Blood Component Replacement 169 Hypotonic solutions (e.g. 5% glucose) are contraindicated because they may cause osmotic swelling and hemolysis of red cells as well as clumping of red cells in the tubing. Although not demonstrated clinically [19] , in theory calcium - containing solu- tions (e.g. lactated Ringer ’ s) may cause coagulation of blood stored in citrate preservatives. Finally, medications should not be added to transfused blood. Should a reaction occur, it will be impossible to determine if its etiology is the drug, the transfused blood, or both. In addition, the high pH of some medications may cause hemolysis, and if a transfusion is interrupted an unknown quantity of medication will have been infused [4,5] . Detecting r ed c ell a ntigen – a ntibody i nteractions Preparatory to a transfusion of red blood cells, it is essential to determine if transfused cells will be destroyed in vivo by antibod- ies in the potential recipient ’ s serum. The fi rst step in obtaining compatible blood is determining the ABO and Rh type of the recipient ’ s red cells. This is followed by procedures to determine the presence of antibodies to RBC antigens in the potential recipi- ent ’ s serum. A type and screen is a three - step process to detect clinically signifi cant antibodies (Figure 11.1 ). The latter are defi ned as those associated with a hemolytic transfusion reaction and/or a marked decrease in survival of transfused RBCs and/or hemolytic disease of the newborn. In the fi rst step, also referred to as a “ quick spin ” , two drops of recipient serum and one drop of reagent red cells are mixed and centrifuged at room tempera- ture. The duration of centrifuging is dictated the calibration of the centrifuge (usually about 5 minutes). The reagent red cells are certifi ed to contain all the clinically signifi cant antigens. Agglutination or hemolysis following this step suggests the pres- ence of an anti - A or anti - B antibody, a “ cold ” antibody, or both. ABO antibodies may be associated with hemolytic transfusion reactions, and thus pose a potential serious risk to the recipient. In contrast, cold antibodies are not likely of clinical signifi cance. The second phase involves centrifugation of the RBC/recipient serum mix following incubation at body temperature. Hemolysis or agglutination at this phase is suggestive of the presence of a clinically signifi cant antibody. In the third, or antiglobulin phase (e.g. rabbit), anti - human IgG is added to the cells which have been incubated and centrifuged in the previous step. If anti - RBC IgG molecules from the recipient ’ s serum have attached to the reagent red cells, the anti - human IgG will form a bridge between those IgG molecules attached to the RBCs, and visible hemolysis or agglutination will occur. If an antibody is detected by this process, its specifi city is identifi ed by the blood bank. When needed, donor blood for the potential recipient that does not contain the antigen corresponding to the detected antibody will be reserved for that patient [4,5] . Because of the possibility of the development of new antibodies a new antibody screen must be performed within 3 days of a possible transfusion for a woman who is pregnant and for a person who has been previously transfused. For a type and cross - match , the same steps as for typing and screening are performed, except that instead of reagent red cells Transfusion p ractices Administration of b lood and b lood c omponents Patient and d onor u nit i dentifi cation Because inadvertent administration of ABO - incompatible cells is the most common cause of fatal hemolytic transfusion reactions [17] , meticulous attention to patient and unit identifi cation is mandatory before initiating transfusion. The spelling of the patient ’ s name and hospital identifi cation number on the patient ’ s wrist band must be identical with that on the blood unit ’ s com- patibility tag [1] . Warming of b lood and d uration of t ransfusion Because blood administered at slower rates rapidly warms to the recipient ’ s body temperature it is usually unnecessary to warm transfused blood, even in the recipient who has cold alloantibod- ies. However, cold stored red cells or plasma infused at a rate faster than 100 mL/min for 30 or more minutes has been associ- ated with cardiac arrest [18] . Therefore, warming is necessary for recipients receiving large volumes of blood within short time periods and for those who have severe cold autoimmune hemo- lytic anemia. Contemporary blood warmers contain sensors to detect changes in rate of fl ow so that uniform temperature of administered blood may be maintained. Warming blood with a water bath or microwave is not permissible, as overheating of red cells may result in hemolysis [5] . Because of the risk of bacterial infection, blood which has been warmed to room temperature must be infused within 4 hours. A unit which has been warmed to 10 ° C or more may not be returned to the blood bank for reuse. Filters All infused blood products must be fi ltered. The standard in - line fi lter has a pore size of 170 – 260 microns and fi lters cellular debris, cell aggregates, and coagulated proteins. Because the aggregated proteins at room temperature foster bacterial growth as well as potentially slow the rate of transfusion, it is probably best to change the fi lter every 4 hours [4] . Microaggregate fi lters (pore size 20 – 40 microns) will fi lter fragments of degenerating leuko- cytes, platelets, and fi brin strands. Their primary use is cardiac bypass surgery. They are not routinely used for transfusions and should not be used for leukocyte reduction. Leukocyte reduction fi lters consist of layers of non - woven fi bers that retain leukocytes but allow platelets and red blood cells to pass. Leukocyte reduc- tion fi lters for red cells and for platelets use different technologies and therefore may be used only for retention of their intended component [4] . For reasons presented previously, in - line leuko- cyte reduction at the time of transfusion is less desirable than prestorage or laboratory leukocyte reduction. Intravenous s olutions u sed with t ransfusions Only normal saline is compatible with transfused blood. It may be used to prime the infusion tubing. It may also be used to dilute concentrated red cells to decrease viscosity and increase fl ow. Chapter 11 170 DNA prepared from a recipient who has received multiple trans- fusions will demonstrate the blood group of the recipient, and not the donor(s) [23] . Molecular blood typing is also of use in typing potential donors who have antigens for which the corre- sponding reagent antibodies either do not exist or are weakly reactive [24] . Finally, molecular identifi cation has been used for some time in determining the RhD type of fetuses of women alloimmunized to this antigen from cells in amniotic fl uid [24,25] . Maintaining b lood i nventory and b lood o rdering p olicies The number of units of blood that a blood bank maintains is a function of hospital acuity [26] and patient volume. A minimum and ideal inventory level may be calculated from analyzing the number of emergency blood shipments, use of ABO - compatible in lieu of type - specifi c units, and outdate rates [4] . To optimize utilization of stored units a blood bank will have a policy of transfusion of the oldest banked unit fi rst. The proportion of cross - matched units that are transfused is a tool for utilization management. Whenever a unit of blood is cross - matched it is held for a specifi c patient for a time period determined by hospital policy. Until released, that unit may not be used for other potential recipients. Thus every time a unit of blood is cross - matched and goes unused its shelf life is decreased. One tool available to guide appropriate cross - matching is the cross - match to transfusion (C : T) ratio. A C : T ratio greater than 2.0 suggests excessive cross - matching [4] . C/T ratios may be cal- culated for individual physicians, procedures, or hospital services. Another tool is the Maximum Surgical Blood Order Schedule (MSBOS) [27] . Under MSBOS the number of units of blood to be cross - matched in advance of elective surgery is calculated by determining the number of units previously transfused at that donor cells are used. Because the reagent red cells used for an antibody screen contain virtually all antigens associated with antibody - mediated in vivo RBC destruction, it is extremely unlikely that a recipient who has no detected antibodies will have a life - threatening transfusion reaction if given ABO - matched blood [20] . Therefore a quick spin cross - match for a recipient found to have no antibodies may be performed by centrifuging the donor cells with the recipient ’ s serum at room temperature for 5 minutes. This procedure will detect any ABO incompatibil- ity, and make cross - matched blood available within 15 minutes [5] . Computer cross - matching is a more recent technology which also may be used in lieu of the antiglobulin phase of a cross - match for a recipient found to have no detected antibodies. The require- ments for allowing the computer to ABO match the unit of donor cells to the recipient are detailed and stringent. These include on - site validation of computer - generated ABO cross - matching, two determinations of the recipient ’ s ABO type, and confi rma- tory testing of donor ABO group and Rh type; the latter in the instance of Rh - negative donor cells. Logic must be built in to the system to alert blood bank personnel to any discrepancies in these tests [1,4] . Published experience with over 270 000 computer cross - matched transfused units includes no instances of hemo- lytic transfusion reactions, a short turnaround time from order- ing to issuing a unit, and a reduction in laboratory testing [21,22] . Advances in genetics have enabled molecular identifi cation of blood groups. This is particularly advantageous for patients who have received recent transfusions, those who have received massive transfusions, and those who require multiple transfu- sions (e.g. sickle cell disease, autoimmune hemolytic anemia). For such patients serotyping is made diffi cult because their circulat- ing blood contains both endogenous and donor cells and plasma. Determine recipient ABO and Rh Type and screen Recipient serum + reagent red cells Centrifuge at room temperature Hemolysis or agglutination indicates ABO incompatibility and/or cold antibodies in recipient’s serum Incubate at 37°C for 30–60 min, then Centrifuge Hemolysis or agglutination indicates warm antibodies in recipient’s serum Wash cells with saline Add anti-human IgG Centrifuge Type and crossmatch Recipient serum + donor red cells Centrifuge at room temperature Hemolysis or agglutination indicates ABO incompatibility and/or cold antibodies in recipient’s serum Incubate at 37°C for 30–60 min, then Centrifuge Hemolysis or agglutination indicates warm antibodies in recipient’s serum Wash cells with saline Add anti-human IgG Centrifuge Hemolysis or agglutination indicates warm antibodies in recipient’s serum Hemolysis or agglutination indicates warm antibodies in recipient’s serum Figure 11.1 Laboratory procedures for type and screen and type and cross - match. Blood Component Replacement 171 exceed compensatory mechanisms. Arterial vasoconstriction ulti- mately leads to tissue hypoxia and accumulation of fi xed acids. Hyperventilation to compensate for the metabolic acidosis increases negative intrathoracic pressure, which in turn leads to increased venous return to the heart and increased stroke volume. The combination of increased systemic vascular resistance and systemic hypotension lead to increased transfer of interstitial fl uid to the vascular space, which may in turn increase intravas- cular volume up to 50%. In addition, a slower osmotically induced transfer of intracellular fl uid to the interstitial space occurs [31] . Deciding when red cell transfusion is necessary to maintain adequate tissue oxygenation in the face of acute hemorrhage is an extremely diffi cult task. Even if a patient is undergoing central monitoring, changes in pulmonary artery mixed venous oxygen tension refl ect global changes in tissue oxygenation but not within critical organs [29,32] . Similarly, measurement of lactate levels may not be of use, because reasons in addition to tissue hypoxia are causal for elevation in serum lactate [32] . Hemoglobin concentration and hematocrit are usually readily accessible. Hemoglobin concentration is the product of the hematocrit and the mean corpuscular hemoglobin content (MCHC). Thus with the exception of diseases characterized by an altered MCHC (e.g. the thalessemias), hemoglobin and hema- tocrit are in an approximate 1 : 3 relationship [33] . Hemoglobin and hematocrit respectively refl ect the volume of hemoglobin and red blood cells per unit volume of blood. Because of altered dynamics in red cell and plasma volume consequent to acute blood loss, measurement of either of these parameters may not accurately refl ect the availability of oxygen carriage. In the hypo- volemic patient the volume of red cells and plasma during the acute phase of blood loss are equivalent. Only after interstitial fl uid is mobilized will a drop in hemoglobin or hematocrit be noted. Studies of controlled blood loss during blood donations have found that these fl uid shifts take place in two phases; the fi rst within minutes and the second over a period of days [34] . Normal changes in blood volume during pregnancy make utilization of hemoglobin or hematocrit during acute obstetric blood loss even more problematic. Plasma volume expansion begins at 6 weeks, accelerates to 24 weeks, and then continues to expand but at a slower rate. Red cell mass increase begins at 20 weeks, and progresses steadily to term [35] . During pregnancy red cell mass expands by about 20%, while plasma volume increases by approximately 40% [36] . The disproportionate expansion in plasma relative to red cell mass lowers the normal hemoglobin or hematocrit during pregnancy. The different rates of expansion in plasma and red cells throughout pregnancy make interpretation of these parameters gestational age dependent. Acute obstetric blood loss is usually unpredictable, sudden, and voluminous, and therefore occurs under circumstances where sophisticated measurements of physiologic parameters are usually unavailable. The obstetrician must decide whether or not to transfuse based on observation of simple parameters such as heart rate, blood pressure, respiratory rate, and persistence of hospital per patient per intended procedure. The MSBOS is pro- cedure specifi c, and must be determined for each individual hos- pital. For those patients undergoing procedures that infrequently require transfusions a type and screen policy may be the appro- priate guideline. The Standard Blood Order (SBO) is a variant of MSBOS [28] . Under the SBO a type and screen is recommended for those procedures requiring