Amotosalen-HCl-UVA pathogen reduction does not alter poststorage metabolism of soluble CD40 ligand,Ox40 ligand and interkeukin-27, the cytokines that generally associate with serious adverse events

Platelets in therapeutic platelet concentrates are commonly acknowledged to release biologically active constituents during storage. This study examined the influence of photochemical pathogen reduction treatment (PRT) using amotosalen-HCl and UVA light vs. untreated control platelet components, on three factors recently reported to be associated with serious adverse events associated with platelet component (PC) transfusions: sCD40L, IL-27 and sOX40 ligand. Levels of such cytokine-like factors increased significantly during storage, but no significant difference was detected between PRT- and control PCs. This suggests that occurrences of AEs are not directly influenced by PRT but rather may depend on alternate determinants.     

Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: a prospective, randomized trial

Compared with conventional transfusion regimes a strong reduction in HLA alloimmunization and refractoriness to platelet transfusions is obtained when both red blood cell concentrates (RBCs) and platelet concentrates (PCs) are depleted of leukocytes by filtration. Because most of the leukocyte contamination is introduced by transfusion of RBCs, filtration of RBCs appears rational, but uncertainty exists regarding the degree of leukocyte-depletion of PCs needed for the prevention of HLA alloimmunization and refractoriness. We conducted a prospective trial and randomized patients with acute leukemia to receive leukocyte-depleted PCs prepared either by centrifugation (mean leukocyte count 35 x 10(6)/PC of 6 U) or by filtration (mean leukocyte count less than 5 x 10(6)/PC of 6 U). Both groups received RBCs that were filtered after prior removal of the buffy coat. Clinical refractoriness occurred in 46% (12 of 26) of the evaluable patients that were transfused with centrifuged PCs and only in 11% (3 of 27) in the filtered group (P less than .005). De novo anti-HLA antibodies were detected in 42% (11 of 26) patients in the centrifuged group and only in 7% (2 of 27) of the patients receiving filtered PCs (P less than .004). In 8 of 11 alloimmunized patients in the centrifuged group antibodies were detected in the first 4 weeks of transfusion therapy while none of the patients in the filtered group became immunized against HLA antigens during that period. We conclude that for the prevention of HLA alloimmunization and refractoriness to platelet transfusions from random donors, both RBCs and PCs have to be leukocyte-depleted by filtration.     

Routine transfusion of platelet concentrates effectively reduces reoperation rate for bleeding and pericardial effusion after elective operations for ascending aortic aneurysm

Patients with ascending aortic aneurysm undergoing complex surgical procedures are at increased risk of early postoperative excessive blood loss. The aim of this study was to analyze safety and efficacy of routine transfusions of platelet (PLT) concentrates in reduction of hemorrhagic postoperative complications. The study involved 396 consecutive patients (289 males and 107 females) with the mean age of 55.9 ± 13.6 years who underwent elective operations for aortic aneurysms. They were divided retrospectively into two groups, without (group A; n = 123) or with the routine use of PLTs (group B; n = 273). PLTs were transfused intraoperatively just after completion of cardiopulmonary bypass. Twelve patients in group A (9.8%) and 10 (3.7%) in group B required re-thoracotomy due to hemorrhage (p = 0.027). Routine transfusions of PLT concentrates reduced postoperative incidence of excessive pericardial effusion from 24.1% in group A to 2.1% in group B (p = 0.002). In a consequence, significantly less units (p < 0.0001) of red blood concentrates and fresh frozen plasma were transfused in group B than in group A. The rates of other adverse events in the early postoperative period did not differ between groups. Patients with pericardial effusion required 6.3 ± 2.7 additional days of hospitalization due to surgical re-intervention. Neither blood transfusion-related infections nor adverse reactions were noted. In conclusion, routine intraoperative transfusions of PLT concentrates in patients with ascending aortic aneurysms significantly reduced a need for re-intervention due to both early bleeding and late cardiac tamponade.     

A Study of the Effect of AB0 Incompatible Plasma in Platelet Concentrates Transfused to Bone Marrow Transplant Recipients

Bone marrow transplant recipients at Huddinge Hospital have routinely received single-donor platelet concentrates (PC) from blood group O donors. These PC contain approximately 350 ml plasma, which is incompatible with patients of group A, B and AB. In 27 patients transplanted with an ABO-identical bone marrow, serological investigations have been performed every week after transplantation (median 6 weeks, range 3-14). Nine of 11 recipients with blood group A developed a positive direct antiglobulin test (DAT) after PC transfusions, while none of 15 patients of blood group O developed a positive DAT. Anti-A could be eluted in DAT-positive cases. In no case was there any clinical sign of hemolysis. Nor did recipients of groups A, B or AB (n = 34) require more red blood cells or PC transfusions compared to recipients of group O (n = 47).     

