Blood utilization in liver transplantation (BUILT): A multidisciplinary survey of transfusion practices.

BACKGROUND: The purpose of this study was to survey liver transplant centers in the United States to assess baseline practices in blood utilization and identify opportunities for standardization to optimize blood use in these complex cases. STUDY DESIGN AND METHODS: Two surveys, one for transfusion medicine physicians and the other for anesthesiologists, were distributed to high-volume liver transplant centers. RESULTS: The response rate was 52% for both surveys. The majority of respondents (90%) indicated they issue a standardized number of blood products to start surgeries. The most common number of products issued before the start of cases were 10 red blood cells (RBC) and 10 plasma units with no platelets or cryoprecipitate. On average, fewer RBC (7.5) and plasma (7) units were transfused than issued. Decisions to transfuse RhD+ RBCs to RhD- patients and use antigen untested units in alloimmunized patients were mainly handled on a case-by-case basis. Many centers reported utilizing viscoelastic testing (97%) and cell salvage (97%). Most centers reported standardized, laboratory-based intraoperative transfusion goals for RBCs (65%) and fibrinogen replacement (52%) but lacked a standardized approach for plasma (55%) and platelets (58%). DISCUSSION: More blood products are issued during surgery than are transfused. Responses from anesthesiology providers suggest a broad consensus on practice. Almost all respondents use viscoelastic testing in the management of intraoperative coagulopathy, either alone or in combination with classical coagulation tests. The majority of programs do not transfuse clotting factor concentrates, including fibrinogen concentrate, prothrombin complex concentrates, and recombinant activated FVII, and do not use antifibrinolytics prophylactically.

Associations of donor, component, and recipient factors on hemoglobin increments following red blood cell transfusion in very low birth weight infants.

BACKGROUND: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single-unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. RESULTS: Data on VLBW infants (n = 254) who received one or more single-unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post-transfusion hemoglobin increments were associated with RBC units donated by female donors (-0.24 g/dL [95% confidence interval (CI) -0.57, -0.02]; p = .04) and donors <25 years old (-0.57 g/dL [95% CI -1.02, -0.11]; p = .02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p < .01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post-transfusion hemoglobin increments. CONCLUSION: Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants.

Therapeutic plasma exchange practices in immune thrombocytopenia related hospitalizations: Results from a nationally representative sample.

Per the American Society for Apheresis, therapeutic plasma exchange (TPE) is a Category III indication in the management of immune thrombocytopenia (ITP). This nationally representative study evaluates TPE utilization in hospitalized adults with a primary admission diagnosis of ITP. Hospitalizations with ITP as the primary admitting diagnosis were analyzed from the 2010 to 2014 National Inpatient Sample, the largest all-payer inpatient database in the United States. Univariate and multivariable logistic regressions were used to determine clinical outcomes in ITP patients undergoing TPE. Sampling weights were applied to generate nationally representative estimates. From 2010 to 2014, there were a total of 56,149 admissions with a primary admitting diagnosis of ITP, of which 0.66% admissions (n = 372) also coded TPE. Most subjects undergoing TPE were the highest disease severity class: major (34.6%) and extreme severity (31.0%), by all-patients refined diagnoses-related groups severity of illness subclass. After multivariable analysis, underlying severity of illness remained the most significant predictor of TPE (P < .001). ITP admissions with TPE had a high rate of comorbidities (50%) and significantly longer mean length of hospital stay than those without (P < .001). TPE was reported in ~0.6% of hospitalizations with ITP as the primary diagnosis in this nationally representative sample from 2010 to 2014. TPE was performed in patients with the highest severity of underlying illness, and higher rates of comorbidities.

Blood component utilization in COVID-19 patients in New York City: Transfusions do not follow the curve.

