity and mortality are associated with unnecessary transfusion, as healthy patients with a hemoglobin of 10 g/dl rarely require a transfusion. Transfusions should be administered when the benefits are thought to outweigh the risks. It should be remembered that there is not one specific laboratory value, or transfusion trigger, that is appropriate to transfuse all patients. The clinician must take into account the entire picture: the estimated blood loss, patient’s vital signs, comorbid illnesses of the patient, and laboratory valves when deciding to transfuse. The three most common parameters that are taken into consideration for transfusing are the degree of anemia, coagulopathy, and thrombocytopenia.
(i) Degree of anemia
The amount of hemoglobin in the RBCs reflects the oxygen carrying capacity of the blood. As blood is lost, the viscosity of the blood decreases, and this may in fact increase the delivery of oxygen to the tissues. This is considered to optimally happen at a hemoglobin of around 10 g/dl. However, a further decline in hemoglobin has to be closely monitored. Most patients tolerate hemoglobin levels between 7 and 9 g/dl. Below a hemoglobin level of 7 g/dl, patients experience impaired cognition and an increase in postoperative mortality. Therefore, most clinicians consider a hemoglobin level of 7 g/dl as an automatic trigger for blood transfusion. In patients with ST changes on the electrocardiogram, blood transfusion is initiated at a higher hemoglobin level (10 g/dl).
(ii) Coagulopathy
Presence of acute coagulopathy may require administration of both FFP (provides clotting factors) and platelets (to correct thrombocytopenia). About 10–15 ml of FFP per kg of body weight can be transfused to rapidly correct anticoagulation with warfarin. About 30 % level of clotting factors is required to achieve hemostasis. Intraoperatively, FFPs are administered when the PT or aPTT is prolonged >1.5 times the reference values or when blood loss exceeds one blood volume (70 ml/kg or when >6 units of PRBCs have been transfused). During massive transfusion, FFPs are administered in a 1:1 ratio with PRBCs. Cryoprecipitate contains concentrated clotting factors VIII, XIII, von Willebrand factor, and fibrinogen and is commonly used for the treatment of hypofibrinogenemia (fibrinogen <150 mg/dl). Commercially available factor VIII concentrates are available for treating hemorrhage due to hemophilia A or von Willebrand disease. In addition, recombinant activated factor VII concentrate can be used in acute hemorrhage.
(iii) Thrombocytopenia
To form an effective clot, platelets are required in sufficient number and adequate function. Platelet transfusions are administered to treat thrombocytopenia. However, in the presence of platelet dysfunction (antiplatelet drugs, cardiopulmonary bypass), it is more effective to treat the cause of the platelet dysfunction. In the surgical setting, thrombocytopenia without platelet dysfunction should be treated with platelet transfusions for a count less than 50,000/μl. In presence of platelet dysfunction, perioperative platelet transfusion is indicated even when the count is greater than 50,000/μl. For neurosurgical/ophthalmologic operations, where small bleeding can create complications, the minimum threshold for platelet transfusion is 80,000–100,000 platelets/μl.
Complications of Transfusion
Human Error
The most common cause resulting in complications from blood transfusion is human error. This can occur during collection of blood sample (labeling error), incorrect patient ID band, or faulty checking before transfusion.
Acute Hemolytic Reaction
This is the most serious complication usually resulting from ABO compatibility, causing an immune reaction in the patient. The transfused cells are lysed by the antibodies present in the patient’s serum. Signs of hemolytic reaction include chills, fever, urticaria, chest and flank pain, hypotension, tachycardia, and hemoglobinuria (red urine). This can progress to shock, renal failure, or DIC. Many of these signs are masked by general anesthesia.
When a hemolytic reaction is suspected, the transfusion is immediately stopped, and supportive care instituted. Blood pressure and renal function are supported by administration of fluids and vasopressors. Diuretics may be administered to initiate diuresis. A blood sample from the patient and the blood being used are sent to the blood bank for confirmation of incompatibility. Additionally, coagulation studies, platelet count, and urinary hemoglobin should be measured.
Delayed Hemolytic Reaction
This type of reaction is called extravascular hemolytic reaction, where there is extravascular hemolysis of donor erythrocytes. The reaction is usually mild, occurs about 3 days–3 weeks after transfusion, and occurs to non-D antigens of the Rh system. Pregnancy can also lead to formation of these antibodies. Following transfusion, antibodies are formed by the patient against the non-D antigens. Subsequent transfusion leads to the antibody response against the antigens. The symptoms are self-limiting and include mild fever, jaundice (increased bilirubin), hemoglobinuria, and spherocytosis on blood smear. Diagnosis of the delayed hemolytic reaction can be confirmed by a Coombs (antiglobulin) test.
Febrile Nonhemolytic Reaction
Febrile reactions can occur as part of an acute hemolytic reaction or due to nonhemolytic causes. The latter occur due to white cell or platelet sensitization. Febrile nonhemolytic reactions are relatively common (1–3 %) and are characterized by an increase in temperature (usually by 1 °C), without hemolysis. Antipyretics should be administered with continuation of the blood transfusion. However, when the febrile reaction is severe, the transfusion may have to be discontinued. Such patients should receive red cells with low white cell count, which are removed by washing, filtration, or centrifugation. Platelets are stored at room temperature, and units are prone to bacterial contamination, which can lead to a febrile reaction and even sepsis.
Allergic Reactions
Allergic reactions may include urticaria or severe anaphylactic reaction. Urticarial reactions are relatively common (1 %) and due to sensitization of the patient to plasma proteins. Signs of an urticarial reaction include itching, hives, and erythema, without any fever. Urticarial reactions can be treated by administering an antihistaminic (diphenhydramine) and then continuing the transfusion. However, anaphylactic reactions, though rare, are life-threatening and require aggressive treatment. These reactions typically occur in patients with IgA deficiency, who have IgA antibodies and receive IgA-containing blood transfusions. Treatment of anaphylaxis includes stopping the transfusion, administering epinephrine, and supportive care. Such patients should receive IgA-free blood units.
Transfusion-Related Acute Lung Injury
Within 3–6 h of transfusion (PRBCs/FFP), an acute respiratory syndrome can develop, which is characterized by non-cardiogenic pulmonary edema, dyspnea, hypoxia, and bilateral chest infiltrates on a chest radiograph and a PaO2/FiO2 ratio <200. Transfusion-related acute lung injury (TRALI) is supposed to occur in 1:5,000 blood transfusions and is considered as the leading cause of death. Most cases of TRALI appear to be caused by donor plasma anti-leukocyte or anti-HLA antibodies that recognize recipient leukocytes or recipient HLA cell surface markers and then activate an inflammatory response. TRALI is more common with FFP transfusions. Treatment is supportive and includes stopping the transfusion, mechanical ventilation, and maintaining the vital signs (correction of any associated hypotension).
Immunosuppression
Blood transfusion causes immunosuppression, which predisposes the patients to infections. Similarly, in patients with cancer, suppression of cell-mediated immunity by blood transfusion may cause tumor recurrence. These effects are, however, difficult to prove because patients receiving blood transfusions may be sicker to start with. Logically, administration of FFPs is more prone to cause immunosuppression than PRBCs.
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