Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery: a prospective randomized pilot study
ISTH Congress. 2009;: Abstract No. PP-WE-206.
Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. A prospective randomised pilot study
Thrombosis and Haemostasis. 2009;102((1):):137-44.
It has been suggested that preoperative fibrinogen plasma concentration is independently associated to postoperative blood loss after cardiac surgery. Theoretically, prophylactic infusion of fibrinogen concentrate may thus reduce postoperative bleeding, but this has not previously been investigated. Twenty elective coronary artery bypass graft (CABG) patients with preoperative plasma fibrinogen levels <3. 8 g/l were included in a prospective randomised pilot study. Patients were randomised to receive an infusion of 2 g fibrinogen concentrate (FIB group) or no infusion before surgery (control group). Primary endpoint was safety with clinical adverse events and graft occlusion assessed by multi-slice computed tomography. Predefined secondary endpoints were postoperative blood loss, blood transfusions, haemoglobin levels 24 hours (h) after surgery, and global haemostasis assessed with thromboelastometry, 2 and 24 hours after surgery. Infusion of 2 g fibrinogen concentrate increased plasma levels of fibrinogen by 0. 6 +/- 0. 2 g/l. There were no clinically detectable adverse events of fibrinogen infusion. Computed tomography revealed one subclinical vein graft occlusion in the FIB group. Fibrinogen concentrate infusion reduced postoperative blood loss by 32% (565 +/- 150 vs. 830 +/- 268 ml/12 h, p=0. 010). Haemoglobin concentration was significantly higher 24 h after surgery in the FIB group (110 +/- 12 vs. 98 +/- 8 g/l, p=0. 018). Prophylactic fibrinogen concentrate infusion did not influence global postoperative haemostasis as assessed by thromboelastometry. In conclusion, in this pilot study preoperative fibrinogen concentrate infusion reduced bleeding after CABG without evidence of postoperative hypercoagulability. Larger studies are necessary to ensure safety and confirm efficacy of prophylactic fibrinogen treatment in cardiac surgery.
Release of PMN elastase, TGF-beta1 and neopterin during blood storage; unfiltered versus filtered blood
Transfusion and Apheresis Science. 2006;35((2):):97-102.
Release of inflammatory mediators from blood cells during prestorage leukocyte filtration may result in recipient immune suppression. To investigate the effects of prestorage leukocyte filtration on the quality of blood components, twenty-four blood units were collected from healthy donors and randomised into 3 groups. Eight units were stored as whole blood, eight units were separated into plasma, red blood cells (RBC) and buffy coat and eight units were collected and filtered through the ASAHI RZ 2000 leukocyte filter and separated into plasma and RBC. The units were stored for 35 days. Samples were collected weekly for analyses of polymorphonuclear elastase (PMN elastase), transforming growth factor-beta1 (TGF-beta1) and neopterin. PMN elastase and neopterin increased during storage of whole blood and RBC. From the beginning and throughout storage, PMN elastase was increased in filtered plasma as compared with unfiltered plasma. Filtration per se did not influence the neopterin concentration in plasma or RBC. TGF-beta1 increased in plasma and RBC during storage. In filtered plasma, an elevation of the TGF-beta1 concentration was observed from the start of storage. The TGF-beta1 levels were higher in filtered plasma compared with unfiltered plasma. Prestorage leukocyte filtration increased the release of PMN elastase and TGF-beta1 in plasma and RBC.
IL-6 and IL-8 response to erythropoietin therapy in radical hysterectomy
Acta Anaesthesiologica Scandinavica. 2005;49((1):):47-51.
BACKGROUND The use of recombinant human erythropoietin (rHuEPO) improves autologous blood donation before elective surgery. However, there are other studies indicating that rHuEPO may suppress postoperative endogenous production of erythropoietin and stimulate inflammatory mediator release. Weekly donations generate only a moderate increase in endogenous erythropoietin production. We scheduled patients with cancer to predeposit three units of blood in 2 weeks, with or without rHuEPO therapy. The aim was to determine whether rHuEPO therapy and/or an aggressive donation schedule alter perioperative erythropoietin concentrations and whether rHuEPO therapy leads to the release of the pro-inflammatory cytokines IL-6 and IL-8. METHODS Thirty women scheduled for radical hysterectomy and pelvic lymphadenectomy were randomly assigned to either a control group with no rHuEPO therapy or to receive rHuEPO. Three units of whole blood were collected from each patient before the operation. Concentrations of haemoglobin, erythropoietin (s-EPO) and cytokines (IL-6 and IL-8) were repeatedly analyzed before and after the operation. RESULTS During the preoperative donation period, median s-EPO levels in the control group increased from 7 to 14 IU l(-1). There was a great increase in s-EPO concentrations 1 h postoperatively in the rHuEPO group compared with the control group (P < 0. 001). IL-6 and IL-8 were not significantly changed after intravenous administration of rHuEPO. CONCLUSION The use of rHuEPO therapy to optimise autologous blood donation does not influence IL-6 and IL-8 release. 1 h postoperatively rHuEPO therapy resulted in elevated s-EPO concentrations. There was, however, no difference in s-EPO between the groups from day 1 postoperatively and until the end of the study.
