1088 SECTION IX Pediatric Critical Care Hematology and Oncology Other Cardiac Patients TAXI suggests using clinical judgment in PICU patients with acquired myocardial dysfunction or pulmonary hyperten[.]
1088 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology Other Cardiac Patients TAXI suggests using clinical judgment in PICU patients with acquired myocardial dysfunction or pulmonary hypertension The experts added, “there is no evidence that transfusion above 10 g/ dL is beneficial.”33,40 Prevention of Anemia and Red Blood Cell Transfusion “Bloodless medicine” is a popular concept; it refers to all strategies that can be used to provide medical care without allogeneic RBC transfusion, including blood conservation Many strategies can prevent or significantly decrease the number of RBC transfusions and exposure to transfusion These strategies are integrated into the concept of a “patient blood management program,” which includes measures to prevent anemia and to limit the number of transfusions.28,55,79,80 Adopting a restrictive RBC transfusion policy in stable critically ill children is one of these strategies Other strategies could include raising the Hb concentration before elective surgery, using blood products only when necessary, limiting blood loss, and administering the patient’s own blood Pre–Pediatric Intensive Care Unit Anemia Bloodless medicine begins before surgery, when applicable In the preoperative period, the use of erythropoietin and iron supplementation can be considered to optimize the preoperative Hb level Collection of autologous donations can take place to minimize or prevent allogeneic transfusion Medications that increase the risk of bleeding should be avoided, including herbal medicine (garlic, ginseng, ginger, etc.),81 and optimal control of any existing coagulation disorders should be attained just before surgery During surgery, maximal attention should be given to limiting blood loss82 and ensuring good hemostasis and rapid control of any bleeding In some instances, desmopressin, fibrin sealants, or antifibrinolytic agents such as tranexamic acid may be used to prevent or control hemorrhage Recombinant activated factor VII (rFVIIa) use is advocated by some practitioners, but it is associated with a significant risk of thrombosis The cost/benefit ratio of rFVIIa in children is not well evaluated and its use should be limited to situations involving uncontrolled life-threatening bleeding The use of prothrombin complex and fibrinogen concentrates are also potential agents that can improve hemostasis in children with significant bleeding, but the appropriate indications for these agents and their safety profile in children are not well established (see Chapter 89) The safety and cost-effectiveness of intraoperative blood conservation strategies—such as normovolemic hemodilution, autologous blood cell salvage modalities, intraoperative autotransfusion, and deliberate hypotension—remains to be determined Pediatric Intensive Care Unit–Associated Anemia Postoperative and PICU management of anemia and bleeding is also important A restrictive transfusion strategy is in line with the concept of “permissive anemia” supported by the British Committee for Standards in Haematology Transfusion Task Force.77 A prospective study reported that 73% of blood loss in the PICU is attributable to blood draws.1 The number and frequency of blood tests must be limited, and the amount of blood collected reduced Many devices can help to minimize blood loss, including the use of loop sampling, pediatric blood collection tubes, microanalysis techniques requiring small volumes of blood, and in-line measurement of parameters such as blood gases and Hb concentration Some of these blood conservation methods have been demonstrated to be effective in reducing RBC transfusion in critically ill children.83 Erythropoietin response to anemia is blunted and poorer than expected in critically ill patients.84 In spite of this, erythropoietin can prevent anemia in critically ill adults,85 in low-birth-weight preterm infants,86 and in the postoperative care of neonates.87 In critically ill children, there are no data to support the use of erythropoietin as a preventive measure because most RBC transfusions are administered within or days after PICU admission,1,29 a period of time too short to allow for a response to erythropoietin, which generally occurs after several days Standard use of erythropoietin is presently not recommended in the PICU Iron supplementation is also not indicated in critically ill patients: it had no discernible effect on iron-deficient erythropoiesis, Hb concentration, and RBC transfusion requirement,88 and can even be harmful.89 Post–Pediatric Intensive Care Unit Anemia Given the results of many trials advocating for restrictive transfusion therapy, one can expect a high incidence of anemia at PICU discharge Jutras