Transfusion medicine: A research agenda for the coming years.

The important scientific and clinical advances of the last century in transfusion medicine include methods for avoiding hemolytic transfusion reactions and preventing transmission of viral infectious diseases. The next great clinical advances will require improving the efficacy and safety of transfusions, as well as acknowledgement of the now proven serious complications of transfusion, including nosocomial infection, thrombosis, inflammation and multi-organ failure. Possible strategies include (1) universal leukoreduction to mitigate transfusion immunomodulation effects and improve storage conditions, (2) minimizing transfusion of ABO incompatible antibodies and cellular/soluble antigens, (3) substituting use of safer solutions for normal saline during apheresis, component infusion and washing (4) new techniques to improve the efficacy and safety of blood components, including improved storage solutions/conditions, supernatant removal by washing, and rejuvenation and (5) maximizing the risk to benefit ratio of transfusions by employing more restrictive and physiologic indications for transfusion (including patient blood management) and improving clinical decision making through novel laboratory and bedside tests such as thromboelastography.

Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence.

BACKGROUND: There are multiple benefits to transfusing only ABO-identical blood components. Historically our institution routinely transfused ABO-nonidentical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO-identical components whenever feasible, regardless of outdating or logistic considerations. STUDY DESIGN AND METHODS: Technical staff closely monitored product usage and adjusted blood center orders based on recent utilization and planned transfusions. When unable to provide ABO-identical PLTs, ABO-compatible PLTs were washed to remove incompatible plasma. Data on outdating were collected for 18 months before and after implementation. We compared transfusion reaction and red blood cell (RBC) alloimmunization incidence for 4 years preceding (2001-2004) and subsequent (2006-2009) to implementation. RESULTS: In the year after implementation, only 11 of 410 surgical patients received ABO-nonidentical PLTs (2.7%). There was a 5.6% increase in outdating of PLTs. Transfusing ABO-identical components was associated with significant reductions in febrile (-46%; 8.0 to 4.3 per 10,000 components; p < 0.0001) and allergic transfusion reactions (-23%; from 7.0 to 5.4 per 10,000 components; p = 0.025). A progressive reduction in de novo RBC alloimmunization incidence also occurred (-50% by 2009; p = 0.03). CONCLUSIONS: Providing ABO-identical PLTs to almost all patients was feasible in our setting by changing ordering and inventorying procedures and making the ABO-identical policy a staff priority. Unexpected and striking reductions in febrile and allergic reactions and RBC alloimmunization were observed, of uncertain causal relationship to this ABO policy change, which will require further study.

An association between decreased cardiopulmonary complications (transfusion-related acute lung injury and transfusion-associated circulatory overload) and implementation of universal leukoreduction of blood transfusions.

BACKGROUND: Cardiopulmonary adverse events after transfusion include transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), which are potentially lethal and incompletely understood. STUDY DESIGN AND METHODS: To determine whether the incidence of TRALI and TACO was affected by leukoreduction we conducted a retrospective, before-and-after study of acute transfusion reactions for the 7years before and after introduction of universal leukoreduction in 2000, involving 778,559 blood components. RESULTS: Substantial decreases occurred in the rates of TRALI (-83%; from 2.8 cases per 100,000 components before to 0.48 after universal leukoreduction; p=0.01), TACO (-49%; 7.4 to 3.8 cases per 100,000; p=0.03), and febrile reactions (-35%; 11.4 to 7.4 cases per 10,000; p<0.0001). The incidence of allergic reactions remained unchanged (7.0 per 100,000 before and after universal leukoreduction). These outcomes were primarily attributable to decreased TRALI and/or TACO associated with red blood cell (RBC) and platelet (PLT) transfusions (-64%) with notably smaller decreases associated with fresh-frozen plasma or cryoprecipitate transfusions (-29%). The incidence of TRALI and/or TACO after 28,120 washed RBC and 69,325 washed transfusions was zero. CONCLUSION: These data suggest novel hypotheses for further testing in animal models, in prospective clinical trials, and via the new US hemovigilance system: 1) Is TACO or TRALI mitigated by leukoreduction? 2) Is the mechanism of TACO more complex than excessive blood volume? and 3) Does washing mitigate TRALI and TACO due to PLT and RBC transfusions?

Post-Transfusion Purpura Mimicking Idiopathic Thrombocytopenic Purpura: A Case Report.

The main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products. The results of an human leukocyte antigen (HLA) class-1 panel reactive antibody assay were 0%, and the results of a platelet-antibody screening assay were positive for HLA class-1 antibodies and glycoprotein (Gp)IIb/IIIa antibodies. Her platelet count reached 42 × 109 per L on day 50, after rituximab on day 22 and daratumumab on day 29. Her clinical scenario was most consistent with the course of PTP.

Prophylactic Preprocedure Platelet Transfusion Is Associated With Increased Risk of Thrombosis and Mortality.

OBJECTIVES: We evaluated thrombosis and mortality rates of hospitalized patients receiving prophylactic platelet transfusion prior to an invasive procedure. METHODS: Patient age and underlying medical condition(s), preprocedure and postprocedure platelet counts, type of procedure, number of platelet products transfused, and any complications were recorded on every prophylactic platelet given prior to an invasive procedure. RESULTS: A total of 376 prophylactic transfusion recipients were identified. Nineteen (5%) thrombotic events were identified and 60 (16%) deaths occurred within 30 days of the preprocedure platelet transfusion. Most deaths were due to infection, sepsis, or organ failure, and none were due to bleeding or thrombosis. CONCLUSIONS: Preprocedure platelet transfusion is associated with an increased risk of thrombosis and 30-day mortality. Whether these findings are due to higher incidences of comorbidities and confounding or to cause and effect is not determinable from these data. This study highlights an association between prophylactic platelet transfusion and thrombosis and poor outcome, including death.

ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia.

BACKGROUND: Despite dramatically improved long term outcomes seen with all-trans retinoic acid therapy, and now arsenic trioxide, in acute promyelocytic leukemia (APL), early mortality remains a substantial challenge. Recent data from a single center study and the Surveillance, Epidemiology and End Results (SEER) registry report 30day mortality rates of 26% (n=18 of 70) and 17% (n=238 of 1400), respectively. Early deaths are predominately due to hemorrhage. Patients with APL invariably have abnormal laboratory hemostasis tests. The standard of practice is to prophylactically transfuse platelets, plasma and cryoprecipitate to mitigate abnormal platelet counts, PT/PTT and fibrinogen levels. Standard blood bank practice is to transfuse platelets, plasma and cryoprecipitate largely without regard to ABO blood group (platelets, cryoprecipitate), and, in some centers, transfusing ABO non-identical universal donor group AB plasma. Evidence from observational studies suggests that use of ABO non-identical blood components may be associated with increased bleeding. We hypothesized that use of ABO identical blood components and saline washed transfusions (red cells and platelets) would be associated with reduced early mortality in APL by avoidance of transfusion induced hemostatic dysfunction. METHODS: This is a single center cohort study of APL patients treated in an 800 bed university community and referral hospital. Novel approaches to transfusion support, based upon randomized trials, include implementation of ABO identical platelet transfusions for all patients with acute leukemia in 1990, use of only ABO identical cryoprecipitate in 2005, and washed transfusions of red cells and platelets for all patients with acute leukemia <50years of age beginning in 2006. Plasma transfusion has always been ABO identical. Two comparison populations were recent literature reports and the New York State Cancer Registry. We characterized 30 day mortality in APL patients seen in our institution since 2000 as a convenience sample comparable to literature reports, beginning approxcimately when ATRA therapy became uniform for induction therapy. Only patients receiving their induction therapy in our hospital were included. RESULTS: Of 41 patients there were 2 early (30 day) deaths (5%; a 71-81% reduction from expected). Early mortality at 100 days was 7% (n=3). The 30 day mortality in the younger cohort <50years of age (n=16) receiving washed transfusions was 0%. Restricting the analysis to patients treated since 2006 (ABO identical transfusions, mostly washed) (n=27; mean age 43 years; median 41 years; range 12-79), the early mortality rate at 30days was 3.7%. Long-term survival (5 years) of our APL patients was similar to New York State Cancer Registry and literature reports (80-83%). DISCUSSION: APL patients supported with transfusion regimens including ABO identical blood components, with or without washing, experienced early mortality at 30 days that was strikingly improved (71% to 86% lower) compared with that reported in the recent literature (3.7% to 5% vs. 17% to 26%). If these observed low rates of early mortality are related to transfusion practices, avoidance of ABO immune complex formation, and subsequent interference with hemostasis, is a plausible contributing mechanism. These favorable results provide a rationale for randomized trials of relatively simple and inexpensive approaches to reducing early hemorrhagic mortality in APL: use of ABO identical transfusions and washing to remove supernatant plasma.

Leukocyte-reduced transfusions in cardiac surgery results of an implementation trial.

An implementation trial of leukocyte-reduced transfusions in cardiac surgery (primary coronary artery bypass graft and valve replacement) was performed from July to December 1998; comparisons were made with data from the same period in 1997. Patients from both periods were similar in important preoperative and intraoperative variables (age, sex, weight, number of units of RBCs transfused, ejection fraction). The mean total number of complications was statistically significantly decreasedfrom 0.26 complications per patient in the non-leukocyte-reduced to 0.19 in the leukocyte-reduced recipients. Overall, the mean +/- ISD costs of care per patient decreasedfrom 1997 ($27,615 +/- $33,973) to 1998 ($27,038 +/- $24,107). Mean costs decreased $1,700 per patient for recipients of leukocyte-reduced blood in 1998 compared with recipients of non-leukocyte-reduced blood in 1997 Mean costs increased $4,000 per patient in patients who did not receive transfusions in 1998 compared with 1997. Hospitalization costs decreased when leukocyte-reduced transfusions were implemented for patients undergoing cardiac surgery in our institution. Implementation of leukocyte reduction may be cost neutral or cost saving in at least some settings.

Efficacy of preoperative autologous blood donation in free TRAM flap breast reconstruction.

BACKGROUND: The authors critically evaluated the use of autologous blood donation in patients who had surgical breast reconstruction using the free transverse rectus abdominis musculocutaneous (fTRAM) flap technique following mastectomy. METHODS: A retrospective chart review of 201 patients was performed. Patients were operated on at one community hospital and one university hospital. Cohorts of 101 blood donors and 100 control nondonors were established. Demographic and premorbid factors and primary outcome variables were evaluated. RESULTS: The autologous donor and nondonor groups were not statistically different in any demographic categories, and there were no significant differences in premorbid factors between the two groups. Total surgical complications were more common in the autologous donor group (48 percent versus 28 percent; p < 0.004). The autologous donor group was also more likely to receive a transfusion intraoperatively (13 percent versus 0 percent, p < 0.001) or postoperatively (28 percent versus 5 percent, p < 0.001) compared with the nondonor group. CONCLUSIONS: Few patients in the nondonor group required perioperative transfusion, and fewer than half of the donors received their blood back. There was a statistically significant higher rate of surgical complications associated with autologous blood donation, most likely due to relative preoperative anemia. Autologous donation was associated with a significantly higher rate of transfusion intraoperatively and postoperatively. The authors do not recommend autologous blood donation before free TRAM flap autogenous breast reconstruction.