Stubbs, James R.

BackgroundPlatelet (PLT) transfusions are an important component of hemostatic resuscitation. The AABB has published several guidelines recommending that PLT units should not be infused through blood warming devices.Study Design and MethodsThirty‐one units of hospital blood bank apheresis PLTs were obtained. PLT‐rich plasma (PRP) aggregometry and thromboelastography (TEG) were performed on the unit samples before and after the units were infused through a Ranger blood/fluid warming device.ResultsThere were no differences in any of the aggregometry results before and after infusion of the PLTs through the blood warmer (all P > .32). There was a significant reduction in the TEG maximum amplitude (MA) of 69.8 ± 7.9 mm before and 66.0 ± 8.8 mm after (P < .001) infusion of the PLTs through the blood warmer and α angle 61.8 ± 9.4° before and 59.3 ± 8.2° after (P = .044) infusion of the PLTs through the blood warmer, although both mean values were within normal range for the TEG and not clinically significant. There were very good correlations of aggregometry and TEG results before and after infusion of the PLTs through the blood warmer device.ConclusionThis study did not demonstrate significant deleterious effect on PLT function from infusing apheresis PLT units through a blood warming device by PRP aggregometry. We did detect a statistically significant—but not clinically significant—reduction in TEG MA and α angle. The prohibition of transfusing PLT units though the Ranger blood warming device is not indicated.

AbstractBackgroundThe COVID‐19 pandemic has placed great strain on blood resources. In an effort to extend platelet (PLT) shelf life and minimize waste, our institution transitioned room temperature to cold‐stored PLTs for administration to bleeding patients.Study Design and MethodsWe describe the administrative and technical processes involved in transitioning room temperature PLTs to cold storage in April 2020. Additionally, we describe the clinical utilization of cold‐stored PLTs in the first month of this practice change, with a focus on changes in PLT counts after transfusion, hemostasis, and safety outcomes.ResultsA total of 61 cold‐stored PLT units were transfused to 40 bleeding patients, with a median (interquartile range [IQR]) of 1 (1‐2) units per patient. The median age was 68 (59‐73) years; 58% male. Median pretransfusion and posttransfusion PLTs counts were 88 (67‐109) and 115 (93‐145). A total of 95% of transfusions were administered in the operating room: 57% cardiac surgery, 20% vascular surgery, 8% general surgery, and 5% solid organ transplantation. Hemostasis was deemed to be adequate in all cases after transfusion. There were no transfusion reactions. One patient (3%) experienced a fever and infection within 5 days of transfusion, which was unrelated to transfusion. Median (IQR) hospital length of stay was 8.5 (6‐17) days. Two patients (5%) died in the hospital of complications not related to transfusion.ConclusionCold‐stored PLT utilization was associated with adequate hemostasis and no overt signal for patient harm. Conversion from room temperature to cold‐stored PLTs may be one method of reducing waste in times of scarce blood inventories.

Abstract Abstract 4332 Background: Hemolytic anemia caused by the passive transfer of isoagglutinins, typically anti-A or anti-B antibodies, is a rare and likely under-recognized complication of intravenous immunoglobulin (IVIG) therapy. The Immunohematology Reference Laboratory at Mayo Clinic Rochester has detected 12 cases of passively acquired isoagglutinins following IVIG administration during the first seven months of this calendar year (January-July 2011). This frequency of detection is much higher than that seen over the three prior calendar years, when only two cases were detected. Given this “cluster” of isoagglutinin detection, we analyzed these 12 cases to determine the clinical significance of this finding as well as characteristics of resulting cases of hemolytic anemia. Materials/Methods: Charts of patients identified as having passively acquired isoagglutinins following IVIG therapy were analyzed for evidence of a significant drop in hemoglobin (defined as >1 g/dL) as well as evidence of hemolysis (elevated lactate dehydrogenase, reticulocytosis, spherocytosis, decreased haptoglobin, indirect hyperbilirubinemia, hemoglobinemia and hemoglobinuria). Cases with a >1 g/dL drop in hemoglobin and two or more of the above findings consistent with hemolysis were considered “confirmed” cases. Those with passively acquired isoagglutinins but without evidence of hemolysis or with an alternative explanation for anemia were considered “asymptomatic”, and cases without a full hemolytic evaluation but still clinically suspicious were categorized as “suspected” cases. Results: Passively acquired isoagglutinins were detected in 11 patients following 12 separate treatments with IVIG (one patient had antibodies noted after two separate treatment episodes >3 weeks apart). Four of these 12 cases were categorized as “confirmed” cases, five as “suspected” and three as “asymptomatic”. The indication for IVIG use was a neurologic disorder in three of the four confirmed cases, with immune thrombocytopenic purpura (ITP) being the indication in the other case. In suspected cases, ITP was the indication in four of the five cases, with the fifth patient carrying a diagnosis of Kawasaki’s disease. During the 7 month period reviewed, 250 unique patients were treated with IVIG, meaning 1.6% of patients (4/250) had confirmed IVIG-associated hemolytic anemia and another 1.6% (4 patients; 5 events) had suspected hemolytic anemia during this period. The mean decrease in hemoglobin was 4.1 g/dL in confirmed cases (range 1.3–7.1 g/dL) and 2.7 g/dL in suspected cases (range 1.7–4.2 g/dL). Eight of nine patients reviewed had blood type A positive; the other was B positive. The median time from initiation of therapy to hemoglobin nadir was eight days in confirmed and three days in suspected cases. The mean dose of IVIG administered in confirmed cases was 300 g (range 180–400 g) and was 162 g (range 50–300 g) in suspected cases. Red cell transfusion was required in three of the four confirmed cases. Privigen™ was the IVIG product utilized in all four confirmed and the first three suspected cases. After removal of Privigen™ from the Mayo Clinic formulary given concerns regarding these cases, two suspected cases of IVIG-associated hemolytic anemia occurred with Gamunex-C™, including one in a patient who previously suffered confirmed hemolysis after receipt of Privigen™. Conclusions: Hemolytic anemia is a rare complication of therapy with IVIG. The rate of hemolytic anemia following IVIG administration over the evaluated period is consistent with previous reports, but it should be noted that these cases were detected without the aid of an active surveillance policy, indicating the actual rate of hemolytic anemia associated with IVIG use was likely greater than that detected by this review. Our series suggests that those with blood type A may be at increased risk for this complication; further work is ongoing to better define risk factors for development of this potentially significant complication of IVIG therapy. Disclosures: Off Label Use: IVIG use in various off-label indications.

