| 1. |
- Karlsson, Martin, 1978, et al.
(author)
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Plasma fibrinogen level, bleeding and transfusion after on-pump coronary artery bypass grafting surgery: a prospective observational study
- 2008
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In: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 48:10, s. 2152-2158
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Journal article (peer-reviewed)abstract
- 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). STUDY DESIGN AND METHODS: A total of 170 patients (mean age, 67 ± 9 years; 75% men) undergoing isolated CABG were included in a prospective observational study. Patient variables (age, sex, operation time, anticoagulation therapy), preoperative laboratory variables (platelet [PLT] count, activated partial thromboplastin time, prothrombin time, and fibrinogen), postoperative bleeding volume, and transfusions during hospital stay were registered. Independent predictors of bleeding volume and transfusion were identified with multiple regression models. RESULTS: Postoperative bleeding volume correlated univariately with preoperative fibrinogen concentration (r = −0.53, p < 0.001) and PLT count (r = −0.26, p = 0.001) but only preoperative fibrinogen concentration was an independent predictor of postoperative bleeding volume. Twenty-nine of the 170 patients (17%) received transfusions with blood products. Independent predictors of transfusion were preoperative fibrinogen concentration (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7 per 1-unit decrease; p = 0.027), female sex (OR, 5.0; 95% CI, 1.8-14.7; p = 0.002), and aortic cross-clamp time (OR, 1.03; 95% CI, 1.01-1.06 per minute; p = 0.013). CONCLUSION: The results indicate that preoperative fibrinogen concentration (even within the normal range) is a limiting factor for postoperative hemostasis. Preoperative measurement of fibrinogen concentration provides information about bleeding volume and transfusion requirements after CABG.
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| 2. |
- Karlsson, Martin, 1978, et al.
(author)
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Prophylactic Fibrinogen Infusion in Cardiac Surgery Patients: Effects on Biomarkers of Coagulation, Fibrinolysis, and Platelet Function.
- 2011
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In: Clinical and applied thrombosis/hemostasis. - : SAGE Publications. - 1938-2723 .- 1076-0296. ; 17:4, s. 393-404
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Karlsson, Martin, 1978, et al.
(author)
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Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery
- 2009
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In: Thrombosis & Haemostasis. ; 102, s. 137-144
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Radulovic, Vladimir, 1969, et al.
(author)
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Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.
- 2012
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In: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 130:5, s. 769-774
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. MATERIAL AND METHODS: Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2h and 24h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. RESULTS: Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. CONCLUSIONS: A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.
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| 5. |
- Ternström, Lisa, 1972, et al.
(author)
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Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study.
- 2010
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In: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:2
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Journal article (peer-reviewed)abstract
- 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.
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| 6. |
- Arnestad, J P, et al.
(author)
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Removal of activated complement from shed blood: comparison of high- and low-dilutional haemofiltration.
- 1998
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In: Acta anaesthesiologica Scandinavica. - 0001-5172. ; 42:7, s. 811-5
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
- Hyllner, Monica, 1964, et al.
(author)
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Complement activation in prestorage leucocyte-filtered plasma.
- 2004
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In: Transfusion medicine (Oxford, England). - : Wiley. - 0958-7578 .- 1365-3148. ; 14:1, s. 45-52
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Journal article (peer-reviewed)abstract
- Complement activation and generation of pro-inflammatory cytokines occur during storage of blood components. Prestorage leucocyte filtration of platelet concentrates and red cells diminishes the accumulation of leucocyte-derived cytokines during storage, however, transfusion reactions are not eliminated. We investigated inflammatory mediator release during storage of plasma and whole blood and the effect of prestorage leucocyte filtration of plasma. Twenty-four blood units were collected from healthy blood donors and stored for 35 days. Eight units were stored as whole blood, eight units as plasma and eight units as prestorage filtered plasma. Samples were collected weekly for analyses of potassium, leucocytes, free plasma haemoglobin, complement activation (C3a and SC5b-9) and pro-inflammatory cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha]. Elevated levels of C3a and SC5b-9 were registered in filtered plasma, from the beginning of storage. C3a levels increased during storage. There was a higher rate of change during storage in C3a (P < 0.01) and SC5b-9 (P < 0.05) in plasma compared with filtered plasma. Interleukin (IL)-8 is released in whole blood. The cytokine levels generated in plasma and filtered plasma were low. Complement activation is present in whole blood, plasma and filtered plasma during storage. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation.