et al.90 reported that 47% of 2073 PICU survivors who never received an RBC transfusion while in the PICU were found to be anemic prior to PICU discharge (anemia was defined as per the Canadian Blood Services diagnostic criteria) Demaret et al.91 reported a prevalence of 57.4% of anemia at PICU discharge in 679 PICU survivors Such anemia is not without consequences Yakymenko et al.92 reported that post-ICU anemia significantly decreased quality of life among critically ill adult survivors Their randomized controlled trial also showed that RBC transfusion improved the quality of life of anemic postICU survivors Consequences of anemia at PICU discharge, how it should be prevented, and how it should be handled post-PICU remain to be determined Types of Red Blood Cell Units Standard Red Blood Cell Units Storage of RBC units is made possible by refrigeration at about 2°C to 6°C and by storage in preservative anticoagulant solutions that contain dextrose, sodium citrate, citric acid, and sodium diphosphate RBCs use dextrose and phosphate to generate ATP, which is essential for their survival Citrate blocks coagulation by chelating calcium; it is also transformed into bicarbonate, which stabilizes the stored RBC unit pH above 6.4 RBCs in CPDA-1 (citrate-phosphate-dextrose-adenine) solution can be stored up to 35 days because the level of ATP is normal after 21 days of storage and is about 50% after 35 days RBC units are prepared by removing 200 to 250 mL of plasma and platelets from one unit of whole blood after centrifugation To support the nutrient needs of RBCs after plasma is removed, additive solutions were developed, such as AS-1 (Adsol), AS-3 (Nutricel) and AS-5 (Optisol), and saline-adenine-glucose (SAG) or SAG-mannitol (SAGM).93–95 These additive solutions further decrease RBC lysis and allow for storage up to 42 days The volume of a CPDA-1 unit is about 250 mL, including 63 mL of preservative solution; it must be diluted with 75 mL of NaCl 0.9% before transfusion (final volume: 325 mL) Volumes of an AS-3 unit and a SAGM unit are about 350 mL and 300 mL, respectively; both include approximately 100 mL of preservative solution and not require any dilution CHAPTER 91 Transfusion Medicine Other Types of Red Blood Cell Units Many other types of RBC units are available: collected by apheresis, leukocyte-reduced, washed, irradiated, cytomegalovirus (CMV) negative, autologous, and directed Leukocyte-Reduced Red Blood Cell Units RBC units contain some nonviable platelets, small amounts of coagulation factors, and WBCs, which can release pro- and antiinflammatory mediators during storage Prestorage leukocyte reduction is a standard procedure for all blood components in many countries, such as Australia, Canada, and the United Kingdom It can decrease the number of WBCs in RBC units from 109 to less than 106 per product and reduce the concentration of cytokines in the supernatant as well as some T cell–regulated immunomodulation.96 In 2015, 90.9% of RBC units administered in US PICUs were leukocyte-reduced at collection.28 Transmission of intracellular viruses, such as CMV and herpes simplex virus, is less frequent if there are fewer leukocytes Clinical trials in adults indicate that leukoreduction does not reduce mortality or ALI; however, it may decrease fever episodes and reduce infections and antibiotic use after RBC transfusion.97–101 Leukoreduction was associated with improvement in several clinical outcomes in premature infants (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and grade or intraventricular hemorrhage).102 Trials have not been performed in children to determine whether leukoreduction improves clinical outcomes Washed Red Blood Cell Units RBCs can be washed with sterile saline; the process removes not only 98% of plasma but also up to 20% of RBCs RBC washing increases the hematocrit to 0.8, but the procedure takes between 45 minutes and hours; thus, it is impractical to use washed RBC units on an emergency basis unless they are prepared in advance Washed units must be used within 24 hours after processing Multiple wash cycles are required Washing effectively reduces supernatant potassium, immunoglobulin A (IgA), cytokines, complement proteins and microparticles.103 The procedure may not completely remove all proteins and therefore does not prevent hypersensitivity reactions (e.g., hypersensitivity to IgA) The overall volume of a washed RBC unit is significantly decreased (from 350 to 200 mL for an AS-3 RBC unit), making it sometimes useful to limit the volume administered in some patients Washed RBC units should not be considered leukocyte reduced A randomized controlled trial that included 161 children reported that washing RBCs transfused in cardiac PICU patients reduced postoperative inflammation and number of transfusions.104 A randomized trial of washed RBC and platelet transfusions in 43 adults with acute