Abstract Background: Little data exists on the incidence rate of transfusion reactions and red cell antibody formation following allogeneic (allo) hematopoietic progenitor cell transplant (HPCT) recipients. Study Design and Methods: Consecutive related and unrelated Allogeneic HPCTs from 2006 to 2013 were retrospectively reviewed regardless of graft source. Allo HPCT recipients were analyzed as a whole as well as divided into ABO compatibility groups of identical, minor mismatch, and major/bidirectional mismatch. Transfusions, transfusion reactions and antibodies were analyzed for the first year post-transplant while survival was recorded throughout the available follow-up period. Results: During the study period, 573 patients ranging in age from 0.6 to 72 years underwent first allo HPCT for various malignant and non-malignant etiologies: 278 acute leukemias, 89 lymphomas, 40 multiple myelomas, 134 other hematologic malignancies, 32 non-neoplastic etiologies. Of these, 52% underwent myeloablative conditioning and 48% reduced intensity conditioning. Transfusion reactions were reported in 93 of the 573 allo HPCT recipients. The incidence rate of transfusion reactions per 10,000 transfusion episodes was 45.54 in the ABO identical, 61.28 in the minor mismatch, and 29.95 in the major mismatch groups (p=0.04). The most common reaction type reported in all groups was allergic followed by febrile non-hemolytic, transfusion associated circulatory overload, and delayed hemolytic or serologic reactions. No acute hemolytic, transfusion related acute lung injury (TRALI), post transfusion purpura, transfusion associated graft-versus-host disease, or transfusion associated sepsis reactions were reported. A total of 43 unique patients(7.5%) developed new antibodies post-transplant: 16 allo HPCT recipients developed clinically significant antibodies, 17 developed clinically insignificant antibodies, and 17 developed auto antibodies post-transplant. Including those patients with pre-transplant antibodies the overall prevalence of red blood cell antibodies was 14.5%. See Table 1 for incidence rate for forming new rbc antibodies post-transplant. Table 1. New RBC Antibody Formation Incidence Rate Post-Transplant ABO Compatibility Group Clinically Significant Antibody Incidence /10,000 RBC Transfusions Clinically Insignificant Antibody Incidence/ 10,000 RBC Transfusions, Auto Antibody Incidence/10,000 RBC Transfusions Total Antibody Incidence/10,000 RBC Transfusions Identical 39.33 16.85 39.33 95.51 Minor Mismatch 35.87 57.39 43.04 136.30 Major Mismatch 8.34 16.67 8.34 33.35 A statistically significant difference (p=0.001) was seen in total antibody incidence when comparing the ABO compatibility groups. The most common, clinically significant allo antibodies formed were Anti-E, Anti-Jka, Anti-A1, Anti-K, Anti-D, and Anti-C. Survival of allo HPCT recipients as a whole was not statistically different for those who formed new rbc antibodies post-transplant following adjustment for ABO compatibility, age at transplant, diagnosis, graft source, and pre-transplant rbc infusions (p=0.068). Allo HPCT recipients that formed new rbc antibodies were not shown to have prolonged engraftment. Engraftment, neutrophils (ANC) and platelets (PLT), were not statistically different (p=0.34 ANC; p=0.20 PLT) when comparing all allo HPCT recipients to those who formed a new rbc antibody. Conclusion: Transfusion reaction and rbc antibody incidence rates were higher in the ABO minor mismatch when compared to the ABO identical and ABO major mismatch groups. The reaction etiology (predominantly antibody mediated) and the formation of new antibodies indicates a surprisingly active humoral immune system. The overall prevalence of antibody formation is likely affected by high exposure to transfusions. Development of a new rbc antibody did not affect engraftment or survival outcomes. Disclosures No relevant conflicts of interest to declare.