Recombinant human erythropoietin in preoperative autologous blood donation did not influence the haemoglobin recovery after surgery
Acta Anaesthesiologica Scandinavica. 2003;47((6):):687-92.
BACKGROUND Recombinant human erythropoietin in combination with preoperative autologous blood donation is an established regime for avoiding allogenic blood transfusions. The aim of the study was to determine endogenous erythropoietin production and haemoglobin recovery after preoperative autologous blood donation and surgery, with or without recombinant human erythropoietin treatment. METHODS Thirty-eight patients having total hip joint replacement surgery were randomised to receive either autologous blood transfusion (control group) or autologous transfusion plus preoperative recombinant human erythropoietin treatment (EPO group). Haemoglobin, haematocrit, erythropoietin and reticulocyte concentrations were repeatedly analysed, before, during, and after surgery. RESULTS No significant differences were found between the groups regarding haemoglobin, haematocrit, and erythropoietin, but the reticulocyte count increased significantly more in the EPO group. There was no difference in the requirement for allogeneic blood transfusions between the groups. The baseline haemoglobin was >13 g dL-1 in all but four patients. CONCLUSIONS In patients with normal preoperative haemoglobin levels, recombinant human erythropoietin treatment did not improve haemoglobin levels, or reduce the need for allogenic blood transfusion. There were no differences in serum erythropoietin concentrations between the groups. We question whether recombinant human erythropoietin treatment facilitates preoperative autologous blood donation in patients with normal haemoglobin levels.
Autologous blood transfusion in radical hysterectomy with and without erythropoietin therapy
Obstetrics & Gynecology. 2002;99((5, Pt 1):):757-62.
OBJECTIVE To investigate whether preoperative treatment with erythropoietin facilitates the collection of a sufficient amount of autologous blood in a short period of time. METHODS Forty-one women scheduled for radical hysterectomy were randomized to preoperative autologous blood donation with or without preoperative recombinant human erythropoietin therapy. All patients were scheduled to deposit three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte volume fraction, blood cells, iron status, and hemolysis were analyzed before and after surgery. RESULTS Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively. With erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels were significantly higher during precollection and day 1 after surgery. Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The additional use of erythropoietin therapy reduced the inability of patients to predeposit blood from 17.8% to 3.4%. CONCLUSION Most women can predeposit three units of whole blood in only 2 weeks without obtaining severe anemia. By treating women with erythropoietin, one out of seven can be prevented from a hemoglobin level below the 100 g/L limit for donation.
Increased serum erythropoietin concentration after allogeneic compared with autologous blood transfusion
Transfusion & Apheresis Science. 2002;27((3):):203-10.
Serum erythropoietin (sEPO) level is known to increase as hemoglobin (Hb) concentration decreases during and after preoperative autologous blood donation (PAD). The endogenous erythropoietin (EPO) production after allogeneic blood transfusion has not to our knowledge, been studied. The aim of the present study was to determine whether there is, after surgery, any change in sEPO concentration after allogeneic blood transfusion, and whether there is any difference in EPO response after autologous or allogeneic blood transfusion. Thirty-one patients approaching total hip-joint replacement surgery, were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). The relationship between Hb, sEPO, and reticulocytes in the recipients were repeatedly analyzed before, during and after surgery. The Hb followed an expected pattern, with a decreased concentration after PAD in the autologous group, then in both groups after surgery. The sEPO concentration was significantly higher in the allogeneic than in the autologous group on day one and day 4-5 postoperatively. The reticulocyte level, on the contrary, was higher in the autologous patients before, one hour after, and one day after surgery. The study showed a greater increase in sEPO concentration after allogeneic blood transfusion than after autologous blood transfusion. There may be an inverse relationship between sEPO and the reticulocyte level.
