| 1. |
- Ehnsio, G., et al.
(författare)
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Platelet Reactivity During Carciopulmonary Bypass : Marked Reduction Followed by Early Restitution
- 2009
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Ingår i: in Intensive Care Medicine, vol 35, Supplement 1, Posters. - : Springer. ; , s. 132-132
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION. Cardiopulmonary bypass (CPB) affects platelets, and platelet dysfunction is considered to be an important risk factor for post-operative bleeding after coronary artery bypass graft (CABG) surgery. Monitoring platelet function in the peri-operative period therefore is of importance to reduce morbidity due to both bleeding and post-operative graft occlusion. Our aim was to study platelet reactivity in CABG patients in the peri-operative period.METHODS. Platelet function in 30 patients undergoing CABG was analyzed using an impedance aggregometry point-of-care (POC) instrument (Multiplate). Platelet reactivity was measured preoperatively at induction of anaesthesia, preoperatively immediately before CPB, after 30 minutes of CPB, after end of CPB, postoperatively at arrival to the ICU and finally at 3 and 18 h after surgery. Whole blood platelet aggregation was measured after activation with ADP (adenosin diphosphate), TRAP (thrombin receptor activating peptide), AA (arachidonic acid) and collagen. Platelet count was measured, and circulating platelet pool was assessed by correcting for hemodilution by indexing to hemoglobin. Non-parametric statistics were used, results are presented as median and 25–75%-percentiles.RESULTS. Reactivity to ADP, TRAP and AA agonists was significantly reduced at 30 min of CPB and at the end of CPB, followed by a rapid increase after CPB to preoperative values. Collagen showed a similar, but not significant, decrease during CPB followed by a post-CPB increase to values above baseline (p\0.001). Platelet count dropped after 30 min of CPB from 240 (204–301) preoperatively to 150 (132–189) after 30 min of CPB and further to 134 (120–151) 9 109/L at the end of CPB (p\0.001). Corrected for blood loss and hemodilution there was a reduced platelet pool at the end of CPB and at arrival at the ICU (p\0.001)CONCLUSION. There is an early decrease in platelet reactivity during CPB followed by a rapid post-CPB restitution of platelet function, despite low preoperative aggregometry values and lower post-CPB platelet count. The rapid preoperative changes in aggregometry points to a possible role for POC analysis of hemostatic function. The post-CPB increase in platelet reactivity simultaneously to the decrease in platelet count could imply increased aggregating tendency for remaining platelets, with possible implications for early graft failure and postoperative anti-platelet therapy.
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| 2. |
- Olsson, Anki, Medicine doktor, et al.
(författare)
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Activated platelet aggregation is transiently impaired also by a reduced dose of protamine
- 2019
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Ingår i: Scandinavian Cardiovascular Journal. - : TAYLOR & FRANCIS LTD. - 1401-7431 .- 1651-2006. ; 53:6, s. 355-360
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes.
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| 3. |
- Olsson, Anki, et al.
(författare)
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Better platelet function, less fibrinolysis and less hemolysis in re-transfused residual pump blood with the Ringer’s chase technique : a randomized pilot study
- 2018
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Ingår i: Perfusion. - : Sage Publications. - 0267-6591 .- 1477-111X. ; 33:3, s. 185-193
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Residual pump blood from the cardiopulmonary bypass (CPB) circuit is often collected into an infusion bag (IB) and re-transfused. An alternative is to chase the residual blood into the circulation through the arterial cannula with Ringer’s acetate. Our aim was to assess possible differences in hemostatic blood quality between these two techniques.Methods: Forty adult patients undergoing elective coronary artery bypass graft surgery with CPB were randomized to receive the residual pump blood by either an IB or through the Ringer’s chase (RC) technique. Platelet activation and function (impedance aggregometry), coagulation and hemolysis variables were assessed in the re-transfused blood and in the patients before, during and after surgery. Results are presented as median (25-75 quartiles).Results: Total hemoglobin and platelet levels in the re-transfused blood were comparable with the two methods, as were soluble platelet activation markers P-selectin and soluble glycoprotein VI (GPVI). Platelet aggregation (U) in the IB blood was significantly lower compared to the RC blood, with the agonists adenosine diphosphate (ADP) 24 (10-32) vs 46 (33-65), p<0.01, thrombin receptor activating peptide (TRAP) 50 (29-73) vs 69 (51-92), p=0.04 and collagen 24 (17-28) vs 34 (26-59), p<0.01. The IB blood had higher amounts of free hemoglobin (mg/L) (1086 (891-1717) vs 591(517-646), p<0.01) and D-dimer 0.60 (0.33-0.98) vs 0.3 (0.3-0.48), p<0.01. Other coagulation variables showed no difference between the groups. Conclusions: The handling of blood after CPB increases hemolysis, impairs platelet function and activates coagulation and fibrinolysis. The RC technique preserved the blood better than the commonly used IB technique.