BACKGROUNDIntraoperative plasma transfusion is common, yet little is known regarding its effects on perioperative coagulation tests or clinical outcomes.STUDY DESIGN AND METHODSThis is a retrospective cohort study of adults receiving intraoperative plasma transfusion at a single center from 2011 to 2015. Relationships between plasma transfusion volume, changes in coagulation test values, and clinical outcomes, including a primary outcome of early postoperative red blood cell (RBC) transfusion, were assessed with multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit (ICU)‐ and hospital‐free days, intraoperative RBC transfusions, and estimated blood loss.RESULTSA total of 3393 unique patients were included, with median (IQR) transfusion of 2 (2‐4) units. In multivariable analyses, higher plasma volumes were associated with worse outcomes, with each 1 mL/kg increase associated with increased odds for postoperative (1.02 [1.01‐1.03], p < 0.001) and intraoperative RBCs (1.17 [1.16‐1.19], p < 0.001) and fewer ICU‐ and hospital‐free days (mean difference [95% CI], –0.08 [−0.12 to −0.05], p < 0.001; and −0.09 [−0.13 to −0.06], p < 0.001, respectively). Greater decreases in international normalized ratio (INR) following plasma transfusion were associated with decreased odds of postoperative RBCs (0.35 [0.25‐0.47], p < 0.001), decreased mortality (0.50 [0.31‐0.83], p = 0.007), and increased mean ICU‐ (1.31 [0.41‐2.21], p = 0.004) and hospital‐free days (1.15 [0.19‐2.10], p = 0.018).CONCLUSIONIn patients receiving intraoperative plasma transfusion, higher transfusion volumes were associated with inferior clinical outcomes; however, greater improvements in INR were associated with improved outcomes. Future prospective studies are necessary to better define these relationships and to explore plasma transfusion triggers beyond the limitations of INR.

BACKGROUND The Food and Drug Administration's requirements for “Blood and Blood Components Intended for Transfusion or Further Manufacturing Use” (Final Rule) effective May 2016 changed eligibility criteria for blood donors. A multivariate analysis was performed to measure its impact on donor deferral rates. STUDY DESIGN AND METHODS Four blood centers submitted data for similar 6‐month periods before and after implementation of the Final Rule. Data included presenting donors, units collected, deferrals, intended products from deferred donors, deferral reasons, presenting donor demographics, donor hemoglobin (Hgb), hematocrit (HCT), pulse, blood pressure (BP), temperature, and other reasons for deferral. Data were aggregated and periods compared. RESULTS After Final Rule implementation, successful donations decreased by 1.3% (83.1%‐81.9%), despite a 0.2% increase in presenting donors. The rate of Hgb/HCT, pulse, and deferrals increased, while deferrals for other reasons decreased. Male Hgb/HCT deferral rates increased 1.2% (4213 total). Black male donors' Hgb/HCT deferral rate increased (2.7%‐5.2%) but was counterbalanced by an overall 3.7% decrease in black female Hgb/HCT deferrals. While Hgb/HCT deferrals of black donors remained stable overall (17.0% vs. 16.2%), this trend was not observed by all centers. Deferrals for pulse increased (0.2%), as did BP deferrals (0.2%). CONCLUSION Although there was a small increase in presenting donors after implementation of the Final Rule, there was a decrease in successful donations. While it appeared that deferral in black donors was unchanged, this trend was not observed across all centers. Pulse and BP deferrals rose dissimilarly among centers, according to individual procedures.

BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related fatalities. While these transfusion-related pulmonary complications (TRPCs) have been well detailed in adults, their burden in pediatric subsets remains poorly defined. We sought to delineate the incidence and epidemiology of pediatric TRPCs after intraoperative blood product transfusion. METHODS: In this retrospective cohort study, we evaluated all consecutive pediatric patients receiving intraoperative blood product transfusions during noncardiac surgeries between January 2010 and December 2014. Exclusion criteria were cyanotic heart disease, preoperative respiratory insufficiency, extracorporeal membrane oxygenation, and American Society of Anesthesiologists physical status VI. Medical records were electronically screened to identify those with evidence of hypoxemia, and in whom a chest x-ray was obtained within 24 hours of surgery. Records were then manually reviewed by 2 physicians to determine whether they met diagnostic criteria for TACO or TRALI. Disagreements were adjudicated by a third senior physician. RESULTS: Of 19,288 unique pediatric surgical patients, 411 were eligible for inclusion. The incidence of TRPCs was 3.6% (95% confidence interval [CI], 2.2–5.9). TACO occurred in 3.4% (95% CI, 2.0–5.6) of patients, TRALI was identified in 1.2% (95% CI, 0.5–2.8), and 1.0% (95% CI, 0.4–2.5) had evidence for both TRALI and TACO. Incidence was not different between males (3.4%) and females (3.8%; P = .815). Although a trend toward an increased incidence of TRPCs was observed in younger patients, this did not reach statistical significance ( P = .109). Incidence was comparable across subsets of transfusion volume ( P = .184) and surgical specialties ( P = .088). Among the 15 patients experiencing TRPCs, red blood cells were administered to 13 subjects, plasma to 3, platelets to 3, cryoprecipitate to 2, and autologous blood to 3. Three patients with TRCPs were transfused mixed blood components. CONCLUSIONS: TRPCs occurred in 3.6% of transfused pediatric surgical patients, with the majority of cases attributable to TACO, congruent with adult literature. The frequency of TRPCs was comparable between genders and across surgical procedures and transfusion volumes. The observed trend toward increased TRPCs in younger children warrants further consideration in future investigations. Red blood cell administration was the associated component for the majority of TRPCs, although platelets demonstrated the highest risk per component transfused. Mitigation of perioperative risk associated with TRPCs in pediatric patients is reliant on further multiinstitutional studies powered to examine patterns and predictors of this highly morbid entity.

BACKGROUND Platelet transfusion–refractoriness is a challenging and expensive clinical scenario seen most often in patients with hematologic malignancies. Although the majority of platelet transfusion–refractory cases are due to nonimmune causes, a significant minority are caused by alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs). Such platelet transfusion–refractory patients can be effectively managed with appropriate antigen‐negative products. STUDY DESIGN AND METHODS Our institution has developed a diagnostic and management algorithm for the platelet transfusion–refractory patient with an early focus on identifying those cases caused by immune‐mediated factors. Using physical platelet cross‐matches to initially classify platelet transfusion–refractory patients as immune‐mediated or not, cross‐match–compatible inventory is then provided to immune‐mediated patients, whereas subsequent HLA (with or without HPA) testing is performed. RESULTS Our blood donor program performs Class I HLA typing of all repeat platelet donors to facilitate the identification of antigen‐negative platelet units (virtual cross‐matching) as well as the recruitment of HLA‐matched donors. The platelet transfusion–refractoriness algorithm realizes an initial net cost savings once two apheresis platelets are saved from use for each newly identified, immune‐mediated platelet transfusion–refractory patient. CONCLUSION An algorithm utilizing physical platelet cross‐matches, Class I HLA and HPA antibody testing, and upfront Class I HLA typing of platelet donors leads to overall resource savings and improved clinical management for platelet transfusion–refractory patients.

BACKGROUNDLaboratory and clinical evidence suggest that cold‐stored platelets (CS‐PLTs) might be preferable to room temperature platelets (RT‐PLTs) for active bleeding. Ease of prehospital use plus potential hemostatic superiority led our facility to pursue approval of CS‐PLTs for actively bleeding trauma patients.STUDY DESIGN AND METHODSFrom November 18, 2013, through October 8, 2015, correspondence was exchanged between our facility, the AABB, and the US Food and Drug Administration (FDA). An initial AABB variance request was for 5‐day CS‐PLTs without agitation. The AABB deferred its decision pending FDA approval to use our platelet (PLT) bags for CS‐PLTs. On March 27, 2015, the FDA approved 3‐day CS‐PLTs without agitation. On October 8, 2015, the AABB approved 3‐day CS‐PLTs without agitation and without bacterial testing for actively bleeding trauma patients. Our facility's goal is to carry CS‐PLTs on air ambulances.RESULTSCS‐PLTs have been used for trauma patients at our facility since October 2015. As of August 2016, a total of 21 (19.1%) of 119 CS‐PLTs have been transfused. The short 3‐day storage period combined with the formation of clots in plasma‐rich CS‐PLTs during storage have been the major causes of a high (80.9%) discard rate.CONCLUSIONIn the future, pathogen‐reduced (PR), PLT additive solution (PAS) CS‐PLTs seem more practical due to low risks of bacterial contamination and storage‐related clotting. This should make longer storage of CS‐PLTs feasible (e.g., 10 days or more). With a longer shelf life, PR PAS CS‐PLTs could potentially be used in a wider range of patient populations.