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Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass
Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping. Blekinge Institute Technology, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
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2016 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 50, no 1, p. 58-63Article in journal (Refereed) Published
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Text
Abstract [en]

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.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2016. Vol. 50, no 1, p. 58-63
Keywords [en]
Cardiopulmonary bypass; platelet aggregation; platelet function tests; protamine
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-124094DOI: 10.3109/14017431.2015.1099720ISI: 000365693900009PubMedID: 26402229OAI: oai:DiVA.org:liu-124094DiVA, id: diva2:897214
Note

Funding Agencies|Blekinge Institute of Technology, Karlskrona; Department of Cardiothoracic Anaesthesiology and Intensive Care, County Council of Ostergotland [LIO-284621]

Available from: 2016-01-25 Created: 2016-01-19 Last updated: 2018-04-03
In thesis
1. Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass
Open this publication in new window or tab >>Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 84
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1612
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-146224 (URN)10.3384/diss.diva-146224 (DOI)9789176853559 (ISBN)
Public defence
2018-04-05, Berzeliussalen, Campus US, Linköping, 13:00 (English)
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Available from: 2018-04-04 Created: 2018-04-03 Last updated: 2018-04-09Bibliographically approved

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Alfredsson, JoakimHåkansson, ErikSvedjeholm, RolfBerg, Sören

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Alfredsson, JoakimHåkansson, ErikSvedjeholm, RolfBerg, Sören
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Department of Anaesthesiology and Intensive Care in LinköpingDivision of Cardiovascular MedicineFaculty of Medicine and Health SciencesDepartment of Cardiology in LinköpingDepartment of Thoracic and Vascular Surgery
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Scandinavian Cardiovascular Journal
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