Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia according to the EU regulation. [Measures for reducing the use of homologous blood. Effects on blood coagulation during total endoprosthesis]. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Does desmopressin improve hemostasis and reduce blood loss from aortic surgery? A randomized, double-blind study. Reduction of blood loss and transfusion requirement by aprotinin in posterior lumbar spine fusion. A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation. Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial. The effect of coagulation protection with combination of epsilon aminocaproic acid and plasma saver in open-heart surgery. The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery.
Erythropoietin-stimulating agents (ESAs) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia (CIA). Recent studies indicate that ESAs increase mortality and accelerate tumour progression. The studies also identify a 1.6-fold increased risk of venous thromboembolism. The ESA labelling was thus revised in Europe and the United States in 2008. This is the first randomised, phase III trial evaluating the efficacy and safety of epoetin-β (EPO), an ESA, dosed in accordance with the revised labelling, which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ≤ 10 g dl⁻¹ and that a sustained haemoglobin level of > 12 g dl⁻¹ should be avoided.
                A total of 186 CIA patients (8.0 g dl⁻¹ ≤ haemoglobin ≤ 10.0 g dl⁻¹) with lung or gynaecological cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.Results:The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl⁻¹ between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group (n=89) than in the placebo group (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality of life were not different. No significant differences in adverse events - for example, the incidence of thromboembolic events was 1.1% for each group - or the 1-year overall survival were observed between groups.
                Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment. Further investigations are needed on the effect of ESAs on mortality. The influence of two different methods of autologous transfusion, preoperative donor plasmapheresis (Abbott Autotrans) and postoperative autotransfusion (intraoperative blood salvage, Dideco Autotrans), on the intravascular hemostatic system was investigated. Forty-two patients undergoing total hip surgery and preoperative donor plasmapheresis were prospectively randomized into three groups. For substitution of blood loss, patients in group 1 (control group, n = 12) received in addition to cristalloids and colloids only homologous blood, group 2 (n = 14) autologous blood, and group 3 (n = 16) additionally intra- and postoperative autologous fresh frozen plasma (FFP). The investigation included blood parameters (hemoglobin, hematocrit, thrombocytes), clotting status (prothrombin time, plasma thromboplastin time, thrombin time, fibrinogen, plasminogen, and antithrombin III), and immunological methods such as fibrinopeptide A (FPA), thrombin-antithrombin III (TAT), and protein C. No significant difference was found with respect to total amount of infusion, intraoperative blood loss, autologous transfusion, and blood parameters. Excellent quality of the autologous FFP was demonstrated by investigation of the specimens before administration. The autologous packed red cells showed high levels of TAT and FPA as an indicator of thrombin generation. Their administration caused a significant increase in TAT and FPA levels in groups 2 and 3 compared to group 1.(ABSTRACT TRUNCATED AT 250 WORDS) Transfusion therapy after cardiac surgery is empirically guided, partly due to a lack of specific point-of-care hemostasis monitors. In a randomized, blinded, prospective trial, we studied cardiac surgical patients at moderate to high risk of transfusion. Patients were randomly assigned to either a thromboelastography (TEG)-guided transfusion algorithm (n = 53) or routine transfusion therapy (n = 52) for intervention after cardiopulmonary bypass. Coagulation tests, TEG variables, mediastinal tube drainage, and transfusions were compared at multiple time points. There were no demographic or hemostatic test result differences between groups, and all patients were given prophylactic antifibrinolytic therapy. Intraoperative transfusion rates did not differ, but there were significantly fewer postoperative and total transfusions in the TEG group. The proportion of patients receiving fresh-frozen plasma (FFP) was 4 of 53 in the TEG group compared with 16 of 52 in the control group (P < 0.002). Patients receiving platelets were 7 of 53 in the TEG group compared with 15 of 52 in the control group (P < 0.05). Patients in the TEG group also received less volume of FFP (36 +/- 142 vs 217 +/- 463 mL; P < 0.04). Mediastinal tube drainage was not statistically different 6, 12, or 24 h postoperatively. Point-of-care coagulation monitoring using TEG resulted in fewer transfusions in the postoperative period. We conclude that the reduction in transfusions may have been due to improved hemostasis in these patients who had earlier and specific identification of the hemostasis abnormality and thus received more appropriate intraoperative transfusion therapy. These data support the use of TEG in an algorithm to guide transfusion therapy in complex cardiac surgery. Implications: Transfusion of allogeneic blood products is common during complex cardiac surgical procedures. In a prospective, randomized trial, we compared a transfusion algorithm using point-of-care coagulation testing with routine laboratory testing, and found the algorithm to be effective in reducing transfusion requirements. The purpose of this study was to determine the effect of desmopressin acetate (DDAVP) on blood loss, transfusion requirements, and thromboembolic complications in patients undergoing elective aortic operations.