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| 8. |
- Hyllner, Monica, 1964
(author)
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Preoperative deposit of autologous blood. Effects on inflammatory mediators
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Blood contains complex cascade systems and substances that can be activated during the processing of blood components and storage. Allogeneic blood, i.e. blood from someone else, is normally separated into components before storage and transfusion, while autologous blood (the patient s own blood) often is used as whole blood. Allogeneic transfusions are associated with a variety of risks and preoperative autologous blood donation (PABD) has therefore become an established alternative. For patients with cancer, the immunosuppressive effect of allogeneic blood may be detrimental, but PABD is difficult because of the urgency of surgery. Normally, PABD begins 4-6 weeks before the scheduled operation and blood is tapped weekly. The additional use of recombinant erythropoietin (rHuEPO) therapy increases the volume of tapped autologous blood before surgery. However, other studies indicate that rHuEPO therapy suppresses postoperative endogenous erythropoietin (EPO) production and stimulates inflammatory mediator release. The aim of the present thesis was to investigate the effects on perioperative erythropoiesis, and the inflammatory mediator release during the predeposit and storage of autologous blood. In the present study, blood from healthy blood donors was collected and stored as whole blood or as separate components. Complement activation and release of pro-inflammatory cytokines were followed during the storage time. In addition, the effect of prestorage leucocyte filtration on inflammatory mediators was studied. Women undergoing radical hysterectomy were scheduled to predeposit three units of autologous blood during two weeks before surgery, with or without rHuEPO therapy. Erythropoiesis and the immune response were investigated during the pre- and postoperative follow-up.The results demonstrate that complement is activated during storage of whole blood and plasma, and the cytokine IL-8 is released during storage of whole blood. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation. Clearly, it was possible for women to predeposit three units of blood in only two weeks prior to surgery. A haemoglobin level below the 100 g/l donation limit can be prevented in one patient out of seven, by treating women with rHuEPO. The use of rHuEPO increases the postoperative endogenous EPO response but does not influence the cytokine release. The present thesis suggests that PABD can be offered to female patients undergoing cancer surgery, and that autologous blood can be transfused as whole blood.
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| 9. |
- Hyllner, Monica, 1964, et al.
(author)
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Recombinant activated factor VII in the management of life-threatening bleeding in cardiac surgery
- 2005
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In: Eur J Cardiothorac Surg. - : Oxford University Press (OUP). - 1010-7940. ; 28:2, s. 254-8
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Massive perioperative bleeding is a potential complication of cardiac surgery, and may persist despite conventional interventions. RFVIIa is being increasingly used as additional therapy, and the aim of the present study was to describe our experience with rFVIIa in the management of life-threatening bleeding in adult cardiac surgery. METHODS: Retrospective chart review of 24 patients undergoing a variety of cardiac procedures was performed at Sahlgrenska University Hospital between January and August 2004. The patients developed life-threatening bleeding during or after surgery despite conventional medical therapy and transfusion of blood products, and received rFVIIa as additional therapy. RESULTS: RFVIIa was administered as a median bolus dose of 60 microg/kg. Nineteen patients received one dose of rFVIIa; the bleeding stopped or decreased in 18 of them. Five patients received repeated doses of rFVIIa. Fifteen patients were reexplored due to massive postoperative bleeding or cardiac tamponade and a surgical source of bleeding was identified in six of these patients. A statistically significant reduction in chest drain losses after administration of rFVIIa was demonstrated. No adverse reactions were noted. CONCLUSIONS: RFVIIa was successfully used as an additional therapy both during and after cardiac surgery, when bleeding was refractory to conventional methods. Bleeding stopped eventually in all patients and none of the patients exsanguinated.
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| 10. |
- Ternström, Lisa, 1972, et al.
(author)
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A structured blood conservation programme reduces transfusions and costs in cardiac surgery.
- 2014
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In: Interactive cardiovascular and thoracic surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 19:5, s. 788-794
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Journal article (peer-reviewed)abstract
- Transfusions of blood products can be lifesaving, but they are also associated with considerable risks and adverse effects, including immune response and infections. In cardiac surgery, transfusions have also been associated with increased mortality. We prospectively studied the effects of a structured programme to reduce transfusions and transfusion-associated costs in cardiac surgery.
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