leukemia reported similar trends.105 However, the washing process is not without consequences; for example, it increases hemolysis and decreases RBC 2,3-DPG content.106 Further studies are required before washing of all RBC units can be recommended for PICU patients Washed RBC units can be considered for patients with severe, recurrent allergic reactions to blood, patients with anti-IgA deficiency, and some patients with a high risk for circulatory overload Irradiated Red Blood Cell Units Some WBCs remain in RBC and platelet units, even in prestorage leukocyte-reduced units The objective of irradiation is to induce enough DNA damage to prevent leukocyte proliferation Irradiation 1089 destroys the ability of transfused lymphocytes to divide and therefore to respond to host foreign antigens, thereby decreasing the risk of developing transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible recipients However, irradiation is not without drawbacks For example, it can damage the RBC membrane, causing the release of significant amounts of free Hb and potassium Moreover, the shelf life of irradiated RBC units is reduced from 42 to 28 days.107 In the United States, 20.6% of RBC units are irradiated before transfusion.28 Irradiated RBCs are indicated for all children with congenital or acquired cellular immunodeficiency (e.g., allogeneic stem cell transplant recipients, certain hematologic malignancies, myeloablative chemotherapy recipients) to prevent TA-GVHD Because DiGeorge syndrome is not rare among infants with congenital heart disease undergoing cardiac surgery, these patients should receive irradiated units Irradiation is also indicated for patients receiving directed donations from family members Irradiation is not mandatory for most solid tumors, routine immunosuppressive therapy (e.g., corticosteroids), solid organ transplants, nonmyeloablative chemotherapy recipients, or humoral immunodeficiency Cytomegalovirus-Negative Red Blood Cell Units RBC transfusion can transmit CMV infection A large proportion (30%–70%) of blood donors are CMV positive Although it would be ideal to administer only CMV-negative RBC units to CMV-negative patients, the high prevalence of CMV infection among donors does not permit this Nevertheless, prestorage leukocyte reduction of blood products decreases transmission of CMV to 1% to 2% (similar to the rate of infection following the transfusion of CMV-negative units) compared with standard products for which transmission is 13% to 37% Administration of a CMV-positive RBC unit is generally not an issue for immunocompetent patients Established indications for CMV-negative units include CMV-negative recipients of organ or bone marrow transplants from CMV-negative donors, CMV-negative bone marrow transplant recipients, and intrauterine transfusions Less well-established indications include CMV-negative patients who are potential candidates for autologous or allogeneic bone marrow transplant, CMVnegative patients undergoing splenectomy, potential seronegative donors for bone marrow transplant, and CMV-negative patients with HIV Directed Red Blood Cell Units Directed blood is donated by family members or friends Parents frequently believe that giving their own blood decreases the risks of transfusion, which, in practice, is not the case A small increase of transfusion-transmitted infectious diseases has been reported.108 Moreover, the risk of contracting a TA-GVHD is increased even in immunocompetent patients In spite of this, directed blood donation remains popular in the lay public; good clinical studies to better estimate the risk/benefit ratio of this practice are warranted All directed RBC units must be irradiated pretransfusion Autologous Red Blood Cell Units Older healthy children can donate their own blood a few weeks before elective surgery It is frequently believed that autologous RBC units are free of risk, which is untrue Moreover, autologous RBC units are not leukocyte reduced, at least in Canada The risk/ benefit ratio of autologous RBC units remains to be determined 1090 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology Transfusion of Red Blood Cells: How Volume and Number of Red Blood Cell Units RBC transfusion is the best way to rapidly increase the Hb concentration Once a practitioner decides that an RBC transfusion is warranted, several issues need to be considered, including the type of RBC unit (see previous section), blood type, volume and rate of transfusion, and the monitoring required Many guidelines have been published on how transfusions should be given.53,55,109,110 Prescribing the right volume of RBC units is important, as this prevents cardiac overload and limits exposure to several donors An easy, albeit simplistic, rule of thumb exists suggesting that administration of 10 mL/kg of RBC units increases the Hb level by to g/dL If the volume prescribed is greater than