Release of interleukin-10 by reinfusion of salvaged blood after knee arthroplasty
Intensive Care Medicine. 2001;27((8):):1379-84.
OBJECTIVES To determine whether the method of the autotransfusion in association with knee arthroplasty leads to differences in anti-inflammatory cytokines in the patient's circulation. DESIGN AND SETTING Prospective study in a university hospital. PATIENTS Twenty-one patients undergoing knee arthroplasty were randomized into two groups assigned to postoperative blood salvage. Seven patients received postoperatively filtered salvaged blood, and seven received centrifuged and washed salvaged blood. Patients with postoperative blood loss less than 400 ml (n=7) did not receive any transfusion. MEASUREMENTS AND RESULTS Plasma levels of interleukin (IL) 1beta, IL-4, and IL-10 and of polymorphonuclear leukocyte elastase were measured by enzyme-linked immunosorbent assay. The plasma concentration of IL-10 was elevated after reinfusion of salvaged blood in all groups 1 day after surgery (p<0.05). Plasma IL-6, IL-10, and PMN elastase was higher (p<0.01) in all groups 1 day after surgery than preoperatively. There were significantly higher plasma levels 1 min after retransfusion of IL-6 (p<0.01) and IL-10 (p<0.05) in patients receiving filtered blood than in those receiving centrifuged and washed salvaged blood. CONCLUSION Total knee arthroplasty results in the release of interleukin-10. Transfusion of filtered salvaged blood leads to higher levels of cytokines IL-6 and IL-10 than after transfusion of washed and centrifuged salvaged blood.
Greater increase in cytokine concentration after salvage with filtered whole blood than with washed red cells, but no difference in postoperative hemoglobin recovery
BACKGROUND Inflammatory mediators are released in association with intraoperative and postoperative salvage of blood. Whether these mediators (cytokines) participate in the modulation of erythropoiesis or not has been investigated. STUDY DESIGN AND METHODS Twenty-seven patients who were to undergo total knee replacement surgery were randomly assigned to postoperative blood salvage with either filtered whole blood or washed red cells. Patients with postoperative blood loss <400 mL were considered a control group. The control group did not receive any transfusions. Plasma concentrations of the anaphylatoxin C3a, the C5b-9 terminal complement complex, and the cytokines interleukins 6 and 8, hemoglobin, reticulocytes, and red cell volume fraction in the patients were repeatedly analyzed before and after surgery. RESULTS Significantly increased concentrations of interleukin 6 appeared in all three groups, which was interpreted as a response to the surgical trauma. The increase was significantly greater in the group that received filtered whole blood after return of shed blood. The recovery of hemoglobin levels did not differ in the groups. CONCLUSION The transfusion of filtered whole blood leads to the formation of interleukin 6 in the circulation, but postoperative hemoglobin recovery was similar in all groups.
Removal of activated complement from shed blood: comparison of high- and low-dilutional haemofiltration
Acta Anaesthesiologica Scandinavica. 1998;42((7):):811-5.
BACKGROUND Perioperative blood salvage is associated with release of inflammatory mediators. Depending on type of processing, the complement system is activated to some extent in the final blood product. The aim of the present study was to evaluate a haemofiltration technique concerning complement system activation and whether the volume of added saline will have an influence on the elimination of activated complement during processing. METHODS Sixteen patients undergoing total hip arthroplasty received wound blood salvaged intraoperatively with a haemofiltration technique. Saline was added to the reservoir for washing in a ratio of 1:1 or 5:1 of estimated blood volume. Samples for determination of the anaphylatoxins C3a and C5a, and the terminal SC5b-9 complement complex (TCC) were drawn from the patients, the collected blood, the ultrafiltrate and the processed blood. RESULTS Increased concentrations of C3a, C5a and TCC were found in aspirated and processed blood. Haemofiltration did not reduce the concentrations of these factors, except that of C3a in the group where saline was added in a ratio of 5:1. There were no increased concentrations of C3a, C5a or TCC in the patient plasma after reinfusion. No differences in blood pressure, heart rate, pH, arterial oxygen tension, arterial carbon dioxide tension, or base excess were found in association with reinfusion of the blood. CONCLUSION Collected shed blood washed through haemofiltration contained moderately elevated concentrations of C3a, C5a and TCC. Reinfusion of the blood neither led to increased systemic concentrations of complement activation products, nor to disturbances in haemodynamic or biochemical parameters.