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Alpha thalassemia intermedia (Hemoglobin H Disease) results from a deletion of three out of four alpha chain gene loci. Infants born with alpha thalassemia intermedia appear normal at birth but often develop anemia and splenomegaly by the end of their first year. Development and life expectancy are usually normal, but some affected individuals may require splenectomy and transfusion therapy.Hepatomegaly is not a common finding and there may be some association with mental retardation. Due to the hemolytic nature of this anemia, there may be an increase in respiratory infections, leg ulcers and gallstones. Skeletal changes are not commonly seen in hemoglobin H disease.Any ethnic group can have occurrences of hemoglobin H disease; but it is most often seen in Southeast Asia, the Middle East and the Mediterranean islands.

A 42-year-old male received 6 units of RBCs during open heart surgery 6 months ago. His antibody screen was negative at that time. He has returned for a follow up surgery and his antibody screen is now positive with both screen cells at the AHG phase.Reactions are occurring at AHG phase, which indicates a possible clinically significant antibody, Jka showing dosage. Refer to Case Study 1 panel below to see reactions of antibody panel.IS = Immediate Spin; AHG = Antihuman Globulin Phase; CC = Check Cells; AC = Auto Control; ND= Not doneCase study 1 conclusion:Patient's previous transfusion 6 months ago exposed him to the Jka antigen, causing the formation of this antibody, which is known for showing dosage.

Antibodies are immunoglobulin proteins secreted by B-lymphocytes after stimulation by a specific antigen. The antibody formed binds to the specific antigen in order to mark the antigen for destruction.The type of antigenic exposure occurring in the body determines if the antibody is a naturally occurring or immune antibody.Naturally occurring antibodies can be formed after exposure to environmental agents that are similar to red cell antigens, such as bacteria, dust or pollen. Sensitization through previous transfusions, pregnancy or injections is not necessary. These antibodies are usually IgM and react best at room temperature or lower. Most of these antibodies are not clinically significant with the exception of ABO antibodies. Examples of naturally occurring antibodies include anti-A, anti-B, anti-Cw, anti-M, and antibodies in the Lewis and P system.

The panel below shows reactions in the AHG phase only (clinically significant). Pattern reactivity of sample matches the pattern displayed by C on the panel. Anti-C is a clinically significant antibody that can cause both hemolytic disease of the newborn (HDN) and hemolytic transfusion reaction (HTR).ND= not done

Antibodies have optimum temperatures for reactivity. Reaction readings can be made at different phases: after immediate spin, after incubation at 37°C, and after the addition of antihuman globulin (AHG) and centrifugation. Reactivity in a certain phase will help to determine whether the antibody is cold reacting (IgM) or warm reacting (IgG). It will also help to distinguish between antibodies that are clinically significant and not significant. Clinically significant antibodies that are capable of causing acute and delayed hemolytic transfusion reactions (HTR) or hemolytic disease of the newborn (HDN) are usually IgG and react best in the AHG phase.Readings can be done at all three phases if a tube method is used. If a gel method is used, readings are done only at AHG. Immediate spin: Antibodies reacting in this phase tend to be cold reactive. They are usually IgM class and not clinically significant (with the exception of the A and B antibodies). 37°: Antibodies that react in this phase include strong IgM or IgG antibodies. After incubation, the tubes are examined for the presence of hemolysis. If complement was bound during incubation then hemolysis could be seen. NOTE: This reaction would only occur in serum samples. If EDTA plasma samples are used for testing, the complement cascade has been halted. Magnesium and calcium ions are not available for complement to be activated. AHG:Antibodies reacting in this phase are considered clinically significant. They are usually warm reactive and IgG.

Beavers C, Kern W, Blick K. Isolated acute thrombocytopenia in a 21-year-old caucasian male. Lab Med. June 2009;40(6):337-339.Bromberg MB. Immune thrombocytopenic purpura, the changing therapeutic landscape. N Engl J Med. 2006; 355:1643-1645. Glassy EF. ed. Color Atlas of Hematology. Northfield, IL: College of American Pathologists; 1998.Kwon JY, Shin JC, Lee JW. Predictor of idiopathic thrombocytopenic purpura in pregnant women presenting with thrombocytopenia. Int J Gynacol Obstet. 2007;85-88. Taghizadeh, M. An update on immune-mediated thrombocytopenia. Lab Med. 2008;39(1):51-54.Tarr PI, Gordon CA, Chandler WE. Shiga like toxin producing Escherichia coli and hemolytic uremic syndrome. Lancet. 2005;365:1073-86.Woelke C , Eichler P. Washington G, etal. Post transfusion purpura in a patient with HPA-1a and GP1a/11a antibodies. Transfus Med 2006;16:69-72. Wyrick-Glatzel J.Thrombotic thrombocytopenic purpura and ADAMTS-13: New insights into pathogenesis, diagnosis and therapy. Lab Med. 2004;35(12):733-737.

Transplacental ITP may occur in newborn infants who are born to mothers with ITP. If the mother has had one baby born with thrombocytopenia, it is usually an indication that all subsequent infants will also be born with thrombocytopenia. A very small percentage of babies born with ITP will have severe thrombocytopenia. Neonatal alloimmune thrombocytopenia (NAIT) is caused by platelet destruction that is the result of alloantibodies stimulated by foreign antigens during pregnancy or blood transfusions. Platelet destruction by alloantibodies may occur in neonates if the mother lacks the platelet-specific antigen but the baby has inherited the antigen from its father. When maternal IgG antiplatelet antibodies cross the placenta, immune destruction of the neonate's platelets occurs. The major concern with both of these conditions is intracranial bleeding if the neonate's platelet count is less than 50 X 109/L. NAIT has a high mortality rate due to bleeding into the central nervous system. Prompt diagnosis of the condition and treatment is critical. The thrombocytopenia lasts on average 3 - 4 weeks postnatal until the maternal antibodies have cleared the newborn's system.

Laboratory quality indicators are commonly measured as averages or percentages. For example:The turnaround time (TAT) for HIV Western Blot averages 3.5 days.Type O units are available 99.9% of the time in an emergency release.In the first example, it might appears that 3.5 days is a reasonable TAT for a sendout test at first glance, but an average of 3.5 days means the result can be available anytime between the same day to a week later. A patient may have to schedule an appointment at least one week later to ensure the result is available. This may potentially delay treatment. As for the physicians, they want to know when their patients' results will come back; they are not interested in knowing the average but exactly when the result will be available. In the second example, 99.9% might sound impressive but it would translated into 1 out of every 1000 patients requiring emergency transfusion being at risk of ABO hemolytic reaction. In fact if 99.9% is used to measured quality of the processes that happened in our everyday life, that would translate into:18 plane crashes daily17,660 mail mix-ups hourly3,700 medication errors daily10 dropped babies daily$24.8 million worth of incorrect charges hourly500 wrong procedures performed weekly.Other industries realized long ago that measuring quality based on percentage or average is not adequate to satisfy the customers. The need for a higher standard of quality led to the use of Six-Sigma.