less than 0.5 units per patient per procedure. Obstetric h emorrhage The purpose of a red cell transfusion is to restore oxygen - carrying capacity in order to maintain adequacy of tissue oxygenation [4,29] . Maintaining adequate tissue oxygenation in the face of acute blood loss is a function of partial pressure of inspired oxygen, pulmonary gas exchange, oxygen delivery to the blood, cardiac performance, tissue oxygen demands, and red cell oxygen content. Oxygen content is the sum of the product of the hemo- globin concentration, the binding coeffi cient of oxygen for hemo- globin (1.39), and oxygen saturation, plus the small amount of oxygen dissolved in plasma. Oxygen consumption is calculated as the product of the difference in oxygen content between arterial and venous blood (Table 11.2 ). Normally as oxygen is extracted from blood as it passes through the tissues, the PO 2 falls from 100 mmHg in the arteries to 40 mmHg in the veins. Respective arterial and venous oxygen saturations are 100% and 75%. Thus the normal extraction ratio, or the proportion of delivered oxygen extracted by the tissues, is 25% [4] . Under con- ditions of decreased tissue oxygen supply such as occurs with acute blood loss tissue acidosis develops, and slowly 2,3 - DPG in red cells increases, both allowing hemoglobin to desaturate at lower oxygen tensions and thus increase tissue oxygen extraction. An extraction ratio of 50% is considered critical [29] . The normal adult tolerates a 10 – 15% acute decrease in blood volume well. Once blood loss has reached 40% a sequence of physiologic changes whose purpose is to maintain tissue oxygen- ation rapidly comes into play [30] . In response to adrenergic stimuli, heart rate increases and systemic venules and small veins contract. Because 50% of blood volume resides in these capaci- tance vessels their constriction increases venous return to the heart, thus increasing stroke volume (preload). If rapid blood loss continues, catecholamines, increased vasopressin, and activation of the renin – angiotensin system cause arterial vasoconstriction of the skin, skeletal muscle, splanchnic organs, and kidneys. Systemic vascular resistance (afterload) increases. Blood is redistributed to the brain and heart. The net effect of these changes is a restoration of cardiac output unless the rapidity and volume of blood loss Table 11.2 Calculation of oxygen content and oxygen consumption. O 2 content = (hgb × 1.39 × % saturation) + ( pO 2 × 0.003) [in mL O 2 /mL blood] O 2 consumption = cardiac output × hgb × 1.39 × (% sat arterial − % sat venous )/100 [in mL O 2 /min] Chapter 11 172 is transfused at a rate exceeding 30 mL/kg/h citrate loading may exceed citrate clearance, and hemodynamic instability may result. Although lactic acid accumulates with storage, metabolic acidosis in the massively transfused patient is usually the result of hypo- perfusion. Because hypothermia below 30 ° C may result in ventricular arrhythmias massively transfused blood should pass through warmers which have adequate capacity but which do not cause thermal injury to RBCs [41] . Autologous b lood Autologous blood collection falls into two major categories: pre- operative donation and perioperative collection. Included under the latter rubric are acute normovolemic hemodilution and intra- operative cell salvage and reinfusion. Preoperative a utologous d onation Preoperative autologous donation (PAD) has some advantages. A unit of autologous blood returned to the donor will not elicit an antibody response to a foreign antigen, will not elicit a transfu- sion reaction, and is unlikely to transmit most bloodborne infec- tions. However, the transfusion of autologous blood does not protect against the most common cause of fatal transfusion reac- tions, namely the transfusion of ABO - incompatible blood due to administration error. Autologous blood may also transmit bacte- rial infections. The minimal hemoglobin required for autologous donation is 11 g/dL. One regimen for preoperative donation is to collect 1 unit of RBCs weekly for 3 weeks, with the last unit collected no later than 72 hours before surgery. Treatment of the donor with iron will help increase RBC production [4] . Recombinant erythropoietin may be used for patients requiring more than 3 units [42] . For a variety of reasons, PAD is rarely utilized in obstetrics. Bleeding requiring transfusion associated with the most common operative procedure (cesarean delivery) is rare. Obstetric bleeding is most often unpredictable, and massive. Women who have identifi able risk factors require trans- fusions [43] . One possible indication for PAD is placenta previa. The proportion of women who have this entity and who require RBC transfusion may be substantial [43 – 45] . A concern is that women who have a placenta previa and are phlebotomized for future autotransfusion may be more likely to be transfused when they start bleeding because of anemia incurred by PAD. One study of women with placenta previa and low - lying placentas found that after initiating routine autologous collection the rate of homologous transfusions decreased from 28 to 8.5% [45] . Changes in fetal hemodynamics during maternal phlebotomy have been reported [46,47,48] . One study found a decrease in middle cerebral artery pulsatility index [47] while another found no change in this parameter [48] . Acute n ormovolemic h emodilution Acute normovolemic hemodilution (ANH) refers to the collec- tion of 1 or more units of whole blood just before initiating surgery followed by the reinfusion of this blood at the end of surgery. Phlebotomy is followed immediately by volume replace- bleeding [29] . An arbitrary approach is to fi rst restore circulating volume with a rapid infusion of 1 – 2 L of crystalloid (normal saline or lactated Ringer ’ s solution) [37] . It must be remembered that only a third of the crystalloid remains in the intravascular space. Colloids (e.g. hydroxyethyl starch, Dextran, gelatins) remain within the intravascular space, but they are more expen- sive than crystalloids. They also carry the risks of serious side effects (e.g. anaphylaxis, fever, hypotension for Dextran; pruritus and prolongation of PT and PTT for hydroxyethyl starch [5] ) and have not been demonstrated to have an advantage over crystal- loids in the management of hypovolemic shock. If after attempted volume restoration signs of hemodynamic instability persist (e.g. tachycardia, tachypnea, hypotension, lowered pulse oxygen satu- ration) red cell transfusion should be administered until vital signs improve and bleeding is arrested. The decision to infuse coagulation factors should be based on clinical and laboratory fi ndings. If generalized capillary bleeding is observed and/or if the INR is 1.6 or greater, consideration should be given to transfusing an initial 2 units of FFP [38] . Platelet counts over 50 000/ µ L generally do not require platelet replacement [38] . Activated recombinant factor VIIa (rFVIIa) has been used as a coagulant for hemorrhage due to a variety of causes (trauma, platelet function disorders, liver disease) [39] . Its successful use in the treatment of postpartum hemorrhage has also been reported [40] . Massive t ransfusion Massive transfusion is defi ned as the replacement of one or more blood volumes (generally 8 – 10 or more RBC units) within 24 hours. The selection of the units to be transfused depends upon whether the recipient ’ s blood type is known, whether a current antibody screen has