BACKGROUND: Blood suppliers and transfusion services have worked diligently to maintain an adequate blood supply during the COVID-19 pandemic. Our experience has shown that some COVID-19 inpatients require transfusion support; understanding this need is critical to blood product inventory management. STUDY DESIGN AND METHODS: Hospital-wide and COVID-19 specific inpatient blood product utilization data were collected retrospectively for our network's two tertiary academic medical centers over a 9-week period (March 1, 2020-May 2, 2020), when most inpatients had COVID-19. Utilization data were merged with a COVID-19 patient database to investigate clinical demographic characteristics of transfused COVID-19 inpatients relative to non-transfused ones. RESULTS: Overall, 11 041 COVID-19 patients were admitted and 364 received blood product transfusions for an overall transfusion rate of 3.3%. COVID-19 patients received 1746 blood components in total, the majority of which were red blood cells. COVID-19 patients' weekly transfusion rate increased as the pandemic progressed, possibly reflecting their increased severity of illness. Transfusion was significantly associated with several indicators of severe disease, including mortality, intubation, thrombosis, longer hospital admission, lower hemoglobin and platelet nadirs, and longer prothrombin and activated partial thromboplastin times. As the pandemic progressed, institutional adherence to transfusion guidelines improved for RBC transfusions compared to prior year trends but did not improve for platelets or plasma. CONCLUSION: There is a need to closely monitor the blood product inventory and demand throughout the COVID-19 pandemic as patients' transfusion needs may increase over time. Daily or weekly trending of patients' clinical status and laboratory values may assist blood banks in inventory management.

Convalescent plasma to treat coronavirus disease 2019 (COVID-19): considerations for clinical trial design.

Case series studying convalescent plasma use in the treatment of COVID-19 have been promising, but additional, high-quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness. Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor. There are many clinical trials studying treatment of, and prophylaxis against, COVID-19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the "Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19" protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.

Thawed solvent/detergent-treated plasma demonstrates comparable clinical efficacy to thawed plasma.

BACKGROUND: Thawed Plasma (TP), plasma thawed and refrigerated for up to 5 days, is a commonly transfused plasma product. This pilot study was conducted to determine whether Thawed Solvent/Detergent-treated Plasma stored refrigerated for up to 5-days post-thaw (T-S/D) was as efficacious as TP. STUDY DESIGN AND METHODS: This single institution retrospective cohort analysis evaluated the efficacy of T-S/D in reversing coagulopathies in comparison to TP. Utilizing the institution's electronic medical records, transfusion data were collected in adult patients who received either TP or T-S/D. The primary outcome was the incidence of subsequent transfusions within 24 hours after first dose of either type of plasma. Secondary outcomes included the number of blood products transfused within 24 hours of first-dose plasma, correction of pre-transfusion coagulation laboratory values, volume transfused, and clinical outcomes. RESULTS: TP was received by 301 patients and 137 received T-S/D during the first 32 months post-implementation of T-S/D. There was no difference in incidence of subsequent transfusions or number of blood products given. The median pre-INR of both the TP and T-S/D cohorts was 1.9, with a similar decrease in INR of 0.2 and 0.3 (p = 0.36), respectively, post plasma transfusion. There was no difference in correction of PT/aPTT, mortality, transfusion reactions, readmission rates, length of stay, or inpatient deep venous thrombosis. The median volume of T-S/D plasma transfused for the first dose was 126 mL less than TP (p = .0001). CONCLUSION: T-S/D was as efficacious as TP for the treatment of coagulopathies and the reversal of coagulation laboratory values.

Additive effects of blood donor smoking and gamma irradiation on outcome measures of red blood cell transfusion.

BACKGROUND: Recent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin (Hb) levels in patients after red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined Hb increments and subsequent transfusion requirements after single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors. RESULTS: We linked data on 4038 transfusion recipients who received one or more single-unit RBC transfusions (n = 5086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n = 326), Hb increments were reduced after transfusion of gamma-irradiated units (0.76 g/dL; p = 0.033) but not unirradiated units (1.04 g/dL; p = 0.54) compared to those from nonsmokers (1.01 g/dL; n = 4760). In parallel with changes in Hb levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (odds ratio [OR], 2.49; p = 0.01) but not unirradiated RBC units (OR, 1.10; p = 0.52). CONCLUSION: Donor smoking was associated with reduced Hb increments and the need for additional transfusions in recipients of gamma-irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion.

Transfusion support and alternatives for Jehovah's Witness patients.