Children with beta thalassemia major, also called Cooley's anemia, usually develop clinical signs during their first year of life. They appear to be malnourished and may exhibit abdominal girth expansion. They show bone marrow expansion and skeletal deformations, which are a result of increased erythropoiesis due to low hemoglobin levels. A common finding is facial bone changes caused by this bone marrow expansion (sometimes referred to as Mongoloid facial features). Other clinical signs include frequent infections, hepatomegaly, splenomegaly, gall stones, leg ulcers, iron toxicity, and poor growth and sexual development. In addition, cardiac failure due to increased burden of the heart attempting to oxygenate the tissues, can lead to serious complications and death if the condition is not treated.In general, death usually occurs by the time these patients are in their early twenties unless treated with blood transfusions along with iron-chelating agents. If no chelating agent is used during treatment life will only be prolonged by about a decade.The different genotypes associated with beta thalassemia major are: B0/B0, B0/B+, or B+/B+.

No blood is found in the urine of healthy individuals although samples from menstruating females, frequently, but not always, test positive for blood. Hematuria is associated with renal or genital urinary disorders in which the bleeding is the result of irritation to the involved organs or trauma. Examples include renal calculi, pyelonephritis, glomerulonephritis, tumors, trauma or exposure to toxic chemicals or drugs and/or strenuous exercise. Hemoglobinuria may be due to the lysis of red cells within the urinary tract. If it is caused by intravascular hemolysis, the hemoglobin is then filtered through the glomeruli. In the normal individual, the hemoglobin molecule attaches to haptoglobin and in this way bypasses the kidney filtration system. When the hemoglobin/haptoglobin system is overwhelmed, as in cases of hemolytic anemia, severe burns, transfusion reaction, infection or strenuous exercise, hemoglobin passes into the urine.

Patients who have factor deficiencies may or may not require immediate treatment based upon their risk of bleeding. For example, a patient may only need therapeutic treatment if they are having an invasive surgery or a dental procedure. For the patients who do require treatment, some of the current options are: Transfusion of Fresh Frozen Plasma (FFP) Administration of factor concentrates

Sequestration crisis occurs in sickle cell disorders when large numbers of RBCs are suddenly pooled in the spleen and liver. These organs can enlarge rapidly causing pain, hypoxemia, and hypovolemic shock. Treatment of sequestration crisis may include chronic transfusion, exchange transfusion, and/or splenectomy, depending on the patient's age and the severity of the sequestration (as determined by the hemoglobin level and degree of drop in hemoglobin).

Before beginning the course take some time to review and think about what you already know about HDFN. For example, jot down brief notes to answer the following questions: Which antibody causes the most severe HDFN? Antibodies in which blood group system are the most common cause of positive direct antiglobulin tests (DATs) in newborns but rarely cause clinically significant hemolysis? Should DATs be performed on all newborns regardless of maternal ABO and Rh blood groups? What is Rh immune globulin (RhIg), its source, constituents, purpose, and mechanism of action? Which tests are used to determine postnatal RhIg dosage? Which type of D variant can produce anti-D? What follow-up tests are typically indicated if a pregnant female has a positive antibody screen when initially tested? Which laboratory findings would suggest that an infant may have ABO HDFN? How can the clinical status of fetuses at risk for HDFN be monitored? What are the characteristics of red cells suitable for intravenous transfusion to fetuses suffering from severe HDFN due to anti-D?

Prenatal treatment of severe HDFN due to anti-D consists of in utero transfusions. Because of significant risks, transfusion is indicated only if fetal monitoring suggests significant hemolytic disease. 1. Intrauterine Transfusion (IUT)IUTs are done when fetal monitoring indicates severe HDFN and the fetus is too premature for early delivery. IUTs involve the intraperitoneal infusion of packed red cells. The success of the procedure depends on absorption of the red cells through the subdiaphragmatic lymphatic vessels of the fetus. 2. Intravenous transfusion (IVT)Because there may be erratic and inconsistent absorption of intrauterine transfusions in severely hydropic fetuses, IVTs were developed. IVTs involve transfusing donor RBC directly into the umbilical vein.

Besides exchange transfusion, postnatal treatment of HDFN may include the following:RBC TransfusionMany infants who have received IUTs also require simple RBC transfusions in the first few weeks of life to treat ongoing hemolysis caused by persistent maternal antibody in the newborn's circulation.Phototherapy Phototherapy is used to treat jaundice in preterm infants without HDFN and in infants with mild HDFN. Intensive phototherapy has also been used to treat moderate and severe HDFN and decrease the need for exchange transfusion. The newborn is placed under a "blue light" which chemically alters the bilirubin in the surface capillaries to a harmless substance. Human Serum AlbuminHuman serum albumin can also be transfused, either separately or as part of an exchange transfusion in place of FFP. Albumin binds unconjugated bilirubin, thus preventing its deposition in the fat-rich brain cells. Albumin must be used judiciously, because it can aggravate congestive heart failure.

Prenatal treatment Prenatal management and treatment of ABO HDFN is not routinely done because: Titers of anti-A and anti-B do not correlate well with severity of disease; The risks of fetal monitoring (e.g., amniocentesis, cordocentesis) and fetal transfusion are greater than the risk of ABO HDFN since it is usually mild and subclinical. However, if a woman has a history of infants with moderate to severe ABO HDFN requiring treatment, she may be monitored so that the infant can be treated for possible HDFN as soon as possible. Postnatal TreatmentTreatment of ABO HDFN usually consists of phototherapy in which the newborn is placed under a "blue light" that chemically alters bilirubin in the surface capillaries to a harmless substance.For more severe cases, exchange transfusion may be performed. Donor RBC for exchange transfusion in cases of ABO HDFN must meet these criteria: Group O; Rh compatible with infant; Less than or equal to 7 days old (or fresher); Reconstituted with AB FFP to obtain a prescribed hematocrit; CMV negative (or equivalent, e.g., leukoreduced by filtration); Negative for hemoglobin S to prevent blood from sickling under conditions of reduced oxygen concentration in the newborn; Irradiated to prevent graft-versus-host disease. Exchange transfusion is also discussed later in the course in the section related to HDFN due to anti-D and other antibodies. Red Blood Cells are crossmatched with maternal plasma, although the infant's plasma can be used if a maternal blood specimen is unavailable.

Diagnosis of ABO HDFN is supported by these findings: ABO incompatibility between mother and child, with mother typically group O; Maternal antibody screen negative; Cord DAT weakly positive or negative; Newborn hyperbilirubinemia with jaundice occurring in first 24 hours; Increased spherocytes and reticulocytosis in the newborn; Presence of IgG anti-A or anti-B in cord plasma / serum.

The Red Blood Cells (RBC) that are chosen for exchange transfusion must meet these criteria: ABO-compatible with mother and infant (usually group O) and lack antigens to any maternal IgG antibodies; If mother has anti-D, RBCs are group O Rh negative; No greater than 7 days old; Reconstituted with AB Fresh Frozen Plasma (FFP) to obtain a prescribed hematocrit, e.g., 45–60% (0.45–0.60); CMV negative (or equivalent, e.g., leukoreduced by filtration); Negative for hemoglobin S to prevent blood from hypoxia-induced sickling; Irradiated with a minimum dose of 25 Gray (Gy) to prevent graft-versus-host disease.RBC are normally crossmatched with maternal plasma, although the infant's plasma can be used if a maternal blood specimen is unavailable.

