Unformatted text preview: Blood Products & Blood Products & Transfusion
Drew Davenport D.O.
6/20/06 Compatibility Testing
Compatibility Testing Compatibility testing involves three separate procedures involving both donor and recipient blood.
1. ABO & Rh blood type identification
2. Antibody screening of donor plasma
3. Donor/recipient crossmatch ABO and Rhesus Typing
ABO and Rhesus Typing Determine the ABO blood type and Rh status of both the donor and recipient.
Most of the fatal hemolytic transfusion reactions result from the transfusion of ABO incompatible blood.
Blood types are defined by the antigens present on the surface of the RBCs. Type A has A antigens on the surface of their red cells.
Type B has B antigens Type AB has both A and B antigens
Type O has neither antigen The serum contains antibodies to the AB antigens that are lacking on the RBC.
Type A has antibodies against the B antigen Type B has antibodies against the A antigen
Type AB has no antibodies
Type O has both antiA and antiB antibodies Compatible Blood Types
Compatible Blood Types To determine which types are compatible you need to focus on which antibodies will be present in the recipient plasma. It is the reaction of the antibodies with donor RBC antigens that can activate the complement system and lead to intravascular hemolysis of the red cell.
Type O is the universal donor
Type AB+ is the universal recipient Rhesus (D) Antigen
Rhesus (D) Antigen Patients with the Rhesus (D) antigen are said to be Rh+ and those without are Rh
AntiD antibodies are not constitutively present in the serum of an Rhnegative patient.
6070% of Rh patients exposed to Rh+ RBCs will develop antiD antibodies
There is a latency period before the antibodies are synthesized. Blood types in the U.S. Population
Blood types in the U.S. Population
Group Whites Blacks O 45% 49% A 40% 27% B 11% 20% AB 4% 4% Rh+ 85% 92% The Antibody Screen
The Antibody Screen The antibody screen (which is an indirect Coombs test) is performed to identify recipient antibodies against RBC antigens.
Commercially supplied RBCs which have been selected for certain antigens they possess, are mixed with both donor and recipient serum to screen for the presence of unexpected antibodies.
If the recipient plasma screen is positive, the antibody will be identified and appropriate antigen negative donor units will be selected. Antibody Screen
Antibody Screen If the patient has been transfused since the last antibody screening test, then the test should be repeated.
Only 4 in 1,000 donations have unexpected antibodies.
Estimated that only 1 in 10,000 screens will miss a potentially dangerous antibody.
If the screen is negative only 1 in 50,000 units given will result in a hemolytic reaction. The Crossmatch
The Crossmatch Donor RBCs are mixed with recipient serum.
The test is performed in three phases and takes about 45minutes.
Phase 1 The Immediate Phase
Phase 2 The Incubation Phase
Phase 3 The Antiglobulin Phase The Immediate Phase
The Immediate Phase The Immediate phase serves primary to ensure that there are no errors in the ABO typing.
The test is performed by mixing donor RBCs and patient serum at room temperature for macroscopic agglutination.
The test takes 15 minutes and detects ABO incompatibility and those antibodies in the MN, P, and Lewis systems. The Incubation Phase
The Incubation Phase This second phase involves incubation of the first phase reaction at 37° C in albumin and/or lowionic strength salt solution.
This aids the detection of incomplete antibodies that are able to attach to a specific antigen but are unable to cause agglutination in a saline solution. This phase takes 3045 minutes to complete and primarily detects antibodies in the Rh system. The Antiglobulin Phase
The Antiglobulin Phase This third phase of the crossmatch involves the addition of antiglobulin sera to the incubated test tubes.
With this addition antibodies present in the sera become attached to the antibody globulin on the RBCs causing agglutination.
This phase identifies the most incomplete antibodies from all blood groups systems including Rh, Kell, Kidd, and Duffy systems.
This third phase is only performed on blood yielding a positive antibody screen and requires 6090 minutes. In previously transfused patients (or exposed during pregnancy), only 1 in 100 will have an antibody other than the antiA, antiB, and/or antiRh antibodies and many of these are none reactive at physiologic temperatures.