Hemostasis Testing during Massive Blood Replacement A Study of 172 Cases

Abstract. A 24-hour service was organized to study changes in the hemostatic system in surgical patients undergoing massive transfusion for excessive bleeding during operation or in the early postoperative period. Hemostasis tests gave normal results in only 12 (7%) of the 172 patients, while in the remaining 160 (93%) one or more tests gave abnormal results. The platelet count was the most frequently abnormal, followed by the prothrombin time and plasma fibrinogen. Well-defined hemostatic disorders (such as DIC, heparinization and liver disease) were ascertained in 82 patients (48%). 78 patients (45%) had less specific laboratory abnormalities, with a particularly high incidence of thrombocytopenia and less pronounced alterations in the coagulation tests. Unlike the patients with defined disorders, the strong inverse correlation in this group between platelet count, prothrombin time, plasma fibrinogen, and the number of transfusions suggests that the laboratory abnormalities were induced by massive blood replacement. Standard schemas involving the administration of platelet concentrates and/or fresh-frozen plasma without evaluation of hemostasis did not help to reduce the incidence of abnormalities. These measures also failed to decrease the requirements for whole blood and/or packed red cells. Therefore, indiscriminate administration in the massively transfused postoperative patient of blood components based on preestablished schemes appears to be unjustified. An approach based on hemostasis screening, identification of the underlying disorder, directed therapeutic intervention and laboratory monitoring is likely to be more effective.     

Safety and clinical efficacy of platelet components prepared with pathogen inactivation in routine use for thrombocytopenic patients

This study was conducted to evaluate the safety and efficacy of platelet concentrates (PC) after photochemical treatment (PCT) with the INTERCEPT Blood System™ and transfused in routine use in a population of patients suffering from a variety of hematological diseases. This was an observational, single-arm, open-label study of pooled buffy-coat PC (n = 298) or apheresis PC (n = 262) treated with INTERCEPT™ and transfused to 51 thrombocytopenic hematology patients. PCT replaced CMV screening and gamma irradiation, and made optional bacterial testing obsolete. The primary study endpoint was the incidence of acute transfusion reactions (ATR). Secondary endpoints included bleeding assessment, platelet count increments, and adverse events (AE). For the 553 transfusions, a total of 55 AE were observed regardless of relationship to platelet transfusion. Ten AE associated with nine transfusions met the criteria for ATR (1.6%). All ATRs were grade 1. Twelve serious AE were reported in 10 patients, none was related to platelet transfusion. Mean 24-h CI and CCI were 10.9 × 10⁹ and 6.6 × 10³/L, respectively. No bleeding complications were attributable to the INTERCEPT-treated PC. This study confirms safety and efficacy of pathogen inactivated PC for support of thrombocytopenia and demonstrated that INTERCEPT technology can easily be implemented in routine operations.     

Clinical experience with transfusion of leukocyte-poor platelet concentrates prepared by filtration with prostacyclin

Repeated transfusions with platelets from randomly selected donors lead to HLA alloimmunization in about 50% of patients due to lymphocyte contamination of platelet concentrates. Attempts to remove the leukocytes from the platelet concentrates by additional centrifugation steps led to substantial loss of platelets. We report a new procedure for removal of almost all leukocytes with excellent platelet recoveries. Single donor concentrates are treated with 50 ng/mL prostacyclin to inactivate the platelets transiently. The concentrates are then passed through a cellulose-acetate filter to remove the leukocytes. In 30 concentrates this treatment reduced the contamination by leukocytes to less than 0.1 million per concentrate with a platelet recovery of 89% +/- 1% (mean +/- SEM). Thirty filtered platelet concentrates transfused to ten thrombocytopenic patients within one hour after filtration were well tolerated and led to corrected count increments of (22.0 +/- 1.1) X 10(6)/mL blood after one hour and normal survival thereafter. In four of five patients these concentrates reduced the bleeding time. We conclude that transient inactivation of platelets by prostacyclin enables optimal removal of leukocytes and may help to reduce alloimmunization during frequent transfusions with platelet concentrates.     