been performed, and whether the recipient has any special requirements (e.g. known antibodies, need for CMV - negative blood). In the selection of RBC units for emer- gency transfusion an effort should be made to transfuse type - specifi c blood when the recipient ’ s type becomes known, as the consumption of type O cells by one patient will deplete inventory needs for other patients. Reproductive - age women should receive Rh - negative blood until their Rh type is known. Guidelines for coagulation components in the face of continued microvascular bleeding include the transfusion of the equivalent of one random donor platelet pack per 10 kg for the patient whose platelet count is less than 50 000/ µ L, of FFP or thawed plasma if the INR is over 1.5, and of cryoprecipitate if the fi brinogen concentration is less than 0.8 g/L [41] . While distinguishing between a dilutional coag- ulopathy and disseminated intravascular coagulation in a massively transfused patient is extremely diffi cult, it must be remembered that the former is much more common than the latter [41] . Massive transfusion is potentially accompanied by a number of complications. Citrate toxicity results from the chelation of calcium and magnesium. Toxicity may be manifest by decreased myocardial contractility and decreased systemic vascular resis- tance. Citrate is metabolized by liver mitochondria. When blood Blood Component Replacement 173 those who may require numerous transfusions, and those who require cellular products (e.g. platelets) from HLA - compatible donors. The assumption that blood from family or friends pro- vides a decreased risk of infectious disease transmission is not supported by data [5] . Furthermore, lymphocytes transfused from blood - related donors may pose an increased risk for graft - vs - host disease [58] . For that reason blood from these family members should be irradiated before transfusion [5,58] . Transfusion r eactions A transfusion reaction is defi ned as any untoward effect following and due to transfusion of a blood product. Up to 10% of all transfusions are complicated by transfusion reactions [5] . Fortunately, the three most common causes of transfusion - related mortality (acute hemolytic reaction, sepsis, and transfusion - related acute lung injury) are the least frequent post - transfusion events [59] . While there is signifi cant overlap in symptoms of the different types of reaction it is important to endeavor to differentiate among them, as treatment and progno- sis differ for each type. Acute t ransfusion r eactions Acute h emolytic r eactions Acute transfusion reactions are defi ned as those which occur within 24 hours of the transfusion. Most fatal reactions occur early in the course of a transfusion. For this reason patients require constant surveillance while a blood product is being administered. A list of acute transfusion reactions is found in Table 11.3 . Some of the clinically more important acute reactions will now be discussed. Acute h emolytic t ransfusion r eaction An acute hemolytic transfusion reaction (AHTR) occurs when RBCs containing antigens to existing antibodies in recipient plasma are transfused. Transfusion of ABO - incompatible blood is the most common cause of hemolytic transfusion reaction - related mortality. This is most often due to patient misidentifi ca- tion during collection, during processing in the laboratory, or at the time of administration of blood. An AHTR typically begins within minutes of initiating the transfusion. The initial event is the binding of complement by anti - A and anti - B antibodies. The C5 – 9 component of complement (the membrane attack complex) then binds to the surface of the red cell, and causes the formation of a pore in the cell membrane. The plasma water entering the results in osmotic lysis of that cell. Laboratory evidence of these events include a decrease in hematocrit, detection of serum - free hemoglobin, a decrease in haptoglobin, increased lactate dehy- drogenase, and hemoglobinuria. The release of infl ammatory cytokines tumor necrosis factor - alpha and IL - 1, - 6, and - 8 results in fever, hypotension, and disseminated intravascular coagula- tion (DIC). Hypotension also results from the release of anaphy- laxis - precipitating complement fragments C3a and C5a. Renal ment with crystalloid. Because of dilution, the volume of RBCs lost at surgery is less than would have been lost had the procedure not been performed. Transfusion of whole blood at the close of the procedure provides fresh RBCs, platelets, and clotting factors [5] . ANH has been used before cesarean delivery for women who have high - risk conditions such as placenta previa, placenta accreta, and large fi broids [49] . A case was reported of a woman undergoing ANH before a cesarean hysterectomy for placenta percreta. Her predonation hematocrit was 41%, her post - hemodilution hematocrit 31%, and her postoperative/post - retransfusion hematocrit 29.8% [50] . Intraoperative b lood s alvage Intraoperative blood salvage (IBS) starts with aspiration of blood from the operative site. It then passes through a heparinized tube and a microfi lter to a reservoir, and after the addition of normal saline the RBCs are separated by hemoconcentration and differ- ential centrifugation. Subsequent washing in normal saline removes debris, microaggregates, fi brin, platelets, plasma, and complement as well as most of the heparin. In obstetrics, further fi ltration of washed blood is performed. Up to 250 mL of RBCs with a hematocrit of 55 – 80% may be reinfused to the patient within 3 minutes of aspiration [5,51] . Reinfusion of blood collected by IBS has been used extensively in non - pregnant patients undergoing traumatic blood loss or cardiovascular surgery. Although its use has been reported in over 400 obstetrics cases [51 – 53] its utilization in pregnancy remains controversial [51,54 – 6] . Two major concerns present, namely the possibility of an amniotic fl uid embolus (AFE) and the infusion of Rh - positive fetal cells into an Rh - negative mother. Although it is unclear which elements of amniotic fl uid are responsible for the cardiovascular collapse and DIC seen with an AFE, removal of amniotic fl uid from IBS - retrieved blood seems prudent. The use of a small - pore microfi ber fi lter after the washing phase of blood retrieved at cesarean delivery has been demonstrated to remove all fetal squames and lamellar bodies [57] . Use of a dou- ble - suction technique, in which amniotic fl uid is drained upon opening the uterus via one suction apparatus followed by aspira- tion of blood from a second has also been reported [53,57] . While these measures may prevent reinfusion of amniotic fl uid con- tents, separation of fetal from maternal erythrocytes during IBS has not been achieved. The suggestion has been made that fol- lowing IBS a Kleihauer – Betke test be performed for Rh - negative women delivering Rh - positive fetuses followed by appropriate doses of Rh immune globulin [51,54] . Finally, the argument has been made that given the need for a dedicated technologist to run the cell saver, the time needed for set - up, and the unpredictability of obstetric hemorrhage this technology has limited application in obstetrics [54,56] . Directed d onation Patients with certain medical conditions may benefi t from receiv- ing transfusions from directed rather than anonymous donors. Included among these are patients who have rare blood types, Chapter 11 174 Acute e xtravascular