the volume of unit of RBCs, blood should be transfused unit at a time to minimize exposure to multiple donors Prior to the administration of additional RBCs, the Hb concentration should be measured after allowing at least 30 minutes posttransfusion for Hb and hematocrit values to equilibrate The transfusion can be completed with another unit or partial unit if a reasonable Hb level is not attained If the volume of RBCs required is less than unit, a partial unit can be given Whole RBC units can be subdivided in half (standard division) or in small pediatric 75-mL transfer packs (Pedi-Pak) Partial units prepared nonsterilely expire 24 hours after preparation On the other hand, partial units prepared sterilely can be kept as long as the original unit (up to 42 days for AS–3) A small volume of RBC unit placed in a syringe must always be administered within 24 hours Blood Types Table 91.2 describes the compatibility of different blood products A complete cross-match is mandatory before any transfusion is given, with few exceptions Transfusion of group O Rh-negative RBCs can be life-saving, but this must be reserved for very severe and acute situations It takes 15 to 20 minutes to type a patient for ABO and Rh If there are no RBC antibodies, fully compatible blood or immediate spin cross-match may be issued quickly In the case of RBC antibodies or other anomalies, a lengthier full serologic cross-match is required The risk of severe reaction to typed, but not cross-matched, RBC units is about in 1000 if the patient has never received a transfusion; the risk is decreased by 10-fold if a cross-match is performed Repeat verification that the correct blood unit has been delivered to a given patient is essential because blood mismatch is the most important cause of severe transfusion reaction For high-risk elective procedures, type and cross-matching, completed prior to any bleeding, allows for compatible RBC units to be reserved If an unforeseen emergency transfusion is required for an actively bleeding patient, it is impossible to deliver RBC units that are typed and cross-matched within a reasonable time frame, in which case group O Rh-negative RBC units can be administered (some hospitals also deliver group O Rh-positive RBC units for men and for women after menopause) STAT ordering a transfusion means that transfusion is required within a few minutes; this is not indicated unless the patient is actively bleeding TABLE 91.2 Compatibility of Blood Products Product Receiver Donor RBC unit and whole blood A A, O B B, O O O AB AB, A, B, O Rh1 Rh1 or Rh– Rh Plasma or platelets Platelets – Rh– A A, AB B B, AB O O, A, B, AB AB AB Rh Rh1 or Rh– Rh– Rh– or Rh1a a Give an anti-D vaccine (Win Rho) if the receiver is Rh– and the platelet concentrate is Rh1 RBC, Red blood cells Length of Storage Regulatory agencies and scientific societies, such as the US Food and Drug Administration (FDA) and the European counterpart to the FDA, mandate that RBC units can be stored up to 42 days based on the criterion that at least 75% of transfused RBCs will be alive 24 hours posttransfusion and that hemolysis will be less than 1%.111 However, a storage lesion, detailed previously, occurs over time, which raises many concerns.17,112 There are safety concerns for transfusion of fresh RBCs as well, including the risk of transmission of some infectious diseases (malaria, Chagas disease, intracellular viruses), cell-free DNA,113 microchimerism,114 TA-GVHD,115 and risk of in-hospital mortality.116 Five randomized controlled trials addressed the question of whether the transfusion of fresher rather than older RBC units improves the outcome of critically ill patients.117–121 All reported that fresher RBC units not improve outcome; the three larger trials rather showed consistent, but not statistically significant, trends against the use of fresher blood.117,119,120 Many intensivists believe that children should receive fresher RBC units, especially for pediatric cardiac surgery patients.122 A large randomized controlled trial, the Age of Blood in Children in PICU study, enrolling 1538 transfused PICU patients to address this question The use of fresh compared with standard-issue RBCs (median length of storage, vs 18 days) did not reduce the incidence of new or progressive MODS (147 vs 133) or PICU mortality (33 vs 26).17 Presently, there is no justification to require fresh RBC units for critically ill children, even for cardiac surgery patients There are less data informing us on the effect on outcomes with the transfusion of old RBC units, such as those stored for weeks or longer, but available evidence suggests that transfusion of blood stored for 35 days or longer has no effect on in-hospital mortality.123,124 Perfusion, Warming, and Filtration An RBC transfusion must be completed within to hours (4 hours in the United States) after the unit is delivered by the