Alloimmunization to RhD by Platelet Transfusions in Autologous Bone Marrow Transplant Recipients

Platelet transfusions from RhD-positive (D-positive) donors are often given to RhD-negative (D-negative) cancer patients. The low observed rate of alloimmunization has been attributed to disease and therapy-related immunosuppression. We have studied the occurrence of alloimmunization in 16 D-negative patients who did not have detectable anti-D prior to autologous bone marrow transplantation for malignant disease. All received D-positive platelets, but no other D-positive blood product. Three patients (19%) developed anti-D at 13, 24 and 83 days, respectively, after first receiving D-positive platelets, and after a total dose of 53, 65 and 119 D-positive platelet unit equivalents, respectively. Two of them also developed anti-C. The 13 patients in whom anti-D was not detected were also heavily transfused with D-positive platelets (mean +/- SD = 136 +/- 82 platelet unit equivalents). In 6 of them, the last recorded antibody screen was less than 3 months after the first D-positive platelets, and may not exclude a primary immune response. Thus, despite profound immunosuppression associated with autologous marrow transplantation, alloimmune responses to D-positive red cells in platelet concentrates can occur in some D-negative recipients.     

Early Immunization against Platelet Glycoprotein Ilia in a Newborn Glanzmann Type I Patient

Alloimmunization against platelet glycoprotein IIb and/or IIIa is a complication rarely observed during the evolution of type I Glanzmann's thrombasthenic patients. The occurrence of such alloantibodies is usually due to repeated blood transfusion and greatly complicates the treatment of these patients since they prevent effective platelet transfusion and might, theoretically, cause posttransfusion purpura. We describe the case of a newborn thrombasthenic patient who developed an IgG platelet allo-antibody 1 month after birth. The diagnosis of Glanzmann's thrombasthenia was complicated by the rare platelet phenotype (PLA1-negative PLA2-positive) of the healthy mother, which was probably heterozygous for the abnormal thrombasthenic gene. Immunofluorescence and immunoblotting techniques demonstrated that the patient antibody was principally directed against the platelet glycoprotein IIIa. Surprisingly, this patient had only received four blood transfusions (fresh frozen plasma on days 1 and 2, and standard red blood cell concentrates on days 5 and 6) before the discovery of the antibody, suggesting prior in utero sensitization. This study emphasizes the need for early diagnosis of the disease. Thrombasthenic patients should be transfused with deleukocyted platelet-free blood products.     

Impact of leucocyte-depleted blood components on the haematological recovery and prognosis of patients with acute myeloid leukaemia

Summary. Use of leucocyte-depleted blood components reduces refractoriness to platelet transfusions, but the cost-effectiveness of this policy has been in doubt. We retrospectively analysed data of 115 patients with acute myeloid leukaemia (AML), treated according to a standardized cytostatic protocol. Fifty patients had received standard (STD) platelet concentrates (PCs) and red blood cell concentrates (RBCs). Sixty-five patients had received leucocyte-depleted (L-D) components, with fewer than one million leucocytes per unit. Refractory patients (22% of the STD group and 3% of the L-D group) were excluded from further observations. There were no differences between the groups during the first cytostatic treatment period. Thereafter, significantly fewer PCs and RBCs were transfused to the L-D group. In the L-D group, granulocytopenia (<0·5 × 10⁹/l) and thrombocytopenia (< 50 × 10⁹/l) were shorter, the lowest leucocyte counts were higher, serious infections were less common (44% v 59%), and the patients spent fewer days in hospital. The median relapse-free survival (RFS) was longer in the L-D group than in the STD group. We conclude that leucocyte depletion of blood components has favourable effects on the recovery of haematopoiesis, consumption of blood components, occurrence of serious infections, and relapse-free survival in AML.     

Prevention of worsening of severe thrombocytopenia after red cell transfusions by the use of leucocyte-depleted blood

Platelet counts were measured before and after red cell transfusions in 30 patients with anaemia and severe thrombocytopenia resulting from haematological diseases. There was a mean reduction of 1.1 x 109/l (P = 0.43) in the platelet count after transfusions of 2-3 units of leucocyte-depleted red cell concentrates (20 patients). However, there was a mean reduction of 2.7 x 109/l (P = 0.03), approximately 10%, in the platelet count after transfusions of non-leucocyte-depleted red cell concentrates (10 patients). The findings suggest that the forthcoming introduction of universal leucocyte depletion of red cell concentrates will minimize the worsening of thrombocytopenia that occurs in severely thrombocytopenic patients receiving standard non-leucocyte-depleted red cell concentrates.     