                A randomized, double-blind trial was carried out during a 3-year period with patients receiving 20 micrograms DDAVP or identical-appearing placebo at the time of aortic cross-clamp placement. In addition to major bleeding and thromboembolic end points, bleeding times and platelet counts were monitored serially.
                Forty-three patients were randomized to receive DDAVP, and 48 were assigned to a placebo. An equivalent proportion of patients with aneurysm and patients with occlusive disease was in each group. In spite of mild prolongation in the postoperative bleeding times and moderate thrombocytopenia, DDAVP had no beneficial effect on blood loss or transfusion requirements. Total blood transfusion amount (mean +/- standard deviation) for patients receiving DDAVP was 3.1 +/- 3.0 U compared with 2.7 +/- 3.0 U for those receiving placebo. For all patients the period associated with the greatest blood loss was the time between heparin administration with cross-clamp application and reversal of heparin with protamine sulfate. The incidence of major thromboembolic complications was similar in both groups.
                Thrombocytopenia and mild platelet dysfunction are common after aortic operation, but DDAVP does not improve hemostasis or lessen transfusion requirements. This study does not rule out a beneficial effect of DDAVP in patients who are undergoing more complex aortic operations or who have major hemostatic aberrations. Aprotinin reduces blood loss in many orthopedic procedures. In posterior lumbar spine fusion, blood loss results primarily from large vein bleeding and also occurs after the wound is closed. Seventy-two patients undergoing posterior lumbar spine fusion were randomly assigned to large-dose aprotinin therapy or placebo. All patients donated three units of packed red blood cells (RBCs) preoperatively. Postoperative blood loss was harvested from the surgical wound in patients undergoing two- and/or three-level fusion for reinfusion. The target hematocrit for RBC transfusion was 26% if tolerated. Total (intraoperative and 24 h postoperative) blood loss, transfusion requirements, and percentage of transfused patients per treatment group were significantly smaller in the aprotinin group than in the placebo group (1935 +/- 873 vs 2809 +/- 973 mL per patient [P = 0.007]; 42 vs 95 packed RBCs per group [P = 0.001]; 40% vs 81% per group [P = 0.02]). Hematological assessments showed an identically significant (a) intraoperative increase in both thrombin-antithrombin III complexes (TAT) and in activated factor XII (XIIa) and (b) decrease in activated factor VII (VIIa), indicating a similar significant effect on coagulation in patients of both groups (P = 0.9 for intergroup comparisons of postoperative VIIa, XIIa, and TAT). Intraoperative activation of fibrinolysis was significantly less pronounced in the aprotinin group than in the placebo group (P < 0.0001 for intergroup comparison of postoperative D-dimer levels). No adverse drug effects (circulatory disturbances, deep venous thrombosis, alteration of serum creatinine) were detected. Although administered intraoperatively, aprotinin treatment dramatically reduced intraoperative and 24-h postoperative blood loss and autologous transfusion requirements but did not change homologous transfusion in posterior lumbar spine fusion.
                In our study, aprotinin therapy significantly decreased autologous, but not homologous, transfusion requirements in posterior lumbar spine fusion. Anemia may be an important factor contributing to an increased risk of bleeding, particularly in patients with thrombocytopenia.
                A multicenter, single-blinded pilot randomized controlled trial (RCT) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin (Hb) concentration on bleeding risk. Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups: standard transfusion strategy (transfusion of 2 units of red blood cells [RBCs] when their Hb level was less than 80 g/L) or an augmented transfusion strategy (transfusion of 2 units of RBCs when their Hb level was less than 120 g/L).
