Monica Hyllner

Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery - A prospective randomised pilot study

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.

Plasma fibrinogen level, bleeding, and transfusion after on‐pump coronary artery bypass grafting surgery: a prospective observational study

BACKGROUND: Early identification of patients with increased risk of excessive bleeding and transfusion after cardiac surgery offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade and thus a potential biomarker for bleeding. We investigated the relationship between preoperative fibrinogen plasma concentration and postoperative bleeding and transfusion after coronary artery bypass grafting (CABG).

Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: A prospective observational study

BACKGROUND Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding. MATERIALS AND METHODS Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2h and 24h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated. RESULTS Adjusted plasma concentration of fibrinogen (-14+/-6%), and plasma activity of FII (-9+/-6%), FV (-13+/-8%), FX (-13+/-7%) and FXIII (-9+/-14%) were reduced two hours after surgery compared to baseline (all p<0.001). FVII (+3+/-12%, p=0.34) and FXI (+1+/-19%, p=0.50) were unchanged, while FVIII (+23+/-44%, p=0.006) and FIX (+23+/-17%, p<0.001) increased. Twenty-four hours after surgery fibrinogen (+45+/-27%), FVIII (+93+/-66%) and FIX (+33+/-26%) were all increased (all p<0.001), while FVII (-37+/-14%, p<0.001), FXI (-4+/-18%, p=0.02) and FXIII (-6+/-15%, p=0.004) were decreased. Median postoperative blood loss was 380 ml/12h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2h after surgery (r=-0.33, p=0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r=-0.34, p=0.009 and r=-0.41, p=0.003, respectively), but not between blood loss and any of the other factors. CONCLUSIONS There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG.

Postoperative Inflammatory Response after Autologous and Allogeneic Blood Transfusion

Background Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. Methods Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. Results Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. Conclusions The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.

Complement activation during storage of whole blood, red cells, plasma, and buffy coat

BACKGROUND: The process of separating whole blood into components and the storage of blood components may cause the release of toxic metabolites from the complement cascade. The aim of this study was to determine whether the storage of blood components leads to the activation of the complement cascade and the release of anaphylatoxins.

Formation of complement split products and proinflammatory cytokines by reinfusion of shed autologous blood

1. The purpose of this study was to determine whether shed autologous blood collected postoperatively contains complement split products (C3a and SC5b-9) and proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) and whether transfusion of shed blood increases the concentrations of inflammatory mediators in the circulation. 2. Twenty consecutive patients undergoing total hip replacement surgery under spinal anaesthesia were studied. The patients were transfused with whole blood collected postoperatively. 3. The median volume shed blood returned to the patients was 350 ml (25-75% range = 300-450). Before transfusion of shed blood was filtered using a 40 microm filter (Solcotrans). Samples for complement and cytokine determinations were drawn from the collected blood. 4. Venous blood samples were drawn 1 min before transfusion, 1 and 60 min after completed transfusion. High concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, IL-6 and IL-8 were found in shed blood. The concentrations were higher than the circulating levels (P < 0.05). The filtration procedure did not significantly reduce the concentrations. 5. Transfusion of the shed blood did not significantly alter the circulating concentrations of C3a, SC5b-9, TNF-alpha, IL-1beta, and IL-8. The plasma concentrations of IL-6 were increased both 1 and 60 min after completed transfusion compared to before (P < 0.05). 6. This study shows that whole blood collected from a surgical wound contains large concentrations of complement split products and proinflammatory cytokines. Transfusion of shed blood leads to elevated plasma levels of IL-6.

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.

Prophylactic Fibrinogen Infusion in Cardiac Surgery Patients: Effects on Biomarkers of Coagulation, Fibrinolysis, and Platelet Function

Objective: We have recently reported that prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass grafting (CABG) surgery. Because fibrinogen for the first time was administered to patients without hereditary fibrinogen deficiency or ongoing bleeding, a detailed analysis of the effects of fibrinogen concentrate on biomarkers of coagulation, fibrinolysis, and platelet function was performed. Methods: Twenty CABG patients with preoperative plasma fibrinogen levels <3.8 g/L were included in a prospective study. Patients were randomized to preoperative infusion of 2 g fibrinogen concentrate (fibrinogen group) or no infusion (control group). Activated partial thromboplastin time (aPTT), prothrombin time, activated clotting time, and plasma concentrations of fibrinogen, antithrombin, thrombin-antithrombin complex, prothrombin fragment 1.2, and D-dimer, thromboelastometry, platelet count, and platelet aggregometry were analyzed before and 15 minutes after infusion, and 2 and 24 hours after surgery. Results: Fifteen minutes after infusion of fibrinogen concentrate, fibrinogen plasma levels increased by 0.6 ± 0.2 g/L (P < .001 between groups), and induced minimal changes in aPTT and plasma levels of antithrombin, while remaining variables remained unchanged. After surgery, fibrinogen levels no longer differed between groups. D-dimer was significantly higher after surgery in the fibrinogen group (P = .03), while none of the other markers were statistically different between groups. Conclusions: Infusion of 2 g fibrinogen to cardiac surgery patients, without hereditary or acquired fibrinogen deficiency or ongoing bleeding, results in no or minimal changes in biomarkers reflecting coagulation and platelet function. An increased release of fibrin degradation products was detected after surgery in fibrinogen-treated patients.

Autologous blood transfusion in radical hysterectomy with and without erythropoietin therapy.

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.

Recombinant human erythropoietin in preoperative autologous blood donation did not influence the haemoglobin recovery after surgery

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.