As applied to pregnancy, RhIg's purpose is to prevent immunization to the D antigen in the perinatal period and thus prevent HDFN due to anti-D. If the mother has already produced anti-D, RhIg is of no use in moderating the immune response.Accordingly, RhIg is routinely administered to Rh negative women not previously sensitized to the D antigen under the following circumstances:1, Antenatal. Antepartum prophylaxis of 300 µg (1500 IU) at about 28 weeks gestation in the USA and Canada, which could be weeks later, depending on how appointments are scheduled. To illustrate variation in antenatal international practice, in the UK, smaller doses of RhIg (e.g., 500 IU) may be given at 28 weeks and 34 weeks, although many UK facilities issue a 1500 IU dose at 28–30 weeks. With antenatal administration, the Rh of the fetus is usually unknown. Some transfusion services recommend a further antenatal dose if the infant is undelivered after 40 weeks.2. Postnatal. Prophylaxis of 300 µg (1500 IU) at delivery of an Rh positive or weak D infant within 72 hours of delivery whenever possible. If RhIg administration is delayed beyond 72 hours, laboratory policies differ as to when it would no longer be administered. The longer the delay, the more likely RhIg may fail to suppress production of anti-D, but it is still worth trying. Note: Because RhIg contains IgG anti-D, when given antenatally, it can cross the placenta and sensitize fetal D-positive red cells. Occasionally the fetus may be born with a weakly positive DAT, but significant hemolysis does not occur. For this reason some guidelines recommend that labs do NOT routinely perform DATs on infants whose mothers have received antenatal RhIg.

Of the main D variants, a female with partial D (or partial weak D) may develop anti-D to the D epitopes that she lacks. Moreover, partial D red cells adsorb little anti-D, thus leaving enough free RhIg to suppress immunization.However, most laboratories do not routinely differentiate between D variants and instead rely on routine tests and associated test protocols to determine a mother's Rh status for the purposes of RhIg administration. Policies differ between countries and even within countries. 1. Some labs do not test pregnant women for weak D and rely on routine D typing to determine Rh status. AABB Standards for Blood Banks and Transfusion Services, ed. 26 (2010) does not require weak D testing for Rh negative pregnant women, nor for patients requiring transfusion. Note, however, that College of American Pathologists (CAP) surveys have shown that more than 50% of responding laboratories do routinely perform weak D testing on such patients.2. Some labs perform weak D tests on pregnant women who appear to be Rh negative and, if weak D, do NOT inject with RhIg.3. Some labs perform weak D tests on pregnant women who appear to be Rh negative and, if weak D, inject with RhIg based on the possibility that they may be partial D and capable of forming anti-D.

The following published literature and online resources, while useful, should not be used as a substitute for technical and clinical judgment. Medical and technical information becomes obsolete quickly and current sources relevant to the user's location should always be consulted.References indicated by * provide a broad overview of HDFN and are highly recommended.LITERATUREAvent ND, Reid ME. The Rh blood group system: a review. Blood 2000 Jan 15;95 (2):375-87.Bowman J. Thirty-five years of Rh prophylaxis. Transfusion 2003 Dec;43(12):1661-6.* Eder AF. Update on HDFN: new information on long-standing controversies. Immunohematology 2006;22(4):188–195. (scroll to article)Eder, AF, Manno, C.S. Alloimmune hemolytic disease of the fetus and newborn. In Wintrobe's Clinical Hematology, 11th ed. (Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader BE, (eds). Philadelphia, PA: Lippincott, Williams & Wilkins, 2004.Flegel WA. Molecular genetics of RH and its clinical application. Transfus Clin Biol. 2006 Mar-Apr;13(1-2):4-12. Kennedy MS, McNanie J, Waheed A. Detection of anti-D following antepartum injections of Rh immune globulin. Immunohematology 1998;14(4):138-40.Koelewijn JM, de Haas M, Vrijkotte TG, van der Schoot CE, Bonsel GJ. Risk factors for RhD immunisation despite antenatal and postnatal anti-D prophylaxis. BJOG. 2009 Sep;116 (10): 1307-14. Epub 2009 Jun 17.* Kumar S, Regan F. Management of pregnancies with RhD alloimmunisation. BMJ. 2005 May 28;330(7502):1255-8. (UK perspective but much valuable information relevant to all)* Murray NA, Roberts IAG. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2007 Mar; 92(2): F83–F88. Oepkes D, Seaward PG, Vandenbussche FP, Windrim R, Kingdom J, Beyene J, Kanhai HH, Ohlsson A, Ryan G; DIAMOND Study Group. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006 Jul 13;355(2):156-64.Ramsey G. Inaccurate doses of Rh immune globulin after Rh-incompatible fetomaternal hemorrhage: survey of laboratory practice. Arch Pathol Lab Med 2009 Mar; 133(3):465-9. Reid ME. The Rh antigen D: a review for clinicians. Blood Bulletin 2008 Apr; 10(1).Sandler SG. Effectiveness of the RhIg dose calculator. Arch Pathol Lab Med 2010 Jul;134(7): 967-8.Shulman IA, Calderon C, Nelson JM, Nakayama R. The routine use of Rh-negative reagent red cells for the identification of anti-D and the detection of non-D red cell antibodies. Transfusion 1994 Aug;34(8):666-70.Tamul KR. Determining fetal-maternal hemorrhage with flow cytometry. Advance 2000. Posted online June 5, 2000.Westhoff CM, Sloan SR. Molecular genotyping in transfusion medicine. Clin Chem 2008;54(12): 1948-50.ONLINE RESOURCESPaxton A. Bringing new rigor to RhIg calculations. CAP TODAY. May 2008. Accessed January 18, 2011.*Wagle S, Deshpande PG. Hemolytic disease of the newborn. eMedicine / WebMD. Updated Apr. 9, 2010. Accessed January 18, 2011.

Phlebotomy is considered the treatment of choice for patients with iron overload due to hereditary hemochromatosis (HH). Each unit of blood contains approximately 200 to 250 mg of iron. As erythrocytes are removed by phlebotomy, iron stores are mobilized and utilized in the production of new, circulating erythrocytes. Through periodic phlebotomies, stored iron is removed until iron-deficient erythropoiesis is induced. The initial, or iron reduction, phase of treatment typically consists of removing one unit (450 mL) of whole blood once or twice weekly. Prior to beginning phlebotomy, the patient's hemoglobin and hematocrit must be checked to ensure that the patient is not anemic. A sample for serum ferritin is also collected at this time.Initial treatment goals include inducing iron deficient hematopoiesis without the development of debilitating symptoms of anemia. A hemoglobin concentration of 10.0 to 12.0 g/dL is often used as a target range. The initial treatment phase continues until excess stored iron is removed and ferritin levels decrease to approximately 50 ng/mL. (13) Ferritin and hemoglobin levels are periodically monitored during this phase. The number of phlebotomies needed to reduce iron levels and induce anemia is related to the degree of initial iron overload. Patients may be referred to a hematologist or gastroenterologist during the initial treatment phase. Many patients receive therapeutic phlebotomy services in a hospital or doctor's office, but patients may also undergo phlebotomy at a blood center. Blood collected from persons with HH may be used for transfusion or as blood products if it has been collected from a facility with an approved variance from the US Food and Drug Administration. Not all blood centers have applied for or been granted this variance.(14)The initial treatment phase continues until excess stored iron is removed and ferritin levels decrease to approximately 50 ng/mL. Removal of excess stored iron may take from one month to three years.

Markely increased stainable iron is present in this biopsy. Iron stores may be increased in sideroblastic anemia, chronic infections, hemochromatosis, hemosiderosis due to numerous blood transfusions, chronic hepatitis, cirrhosis, and uremia.