h emolytic t ransfusion r eaction In an acute extravascular hemolytic transfusion reaction (AEHTR) the antibody to the transfused incompatible cells does not fi x complement, but does bind onto the corresponding antigens of the transfused cells. Fever, a positive direct antibody (Coombs) test, and a falling hematocrit characterize this reaction. Because of the marked diminution of complement and cytokine activa- tion [60] the hypotension, DIC, hemoglobinuria and renal failure that characterize an AHTR are rarely found with an AEHTR [5] . Febrile n on - hemolytic t ransfusion r eactions Fever is common to acute hemolytic transfusion reactions and sepsis. A febrile non - hemolytic transfusion reaction (FNHTR) is defi ned as a temperature elevation of 1 ° C or more within 2 hours of a blood transfusion and for which no cause can be found [4,5] . It is thus a diagnosis of exclusion, and occurs more commonly in patients who have previously been exposed to blood antigens, such as multiparous women and patients who have had previous transfusions. FNHTRs may develop by different pathways. One mechanism is the binding of recipient antibodies to (most often HLA) antigens on transfused leukocytes, lymphocytes, or plate- lets. These antibody – antigen complexes then cause phagocytes to release pyrogens. A second mechanism is the release of cytokines from leukocytes contained within units of stored cellular prod- ucts (e.g. following leukocyte apoptosis). The transfusion of cel- lular blood products from which leukocytes have been fi ltered out at the time of blood collection has been reported to decrease the frequency of FNHRs [61,62] . FNHTRs occur more often fol- lowing platelet transfusions than following transfusions of RBCs. Over 90% of FNHTRs accompanying platelet transfusions are due to the passive infusions of leukocyte - derived cytokines. The passage of platelet products through polyester fi lters has been shown to remove some cytokines and complement fragments [63] . A more effi cient means of reducing the incidence of FNHTRs is the removal of supernatant plasma before transfusion of a platelet product [63] . The fi rst step in the management of a sus- pected FNHTR is to rule out potentially life - threatening causes of transfusion - associated fever, i.e. AHTR and sepsis (Table 11.4 ). Once these entities have been ruled out, some feel that transfu- sion of the same unit may be resumed [4] . Antipyretics are the standard treatment for FNHTRs. For patients with thrombocy- topenia acetaminophen or non - steroidal anti - infl ammatory agents are preferable to aspirin [4,5] . Allergic r eactions Allergic reactions are seen more frequently in patients who have received multiple transfusions. While most are characterized by mild cutaneous manifestations (e.g. urticaria), they may be more severe, with systemic symptoms such as nausea, vomiting, diar- rhea, and bronchospasm. Rarely a full - blown anaphylactic reac- tion may occur in response to a transfusion. Fever rarely accompanies an allergic reaction, a feature which distinguishes it from a hemolytic transfusion reaction and from sepsis. The mechanism of development of an allergic reaction is the binding ischemia is exacerbated by the binding of nitric oxide, an endo- thelial relaxing factor, which may in turn lead to acute tubular necrosis and acute renal failure [5] . The fi rst step in the treatment of a patient who acutely develops fever, hypotension, intravascu- lar hemolysis, and renal failure, either alone or in combination, is cessation of the transfusion. After applying supportive mea- sures careful evaluation seeking the cause of the reaction should follow (Table 11.4 ). If ABO incompatibility is not found then another source of this reaction should be sought. Table 11.3 Workup of an acute transfusion reaction. If an acute transfusion reaction occurs: 1. Stop blood component transfusion immediately 2. Verify the correct unit was given to the correct patient 3. Maintain IV access and ensure adequate urine output with an appropriate crystalloid or colloid solution 4. Maintain blood pressure and pulse 5. Maintain adequate ventilation 6. Notify attending physician and blood bank 7. Obtain blood/urine for transfusion reaction workup 8. Send report of reaction, samples, blood bag, and administration j set to blood bank 9. Blood bank performs workup of suspected transfusion reaction as follows: A. Clerical check is performed to ensure correct blood \j ″ component was transfused to the right patient B. The plasma is visually evaluated for hemoglobinemia C. A direct antiglobulin test is performed D. Other serologic testing is repeated as needed (ABO, Rh, crossmatch) If intravascular hemolytic reaction is confi rmed: 1. Monitor renal status (BUN, creatinine) 2. Initiate diuresis; avoid fl uid overload if renal failure is persent 3. Analyze urine for hemoglobinuria 4. Monitor coagulation status (PT, aPTT, fi brinogen, platelet count) 5. Monitor for signs of hemolysis (LDH, bilirubin, haptoglobin, plasma hemoglobin) 6. Monitor hemoglobin and hematocrit 7. Repeat compatibility testing (crossmatch) 8. Consult with blood bank physician before further transfusion. If bacterial contamination is suspected: 1. Obtain blood culture of patient 2. Return unit or empty blood bag to blood bank for culture and Gram ’ s stain 3. Maintain circulation and urine output 4. Initiate broad - spectrum antibiotic treatment as appropriate; revise antibiotic regimen on the basis of microbiological results 5. Monitor for signs of DIC, renal failure, respiratory failure IV = intravenous; BUN = blood urea nitrogen; PT = prothrombin time; aPTT = activated partial thromboplastin time; LDH = lactate dehydrogenase; DIC = disseminated intravascular coagulation. Adapted from Snyder EL. Transfusion reactions. In: Hoffman R, Benz EF Jr, Shattil SJ, et al. Hematology: basic principles and practice. 2nd ed. New York: Churchill Livingstone, 1995;2045 – 53. Blood Component Replacement 175 classes. In addition, while anti - IgA antibodies are common, ana- phylactic reactions in patients bearing these antibodies are not [4] . Thus the mechanism of development of most transfusion - related allergic reactions remains unexplained. The treatment of an allergic reaction depends on its severity. A mild reaction may be treated with antihistamines. If following medication adminis- tration the signs and symptoms abate, the transfusion may be resumed. A severe or anaphylactic reaction requires immediate of soluble substances in transfused plasma with preformed IgE antibodies on mast cells, resulting in histamine release. IgA - defi cient patients have an increased susceptibility to allergic reac- tions. These patients make anti - IgA antibodies to IgA - like substances in the environment. When challenged with IgA in transfused plasma protein, an allergic reaction may result. While IgE anti - IgA antibodies have been demonstrated, it must be noted that the majority of anti - IgA antibodies belong to the IgG or IgM Table 11.4 Acute transfusion reactions. Type Signs and Symptoms Usual Cause Treatment Prevention Intravascular hemolytic (immune) Hemoglobinemia and hemoglobinuria, fever, chills, anxiety, shock, DIC, dyspnea, chest pain, fl ank pain, oliguria ABO incompatibility (clerical error) or other complement - fi xing red cell antibody Stop transfusion; hydrate, support blood pressure and respiration; induce diuresis; treat shock and DIC, if present Ensure proper sample and recipient identifi cation Extravascular