Platelet Alloimmunization after Transfusion

Background and objectives: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. Materials and methods: We studied the frequency of alloimmunization against platelet antigens in 117 patients who received a single series of blood transfusions. They received mostly saline-adenine-glucose + mannitol red blood cell components (poor in leukocytes and platelets) in connection with cardiac surgery. Platelet-specific antibodies were detected with the platelet ELISA and the monoclonal-antibody-specific immobilization of platelet antigen assay. HLA antibodies were detected by the standard lymphocyte cytotoxicity techniques. Results: We found platelet-specific anti-HPA-5b (anti-Br^a) in 2 cases (1.7%). One antibody was the result of de novo immunization. We detected lymphocytotoxic HLA antibodies in 21 patients (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous immunization. Conclusion: There was a low incidence of platelet-specific antibodies after one series of blood transfusions in this group of patients. This is similar to the results of some previous studies in multiply transfused patients, but not with those of others who found a higher incidence.     

Decreased transfusion requirements in patients given stem cell allografts using a non-myeloablative conditioning regimen: a single institution experience

We report our experience of allogeneic peripheral blood stem cell transplantation using non-myeloablative conditioning regimens delivered and supported on an outpatient basis. A group of 44 patients underwent 47 allograft procedures using peripheral blood stem cells. Approximately one third of the individuals did not require red blood cells transfusions: the median of transfused red blood cells units was 1 (range 0-10). In addition one out of three did not require platelet transfusions either, the median of platelet transfusions being 1 (range 0-6). In fourteen allografts (30%) neither red blood cells nor platelet transfusions were used. An inverse correlation was found between the number of CD34 cells infused and the PRBC and PLT transfusion requirements, those patients receiving high numbers of CD34 cells needing fewer transfusions of both PRBC and platelets. The possibility of conducting allografts without transfusion of blood products in some patients may result in a decrease in both cost and the risks stemming from exposure to human blood derivatives.     

The annual cost of blood transfusions in the United Kingdom

This study estimated the annual cost of blood transfusions in the UK during 1994/1995. The analysis was based on published data, information derived from interviews with relevant NHS personnel and a purpose-designed structured questionnaire of blood donors. The cost to the UKs blood transfusion services of providing blood and blood products for transfusion was £165.5 million in 1994/1995. During this period, 2.75 million conventional donations of whole blood and 144 000 apheresis donations of platelets and plasma were collected: 2.58 million units of red blood cells were issued, resulting in ≈ 866 000 red blood cell transfusions; 334 000 units of fresh frozen plasma and 1.16 million units of platelets were issued, resulting in ≈ 17 000 and 188 000 isolated plasma and platelet transfusions, respectively. Hospital resource use attributable to providing blood transfusions during 1994/1995 cost the NHS £52.6 million. In total, blood transfusions cost the NHS £218.2 million during 1994/1995. Of this, red blood cell transfusions accounted for 76% of the annual cost, isolated platelet transfusions 16%, isolated plasma transfusions 1% and other products 7%. Donors incurred direct costs of £3.1 million and indirect costs of £11.2 million were accrued due to lost productivity. Additionally, blood donors gave up 2.5 million hours of their leisure time donating blood.     

False-positive Aspergillus antigenemia due to blood product conditioning fluids

The presence of Aspergillus antigens in blood transfusion components from different manufacturers was analyzed. Galacomannans were found in transfused patients, pooled platelet concentrates, fresh frozen plasma, and packed red cells collected using Fresenius Kabi bags. Galacomannans were also found in blood collection anticoagulant and platelet additive solution from this manufacturer.     

Transfusion of ABO non-identical platelets does not influence the clinical outcome of patients undergoing autologous haematopoietic stem cell transplantation

BackgroundThere are ABO antigens on the surface of platelets, but whether ABO compatible platelets are necessary for transfusions is a matter of ongoing debate. We retrospectively reviewed the ABO matching of platelet transfusions in a subset of patients undergoing autologous haematopoietic progenitor cell transplantation during a 14-year period. Our aim was to analyse the characteristics and outcomes of patients who received platelet transfusions that were or were not ABO identical.ResultsThe patients received a total of 2,772 platelet concentrates, of which 2,053 (74.0%) were ABO identical and 719 (26.0%) ABO non-identical; of these latter 309 were compatible and 410 incompatible with the patients’ plasma. Considering all transplants, 36 (6.5%) did not require any platelet transfusions, while in 246 (44.5%) cases, the patients were exclusively transfused with ABO identical platelets and in 47 (8.5%) cases they received only ABO non-identical platelet transfusions. The group of patients who received both ABO identical and ABO non-identical platelet transfusions had higher transfusion needs and worse clinical outcomes compared to patients who received only ABO identical or ABO non-identical platelets.DiscussionIn our hospital, patients undergoing autologous haematopoietic stem cell transplantation who received ABO identical or ABO non-identical platelet transfusions had similar transfusion and clinical outcomes. The isolated fact of receiving ABO non-identical platelets did not influence morbidity or survival.     