hospital blood bank An RBC unit is usually given over to hours but can be given more slowly (up to hours) or divided into two transfusions if there is some risk of cardiac overload.108 CHAPTER 91 Transfusion Medicine 1091 RBCs can also be given through a rapid infuser in a few minutes for life-threatening bleeding The viscosity of RBC units is high, which implies that it is preferable to use larger-bore needles to administer them No drugs should be given in the line used for RBC unit perfusion There is in theory a risk of hemolysis if RBCs are given with 0.2% saline or dextrose 10%, but the coinfusion of RBCs and hypotonic or hypertonic solution seems safe if it is short lasting (a few minutes).125 On the other hand, coinfusion of dextrose-containing fluids with RBC units is safe.125 It is inappropriate to mix RBC units with Ringer’s lactate (risk of coagulation) or calcium salts RBC units must be warmed before administration to diminish the viscosity of the blood product and to avoid hypothermia Blood viscosity decreases by about 7% for each 1°C increase, reducing resistance and making it easier to administer blood products through catheters RBC units are stored at 2°C to 6°C and could cause significant hypothermia if given to a patient without warming Blood products are warmed to room temperature (about 20°C) before delivery to the bedside unless the RBC units are required on an emergency basis (e.g., in a case of hemorrhagic shock) Warming to body temperature (37°C) may be required for patients weighing less than 10 kg or if large volumes need to be given (.20%–30% of the circulating blood volume) RBC units can be warmed by ambient temperature or by active warming with a device Standard blood-warming devices are used to raise the temperature of whole blood or RBC units and not microwave ovens, which can cause severe hemolysis Because all RBC units (even prestorage leukocyte-reduced RBC units) contain fibrin, platelets, and WBC aggregates, a filter (with 80-, 179- or 260-micropores) must always be used to filter these aggregates before they are administered Although their cost-usefulness has not been determined, filters with 20- to 40-micropores are more effective, and some evidence suggests that they can prevent cases of TRALI Filters with smaller micropores are not considered standard treatment storage, and preparation for transfusion.127 The levels of coagulation factors in SD plasma are more standard with little variation among units, as it is a pooled plasma product FP is stored at –18°C up to year after collection SD plasma can be stored for up to 48 months Compared with FFP, SD plasma is practically cell free and contains significantly lower residual platelet concentrations and negligible amounts of microparticles due to its manufacturing process.128 Multiple dried plasma products are currently used in a few European countries to allow for immediate availability of plasma for severely bleeding patients.129 Dried plasma products maintain hemostatic and endothelial repair properties similar to that of FP products.130,131 The licensing of dried plasma for adults and children is anticipated soon in the United States Epidemiologic studies reported that adults transfused with plasma are more prone to contract ventilator-associated pneumonia, bloodstream infection, and septic shock (relative risk for all infections, 2.99; 95% CI, 2.28–3.93; P 02).132 A prospective cohort study involving 831 critically ill children reported an increased incidence rate of morbidity and nosocomial infections The adjusted odds ratios were 3.2 (95% CI, 1.6–6.6) and 2.3 (95% CI, 1.0–5.3), respectively There was also a significant difference in the adjusted length of PICU stay.133 Plasma transfusions are associated with adverse clinical outcomes; this might be attributable to their immunomodulative properties or due to confounding by indication134 given that plasma is transfused to patients with increased severity of illness It also might be that the association between plasma and outcomes is due to severity of illness and not due to the plasma In a secondary analysis of a prospective observational study that included 443 critically ill children who received plasma transfusions, FFP and SD plasma were associated with similar reductions in INR (P 80) However, ICU mortality was significantly lower with SD plasma compared with FFP (14.5% vs 29.1%, P 02).135 Plasma Transfusion of Plasma: Indications (When) Types of Plasma Generally, FP is transfused to correct multiple coagulation factor deficiencies (or single-factor deficiencies when no recombinant or plasma-derived coagulation factor concentrates are available) in patients with active bleeding or prior to invasive procedures when no alternative therapies are available or appropriate Common coagulopathies for which FP may be given include liver disease and symptomatic disseminated intravascular coagulation (DIC) FP can be given for the emergency reversal of warfarin or vitamin K deficiency when prothrombin complex concentrates are not available.136 FP is also given to prevent bleeding in patients with abnormal coagulation tests Guidelines suggest transfusing FP only when the INR, prothrombin time (PT), or activated partial thromboplastin time (aPTT) is more than 1.5 times normal, as coagulation factors are generally adequate for hemostasis below this level However, recent data suggest that FP is not very effective at normalizing mild abnormalities of coagulation tests, and the potential clinical benefit of FP transfusion seems minimal when the INR is less than 2.5 or an aPTT is less than 60.137 Plasma is also indicated for plasma exchange therapies for certain conditions, such as thrombotic thrombocytopenic purpura.136 FP should be administered empirically during massive transfusion for life-threatening bleeding A randomized controlled trial in adults revealed that the early use of FP in the prehospital setting for severe traumatic bleeding improved 24- and 30-day Plasma is separated from RBCs after collection of whole blood or collected using an apheresis machine It is then frozen for storage to preserve coagulation factors The term fresh frozen plasma (FFP) is used if the unit is refrigerated within hours of collection; the term frozen plasma (FP) is used if refrigerated within 24 hours of collection There is a slight reduction in factor VIII levels in FP In clinical practice, however, these two types of plasma are presumed to be essentially interchangeable.126 FP (frozen plasma) is used in this section to designate both types of plasma units FP units are collected from a single donor, while units of solvent detergent (SD) plasma (Octaplas, Octapharma) are constituted from a pool of FP collected from approximately 630 to 1520 donors and processed using SD for inactivation of lipidenveloped viruses In many countries, only FP may be available, but FFP is still available in some countries FP units are systematically leukocyte reduced by filtration before storage in many countries, but not in the United States FP volume is about 200 to 250 mL/U,108 while the volume of SD plasma is about 200 mL/U On average, FP contains U/mL of all coagulation factors, but there is significant variability among individual units, which is attributable to biological variation in factor levels among individual donors and differences in processing, 1092 S E C T I O N I X Pediatric Critical Care: Hematology and Oncology survival.138 Some experts advocate early replacement of FP in a 1:1 or 1:2 ratio with RBC units in trauma patients with massive transfusion.35,40,139 According to two systematic reviews, application of a thromboelastography (TEG or rotational thromboelastometry [ROTEM])–guided transfusion strategy reduces the amount of bleeding in patients with massive transfusion, blood product utilization, and renal failure, and seems to improve morbidity and mortality.140,141 However, these results were primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence was low.141 Many pediatric intensivists state that abnormal coagulation tests (INR, TEG, and so on) could prompt them to prescribe FP even if the patient is not bleeding.142 Actually, there is no evidence that FP should be given in prophylaxis to nonbleeding patients For decades, there has been consensus that plasma should not be used as a volume expander;142 crystalloids, synthetic colloids, or purified human albumin solutions are preferred This concept is currently being challenged by some who are considering reexamination of the use of plasma for volume resuscitation of patients who are in hypovolemic or septic shock.143 In vitro and animal data in septic models support the concept that plasma improves preload more effectively than crystalloids, can correct both hyper- and hypocoagulable states, repair endothelial injury, and is, in fact, less inflammatory than crystalloids.144–148 Until trials are performed in humans, plasma should not be routinely used for volume resuscitation even in patients with hypovolemic shock Epidemiologic studies reported that adults transfused with plasma are more prone to contract ventilator-associated pneumonia, bloodstream infection and septic shock (relative risk for all infections: 2.99; 95% CI, 2.28–3.93; P 02).132 A prospective cohort study involving 831 critically ill children reported an increased incidence rate of morbidity, nosocomial infections, and duration of stay associated with FP transfusion In a secondary analysis of a prospective, observational study that included 443 critically ill children who received plasma transfusions, FFP and SD plasma were associated with similar reductions in INR (P 0.80) However, ICU mortality was significantly lower with SD plasma compared with FFP (14.5% vs 29.1%, P 02).135 Transfusion of Plasma: How The typical