The predictability of ABO antibodies appearing in serum lacking the corresponding antigens makes ABO typing a simple process in most cases. However, the importance of getting it right cannot be stressed enough when a patient will be transfused with blood from a donor. If a patient receives donor cells containing A or B antigens and the transfused patient's serum contains the corresponding antibody, the donor cells will be destroyed almost immediately, causing a severe (hemolytic) and sometimes fatal reaction. Therefore, it is of utmost importance to thoroughly understand the ABO blood group system. In addition to red cells, ABO antigenic determinants (epitopes) are found in many tissues, body fluids, and other cells, including endothelial cells and platelets. Because ABO antigens are so widely expressed, ABO antigens are also a major consideration in solid organ and bone marrow transplants.

A person exposed to a specific immunizing event may produce “immune” ABO antibodies of the same specificity as the naturally occurring antibody, but with different biological behavior. Such immunizing events include pregnancy with an ABO incompatible fetus, or transfusion of ABO incompatible red cells. After immunization, the subject’s antibody may increase in titer and/or avidity, develop powerful hemolyzing properties, or become more active at 37°C.

The composite image shown on the right illustrates the ABO typing reactions that were obtained for a patient. This particular case illustrates an ABO discrepancy. An ABO discrepancy occurs when the results of forward and reverse typing do not match. The reactions shown are described below in descending order:Patient red cells with reagent anti-A: negative reaction.Patient red cells with reagent anti-B: 4+ agglutination.Patient red cells with reagent anti-D: 4+ agglutination.Patient serum with reagent A1 red cells: negative reaction.Patient serum with reagent B red cells: negative reaction.This patient forward types as a group B, but reverse types as a group AB. (A group B patient should have anti-A. This patient demonstrates neither anti-A nor anti-B, similar to an AB patient). Further workup is necessary to determine the ABO type since the forward and back typing do not match. In this case, incubation at 40 C demonstrated the presence of weakened anti-A. The patient was therefore typed as group B. This case is an example of an ABO discrepancy which was due to a "missing" anti-A antibody. This could be due to old age, severe illness, or immunosuppression. Although evaluation of ABO discrepancies is beyond the scope of this course, it is important to note that all ABO discrepancies must be resolved before blood products can be released for transfusion.This patient is Rh (D) positive, as evidenced by the strong agglutination of his cells with reagent anti-D antibody.

Specialists in immunohematology perform all testing prior to blood transfusions and work to prevent transfusion infections. They also investigate any post-transfusion reactions. This specialty includes all lab procedures performed in the specialty of histocompatibility. Specialists in clinical chemistry analyze body fluids such as blood, urine, and spinal fluid to determine the chemical makeup, including the amount of carbohydrates, proteins, enzymes, and trace elements. The special covers urine microscopics and chemical evaluation of the liver, kidneys, lungs, heart, and other vital organ systems. This specialty also covers all testing performed in the specialties of radioassay and blood gas analysis. Specialists in blood banking can perform all immunohematology testing as well as testing from the specialties of clinical chemistry, hematology and serology/immunology that relates to donor blood. Clinical laboratory personnel who are licensed in the specialties of immunohematology, clinical chemistry, hematology, and serology / immunology may perform all tests in the blood banking specialty.

Sentinel Events are sentinels--they function as guards or watchkeepers. They indicate serious situations that require immediate attention: Patient deathParalysisComaPermanent loss of functionAny procedure on the wrong patient, the wrong side of the body, or the wrong organ Hemolytic transfusion reaction involving major blood group incompatibility

Errors also occur after analyses are completed and reported. Postanalytic errors begin with the medical professionals who receive test results, and they include interpretation of the results. These errors can occur at--the bedside, chair-side, hospital, clinic-- wherever the patient and the medical professional are located. The possibility for postanalytic medical error continues through diagnosis and treatment procedures and processes. These medical errors occur during the time after the laboratory reports test results. Examples: Wrong test value associated with patient Wrong test interpretation Wrong diagnosis Wrong treatmentLaboratory professionals might believe they are not associated with postanalytic medical errors, but they can be. One deadly example is fatal hemolytic transfusion reaction involving laboratory error.

When the results on Mr. John Ready were called to the nurse, she was very surprised that the result of his CBC was normal. The nurse explained to the lab tech that Mr. John Ready had a known diagnosis of lower GI bleeding. His hemoglobin had been very low for the past 24 hours because of the internal bleeding, and she thought it was very surprising that his hemoglobin had normalized so quickly without having received a blood transfusion. Mr. Ready's doctor decided the patient should be redrawn to ensure a correct result. The nurse further questioned if the phlebotomist could possibly have drawn the wrong patient because earlier that day Mr. Ready had been moved to room 831, and room 825 was presently occupied by a patient named Walter Redding. If Julie had checked the patient's armband, she would have realized that the patient in 825 was the wrong patient.Relevant topics:Importance of patient ID, Patient identification continued, Specimen labeling, Specimen labeling Continued, Blood bank specimens

Labeling of blood bank specimens is even more critical than labeling of other specimen types.If a patient gets the wrong unit of blood, a serious or even fatal transfusion reaction may occur.

Anisocytosis is a general term reflecting increased variation in the size of red blood cells. The MCV will be within normal limits, but RDW will be increased. Variation usually affects a continuum of red cell sizes, but occasionally two distinct red cell populations can be observed(for example in sideroblastic anemia, or after red cell transfusion.)

Patient A.D., a 30 year old female, was admitted to the hospital in active labor to deliver at 37 weeks gestation. Transfusion service (TS) records showed A.D. to be group O Rh negative with no record of unexpected red cell antibodies.Maternal history showed two prior pregnancies. Her first pregnancy four years ago ended in spontaneous abortion at 9 weeks gestation and she received a mini-dose (50 µg) of RhIg.In the second pregnancy, two years ago, the infant typed as Group A Rh positive, DAT negative. Patient A.D. was injected with RhIg within 72 hours of delivery. The laboratory also confirmed that in the current pregnancy RhIg was administered at approximately 28 weeks gestation subsequent to a negative antibody screen.After many hours of non-productive labor, the physician considered that labor had stalled and decided to do a cesarian section (C-section). According to hospital policy for C-sections, a type and screen was ordered.

As applied to pregnancy, RhIg's purpose is to prevent immunization to the D antigen in the perinatal period and thus prevent HDFN due to anti-D. If the mother has already produced anti-D, RhIg is of no use.Accordingly, RhIg is routinely administered to Rh negative women* not previously sensitized to the D antigen under the following circumstances:1, Antenatal. Antepartum prophylaxis of 300 µg (1500 IU) at about 28 weeks gestation in the USA and Canada, which could be weeks later, depending on how physician appointments are scheduled. To illustrate variation in antenatal international practice, in the UK smaller doses of RhIg (e.g., 500 IU) may be given at 28 weeks and 34 weeks, although many UK facilities issue a 1500 IU dose at 28–30 weeks. With antenatal administration, the Rh of the fetus is usually unknown. Some transfusion services recommend a further antenatal dose if the infant is undelivered after 40 weeks.2. Postnatal. Prophylaxis of 300 µg (1500 IU) at delivery of an Rh positive or weak D infant, preferably within 72 hours of delivery but can be given up to 28 days later if administration is delayed. If RhIg administration is delayed beyond 72 hours, laboratory policies differ as to when it would no longer be administered.* Policies related to women who are weak D (formerly Du) are discussed later.Note: Because RhIg contains IgG anti-D, when given antenatally, it can cross the placenta and sensitize fetal D-positive red cells. Occasionally the fetus may be born with a weakly positive DAT, but significant hemolysis does not occur.