hemolytic (immune) Fever, malaise, indirect hyperbilirubinemia, increased LDH, urine urobilinogen, falling hematocrit lgG non - complement - fi xing antibody Monitor hematocrit, renal and hepatic function, coagulation profi le; no acute treatment generally required Review historical records; ensure proper sample and recipient identifi cation; give antigen - negative units as appropriate; possible high - dose IVIG Febrile Fever, chills Antibodies to leukocytes or plasma proteins; hemolysis; passive cytokine infusion; bacterial contamination; commonly due to patient ’ s underlying condition Stop transfusion; give antipyretics, eg, acetaminophen; for rigors in adults, use meperidine 25 to 50 mg IV or IM Pretransfusion antipyretic; leukocyte - reduced blood components Allergic (mild to severe) Urticaria (hives), dyspnea, wheezing, throat tightening, rarely, hypotension or anaphylaxis Antibodies to plasma proteins; rarely, antibodies to IgA Stop transfusion; give antihistamine (PO or IM); if severe, epinephrine and/or steroids Pretransfusion antihistamine; washed red cells, if recurrent or severe; check pretransfusion IgA levels in patients with a history of anaphylaxis to transfusion Hypotension Hypotension, tachycardia Bradykinin generation; may be exacerbated by ACE inhibitor Stop transfusion; fl uids; Trendelenberg position Discontinue ACE inhibitor; avoid bedside leukocyte - reduction fi lters Hypervolemia Dyspnea, hypertension, pulmonary edema, cardiac arrhythmias Too rapid and/or excessive blood transfusion Induce diuresis; phlebotomy; support cardio - respiratory system as needed Avoid rapid or excessive transfusion Transfusion - related acute lung injury (TRALI) Dyspnea, fever, hypoxia, pulmonary edema, hypotension, normal pulmonary capillary wedge pressure Donor HLA or leukocyte antibody transfused with plasma in component; neutrophil - priming lipid mediator; less commonly, recipient antibody to donor white cells Support blood pressure and respiration (may require intubation) Leukocyte - reduced red cells and platelets; notify transfusion service and blood center to test donors(s); quarantine remaining components from donor(s) Bacterial contamination Rigors, chills, fever, shock Contaminated blood component Stop transfusion; support blood pressure; culture patient and blood unit; give antibiotics; notify blood transfusion service Care in donor selection, blood collection and storage; careful attention to arm preparation for phlebotomy DIC = disseminated intravascular coagulation; IV = intravenous; IM = intramuscular; PO = by mouth; ACE = angiotensin - converting enzyme; LDH = lactate dehydrogenase; IVIG = intravenous immune globulin. Chapter 11 176 cells which then activates the neutrophils to cause the damage to the endothelium leading to a capillary leak [4,5] . Because donor antileukocyte antibodies are found in 65 – 85% of cases of TRALI [66] , ascertainment of such antibodies precludes that individual as a future donor. Because women have been found to have a progressive increase in the frequency of HLA antibodies with each successive pregnancy [67] , caution should be exercised in using multiparous blood donors for transfusions to critically ill patients. Bacterial c ontamination Bacterial contamination of transfused blood products results from contamination of phlebotomy sites, undetected asymptom- atic bacteremia in a donor, or, rarely, while handling the product during processing [59] . Likely due to screening of potential donors for clinically signifi cant bloodborne viral infections, the incidence of viral sepsis following transfusions has markedly decreased in recent years, while the incidence of bacterial sepsis has remained static. Because platelets are stored at room tempera- ture and because many bacteria (e.g. staphylococcus and Escherichia coli ) proliferate at these temperatures bacterial con- tamination of platelets occurs more frequently than bacterial contamination of stored RBCs. The organisms contaminating RBC products most commonly are those which proliferate at colder temperatures. Yersinia and Pseudomonas species, both of which thrive at the temperatures required for RBC storage and which require a source of iron, are the most and secondmost common organisms contaminating RBC products, respectively [68] . While a common perception is that HIV infection poses the greatest infectious risk from blood transfusion [69] , bacterial sepsis by far exceeds the risk of any bloodborne viral infection. The incidence of transfusion - associated mortality due to bacterial contamination is exceeded only by that resulting from transfu- sion of ABO - incompatible RBCs [68] . Clinical fi ndings common to bacterial sepsis and acute intravascular hemolysis include fever, chills, hypotension, and DIC. While AIHTR occurs early in the course of transfusion, signs of sepsis may become evident either during or following transfusion. Unlike AIHTR, bacterial contamination is rarely associated with hemoglobinemia or hemoglobinuria [5] . Immediate care of the recipient suspected of having received a bacterially - contaminated blood product includes discontinuation of that product and Gram stain and blood culture of both the transfused unit and the recipient. Broad - spectrum antibiotics as well as supportive measures should be initiated. The blood bank should be notifi ed so that it may recall any other blood components from the same donor [5] . Delayed t ransfusion r eactions Delayed h emolytic t ransfusion r eactions Delayed hemolytic transfusion reactions (DHTRs) differ from acute intravascular hemolytic transfusion reactions in both mechanism and severity of clinical presentations. Those DHTRs that are due to an anemnistic antibody response to transfused RBCs may occur within days of transfusion, while those due to cessation of the transfusion. Fluid resuscitation, epinephrine, ste- roids, vasopressors and intubation may be required either alone or in combination. Once a patient has had an allergic reaction to transfusion of a blood product preventative steps to avoid recur- rence of such a reaction should be taken before a subsequent transfusion. Pretransfusion treatment with an antihistamine is usually suffi cient for the patient who has had a mild reaction. IgA - defi cient patients who have had severe reactions and who are found to have anti - IgA antibodies should be given blood prod- ucts from IgA - defi cient donors. They and others who have had severe reactions but are not IgA - defi cient should be transfused with washed or thawed deglycerolized cells, to minimized the volume of transfused plasma. Autologous components are also appropriate for these transfusion recipients. Management of the rare patient who has had a severe allergic reaction but who requires transfusion of plasma products (e.g. the patient with thrombotic thrombocytopenic purpura) poses a serious chal- lenge. Pretreatment with antihistamines, steroids, and epineph- rine has been suggested for such cases [4,5] . Transfusion - related a cute l ung i njury Transfusion - related acute lung injury (TRALI) should be sus- pected by the development of acute pulmonary insuffi ciency within 1 – 6 hours of a transfusion that is unexplained by other cardiac or respiratory diseases. Its diagnosis is supported by oxygen saturation < 90% on room air and clinical and X - ray evi- dence of bilateral pulmonary edema [4,5,64] . It is often accom- panied by fever, chills, and hypotension. Although the respiratory signs and symptoms of