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| 4. |
- Olsson, Anki
(författare)
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Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiopulmonary bypass (CPB) contributes to perioperative platelet dysfunction, increased fibrinolysis and impaired coagulation, which can have an impact on postoperative bleeding. During CPB the blood is exposed to foreign surfaces leading to activation of the coagulation system and a systemic inflammatory response with complement and leukocyte activation. Anticoagulation with heparin is used to prevent immediate blood clotting within the circuit. The heparin effect is reversed with protamine sulfate after weaning from CPB. Protamine has been suggested to impair platelet function in high doses although the mechanism is incompletely understood. Platelet dysfunction can promote bleeding which can necessitate transfusion and sometimes surgical re-exploration.After weaning from CPB the residual blood in the heart lung machine is usually retransfused to the patient in order to reduce the need for blood transfusion. The most common technique to transfuse residual blood is to collect the blood from the CPB circuit in an infusion bag (IB). An alternative way to re-transfuse the residual blood is by chasing it through the heart lung machine with Ringers solution, the Ringer chase technique (RC).The aim of this thesis was to examine a possible inhibitory effect of protamine on platelet aggregation. A second aim was to evaluate different techniques for retransfusion after weaning from CPB.Study I and II in this thesis are focused on the protamine effect on platelet aggregation and study III and IV on the quality of the blood in relation to the two different retransfusion techniques.In Study I we found that platelet aggregation evaluated by impedance aggregometry was reduced by approximately 50% after in vivo protamine administration. Protamine added in vitro also reduced platelet aggregation, by itself or in combination with heparin. Study II showed that protamine induces a marked but transient decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1, which also was sufficient to reverse the heparin anticoagulation as measured by activated clotting time (ACT). No further decrease was observed when additional protamine was given within three minutes. Platelet aggregation had begun to recover 20 minutes after protamine administration.In study III and IV we evaluated possible differences in quality of the retransfused residual blood from the heart-lung machine depending on if it is returned to the patient by the RC-technique or by an IB. Study III focused on biochemical markers of hemostasis, coagulation and fibrinolysis. Study IV concerns biochemical markers of inflammatory activity characterizing the inflammatory response during cardiac surgery with CPB including heparin binding protein (HBP) a new marker of neutrophil activation. CPB is associated with a marked systemic inflammatory response and levels of HBP indicates a pronounced neutrophil activation as part of a systemic inflammatory process. HBP levels during CPB was much higher than previously found during severe inflammatory conditions. We also concluded that the handling of the blood after weaning from CPB reduces platelet function, activates coagulation and fibrinolysis, increases hemolysis and the inflammatory response. Retransfusion of pump blood with the RC-technique was associated with better preserved platelet function, less hemolysis, less signs of activation of coagulation and fibrinolysis and less pronounced inflammatory activity than the commonly used IB technique. In the event of cell salvage technique not being feasible, we suggest that the RC technique is preferable to the IB technique but acknowledge that the clinical importance of this finding in terms of outcomes warrants further investigation
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| 5. |
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| 6. |
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| 7. |
- Olsson, Anki, et al.
(författare)
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Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass
- 2016
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Ingår i: Scandinavian Cardiovascular Journal. - : TAYLOR & FRANCIS LTD. - 1401-7431 .- 1651-2006. ; 50:1, s. 58-63
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Tidskriftsartikel (refereegranskat)abstract
- Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but may affect platelet aggregation. We assessed changes in platelet function in relation to protamine administration. Design: Platelet aggregation was analyzed by impedance aggregometry before and after protamine administration in 25 adult cardiac surgery patients. Aggregation was also studied after in vitro addition of heparin and protamine. The activators adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used.Results: Platelet aggregation was reduced by approximately 50% after in vivo protamine administration; ADP 640 +/- 230 (AU*min, mean +/- SD) to 250 +/- 160, TRAP 939 +/- 293 to 472 +/- 260, AA 307 +/- 238 to 159 +/- 143 and COL 1022 +/- 350 to 506 +/- 238 (all p<0.001). Aggregation was also reduced after in vitro addition of protamine alone with activators ADP from 518 +/- 173 to 384 +/- 157 AU*min p<0.001, and AA 449 +/- 311 to 340 +/- 285 (p<0.01) and protamine combined with heparin (1:1 ratio) with activators ADP to 349 +/- 160 and AA to 308 +/- 260 (both p<0.001); and COL from 586 +/- 180 to 455 +/- 172 (p<0.05). Conclusions: Protamine given after CPB markedly reduces platelet aggregation. Protamine added in vitro also reduces platelet aggregation, by itself or in combination with heparin.