Of the main D variants, a female with partial D (or partial weak D) may develop anti-D to the D epitopes that she lacks. Fortunately, partial D red cells adsorb little anti-D, thus leaving enough free RhIg to suppress immunization.However, most laboratories do not routinely differentiate between D variants and instead rely on routine tests and associated test protocols to determine a mother's Rh status for the purposes of RhIg administration. Policies differ between countries and even within countries. 1. Some labs do not test pregnant women for weak D and rely on routine D typing to determine Rh status. AABB Standards for Blood Banks and Transfusion Services, ed. 26 (2010) does not require weak D testing for Rh negative women.2. Some labs perform weak D tests on pregnant women who appear to be Rh negative and, if weak D, do NOT inject with RhIg.3. Some labs perform weak D tests on pregnant women who appear to be Rh negative and, if weak D, inject with RhIg based on the possibility that they may be partial D and capable of forming anti-D.

Some TS laboratories try to determine if anti-D is passive or immune by performing titrations to determine the titer of the anti-D. Such a protocol usually assumes that an anti-D titer greater than 4 likely represents active immunization. Unfortunately, a titer of 4 or 8 could be active or passive, although a high titer (e.g., 64 or more) almost certainly means the anti-D is immune.Titration results can be affected by several variables: Red cell phenotype; Donor antigen variability (even if the same phenotype); Method used; Operator variability.Because lower titers could be due to both passive and immune anti-D, in the absence of test results that suggest immune anti-D, routine antibody titration is not a good use of time compared to assuming that anti-D is passive. Most transfusion medicine best practice guidelines do NOT recommend routine titration for women known to be injected with RhIg and exhibiting a 2+ or less reaction with D+ red cells, i.e., test results consistent with RhIg-derived passive anti-D.

In this case the mother did not require transfusion. For reference, the TS laboratory routinely uses an electronic crossmatch to detect ABO incompatibility for cases where patients do not have unexpected clinically significant antibodies in current antibody screen tests nor a history of clinically significant antibodies. When the laboratory information system (LIS) is down, the lab performs an immediate spin crossmatch.Should transfusion have been needed, these questions arise:1. Does a mother with a detectable passive anti-D due to RhIg qualify for an immediate spin (IS) or electronic crossmatch should transfusion be necessary?The issue also extends to the future:2. Should having a record of passive anti-D that is no longer detectable disqualify a woman from being a candidate for an immediate spin or electronic crossmatch?Before proceeding, consider the policies used in your TS laboratory and which rationales are used to support them.

Before discussing crossmatch policies for women with passive anti-D likely due to RhIg, LIS-related issues will be outlined. A transfusion service's LIS and how it is configured determines under which circumstances an electronic crossmatch is possible.Regardless of crossmatch policy, almost all laboratories use a special designation or code in their LIS for anti-D likely due to RhIg. Often this designation is entered in the patient history comment field and not the antibody field, thus eliminating the need to remove the passive anti-D from the antibody field when the antibody disappears. Using this policy, once the passive antibody no longer reacts, the patient becomes eligible for an electronic crossmatch without the need to remove the antibody history.In essence, using a special designation for passive anti-D allows the lab to bypass the LIS's normal requirements for patients with clinically significant antibodies, i.e., allows them to omit doing an IAT crossmatch. Examples of how RhIg-derived anti-D is designated in lab information systems: Passive anti-D (eg., code 'PD', 'DPAS', etc.); Probably passive anti-D; Anti-D consistent with RhIg; Anti-D due to RhIg.Depending on the LIS, other variations are possible.

ABO and Rh typing ABO Forward Group ABO Reverse Group Rh anti-A anti-B A1 cells B cells anti-D* 0 0 4+ 4+ 0 * Transfusion medicine standards used in the hospital's region do not require weak D testing on D-negative pregnant patients and none was done.Antibody screen Cells Gel IAT* Screen Cell I (R1R1) 1+ Screen Cell II (R2R2) 2+ Screen Cell III (rr) 0 * IAT = indirect antiglobulin test

The Commission on Laboratory Accreditation (COLA) was founded in 1988 and in 1993 was granted deeming authority by CMS. Although COLA was initially created to provide voluntary inspections of physicians' offices, COLA now accredits not only laboratories in physicians' offices but also laboratories associated with hospitals, mobile clinics, Veterans Administration, Department of Defense and independent laboratories. Its laboratory accrediting program is also recognized by the Joint Commission. COLA is approved by CMS to accredit the following specialties: Chemistry Hematology Microbiology Immunology Immunohematology/transfusion services Pathology, including cytology, histopathology, and oral pathology

When the results on Mr. John Ready were called to the nurse, she was very surprised that the result of his CBC was normal. The nurse explained to the laboratory technologist that Mr. John Ready had a known diagnosis of lower GI bleeding. His hemoglobin had been very low for the past 24 hours because of the internal bleeding, and she thought it was very surprising that his hemoglobin had normalized so quickly without having received a blood transfusion. Mr. Ready's doctor decided the patient should be redrawn to ensure a correct result. The nurse further questioned if the phlebotomist could possibly have drawn the wrong patient because earlier that day Mr. Ready had been moved to room 831, and room 825 was presently occupied by a patient named Walter Redding. If Julie had properly identified the patient by asking him to state his name and then checking the name and identification number on the wristband, she would have realized that the patient in 825 was the wrong patient.

Mr. R.M., a 55-year old male, was admitted to a hospital emergency department with severe lower gastrointestinal bleeding. His history revealed multiple prior transfusions, the last of which he received five years earlier.Physical examination revealed hemodynamic instability (systolic BP 60 mmHg). Blood tests revealed a hemoglobin (Hb) of 8 g/dL (80 g/L) and a hematocrit (HCT) of 28% (0.28). The patient received aggressive fluid resuscitation with Ringer's lactate and was sent to the operating room (OR) for an emergency laparotomy.The physician ordered four units of Red Blood Cells to be crossmatched.Two units of uncrossmatched group O Rh-negative Red Blood Cells were also ordered and authorized for immediate emergency transfusion.

Similar to evaluating inconsistencies, one of the post-analytic tools for confirming that the serological data fit the solution is to consider the "big picture." For example: Is there a likely red cell stimulus (prior transfusion or pregnancy) for IgG antibodies such as anti-Jka? Can different reaction strengths with panel cells be explained by the identified antibody (e.g., dosage) or by the presence of more than one antibody? Is the antibody unusual for a patient of a particular race? For example, anti-Dib is more likely to occur in Native Americans than in Caucasians.

This case study presents a scenario in which a patient had an unexpected antibody that disappeared after he was transfused with 2 units of unmatched group O Rh negative RBC. The patient developed a positive DAT with MFA but an antibody identification using the post-transfusion red cell eluate was inconclusive, making the antibody unidentifiable. Fortunately, the patient improved and further transfusion was not required. Ultimately, the patient's antibody was identified as anti-Jka, with a second antibody to a low frequency antigen (Radin) also unexpectedly present.The case illustrates the risks involved in using unmatched blood.