TRALI closely resemble those of circula- tory overload, the former is suggested by the absence of a response to diuresis, a pulmonary artery wedge pressure < 18 mmHg, and alveolar fl uid edema/protein concentration > 0.65 at the onset of acute respiratory failure [64] . The treatment of TRALI requires cessation of the transfusion and support with oxygen and ventila- tion. While it has a mortality of about 10%, most patients recover within 2 – 4 days [4] . Although a variety of mechanisms for the development of this entity have been proposed, its root cause appears to be immunologic. Most commonly the binding of anti- bodies in donor plasma to recipient HLA or leukocyte (HNA and CD 16 [65] ) antigens appear to be the precipitating event. These antibody – antigen interactions cause a sequence of events leading to the increased permeability of pulmonary capillaries to plasma proteins. These proteins then leak into the pulmonary intersti- tium and alveoli. Less common is the interaction between recipi- ent antibodies and donor granulocytes. Complement activation, activation of anaphylaxotoxins C3a and C5a, the aggregation of leukoemboli in pulmonary capillaries and transfusion of cyto- kines specifi c for target antigens have also been proposed as pre- cipitating mechanisms [4] . A “ two - hit ” theory has been proposed, in which the initial hit is an antecedent condition in the recipient (e.g. trauma) which initiates endothelial activation and neutro- phil priming with sequestration of these neutrophils in the pul- monary capillaries. The second hit is caused by a donor factor such as antibodies, cytokines, or lipids from membranes of stored Blood Component Replacement 177 10 and 15% of cases are fatal, most often from intracranial hem- orrhage. The typical patient is a multiparous Caucasian woman who is among the 2% of the population whose platelets lack the HPA - 1a antigen. Of interest is the observation that both donor platelets, which lack the antigen, and recipient platelets, which contain the antigen, are destroyed in PTP. A number of theories have been proposed to explain this phenomenon. One is that either antigen - containing fragments of destroyed transfused platelets or antibody – antigen complexes are adsorbed onto the recipient ’ s platelets. The latter are then destroyed either by com- plement activation or by phagocytosis within the reticuloendo- thelial system. Another is that antigens common to donor and recipient platelets along with foreign platelet antigens elicit an autoantibody response parallel with the alloantibody response [72] . Although PTP is usually self - limited, treatment is indicated for patients whose low platelet counts are accompanied by active bleeding. Currently the treatment of choice is high - dose intrave- nous IgG, whose proposed mechanism of action is blockade of Fc receptors on autologous platelets and within the reticuloendo- thelial system [72] . The transfusion of antigen - matched platelets does not seem practical, in that fi nding matched donors is unlikely, and also because in PTP both donor and recipient plate- lets are destroyed [5,72] . Transfusion - transmitted d isease The routine screening of blood donors for hepatitis B surface antigen (HBsAg) and core antibody (HBcAb), hepatitis C (HCV) antibody, antibody to HIV 1 and 2, antibody to human T - lymphotropic virus types I and II (HTLV I/II), and syphilis have decreased, but not eliminated the possibility of transmission of these diseases by blood transfusion. Of concern is the window of time between donor infection and the ability to detect the disease [73] . In the past, the latter was possible only by antibody detection. The duration of the latency window has been narrowed by the ability to detect some of these viruses by nucleic acid testing (NAT). In the United States NAT testing is routinely performed for HIV, HCV, and West Nile virus. Current estimates of the risk of transfusion - related transmission of HIV and HCV are respectively 1 in 2 million units and 1 in 1.7 million units [74] . Because of its slow replication hepatitis B has a longer window of latency. Because the time from infection to the time of detection of HBsAg is 40 days, the risk of transfusion - associ- ated hepatitis B infection is from 1 : 50 000 to 1 : 250 000 units. It has been estimated that latency period and thus the risk of trans- mission of this virus may be halved by routine NAT testing [74] . Other viruses may be transmitted by transfusions. Transfusion - associated transmission of West Nile virus is unusual. It has, however, caused serious febrile illness, encephalitis, and menin- gitis [5] . The scheme of seasonal testing for this virus has been previously discussed [3] . HTLV I/II are retroviruses unrelated to HIV. They are causal agents of adult T - cell lymphoma/leukemia (ATL) and peripheral de novo antibodies may not manifest signs and symptoms for weeks or months. The destruction of donor RBCs that are coated with recipient IgG antibodies takes place extravascularly, i.e. within the reticuloendothelial system. However, anemnistic anti- body production rarely results in hemolysis, and may be referred to as a “ delayed serologic transfusion reaction ” . DHTRs antibod- ies rarely fi x complement, and elicit a lower level of proinfl am- matory cytokines and C3a and C5a anaphylatoxins than do AIHTRs. The most common fi ndings of a DHTR are decreased hemoglobin concentration and a positive antibody screen. Others include mild fever, leukocytosis, anemia, and jaundice. Laboratory fi ndings include those consistent with antibody - mediated RBC destruction, e.g. decreased haptoglobin, increased LDH, and reticulocytosis. Hemoglobinuria is rarely found. Because DHTRs are rarely severe, treatment is rarely necessary. Observation of coagulation tests and urine output may be advisable. If additional transfusions are needed, units should be sought which do not contain the antigen corresponding to the recipient ’ s antibody [4,5] . Transfusion - associated g raft - vs - host d isease Transfusion - associated graft - vs - host disease (TA - GVHD) may occur when donor T lymphocytes escape immune destruction in the recipient, engraft, and then destroy host tissues. A predispos- ing factor is similarity in HLA antigens between donor and recipi- ent, e.g. when blood is transfused from a related donor, or when the donor is homozygous for an HLA haplotype for which the recipient is heterozygous. While extremely rare in the US, it is seen more often in Japan, where a relative homogeneity of HLA haplotypes is found [4,70] . The disease characteristically is mani- fest 4 – 30 days following transfusion with fi ndings of a maculo- papular rash beginning on the face and trunk and progressing to the extremities, fever, diarrhea, hepatitis, and bone marrow aplasia. Death occurs in 90% of cases, most often from bone marrow failure leading to infection and pancytopenia [70,71] . While no treatment exists for TA - GVHD, radiation of cellular products before transfusion to susceptible individuals (e.g. blood from relatives and HLA - matched donors) will prevent TA - GVHD. A dose of at least 2500 cGy is mandated by the Food and Drug Administration (FDA) to render T lymphocytes incapable of replication. This dose of radiation does not affect platelets and granulocytes [4] . However, because the viability of RBCs is short- ened by irradiation, the FDA advises that irradiated red cells be used no later than 28 days following treatment of these cells [71] . Post - transfusion p urpura Post - transfusion purpura (PTP) is a rare complication of transfu- sions, with only 200 cases having been reported [4,72] . It is char- acterized by the sudden onset of profound thrombocytopenia (e.g. < 20 000/mm 3 ) within 1 – 2 weeks of transfusion of a blood product. Clinical fi ndings include bleeding from virtually any site, including cutaneous purpura, bleeding from wounds, epi- staxis, gastrointestinal hemorrhage, and hematuria. Although the disease usually resolves spontaneously within 1 – 8 weeks, between Chapter 11 178 US, universal leukodepletion of blood products has not been adopted. However, since 2002 donor deferrals for a cumulative stay in the UK since 1980 longer than 3 months, in Europe for longer than 5 years, or on a US military base in Europe for over 6 months have been instituted [78] . Concluding c omments The transfusion of blood or blood components is often lifesaving. Because blood products for obstetrical complications may be required with little notice and in massive amounts the mecha- nisms for obtaining and administering blood and its components rapidly should be maintained at any institution delivering care to pregnant women. The likelihood of a serious complication due to transfusion of a blood product is remote. However, despite standard precautions and blood banking and hospital proce- dures, serious immune and infectious complications during and following transfusions still occur. Therefore the practicing obste- trician should be prepared to rapidly decide the necessity for and quantity of blood products to be administered as well as to rec- ognize and initiate care for transfusion complications. References 1 American Association of Blood Banks . Standards for Blood Banks and Transfusion Services , 23rd edn. Bethesda, MD : AABB , 2004 . 2 Kuehn B . Studies propose targeting screening of blood for West Nile Virus . JAMA 2005 ; 295 : 1235 – 1236 . 3 C u s t e r B , B u s c h M P , M a r fi n AA , Petersen LR . The cost - effectiveness of screening the US blood supply for West Nile virus . Ann Intern Med 2005 ; 143 : 486 – 492 . 4 B r e c h e r M E , e d . American Association of Blood Banks. Technical Manual , 15th edn. Bethesda, MD : AABB , 2005 . 5 Gottschall J , ed. Blood transfusion therapy. A physician ’ s handbook , 8th edn. Bethesda, MD : AABB , 2005 . 6 Latham JT , Bove JR , Weirich FL . Chemical and hematologic changes in stored CPDA - 1 blood . Transfusion 1982 ; 22 : 158 – 159 . 7 Heaton A , Keegan T , Holme S . In vivo regeneration of red cell 2,3 - diphosphoglycerate following transfusion of DPG - depleted AS - 1, AS - 3 and CPDA - 1red cells . Br J Haematol 1989 ; 71 : 131 – 136 . 8 Yazer MH , Podlosky L , Clarke G , Nahirniak SM . The effect of prestor- age WBC reduction on the rates of febrile nonhemolytic transfusion reactions to platelet concentrates and RBC . Transfusion 2004 ; 44 : 16 – 24 . 9 Buckholz DH , AuBuchon JP , Snyder EL et al. Effects of white cell reduction on the resistance of blood components to bacterial multi- plication . Transfusion 1994 ; 34 : 852 – 857 . 10 Lane TA , Anderson KC , Goodnough LT et al. Leukocyte reduction in blood component therapy . Ann Intern Med 1992 ; 117 : 151 – 162 . 11 Laupacis A , Brown J , Costello B et al. Prevention of posttransfusion CMV in the era of universal WBC reduction: A consensus statement . Transfusion 2001 ; 41 : 560 – 569 . 12 Daly PA , Schiffer CA , Aisner J , Wiernik PH . Platelet transfusion therapy: One hour posttransfusion increments are valuable in pre- neuropathy (HAM, or HTLV - associated myelopathy). These dis- eases are rarely reported in the United States. Cytomegalovirus (CMV), a DNA virus of the herpesvirus family, usually causes a mononucleosis - like syndrome in suscep- tible adults. A woman who experiences a primary CMV infection stands a 40% chance of transmitting the virus to her fetus. Fetal infection may result in cerebral calcifi cations, mental retardation, deafness, motor retardation, thrombocytopenia, jaundice, and death. Approximately 40 – 90% of the population has anti - CMV antibodies. The risk of transfusion - associated transmission of CMV during pregnancy is unknown. While most pregnancy - related transfusions occur postpartum, it seems prudent to trans- fuse the pregnant seronegative woman or her fetus with blood from a seronegative donor [70] . Although controversial, the transfusion of leukoreduced RBCs is considered by some to be equivalent in risk of transmission of CMV to that of transfusion from CMV - seronegative donors [4,5,70] . Parvovirus B19 is a DNA virus that may attack and lyse RBC progenitor cells in the marrow. It is of particular concern in patients whose active erythropoiesis compensates for their chronic hemolytic anemia (e.g. hemoglobinopathies and pure red cell aplasias [75] ). From 30 to 60% of blood donors have antibod- ies to parvovirus, and therefore will not transmit the disease. In addition, because the red cell P - antigen is the receptor for parvo- virus B19 those defi cient in the P - antigen are not susceptible to parvovirus infection [4] . Transfusion - associated transmission of parvovirus is rare [76] . However, a theoretical concern for preg- nant recipients of blood products is that parvovirus B19 may cause a severe aplastic hemolytic anemia in the fetus, resulting in hydrops and fetal demise. Parvovirus is rarely transmitted by cel- lular components and plasma, but has been reported with trans- fusion of clotting factor concentrates. NAT screening for high - titer parvovirus B19 is currently classifi ed as an in - process manufac- turing control but not as a screening test [4] . Transmissible spongiform encephalopathies (TSEs) are degen- erative brain disorders caused by protein particles called prions. Creutzfeldt – Jakob disease (CJD) is a TSE characterized by rapid progression to death once dementia is manifest. While 85% of cases are sporadic, another 15% are due to transmission of a mutated prion gene. To date, there have been no reports of CJD transmission by blood transfusions. In contrast, based on the demonstration of variant Creutzfeldt – Jakob disease (vCJD) by transfusion in a mouse model [77] , human transmission of vCJD by blood products seems plausible [5] . While the prion respon- sible for vCJD is distinct from that of CJD, it appears identical with that which causes bovine spongiform encephalopathy (BSE). Following a cluster of cases of vCJD in the United Kingdom, all of which were likely due to consumption of animal products from cattle infected with BSE, the UK Department of Health instructed the UK Blood Transfusion Services to institute universal leu- kodepletion as a precautionary measure against vCJD transmis- sion. Subsequently leukodepletion was demonstrated to decrease prion protein content in whole blood, RBCs, and plasma [77] . Because no cases of either BSE or vCJD have been reported in the . blood unit; give antibiotics; notify blood transfusion service Care in donor selection, blood collection and storage; careful attention to arm preparation for phlebotomy DIC = disseminated. multi- plication . Transfusion 199 4 ; 34 : 852 – 857 . 10 Lane TA , Anderson KC , Goodnough LT et al. Leukocyte reduction in blood component therapy . Ann Intern Med 199 2 ; 117 : 151 – 162 . . CMV - seronegative donors [4,5,70] . Parvovirus B19 is a DNA virus that may attack and lyse RBC progenitor cells in the marrow. It is of particular concern in patients whose active erythropoiesis