                Sixty patients were enrolled: 29 in the control group and 31 in the experimental group. The proportions of patients experiencing clinically significant bleeding and the time to first bleed were not significantly different between the control and experimental groups. The experimental group received more RBC transfusions (transfusions/patient-day) than the control group (0.233 vs. 0.151; relative risk, 1.56; 95% confidence interval, 1.16-2.10; p = 0.003). The proportion of patient-days with platelet (PLT) transfusions was not different between the experimental and control groups. The mean number of donor exposures (PLT and RBC transfusions) was not different between experimental and control groups. Bleeding symptoms were systematically documented.
                This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients. Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy.
                Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events.
                No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups.
                Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified. Bleeding remains a major complication and a major determinant in the prognosis of open-heart surgery. Coagulopathy related to cardiopulmonary bypass (CPB) seems to be the culprit. Since homologous blood transfusion in many occasions is not only responsible for mobidity and mortality but also increases medical costs. Therefore, the application of autologous blood transfusion including components such as PRBC, FFP and platelets concentrate is inevitable and comes in its stead. To reduce the use of homologous plasma and platelets transfusion in open-heart surgery, we designed a study to utilize the combination of autologous platelet rich plasma (PRP) and epsilon aminocaproic acid (EACA) to evaluate its effects on blood loss and blood component transfusion in open-heart patients.
                Sixty patients who received elective cardiac surgery were randomly divided into 3 groups: 1. Control group; 2. EACA group (150 mg/kg, i.v. before CPB); 3. PRP-EACA group (PRP 10 ml/kg harvested with a plasma saver followed by i.v. EACA 150 mg/kg). Anesthesia was uniform in all patients. Coagulation profile was evaluated by thromboelastography (TEG) during the operation. Blood loss during operation and the amount of drainage from the chest tubes in the postoperative period were recorded and compared between groups.
                Patients who were given EACA injection before CPB saw less blood loss perioperatively and received less transfusion of blood components. TEG analysis showed that patients who received EACA injection had a better coagulation profile and the platelet function was also better after CPB. However, no additive effect can be attained from combination of autologous PRP transfusion and EACA injection.
                With Pre-CPB EACA as protection, reduction of both blood loss and blood transfusion could be realized in open-heart surgery. Controlled study to assess the efficacy of aprotinin and Amicar in reducing blood loss during complex spinal fusions.
                To compare blood loss and the clotting profile with a thromboelastogram in patients with spinal deformities undergoing sequential anterior and posterior spinal fusions treated intraoperatively with either aprotinin or Amicar.
                Spinal fusion for correction of adult spinal deformities is associated with large blood losses despite the implementation of multiple factors to reduce this blood loss. The antifibrinolytics aprotinin and Amicar have both been shown to reduce blood loss in other surgical procedures with the potential for large blood loss. Hence, we compared their efficacy for reducing blood loss in complex spinal fusions.
                Sixty patients for elective sequential anteroposterior thoracolumbosacral fusions were randomly assigned to three groups: control, aprotinin, and Amicar. Patients were assessed for blood loss, transfusion requirements, postoperative complications, and coagulation profile using a thromboelastogram.
                The study demonstrated a significant reduction in total blood loss (aprotinin 3628 mL, Amicar 4056 mL, control 5181 mL) and transfusion requirements using the half-dose aprotinin regimen compared with Amicar or control. Aprotinin also preserved the thromboelastogram mean clot formation time, clot strength, and clotting index compared with Amicar or control.
                For complex spinal operations with large blood losses, the half-dose aprotinin regimen will reduce blood loss and the need for blood components and may have a role in reducing postoperative lung injury.
ESAs reduce the need for red blood cell transfusions but increase the risk for thromboembolic events and deaths. There is suggestive evidence that ESAs may improve QoL. Whether and how ESAs affects tumour control remains uncertain. The increased risk of death and thromboembolic events should be balanced against the potential benefits of ESA treatment taking into account each patient’s clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumour progression. Further research is needed to clarify cellular and molecular mechanisms and pathways of the effects of ESAs on thrombogenesis and their potential effects on tumour growth.