PURPOSE OF REVIEW: Jehovah's Witness patients with critical anemia or undergoing major surgery are challenging for healthcare providers to manage, as most will decline transfusion of whole blood and its main components. Recent advances in our understanding of hemostatic agents, alternative hemoglobin-based oxygen carriers, and patient blood management have culminated in a complex array of options to manage critical anemia and bleeding in this patient population. RECENT FINDINGS: Refusal of blood products in the setting of critical anemia is associated with significant risk of morbidity and mortality. With implementation of patient blood management measures, targeted treatment of anemia and coagulopathy has reduced the need for transfusions. Likewise, increased clinical experience with hemoglobin-based oxygen carriers in Jehovah's Witnesses with critical anemia has provided new insights into their potential benefits and pitfalls. SUMMARY: Options and alternatives to manage the Jehovah's Witness patient in the perioperative setting or in the setting of critical anemia will be reviewed.

Efficacy of a new pathogen-reduced cryoprecipitate stored 5 days after thawing to correct dilutional coagulopathy in vitro.

BACKGROUND: Fibrinogen supplementation during bleeding restores clot strength and hemostasis. Cryoprecipitate, a concentrated source of fibrinogen, has prolonged preparation time for thawing, a short shelf life resulting in frequent wastage, and infectious disease risk. This in vitro study investigated the efficacy of a new pathogen-reduced cryoprecipitate thawed and stored at room temperature for 5 days (PR Cryo) to treat dilutional hypofibrinogenemia, compared to immediately thawed standard cryoprecipitate (Cryo) or fibrinogen concentrate (FC). STUDY DESIGN AND METHODS: Ten phlebotomy specimens from healthy volunteers were diluted 1:1 with crystalloid and supplemented with PR Cryo and Cryo (at a dose replicating transfusion of two pooled doses [10 units]) and FC at a dose replicating 50 mg/kg. Changes in clot firmness (thromboelastometry) and in coagulation factor activity were assessed at baseline, after dilution, and after supplementation. RESULTS: Clinical dosing was used, as described above, and consequently the FC dose contained 24% and 36% more fibrinogen versus PR Cryo and Cryo, respectively. At baseline, subjects had a median FIBTEM maximum clot firmness of 13.5 mm, versus 6.5 mm after 50% dilution (p = 0.005). After supplementation with PR Cryo, a median FIBTEM maximum clot firmness of 13 mm was observed versus 9.0 mm for Cryo (p = 0.005) or 16.5 mm for FC (p = 0.005). Median factor XIII was higher after PR Cryo (64.8%) versus Cryo (48.3%) (p = 0.005). Fibrinogen activity was higher after FC (269.0 mg/dL) versus PR Cryo (187.0 mg/dL; p = 0.005) or Cryo (193.5 mg/dL; p = 0.005); the difference between PR Cryo and Cryo supplementation (p = 0.445) was not significant. CONCLUSION: PR Cryo used 5 days after thawing effectively restores clot strength after in vitro dilution.

Red blood cells donated by smokers: A pilot investigation of recipient transfusion outcomes.

BACKGROUND: Current regulations do not require blood collection facilities to ask donors about cigarette smoking, and the prevalence of nicotine and its metabolites in blood products is not well established. Although smokers have higher hemoglobin (Hb) levels, smoking may adversely affect the quality of donated red blood cells through higher carboxyhemoglobin (COHb) content and premature hemolysis. STUDY DESIGN AND METHODS: Red blood cell (RBC) unit segments from 100 unique donors were tested for nicotine and its metabolite cotinine by mass spectrometry and for COHb spectrophotometrically. Outcomes were evaluated retrospectively in adult non-bleeding patients receiving single RBC units. RESULTS: Thirteen of 100 RBC segments (13%) were positive for cotinine at levels consistent with current smoking (> 10 ng/mL). The cotinine positive RBCs showed significantly greater COHb content compared to cotinine negative units (median 3.0% vs. 0.8%, p = 0.007). For patients transfused cotinine-positive units, there was no significant change in their vital signs following transfusion and no transfusion reactions were observed. However, patients transfused cotinine-positive units showed significantly reduced hematocrit and hemoglobin increments (median +1.2% and +0.4 g/dL) following transfusion compared to patients receiving cotinine negative units (median +3.6% and +1.4 g/dL) (p = 0.014). CONCLUSION: Thirteen percent of RBC units tested positive for cotinine at levels consistent with active smoking, accordant with the estimated national smoking rate of 15.5%. Cotinine-positive RBC units had greater COHb content and showed reduced hematocrit and hemoglobin increments following transfusion. These preliminary results should be validated in a larger cohort.