Determining the ABO & Rh status alone yields a probability that the transfusion will be compatible in 99.8% of instances.
The addition of the antibody screen improves the compatibility to 99.94% and with a complete crossmatch to 99.95%. Blood Products
Blood Products Whole Blood
Red Blood Cells
Fresh Frozen Plasma
Cryoprecipitate Red Blood Cells
Red Blood Cells Whole blood is collected in bags containing citratephosphatedextroseadenine (CPDA) solution. The citrate chelates the calcium present in blood and prevents coagulation. The PRBCs are then prepared by centiugation of the whole blood.
CPDA blood has a Hct of 7075% and contains 5070 mL of residual plasma for a total volume of 250275 mL and a shelf live of 35 days. Additive Solution
Additive Solution With the additive solution preparation the original preservative and most of the plasma is removed and replaced with 100 mL of Additive Solution. Lower Hct, 60% Less citrate per unit
7580% fewer microaggregates
Longer shelf life, 42 days
Blood is able to regenerate 2,3DPG more rapidly. RBC Preparations
RBC Preparations Salinewashed RBCs may be used for patients that experience reactions to foreign proteins.
White cells can be removed by washing, irradiation, or leukofiltration.
One unit of RBCs will increase the Hb and Hct of a 70kg adult by approximately 1g/dL and 3% respectively. ASA Task Force Guidelines
ASA Task Force Guidelines RBCs should usually be administered when the hemoglobin concentration is low (for example less than 6 g/dL in a young otherwise healthy patient) and the blood loss is acute, and transfusion is usually unnecessary when the hemoglobin is greater than 10 g/dL
The determination of whether intermediate levels of hemoglobin (between 610) justify or require RBCs should be based on any ongoing indication of organ ischemia, potential or ongoing bleeding, patient’s intravascular volume status and the patient’s risk factor for complications of inadequate oxygenation Fresh Frozen Plasma
Fresh Frozen Plasma Plasma is separated from the RBC component of whole blood by centrifugation.
One unit has a volume of 200250 mL and contains all the plasma proteins, particularly factors V and VIII. It also contains the preservative added at the time of collection. FFP is frozen promptly to preserve two labile clotting factors (V and VIII) and thawed only immediately prior to administration.
FFP must be ABO compatible but Rh+ plasma can be given to Rh recipients, but should be avoided in young females because of the possibility of alloimmunization to the Rh antigen. ASA Task Force Guidelines ASA Task Force Guidelines For urgent reversal of warfin therapy (dose is 58 mL/kg of FFP)
For correction of known coagulation factor deficiencies for which specific correlates are unavailable.
For correction of microvascular bleeding in the presence of increased (>1.5 times normal) prothrombin time or partial thromboplastin time. For correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than one blood volume and when PT and aPTT cannot be obtained in a timely fashion.
FFP should be given in doses calculated to achieve a minimum of 30% of plasma factor concentration. (usually achieved with 1015mL/kg of FFP)
FFP is contraindicated for augmentation of plasma volume or albumin concentration
For cases of antithrombin III deficiency
Treatment of immunodeficiencies Treatment of thrombotic thrombocytopenia purpura Platelets
Platelets The platelets are separated from the plasma by centrifugation.
Platelets are supplied either as single donor units or as a combination of multiple donors.
One unit of platelets will increase the platelet count of a 70 kg adult by 5 to 10,000/mm³. Platelet viability is optimal at 22° C but storage is limited to 45 days.
Platelets have both the ABO and HLA antigens. ABO compatibility is ideal but not required. (incompatibility will shorten the life span of the platelet) ASA Task Force Recommendations
ASA Task Force Recommendations Prophylactic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (e.g. ITP)
Prophylactic platelet transfusion is rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when the platelet count is >100,000 and is usually indicated if the count is <50,000. ASA Task Force Recommendations
ASA Task Force Recommendations Vaginal deliveries or operative procedures ordinarily associated with insignificant blood loss may be undertaken in patients with platelet counts less than 50,000.
Platelet transfusion may be indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding. Cryoprecipitate
Cryoprecipitate Cryoprecipitate is the precipitate that remains when the FFP is thawed slowly at 4° C. It is a concentrated source of factor VIII, factor XIII, vWF, and fibrinogen.