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| 8. |
- Tornudd, Mattias, et al.
(författare)
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Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine
- 2023
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier. - 1053-0770 .- 1532-8422. ; 37:7, s. 1110-1120
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort.DESIGN: Prospective, controlled clinical study.SETTING: A single-center university hospital.PARTICIPANTS: Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB.INTERVENTIONS: Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. MEASUREMENTS ANDMAIN RESULTS: Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001).CONCLUSIONS: During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.
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| 9. |
- Törnudd, Mattias, 1974-
(författare)
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Protamine, Platelet Function and Coagulation in Cardiac Surgery
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bleeding is a serious and common complication in cardiac surgery. Complicated surgery together with alterations in hemostatic conditions from the use of cardiopulmonary bypass (CPB), presents challenges in how to preserve hemostasis in the patient. CPB is thought to affect platelet function and coagulation in many ways. Before connecting the patient to the CPB system, heparin is used as anticoagulation. With the connection between the patient and the CPB tubing there is a dilution of platelets and coagulation proteins and despite anticoagulation there is an activation of coagulation and inflammation resulting in consumption of coagulation factors and triggering of fibrinolysis. After disconnection of the CPB system, protamine is used to reverse the effect of heparin and restore the coagulation capacity of the patient. When protamine binds to heparin, the anticoagulant effect of heparin is removed but protamine is known to affect both platelet function and coagulation. There is uncertainty about how to best dose protamine to limit the negative effects from protamine without risking remaining heparin effect. A lot is known about how and to what extent cardiac surgery with the use of CPB affect the hemostasis in the patient, but there are still many uncertainties. The aims of this thesis were to examine how platelets are affected by CPB and protamine and to investigate if dosing of protamine had an impact on the risk of remaining or reappearing heparin after cardiac surgery. We also wanted to investigate whether sampling site matters when studying platelet function. In paper I, we found that protamine in vitro interacts with platelets by both a direct activating effect and by a secondary impairment of function when exposed to other activators. The impairment of platelet function from protamine could also be seen in vivo and is described in paper III. In paper III, we also conclude that, in contrast to prior studies, there was no increase in activation in platelets, nor net loss of platelets, during moderate CPB times. After CPB we found no impairment of platelet function compared with before surgery. In paper II, we found no differences in platelet aggregability between venous and arterial blood when measured with impedance aggregometry. Also, with flow cytometry most of our parameters showed no differences between venous and arterial blood. However, there were some differences. For example, the level of monocyte-platelet-aggregates was higher in venous- compared with arterial blood, which raises questions whether platelet function changes with oxygenation and flow conditions. In paper IV, we found a dose dependent risk of remaining heparin activity in the first postoperative period. We also found reappearance of heparin activity that was independent of the protamine dose in almost all our patients. We did not find any correlation between remaining or reappearing heparin activity and bleeding. In conclusion, this thesis describes that moderate CPB times do not have the severe impairment on platelet function earlier described in the literature. The thesis also increases the knowledge regarding how protamine affects platelet function and how dosing of protamine does and does not affect the risk of remaining and reappearing heparin activity. Finally, we conclude that in most cases platelet function can be studied in venous and arterial blood interchangeably, but there might be some differences in platelet function depending on whether they are in the venous our arterial system.
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| 10. |
- Törnudd, Mattias, et al.
(författare)
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Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors
- 2021
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Ingår i: Platelets. - : Taylor & Francis. - 0953-7104 .- 1369-1635. ; 32:1, s. 90-96
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Tidskriftsartikel (refereegranskat)abstract
- Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 mu g/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 mu g/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p < .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 mu g/mL reduced aggregation, from 73.8 +/- 29.4 U to 46.9 +/- 21.1 U (p < .001) with ADP and from 126.4 +/- 16.1 U to 94.9 +/- 23.7 U (p < .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 +/- 0.20 (0 mu g/mL) to 10.2 +/- 3.1 (80 mu g/mL), p < .001. Protamine 80 mu g/mL by itself resulted in higher MFI (10.16 +/- 3.09) than activation with ADP (2.2 +/- 0.7, p < .001) or TRAP (5.7 +/- 2.6, p < .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.
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