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.     

Use of blood products and risk of stroke after coronary artery bypass surgery

Background

The impact of blood transfusion on the development of post-operative stroke after coronary artery bypass grafting (CABG) is not well established. We, therefore, investigated this issue.

Materials and methods.

Complete data on peri-operative blood transfusion were available for 2,226 patients who underwent CABG in three Finnish hospitals.

Results

Stroke occurred post-operatively in 53 patients (2.4%). Logistic regression showed that pre-operative creatinine (OR 1.003, 95% CI 1.000–1.006), extracardiac arteriopathy (OR 2.344, 95% CI 1.133–4.847), pre-operative atrial fibrillation (OR 2.409, 95% CI 1.149–5.052), and the number of packed red blood cell units transfused (OR 1.121, 95% CI 1.065–1.180) were significantly associated with post-operative stroke. When the various blood product transfusions instead of transfused units were included in the multivariable analysis, solvent/detergent treated plasma (Octaplas^®) transfusion (OR 2.149, 95% CI 1.141–4.047), but not red blood cell transfusion, was significantly associated with postoperative stroke. Use of blood products ranging from no transfusion (stroke rate 1.6%) to combined transfusion of red blood cells, platelets and Octaplas^® was associated with a significant increase in post-operative stroke incidence (6.6%, adjusted analysis: OR 1.727, 95% 1.350–2.209). Patients who received >2 units of red blood cells, >4 units of Octaplas^® units and >8 units of platelets had the highest stroke rate of 21%. CART analysis showed that increasing amount of transfused Octaplas^®, platelets and history of extracardiac arteriopathy were significantly associated with post-operative stroke.

Conclusions

Transfusion of blood products after CABG has a strong, dose-dependent association with the risk of stroke. The use of Octaplas^® and platelet transfusions seem to have an even larger impact on the development of stroke than red blood cell transfusions.     

Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation

Background

Traditionally, single-unit red blood cell transfusions were believed to be insufficient to treat anemia, but recent data suggest that they may lead to a safe reduction of transfusion requirements. We tested this hypothesis by changing from a double- to a single-unit red blood cell transfusion policy.

Design and Methods

We performed a retrospective cohort study in patients with hematologic malignancies receiving intensive chemotherapy or hematopoietic stem cell transplantation. The major end-points were the reduction in the total number of red blood cell units per therapy cycle and per day of aplasia. The study comprised 139 patients who received 272 therapy cycles. Overall 2212 red blood cell units were administered in 1548 transfusions.

Results

During the periods of the double- and single-unit policies, one red blood cell unit was transfused in 25% and 84% of the cases and the median number of red blood cell units per transfusion was two and one, respectively. Single-unit transfusion led to a 25% reduction of red blood cell usage per therapy cycle and 24% per aplasia day, but was not associated with a higher out-patient transfusion frequency. In multivariate analysis, single-unit transfusion resulted in a reduction of 2.7 red blood cell units per treatment cycle (P=0.001). The pre-transfusion hemoglobin levels were lower during the single-unit period (median 61 g/L versus 64 g/L) and more transfusions were administered to patients with hemoglobin values of 60 gl/L or less (47% versus 26%). There was no evidence of more severe bleeding or more platelet transfusions during the single-unit period and the overall survival was similar in both cohorts.

Conclusions

Implementing a single-unit transfusion policy saves 25% of red blood cell units and, thereby, reduces the risks associated with allogeneic blood transfusions.     

Blood component use in critical care in patients with COVID-19 infection: a single-centre experience

There has been a significant surge in admissions to critical care during the coronavirus disease 2019 (COVID-19) pandemic. At present, the demands on blood components have not been described. We reviewed their use during the first 6 weeks of the outbreak from 3 March 2020 in a tertiary-level critical care department providing venovenous extracorporeal membrane oxygenation (vv-ECMO). A total of 265 patients were reviewed, with 235 not requiring ECMO and 30 requiring vv-ECMO. In total, 50 patients required blood components during their critical care admission. Red cell concentrates were the most frequently transfused component in COVID-19-infected patients with higher rates of use during vv-ECMO. The use of fresh frozen plasma, cryoprecipitate and platelet transfusions was low in a period prior to the use of convalescent plasma.