Life-Threatening HemorrhageDespite potential risk, sometimes immediate transfusion is necessary, even for patients with red cell antibodies. In such cases transfusion service staff should alert the medical director, who can discuss options with clinical staff.The medical director will generally talk to the staff attending the patient and indicate that, if possible, they should hold off transfusion. But if it is a case of massive bleeding where exsanguinating hemorrhage is likely, it is better to give some blood and monitor for a delayed hemolytic transfusion reaction than to let the patient bleed to death.Transfusing when bleeding is brisk will result in much of the autologous and incompatible blood bleeding out, with the possibility of a delayed hemolytic reaction once the patient's antibody rebounds and destroys still present antigen-positive donor red cells.Some transfusion services also try to minimize the risk of unmatched blood by typing their emergency supply of O Rh negative RBCs for the K antigen, since anti-K is a relatively common clinically significant antibody. See Resources for two papers that discuss the risks of transfusing un-crossmatched emergency blood.

LiteratureDutton RP, Shih D, Edelman BB, Hess J, Scalea TM. [abstract]. Available at: Safety of uncrossmatched type-O red cells for resuscitation from hemorrhagic shock.J Trauma. 2005 Dec;59(6):1445-9. Accessed November 5, 2012.Johnson ST, Rudmann SV,Wilson, SM. Serologic problem solving strategies:a systematic approach. Bethesda, MD: AABB, 1996.Online resourcesThe following are online examples of good practice. The information should not be used as a substitute for technical and clinical judgment. Medical and technical information becomes obsolete quickly and current sources relevant to the user's location should always be consulted.Transfusion reactions: Transfusion complications (Canadian Blood Services)Education website for CBS's hospital customersREACT (Sunnybrook HSC, Toronto, ON, Canada) Pocket reference card for nurseson signs and symptoms of transfusion reactionsQuick cals (online calculator of p values for Fisher's exact test) Use a one-tailed test (since we would expect an antibody to react with red cells that are positive for the corresponding antigen)

The patient's physician was notified that compatible blood was unavailable and that the patient's antibody was still being investigated.When asked whether or not the patient was experiencing a transfusion reaction due to the transfusion of the two unmatched and incompatible O Rh negative RBC, the nurse in the OR stated that the patient was undergoing surgery and completely sedated. A transfusion reaction was not apparent but they would investigate and closely monitor.Hemolytic Transfusion Reactions (HTR)Before proceeding to the next page, make a short list of signs and symptoms associated with immediate hemolytic transfusions reaction and another list associated with delayed hemolytic transfusion reactions.

Delayed HTR often go undetected as the symptoms are usually mild and subclinical (death has occurred, but rarely). Symptoms may not occur until days after transfusion when the patient has left the hospital. Donor red cell destruction is usually by extravascular hemolysis (EVH). Signs and symptoms can include: Fever with or without chills Unexplained drop in hemoglobin and hematocrit Transient jaundice due to elevated serum bilirubin

Signs and symptoms are used only as a general guide to the type of transfusion reaction that may be occurring.Lower back pain, for example, would suggest an acute hemolytic reaction, whereas fever is associated with several types of reactions: Hemolytic (immediate and delayed) Febrile Bacteriogenic

Fortunately, the patient's condition stabilized and additional transfusions were not required. Two weeks later, new patient specimens were drawn for antibody studies. Antibody identification results Cell Rh Rhesus Kell Duffy Kidd MNSs P Lewis Lu Results Cell C D E c e Cw K k Kpa Fya Fyb Jka Jkb M N S s P1 Lea Leb Lua Gel IAT* 1 rr 0 0 0 + + 0 0 + 0 + 0 + 0 0 + + + +S + 0 0 1+ 1 2 rr 0 0 0 + + 0 0 + 0 + 0 + + 0 + + + +S + 0 0 w+ 2 3 rr 0 0 0 + + 0 0 + 0 + + 0 + 0 + + 0 + 0 + 0 0 3 4 r"r 0 0 + + + 0 0 + 0 + + 0 + 0 + 0 + + + 0 0 0 4 5 R2R2 0 + + + 0 0 + 0 0 + + + + + 0 + 0 + 0 + 0 w+ 5 6 R2R2 0 + + + 0 0 + + 0 + + + + + 0 + 0 + 0 + 0 w+ 6 7 R1R1 + + 0 0 + 0 0 + 0 0 + 0 + + 0 + 0 +S 0 + + 0 7 8 R1R1 + + 0 0 + 0 0 + 0 0 + + 0 + 0 0 + + + 0 0 1+ 8 9 RZR1 + + + - + 0 + + 0 + 0 0 + + 0 0 + + + 0 0 0 9 10 r'r + 0 0 + + 0 0 + 0 + 0 0 + + 0 + 0 +S 0 + 0 0 10 11 Auto 0 11

A standard follow-up to antibody identification is to antigen phenotype: Patient's red cells (expecting them to lack the corresponding antigen) Donor red cells (in this case, those transfused before an antibody was identified, or, more typically, to find suitable antigen-negative donors to crossmatch prior to transfusion).If you had wanted to type the patient for any antigens at this point in the investigation (2-weeks post-transfusion), which specimen would you have used? Think about any antigen typing problems and how to overcome them before proceeding to the next page.

Transfusion of blood components has the potential for both benefit and risk to the patient. According to the FDA Annual Summary of Fiscal Year 2009, 74 fatalities were reported following blood transfusions; forty-four of those fatalities were transfusion-related. Medical errors that could result in transfusion reactions include: Patient misidentification Sample labeling error Wrong blood type issued Transcription error Technical error Storage error Transfusion policies and procedures must be carefully followed to reduce transfusion reactions and prevent transfusion related death or serious injury.Several causes of transfusion-related deaths are summarized in the table below.Reference: U.S Food and Drug Administration. (2009). Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2009. Retrieved from http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM205620.pdf. Accessed April 26, 2011.

The table below lists the incidence rates of several different types of transfusion reactions.Reference: Hillyer, C.D., Silberstein, L.E., Ness, P.M., Anderson, K.C., & Roback, J.R. (2007) Blood Banking and Transfusion Medicine: Basic Principles and Practice 2nd Ed. Philadelphia, PA: Churchill Livingstone.

A unit of red blood cells (RBCs) contained 250 mg of iron as part of the hemoglobin molecule. A long-term complication of red cell transfusion is iron overload, or hemosiderosis. As red cells are destroyed, they release iron. The iron cannot be excreted and is stored as hemosiderin and ferritin. Iron accumulates in the liver, heart, spleen, and endocrine organs. Tissue damage, heart failure, liver failure, diabetes, and hypothyroidism can occur. Patients who are transfused frequently are at the greatest risk for iron overload. Diseases such as sickle cell disease, thalessemia, aplastic anemia, and other chronic anemias usually require frequent transfusions. Signs and symptoms of hemosiderosis include muscle weakness, fatigue, weight loss, mild jaundice, anemia, and cardiac arrhythmias. Ferritin levels and other iron studies should be assessed. Specific stains may be used to detect iron in tissue biopsies. Iron chelation may be used to treat and prevent iron overload. Chelation works by using an agent which binds to iron and helps remove it through the urine or feces.