dose of plasma in nonmassively bleeding children ranges between 10 and 15 mL/kg The effectiveness of FP transfusion should be estimated by clinical judgment of ongoing bleeding and functional measurements of hemostasis when time allows For life-threatening bleeding, FP is empirically transfused without guidance from laboratory measurements of hemostasis due to the inherent delay in reporting of these parameters In patients with non–life-threatening bleeding, FP may be indicated by functional measures of hemostasis that indicate a hypocoagulable state Karam et al.137 reported that a dose-response relationship was found in patients only with an INR greater than 2.5; patients with a lower INR had no significant change in coagulation tests Normalization of coagulation tests often does not occur and therefore should not be used as the only guide for additional FP transfusions FP transfusions should be ABO compatible but not require cross-matching In contrast to RBCs, group AB–positive plasma is the universal plasma donor and can be given in emergency situations when a blood group is not available When group AB plasma is not available, evidence data in adults indicate that it is safe to use group A plasma for emergency release for patients with life-threatening bleeding.149,150 Cross-matching is not required, as FP units are screened for antibodies against non-ABO and Rh antibodies, which may cause hemolytic reactions FP must be thawed prior to transfusion (20–30 minutes with the water bath method) Thawing FP can be shortened to minutes using microwave ovens specifically designed for this task A thawed unit of FP is ideally transfused within hours, but thawed plasma can be relabeled and stored for up to days (American Association of Blood Banks [AABB] Technical Manual) The clinical indications for thawed plasma are similar to FP but there is some decrease in the labile coagulation factors (factor V and VIII), and reduction in thrombin generation capacity.128 An 80or 170-micropore filter must be used Platelets Types of Platelet Products Standard Platelet Products Different methods can be used to obtain platelet products: 13% are derived from whole blood, either by the platelet-rich plasma (United States and United Kingdom) or the buffy-coat method (Europe and Canada), and 87% are obtained by apheresis (singledonor) platelets.151 For platelets derived from whole blood, platelet concentrates are often pooled (4–6 units) for a single platelet transfusion Platelet units can be stored either warm (20°C–24°C) for to days or cold (2°C–6°C) for days The benefit of warm storage of platelets is increased circulation time, which is advantageous for patients who need platelets for prophylaxis of bleeding The risk of warm storage is increased incidence of bacterial contamination.152 The benefit of cold storage of platelets is reduced bacterial contamination and increased hemostatic activity, which is advantageous for patients with active bleeding.153 The disadvantage of cold storage of platelets currently is the short shelf life of days Trials are in progress examining the effect of platelet storage temperature and duration of storage (up to 14 days) on hemostasis (NCT02495506; https://clinicaltrials.gov) Endogenous platelets also have immune functions and can influence both innate and adaptive immune response, which may affect outcomes in critically ill patients.154 The effect of platelet manufacturing methods (collection, processing, and storage) on hemostatic and immune function deserves thorough examination.155 Special Platelet Concentrates Leukocyte-Reduced Platelets A platelet concentrate must contain less than 8.3 105 WBCs to be labeled leukocyte reduced Prestorage leukocyte reduction is a standard procedure in many countries Bedside leukocyte reduction filter should not be used when prestorage leukocyte reduction is done because it is useless and can decrease the number of platelets Irradiated Platelets The risk of TA-GVHD is increased in patients who receive human leukocyte antigen (HLA)–compatible platelets Therefore, pretransfusion irradiation is mandatory for all HLA-compatible platelet concentrates Irradiation is also recommended for intrauterine transfusion and infants at risk of TA-GVHD.108 In 2017, 80% of transfused platelets were irradiated.151 ... immunocompetent patients In spite of this, directed blood donation remains popular in the lay public; good clinical studies to better estimate the risk/benefit ratio of this practice are warranted All... women after menopause) STAT ordering a transfusion means that transfusion is required within a few minutes; this is not indicated unless the patient is actively bleeding TABLE 91.2 Compatibility... frozen plasma (FFP) is used if the unit is refrigerated within hours of collection; the term frozen plasma (FP) is used if refrigerated within 24 hours of collection There is a slight reduction