The impact of Daratumumab on transfusion service costs.

BACKGROUND: Daratumumab (DARA) is a human IgG1κ monoclonal antibody directed against CD38, approved for the treatment of multiple myeloma. As CD38 is expressed on RBCs, DARA can interfere with pretransfusion testing. DARA interference can be negated by denaturation of CD38 on RBCs with dithiothreitol (DTT) reagents. Because of this interference in pretransfusion testing, our hospital implemented a notification and testing/transfusion algorithm (NATTA) for pretransfusion testing and RBC product provision for DARA patients. This standardized approach combines DTT-based testing with selective genotyping and the provision of phenotypically similar RBCs for patients with clinically significant antibodies. STUDY DESIGN AND METHODS: We evaluated pretransfusion test results and transfusion requirements for 91 DARA patients in an academic medical center over 1 year to determine the incremental cost of pretransfusion testing and RBC selection. The actual costs for the NATTA approach were compared to a theoretical approach using universal genotyping with a provision of phenotypically similar RBC transfusions. RESULTS: The annual cost of testing related to DARA after NATTA implementation was $535.76 per patient. The simulated annual cost for the alternative genotyping with provision of phenotypically similar RBC transfusions approach was $934.83 per patient. CONCLUSION: In our entire cohort of DARA patients, a DTT-based testing algorithm with selective genotyping and provision of phenotypically similar RBCs only for patients with clinically significant antibodies was less expensive than a simulated model of universal genotyping and provision of phenotypically similar RBCs.

Combined heparin/acid citrate dextrose solution A anticoagulation in the Optia continuous mononuclear cell protocol for pediatric lymphocyte apheresis.

Collecting a sufficient number of T-cells is a critical first step in the production of chimeric antigen receptor (CAR)-T cells. Herein, we report a successful implementation of anticoagulation with combined heparin and acid citrate dextrose solution A (ACD-A) for the continuous mononuclear cell (CMNC) protocol on the Spectra Optia in a 20-month-old, 7.5 kg patient with refractory acute lymphoblastic leukemia for manufacture of tisagenlecleucel, a CAR-T cell therapy. Combined heparin/ACD-A was used following clotting issues when ACD-A was used alone during initial CMNC collections. To our knowledge, this is the first reported case in pediatrics of combined heparin/ACD-A anticoagulation with the Spectra Optia CMNC protocol.

Investigational use of PEGylated carboxyhemoglobin bovine in a Jehovah's Witness with hemorrhagic shock.

BACKGROUND: Jehovah's Witnesses pose a clinical challenge in the setting of critical anemia. Most do not accept transfusions, but some accept hemoglobin-based oxygen carriers on a compassionate-use basis. PEGylated carboxyhemoglobin bovine (PCHB) is an acellular dual-action carbon monoxide (CO)-releasing and oxygen transfer agent currently being investigated in Phase II clinical trials. CASE REPORT: We present the case of a 42-year-old Jehovah's Witness with an acute upper gastrointestinal bleed and hemorrhagic shock who required emergent PCHB for stabilization during lifesaving interventions. After PCHB infusion, the patient's shock and encephalopathy improved with decreased vasopressor requirement. Through gastroenterology and interventional radiology procedures, the patient's bleeding stabilized. While receiving five additional doses of PCHB and other supportive therapies (iron, folate, vitamin B12, darbepoetin alfa), the patient was extubated and weaned off vasopressors. CONCLUSIONS: PCHB was used to stabilize (bridge) a critically ill anemic patient for lifesaving interventions without adverse effects. Additional studies are warranted to explore the drug's safety profile and efficacy in patients declining blood products.

Logistical and safety implications of temperature-based acceptance of returned red blood cell units.