If preliminary testing suggests hemolysis or if the results are misleading, additional testing may be required. If human error has been ruled out during the clerical check, repeat ABO/Rh testing should be performed on the unit of blood or its segment and the pre-transfusion sample to detect any sample mix ups and clerical errors. Antibody detection studies should be performed on the pre- and post-transfusion samples to look for any unidentified antibodies. If an antibody is identified, the donor cells should be tested for the corresponding antigen. The crossmatch should be repeated with pre-and post-tranfusion specimens using the indirect antiglobulin test (IAT). An incompatible crossmatch with the pre-transfusion sample indicates an original error, either clerical or technical. Incompatibility with only the post-transfusion sample indicates a possible anamnestic response, as in a delayed hemolytic transfusion reaction (DHTR), or sample misidentification. The patient's first voided urine specimen should be examined for the presence of free hemoglobin. The patient's bilirubin levels may also be evaluated. A change from normal pale yellow serum to a post-transfusion bright or deep yellow serum should prompt an investigation for hemolysis. The maximum concentration of bilirubin following hemolysis is not usually detectable until 3 to 6 hours after transfusion. The hemoglobin and hematocrit can be tested to detect a drop in hemoglobin or failure of the hemoglobin to rise after transfusion. Important information about physical or chemical hemolysis may be gained from examining the returned unit bag. If hemolysis is present in the bag or tubing, a process which affected the blood, such as inappropriate warming or faulty infusion pump, should be suspected. If bacterial contamination is suspected, the unit can be cultured. A positive culture indicates a reaction due to bacterial contamination.

Adverse reactions after transfusion of blood components must be evaluated promptly. Most serious reactions occur within the first 15 minutes of starting a transfusion. Continuous monitoring allows reactions to be discovered in a timely manner. The transfusionist must be able to recognize the symptoms of a transfusion reaction and know the appropriate steps to take when one occurs. The first critical step is to stop the transfusion immediately, but keep the patient's line open with saline. The physician should be contacted immediately for instructions regarding patient care. The transfusion service must be notified of the reaction. They will usually provide instructions on proper documentation of the reaction, and the return of any remaining component and/or tubing. The appropriate patient samples are to be sent to the laboratory and usually include blood and urine. The transfusionist must be sure to follow all hospital policies.

Harmening, DM. Modern Blood Banking and Transfusion Practices. 5th ed.Philadelphia, PA: FA Davis; 2005.Hillyer CD, Silberstein LE, Ness PM, Anderson, KC, Roback, JR. Blood Banking and Transfusion Medicine: Basic Principles and Practice. 2nd ed. Philadelphia, PA: Churchill Livingstone; 2007.Roback JD, Combs MR, Grossman BJ, Hillyer CD ed. AABB Technical Manual. 16th ed. Besthesda, MD: AABB; 2008.Rudman, SV. Textbook of Blood Banking and Transfusion Medicine. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2005.U.S. Food and Drug Administration. Blood Products Advisory Committee. April 27, 2007. Available at: http://www.fda.gov/ohrms/dockets/AC/07/briefing/2007-4300B2_01.htm. Accessed December 15, 2010.U.S. Food and Drug Administration. Infectious Disease Tests. 2009. Available at: http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/default.htm. Accessed December 15, 2010.U.S. Food and Drug Administration. Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2009. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/SafetyAvailability/ReportaProblem/TransfusionDonationFatalities/UCM205620.pdf. Accessed December 15, 2010.

A post transfusion specimen should be sent to the laboratory for work-up. A clerical check should be performed to investigate possible errors in specimen labeling, blood product issuance, or patient identification. The plasma must be examined for hemolysis. A direct antiglobulin test must be performed. The patient's ABO, Rh and antibody screen should be repeated and confirmed. The blood product ABO/Rh can be confirmed. Other laboratory tests include: complete blood count (CBC), urinalysis, serum bilirubin, creatinine, coagulation profile, and disseminated intravascular coagulation (DIC) evaluation. The full laboratory work-up and details of other laboratory tests will be discussed later in the course.

Diagnosing a febrile non-hemolytic transfusion reaction (FNHTR) involves excluding all other options that may present with fever. If this type of reaction is suspected, the transfusion should be stopped. A transfusion reaction work-up should be initiated, although the antibodies involved with these reactions are not routinely identified because of the difficulty in demonstrating their presence in vitro. Antipyretics, such as acetaminophen, should be administered to the patient and the transfusion can continue once the symptoms subside.A patient with two or more documented febrile nonhemolytic transfusion reactions (FNHTRs) should receive leukocyte-reduced blood components.Pre-storage leukocyte reduction prevents reactions that occur due to cytokine accumulation during storage. Red cell component prevention techniques include the transfusion of fresher blood or washed blood. For platelets, residual plasma may be removed. Antipyretics can be administered prior to transfusion.

Diagnosis of allergic reactions is based on the recognition of a skin rash associated with itching. Treatment involves temporarily discontinuing the transfusion and administering an antihistamine. The rash will usually heal when the transfusion is stopped or when an antihistamine is given. Once symptoms have been alleviated, the transfusion may be resumed. If symptoms continue or progress, the transfusion must be stopped and a new donor unit obtained. Premedication will usually prevent urticarial reactions in patients with a history of allergic reactions. If premedication is unsuccessful, washed cellular products may prevent a reaction. Leukoreduction has no role in preventing an allergic reaction. Anaphylatic and anaphylactiod reactions should be recognized when patients develop symptoms described on the previous page. The transfusion must be stopped immediately. Differential diagnosis includes hypotensive reactions, transfusion-related acute lung injury (TRALI), myocaridal infarction, and pulmonary embolus. An IgA deficiency should be investigated and is confirmed by the presence of anti-IgA. Treatment includes timely administration of epinephrine in addition to other supportive care such as vasopressors and airway support. Prevention involves avoiding transfusion of IgA. Cellular products should be washed to remove residual plasma. Products may also be collected from donors who are known to be IgA deficient. Autologous donations are an alternative.

Symptoms begin within 6 hours of transfusion and include acute respiratory distress, severe hypoxemia, hypotension, fever and bilateral fluffy infiltrates on chest radiograph. Respiratory distress is due to noncardiongenic pulmonary edema. Patient may have shortness of breath. Signs and symptoms may be mild, and resolve after a few days, or they may be severe and result in pulmonary failure. Laboratory findings include leukopenia and hypocomplementemia.

There are no conclusive tests to diagnosis transfusion-related acute lung injury (TRALI). The condition should be suspected if the clinical picture corresponds with TRALI clinical findings, such as hypoxemia within 6 hours of transfusion. The clinical findings should correlate with chest radiograph findings of bilateral infiltrates. It is important to rule out cardiac causes of pulmonary edema. One way of differentiating is evaluating the B-type natriuretic peptide (BNP) level, which is known to be elevated in congestive heart failure and not TRALI. In the majority of cases, the donor plasma will demonstrate anti-HLA antibodies. Urgent treatment consists of respiratory and volume support. Patients usually require supplemental oxygen, some by a mechanical ventilator. Vasopressor medications can be used to treat the hypotension. Extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass have been successful in treating TRALI when conventional methods do not work. Diuretics are contraindicated in TRALI.Patients with TRALI usually improve within 48 to 96 hours. TRALI is fatal in about 5% to 10% of cases.