One unit of cryoprecipitate (which is the yield from one unit of FFP) contains sufficient fibrinogen to increase fibrinogen level 5 to 7 mg/dL. It usually comes in containers with 10 to 20 units. Cryoprecipitate
Cryoprecipitate ABO compatibility is not essential because of the limited antibody content of the associated plasma vehicle (10 to 20 mL)
Viruses can be transmitted with cryoprecipitate.
It is stored at 20°C and thawed immediately prior to use.
Cryoprecipitate is used in the treatment of factor VIII deficiency, hemophilia A and fibrinogen deficiencies. Transfusion Risks
Transfusion Risks Risks of blood transfusion can be divided into two catagories
NonInfectious Infectious Risks
Infectious Risks The transmittable risks are numerous and include:
Hepatitis A, B, C, D, E
Human Tcell lymphotropic viruses (HTLV1 & HTLV2)
HIV1 & HIV2
West Nile Virus
EpsteinBarr virus Infectious Risks
Infectious Risks Parvovirus B19
GBVC virus (also called hepatitis G)
Transfusiontransmitted virus (TTV)
Prions including CreutzfeldtJakob and variant
Bacterial infections including: malaria, Chagas disease, ehrlichiosis, babesiosis, and syphilis. Transfusion Estimates
Transfusion Estimates Estimates of the frequency of infections are from North America and derived from the observed rates of seropositivity among donors and the statistical likelihood of administration of blood from donors whose infection is in the “window period” between contracting the virus and detectability by the available assays. With the recent advent of nucleic acid testing transmission rates are at very low levels. Hepatitis B
Hepatitis B Rate of infection 1 in 350,000
A NAT is now available and will most likely be implemented by 2008
Estimated that only 35% of HBV exposed patients will develop acute disease
85% of patients the disease resolves spontaneously, 9% develop chronic persistent hepatitis, 3% develop chronic active hepatitis, 1% develop hepatocellular carcinoma. Hepatitis C
Hepatitis C Rate of infection is 1 in 2,000,000
HCV generally has a mild initial presentation, however, 85% of patients progress to a chronic state with significant associated morbidity and mortality.
20% of chronic carriers develop cirrhosis 1 to 5% develop hepatocellular carcinoma Hepatitis A
Hepatitis A Rate of infection is very rare.
Blood banks screen for HAV by history only and there is no carrier state for this virus.
The infectious period is limited to 1 to 2 weeks
The diagnosis depends on hepatitis antibody seroconversion. Human Immunodeficiency Virus
Human Immunodeficiency Virus The most feared complication of any blood transfusion is the transmission of HIV
The rate of transmission is 1 in 2,000,000
HIV is a retrovirus, so called because its propagation requires translation of RNA to DNA
The incidence has fallen dramatically since NAT testing.
In the 1980’s rate of infection was 1 in 100. In 1997 the rate was 1 in 400,000. Human TCell Lymphotropic Virus
Human TCell Lymphotropic Virus HTLV1 and HTLV2 belong to the same retrovirus family as HIV.
The rate of infection is 1 in 2,900,000
The incidence of clinical disease is very low. They are associated with Tcell leukemia and lymphoma rather than the generalized immunodeficiency of AIDS. Cytomegalovirus
Cytomegalovirus Transfusionassociated CMV infections are usually benign and selflimited.
CMV can cause serious, even fatal infections in the immunocompromised. Patients at risk include premature neonates, solid organ and bone marrow transplant recipients, and those with severely depressed immune function.
Leukoreduction of RBCs reduces but does not prevent CMV transmission. West Nile Virus
West Nile Virus WNV is a mosquitoborne flavivirus. It became epidemic in 2002 in the Midwestern states.
The majority of infected individuals are either asymptomatic or develop only a mild illness, encephalitis or meningitis can occur.
Death rate among confirmed cases is between 510%.
Transmission by blood transfusion and organ transplantation has been confirmed. West Nile Virus
West Nile Virus The window period between infection and clinical symptoms is short around 3 days.
The period of infectivity also appears to be relatively brief also.