BACKGROUND: AABB requires that red blood cells (RBCs) are maintained at 1 to 10°C during transport. Historically, blood banks used the 30-minute rule for returned RBCs transported outside of validated containers. The implications of this policy have not been previously reported in a real-life hospital setting. STUDY DESIGN AND METHODS: A 2-year, retrospective review of RBC units returned outside of qualified containers was conducted. During the first year, the 30-minute rule was used to accept RBCs back into inventory. Sequentially, the following year, a temperature-based approach was implemented using a thermometer with an accuracy of ±1°C. Time out of the blood bank, temperature upon return, wastage, and transfusion reactions associated with the reissued RBCs were analyzed. RESULTS: In our practice, the 30-minute rule would have accepted 15.2% of RBC units outside of the allowed temperature. Compared to the 30-minute rule, temperature-based acceptance was associated with a 13% increase in wastage (p < 0.001). During the 30-minute rule period, transfusion of returned and subsequently reissued RBCs was associated with a nonsignificant trend toward a higher transfusion reaction rate compared to the overall RBC transfusion reaction rate (1.4% vs. 0.6%, p = 0.084). During the temperature period, transfusion of returned and subsequently reissued RBCs had the same transfusion reaction rate compared to the overall RBC transfusion reaction rate (0.5% vs. 0.5%, p = 1.0). CONCLUSION: Temperature-based acceptance of returned RBCs is associated with significantly higher wastage compared to the 30-minute rule. A temperature-based acceptance practice mitigates the risk of accepting RBCs with unacceptable temperatures returned within 30 minutes of issue.

Extracorporeal photopheresis in pediatric patients: Practical and technical considerations.

In adults, extracorporeal photopheresis (ECP) is widely utilized for a variety of indications, most commonly cutaneous T-cell lymphoma, acute or chronic graft-versus-host disease (GVHD), solid organ transplant rejection, and other autoimmune and T-cell-mediated disorders. In pediatric patients, the majority of case series and reports have focused on its use in the management of acute and chronic GVHD. Currently utilized ECP technologies were designed for adult patients and there are several challenges in adapting these technologies for use in children. In our review, we focus on practical considerations and procedural modifications for ECP use in pediatric patients, with special attention to patient safety.

Acute mechanical hemolysis as a complication of extracorporeal photopheresis in a low-weight child.

Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic stem cell transplantation with high morbidity and mortality. Extracorporeal photopheresis (ECP) is an effective therapy for treating medication-refractory GVHD, however, there is scant evidence of whether ECP can be safely performed in patients weighing less than 15 kg. Here, we report the implementation of a successful protocol to perform ECP in a 21-month-old, 10.6 kg female with medication-refractory GVHD. Our initial ECP treatment resulted in significant hemolysis that was most likely mechanical. After procedural adjustments that included modifying the anticoagulation dose and whole blood:anticoagulant ratio, as well as whole blood processing time, the patient tolerated future procedures safely without hemolysis or other adverse events. With appropriate technical modifications, we provide a framework for safely performing ECP in children less than 15 kg.

Cryoprecipitate indications and patterns of use in the pediatric intensive care unit: inappropriate transfusions and lack of standardization.

BACKGROUND: The dosage and indications for cryoprecipitate are not well studied for any patient population. Prior observational studies have suggested that 24% to 62% of cryoprecipitate transfusions are inappropriate, and there is limited information on patterns of cryoprecipitate use in children. The purpose of this retrospective study was to explore the indications and appropriateness of the use of cryoprecipitate in critically ill children. STUDY DESIGN AND METHODS: We retrospectively reviewed the electronic medical records for cryoprecipitate ordering and utilization in the pediatric intensive care unit at a large tertiary care center during a 4.5-year period. RESULTS: For the 44 patients receiving cryoprecipitate, the only indication was for fibrinogen replacement and the most common clinical scenarios were recent cardiac surgery (39%) and disseminated intravascular coagulation in the setting of sepsis (32%). Cryoprecipitate was often transfused empirically at higher-than-recommended doses without a known pretransfusion fibrinogen level, and the majority (61%) of cryoprecipitate transfusions were deemed inappropriate according to our institutional guidelines. The indications selected for cryoprecipitate by providers during physician order entry matched the clinical scenario, assessed by chart and laboratory data review, in only 18% of patients. There was no significant difference in red blood cell usage in the 6-hour windows before and after cryoprecipitate transfusion. CONCLUSION: Our study demonstrates a lack of standardization for the use of cryoprecipitate in critically ill children, including many inappropriate transfusions at higher-than-recommended dosing. Prospective randomized clinical trials are warranted to help determine appropriate indications and efficacious cryoprecipitate dosing in the pediatric population.