The AABB has made several recommendations for preventing TRALI including: Blood collection facilities should implement interventions to minimize the preparation of high-plasma-volume components from donors known to be leukocyte-alloimmunized or at increased risk for leukocyte alloimmunization. Blood transfusion facilities should work toward implementing appropriate evidence-based hemotherapy practices to minimize unnecessary transfusion. Blood collection and transfusion facilities should monitor the incidence of reported TRALI and TRALI-related mortality. Transfusion services should work with clinicians to educate providers about the risks of TRALI and about the need to work toward implementing evidence-based transfusion practices for all blood components, with special emphasis on high plasma-volume components. High-plasma-volume components include the following: FFP obtained from whole blood or apheresis Plasma frozen within 24 hours Cryoprecipitate-reduced plasma Apheresis platelets Whole bloodThere have been several other suggestions for preventing TRALI, which include: Screening of all donors for anti-neutrophil or anti-HLA antibodies. Once donors are identified, they are excluded from donating, or their blood is used for products that do not contain much plasma. This method would not prevent TRALI in recipients who have alloantibodies. Use of pre-storage leukoreduced blood. Use of younger blood products. Appropriate utilization of blood products. Using blood products only when clinically indicated may reduce the frequency of TRALI. Because TRALI can coexist with other transfusion reactions and with pulmonary complications unrelated to transfusion, the diagnosis of TRALI is difficult, but it is an important step in monitoring the effectiveness of TRALI risk-reduction strategies.

Yersina entercolitica is most likely responsible for septic reactions in transfusions of Red Blood Cells. This organism is usually acquired by ingestion of contaminated food and causes mild symptoms of abdominal pain and diarrhea. Growth of Y. entercolitica is enhanced in iron-rich environments such as red blood cells. Other organisms reportedly found in Red Blood Cell units are Campylobacter species, Serratia species, Pseudomonas species, Enterobacter species, and Echerichia coli. These bacteria can produce endotoxins which cause a reaction in the patient. The majority of organisms associated with platelets transfusions are normal skin flora. Staphylococcus aureus, coagulase-negative staphylocci, aerobic and anerobic diptheroid bacilli, streptococci, and gram-positive bacilli are frequently isolated. Some transfused organisms have been implicated in a delayed post-transfusion illness. Pseudomonas aeruginosa and Burkholderia capacia have been isolated in cryoprecipitate and plasma. These organisms grow optimally at 30oC and have been found in water baths, accentuating the importance of overwrapping components that are thawed in a water bath. Rickettsia organisms are intracellular bacteria which are transmitted by ticks or insects. These bacteria are the causes of Rocky Mountain spotted fever, ehrlichiosis, and scrub typhus, and may be transmitted by transfusion. Similarly, the organism which causes Lyme disease may be transmitted as well. There have no reports of either of these organisms transmitted by transfusion.

Transfusion-associated circulatory overload (TACO) is caused by the inability of the circulatory system to handle an increased blood volume. This usually occurs if the product is infused into the patient too quickly. The very young, elderly, patients with small stature, and patients with compromised cardiac function are at heightened risk for circulatory overload. The frequency is difficult to determine since many instances go unreported. The patient will present with acute pulmonary edema when cardiac output cannot be maintained. Other symptoms include, cyanosis , orthopnea, hypertension, headache, tachycardia, chest tightness, and cough. Symptoms set in near the end of the transfusion or within six hours of completion. Symptoms may be confused with transfusion-related acute lung injury (TRALI). Recently, B-type natriuretic peptide (BNP), a cardiac marker, has been used as a diagnostic tool. BNP is elevated with TACO.The transfusion should be stopped as soon as TACO is suspected. The patient should be in a sitting position and provided with supplementary oxygen. Intravascular volume may be reduced by the administering of diuretics. Blood components should be adminstered slowly when possible, particularly in patients at risk for TACO.

Delayed hemolytic transfusion reactions (DHTR) are reactions that occurs 3 to 10 days after the transfusion. Usually, the blood appears serologically compatible at initial testing. Delayed reactions are common in patients who have been immunized to a foreign antigen from a previous transfusion or pregnancy, but the antibody titers decrease over time and the antibody is not detectable during pre-transfusion testing. The transfusion leads to a secondary (anamnestic) response, causing increased antibody production that sensitizes antigen-positive donor red cells. Hemolysis is extravascular. Sensitized cells are removed from circulation by the reticuloendothelial system, also called the monocyte-macrophage system. Because there is a delay in the presentation of symptoms, DHTR is not usually considered as a cause of the clinical presentation. The transfusion service usually initiates investigation of a DHTR because of serologic findings in a post-transfusion specimen. DHTRs occur more frequently than acute hemolytic reactions. Approximately 1:2500 transfusions result in a DHTR.

Generally, the clinical symptoms of a delayed hemolytic transfusion reaction (DHTR) resolve within 2-3 weeks without medical intervention other than transfusion support. On the other hand, severe DHTRs can occur with a life-threatening anemia. Severe delayed reactions occur most often in patients with sickle cell anemia. Sickle cell anemia patients have a high alloimmunization rate which puts them at greater risk for developing a DHTR. Diagnosis of a DHTR can be difficult in sickle cell patients because symptoms can be misdiagnosed as sickle cell crisis pain. Delays in medical treatment may lead to death. It is important for the transfusion service to obtain an accurate transfusion history. It is unclear what causes such severe reactions in sickle cell patients. Several explanations include bystander hemolysis, sickle cell hemolytic transfusion syndrome, and hyperhemolysis. In any case, it is important to recognize that severe DHTR in sickle cell patients is not uncommon. Treatment requires rapid diagnosis and transfusion support with antigen-negative red cells.

Patients present with fever, a characteristic red rash from trunk or face to the extremities, watery diarrhea, nausea, vomiting, and hepatitis within seven to ten days following the transfusion. The rash may progress to blister-like lesions and erythroderma. Pancytopenia will develop due to the immune destruction of the recipient's bone marrow. The low platelet count causes hemorrhaging while a low white blood cell count can lead to infection. Most patients die within one to three weeks after the onset of symptoms. The diagnosis is often missed and is usually made too late or after death. Routine laboratory studies are not helpful. The only definitive method is the identification of donor lymphocytes in the circulation or tissues of the recipient which is accomplished through human leukocyte angtien (HLA) typing or cytogenic analysis.

Post-transfusion purpura (PTP) is caused by platelet-specific antibodies in a patient who has been previously exposed to platelet antigens through pregnancy or transfusion. The most frequently identified antibody is Anti-PLA1 which reacts with platelet antigen HPA-1a. The platelet antibody binds to the platelet surface which allows for extravascular removal through the liver or the spleen. The patient's own platelets are destroyed as well, thus aggravating the thrombocytopenia. Three theories are suggested regarding the destruction of autologous platelets. One suggests that immune complexes bind to the platelets through the Fc receptor and cause destruction. The second theory proposes that the patient's platelets absorb a soluable platelet antigen from the donor plasma. The third hypothesis, which has the most support, states that the platelet alloantibody has autoreactivity that develops when the patient is exposed to the foreign platelet antigen. Platelet transfusion is NOT a treatment option. Steroids, whole blood exchange, and plasma exchange are accepted options for treatment. According to the AABB, intravenous IgG (IVIG) is the treatment of choice (AABB Technical Manual, p. 744). Most patients will respond to treatment within several hours to four days. PTP does not usually re-occur but it is recommended that patient's with a previous reaction be transfused with antigen-matched components. Autologous donations or directed donations from antigen matched family members may be the best sources of blood. PTP has been known to occurr even after the transfusion of deglycerolized rejuvenated or washed red cells, so these processes do not prevent a reaction.