NAT testing for WNV is being performed in areas of high incidence. Parasitic Diseases
Parasitic Diseases Transfusiontransmitted malaria is relatively common in regions where the disease is endemic, but has been rare in the United States.
The parasites reside within the red blood cell, so the hazard is almost exclusively with RBC transfusion.
Chagas disease is caused by a protozoan and is endemic to South and Central America PrionRelated Diseases
PrionRelated Diseases Prions are the causative agents of CreutzfeldtJakob disease (CJD) and variant CreutzfeldtJakob disease (vCJD).
Both are fatal degenerative neurologic diseases caused by an abnormally folded variant of a protein that is constitutively present.
The risk of transfusion related transmission is undefined. Only one case of transfusion related vCJD reported.
The incubation period is up to 6 years, so the true rate may be under recognized. Between 1984 and 2004 156 cases of vCJD had been reported. All within the U.K. except for 10 cases. Bacterial Contamination
Bacterial Contamination occurs at a much higher frequency than any other infections and is associated with substantial mortality. Rate of bacterial infection/contamination:
RBCs 1 in 30,000
Platelets 1 in 2,000
The higher rate with platelets is because they are stored at room temperature and the units are generally pooled between 6 and 10 donor units. Bacterial Contamination
Bacterial Contamination Fatalities are estimated to be between 1 in 16 million transfused units.
The source of the bacteria can be donor blood, donor skin flora, or contaminants introduced during collection, processing, and storage.
Numerous grampositive and gramnegative organisms can occur. In order of frequency they are; Staphyloccus aureus, Klebsiella pneumoniae, Serratia marcescens, and Staphyloccus epidermidis. Bacterial Contamination
Bacterial Contamination The patient who receives contaminated blood will rapidly experience some combination of fever, chills, tachycardia, emesis, and shock. The patient may also develop DIC and acute renal failure.
If the index of suspicion is high then the blood transfusion should be stopped immediately and blood cultures taken. Exposure Estimates
Hepatitis B 1 in 350,000 Hepatitis C 1 in 2,000,000 HIV 1 in 2,000,000 HTLV 1 in 2,900,000 Bacterial reactions from RBC 1 in 30,000 Platelets 1 in 2,000 Noninfectious Risks
Noninfectious Risks The noninfectious risks associated with blood products are generally immunologically mediated.
Reactions can occur as a result of the antibodies that are constitutive (AntiA or AntiB) or ones that have been formed as a result of prior exposure to donor RBCs, WBC, platelets, or proteins. Noninfectious Risks
Noninfectious Risks The noninfectious adverse reaction with their approximate incidences are:
Acute hemolytic transfusion reaction 1 in 25,000 to 50,000
Delayed hemolytic transfusion reaction 1 in 2,500
Minor allergic reactions 1 in 200 to 250
Anaphylactic/toid reactions 1 in 25,000 to 50,000
Febrile reactions 1 in 200
Transfusion related acute lung injury 1 in 5,000 Acute Hemolytic Transfusion Acute Hemolytic Transfusion Reactions (AHTR) Hemolysis of donor RBC’s often leads to acute renal failure, DIC, and death
Of the >300 antigens on the RBC, only several will produce these reactions: antiA, antiB, antiKell, antiKidd, antiLewis, and anti
ABO incompatibility is second only to TRALI of the three leading causes of transfusion related death AHTR
AHTR When incompatible blood is given, antibodies and complement in the recipient plasma attack the antigens on the donor RBC.
The antigenantibody complex activate the Hageman factor (factor XII), which acts on the kinin system to produce bradykinin
Bradykinin increases capillary permeability and dilates arterioles, both which cause hypotension AHTR
AHTR Activation of the complement system results in the release of histamine and serotonin from mast cells resulting in bronchospasm.
