| 1. |
- Karlsson, Martin, 1978, et al.
(författare)
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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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Ingår i: Transfusion. - : Wiley. - 1537-2995 .- 0041-1132. ; 48:10, s. 2152-2158
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Tidskriftsartikel (refereegranskat)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.
(författare)
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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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Ingår i: Clinical and applied thrombosis/hemostasis. - : SAGE Publications. - 1938-2723 .- 1076-0296. ; 17:4, s. 393-404
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery
- 2009
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Ingår i: Thrombosis & Haemostasis. ; 102, s. 137-144
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.
- 2012
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 130:5, s. 769-774
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Tidskriftsartikel (refereegranskat)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.
(författare)
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A structured blood conservation programme reduces transfusions and costs in cardiac surgery.
- 2014
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Ingår i: Interactive cardiovascular and thoracic surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 19:5, s. 788-794
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Ternström, Lisa, 1972
(författare)
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Clinical Aspects of Bleeding and Transfusion in Cardiac Surgery
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Excessive bleeding after cardiac surgery is a serious complication that is associated with increased morbidity and mortality. The bleeding is multifactorial and influenced by both surgical factors and impaired haemostasis. It is important to identify patients with increased risk of bleeding before the operation so countermeasures can be initiated. A large proportion of cardiac surgical patients receive blood transfusions during and after surgery. Transfusion therapy can save lives, but is also associated with increased risk of morbidity and mortality, so unnecessary transfusions should be avoided. There is little knowledge about when and on what indication blood transfusions are administered, and how well treating physicians follow current guidelines. Aims: One aim was to examine the relationship between preoperative levels of fibrinogen and other coagulation factors, and their relationship to postoperative bleeding and blood transfusion. Another was to assess the effects of a structured blood conservation programme, with the objective of reducing the administration of blood transfusions in cardiac surgical patients. A third aim was to study the prevalence, volumes and indications for red blood cell transfusions in cardiac surgery patients. The final aim was to examine adherence to institutional transfusion guidelines. Materials and methods: The first study (Paper I) involved 170 patients undergoing coronary artery bypass grafting (CABG). Data on each patient´s preoperative fibrinogen plasma concentration and other haemostatic tests, and postoperative bleeding and transfusion requirements, were collected. In Paper II, the study concerned 57 CABG patients. Plasma activity of coagulation factors involved in plasma coagulation was measured before and after surgery and related to haemodilution and postoperative blood loss. In Paper III, the study involved all 2162 patients who underwent cardiac surgery at our institution during a 24-month period. Transfusion requirements and transfusion-associated costs before and after introduction of a blood conservation programme were compared. In the study described in Paper IV, timing and indications for red blood cell transfusion in 1034 cardiac surgery patients were investigated and the adherence to institutional guidelines was assessed. Results: Paper I demonstrated that preoperative plasma levels of fibrinogen correlates significantly to postoperative blood loss. Preoperative fibrinogen level was also an independent predictor of red blood cell transfusion, together with female gender and long operation time. Paper II demonstrated a marked disparity of clotting factor activity after cardiac surgery. Only plasma concentration of fibrinogen and coagulation factor XIII activity correlated to postoperative bleeding. Paper III showed that the introduction of a simple structured multifactorial blood conservation programme significantly reduces blood transfusions to cardiac surgery patients, and reduces transfusion-associated costs without compromising medical safety. The result persists for at least three years after the implementation of the programme. Paper IV demonstrated that red blood cells are often transfused for other reasons than anaemia. The adherence to institutional transfusion guidelines was low. Conclusions: Pre- and postoperative fibrinogen concentration and factor XIII activity predict postoperative bleeding volume after CABG and may be used to identify patients with increased risk of bleeding. The introduction of a structured blood conservation programme is safe and reduces the use of blood products in cardiac surgery. The adherence to transfusion guidelines among treating physicians is low.
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| 7. |
- Ternström, Lisa, 1972, et al.
(författare)
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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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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 126:2
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Ternström, Lisa, 1972, et al.
(författare)
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Tumor necrosis factor gene polymorphism and cardiac allograft vasculopathy
- 2005
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Ingår i: J Heart Lung Transplant. - 1053-2498. ; 24:4, s. 433-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after cardiac transplantation. Tumor necrosis factor-alpha (TNF-alpha) may be a key factor in the development of CAV. Two bi-allelic polymorphisms associated with high TNF-alpha production have been identified in the TNF gene locus, TNFA1/2, at position -308 and TNFB1/2 at +252. We hypothesized that recipient TNFA2 and TNFB2 homozygosity is associated with the development of CAV after heart transplantation. METHODS: TNF gene polymorphisms were analyzed by multiplex fluorescent solid-phase mini-sequencing in 70 cardiac transplant recipients. Recipients homozygous for TNFA2 or TNFB2 (Group A, n = 29) were compared with recipients heterozygous or homozygous for TNFA1 and TNFB1 (Group B, n = 41). Coronary arteriography was performed annually or when indicated. Cumulative freedom from CAV and survival was calculated according to the Kaplan-Meier test. RESULTS: Mean follow-up was 3.8 +/- 0.3 years. In Group A, 11 of 29 recipients (38%) developed CAV compared with 9 of 41 (22%) in Group B (p = 0.12). Cumulative freedom from CAV at 3 years was 42% in Group A and 80% in Group B (p = 0.043). In Group A, 11 of 29 recipients (38%) died during follow-up compared with 4 of 41 (10%) in Group B (p = 0.006). Cumulative survival at 3 years was 72% in Group A and 93% in Group B (p = 0.003). CONCLUSIONS: The results suggest that TNFA2 and TNFB2 allele homozygosity is associated with cardiac allograft vasculopathy and mortality in heart transplant recipients.
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