30% to 50% of patients develop DIC
Renal damage occurs for several reasons, blood flow is reduced because of hypotension and renal vasoconstriction, free hemoglobin can cause a mechanical obstruction, and if DIC occurs fibrin thrombi can be deposited in the renal vasculature Signs and Symptoms of AHTR
Signs and Symptoms of AHTR Fever
Nausea and Vomiting
Flushed appearance and dyspneic
Chest pain and back pain
Pt is restless, and has a headache
Hemoglobinuria, and possible diffuse bleeding Symptoms under GA
Symptoms under GA Many signs and symptoms will be masked by general anesthesia. Hypotension, hemoglobinuria, and diffuse bleeding may be the only clues that a transfusion reaction has occurred
A reasonable index of suspicion should be maintained while administering blood products under GA Management of AHTR
Management of AHTR If a reaction is suspected, the transfusion should be stopped and the identity of the patient and the labeling of the blood rechecked.
Management has 3 main objectives
Maintenance of systemic blood pressure
Preservation of renal function
Prevention of DIC Management of AHTR
Management of AHTR Lab tests should include a repeat crossmatch and a direct antiglobulin (Coombs) test.
The direct antiglobulin test is the definitive test for an acute hemolytic transfusion raction.
It examines recipient RBCs for the presence of surface immunoglobulins and complement. Patient serum is also examined for antibodies that react with donor cells Delayed Hemolytic Transfusion Delayed Hemolytic Transfusion Reaction (DHTR) This reactionoccurs when the donor RBCs have an antigen to which the recipient has been previously exposed by transfusion or pregnency, however over time the antibodies fall to levels too low to be detected by compatibility testing
When reexposure occurs the pt. undergoes an anamnestic response and produces more antibody that eventually lyses the foreign RBCs DHTR
DHTR Evidence of hemolysis is usually evident by the first or second week after exposure
Symptoms are a low grade fever, increased bilirubin with or without jaundice, and a reduction in hemoglobin
Diagnosis confirmed by a Coombs test
The reaction is selflimiting and the clinical manifestations resolve as the transfused cells are removed Minor Allergic Reactions
Minor Allergic Reactions Allergic reactions to proteins in donor plasma can cause urticarial reactions in 0.5% of all transfusions
The reaction is almost always associated with FFP administration
The pt. may have itching, swelling, and a rash as a result of histamine release
Treatment is with diphenhydramine Anaphylactic Reactions
Anaphylactic Reactions This occurs in pts with hereditary IgA deficiency who have been sensitized by previous transfusions or pregnancy an are exposed to blood with foreign IgA protein
Reactions include dyspnea, bronchospasm, hypotension, laryngeal edema, chest pain, and shock
Treatment is with epinephrine and methylprednisolone Febrile Reactions
Febrile Reactions Patients who receive multiple transfusions often develop antibodies to the HLA antigens on the passenger leukocytes
During subsequent RBC transfusions, febrile reactions may occur as a result of antibody attack on donor leukocytes
The response occurs in 12% of all RBCs transfused
Temperature increase of greater than 1 degree centigrade within 4 hours that resolves within 48 hrs TransfusionRelated Acute Lung TransfusionRelated Acute Lung Injury (TRALI) TRALI is a noncardiogenic form of pulmonary edema associated with blood product administration It is associated with administration of all blood products but occurs most frequently with RBCs, FFP, and platelets
The incidence is 1 in 5000 units transfused TRALI has a mortality of 5 to 8%
TRALI was the most common cause of transfusion related death from 20012003 TRALI
TRALI TRALI occurs when agents present in the plasma phase of donor blood activate leukocytes in the host
Those agents are usually antileukocyte antibodies in donor blood formed as a result of a previous transfusion or pregnancy
TRALI usually requires a preexisting condition such as sepsis, trauma or surgery TRALI
TRALI The clinical appearance is similar to adult respiratory distress syndrome (ARDS)
Symptoms usually begin within 6 hours after the transfusion and often more rapidly, the patient develops dyspnea, cyanosis, chills, fever, hypotension and noncardiogenic pulmonary edema
CXR reveals bilateral infiltrates
Severe pulmonary insufficiency can develop TRALI
TRALI Treatment is largely supportive
The transfusion should be stopped if the reaction is recognized in time
The patient should receive oxygen and ventilatory support as necessary, usually with a low tidal volume strategy Other NonInfectious Risks
Other NonInfectious Risks Hypothermia
Decrease in 2,3DPG
Microaggregate Delivery ...
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