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

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Törnudd, MattiasLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Thorax-kärlkliniken i Östergötland (author)

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

Article/chapterEnglish2021

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2020-01-28
Taylor & Francis,2021
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LIBRIS-ID:oai:DiVA.org:oru-80044
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-80044URI
https://doi.org/10.1080/09537104.2020.1719992DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-163707URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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Funding Agency:County Council of Östergötland LIO661221 LIO-603321
Funding Agencies|County Council of Ostergotland [LIO661221, LIO-603321]
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
NATURVETENSKAP Biologi Cellbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Cell Biology hsv//eng
Flow cytometry
impedance aggregometry
platelet function
protamine
thrombin generation

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Ramström, Sofia,1973-Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden,Medicinska fakulteten,Avdelningen för klinisk kemi och farmakologi,Region Östergötland, Klinisk kemi,Orebro Univ, Sweden(Swepub:liu)sofra86 (author)
Kvitting, John-Peder EscobarDepartment of Cardiothoracic Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway,Oslo Univ Hosp, Norway (author)
Alfredsson, Joakim,1962-Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Kardiologiska kliniken US(Swepub:liu)joaal38 (author)
Pihl, RichardLinköpings universitet,Institutionen för biomedicinska och kliniska vetenskaper,Institutionen för hälsa, medicin och vård,Medicinska fakulteten,Region Östergötland, Klinisk kemi,Region Östergötland, Thorax-kärlkliniken i Östergötland(Swepub:liu)n/a (author)
Berg, SörenLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Thorax-kärlkliniken i Östergötland(Swepub:liu)sorbe67 (author)
Linköpings universitetAvdelningen för diagnostik och specialistmedicin (creator_code:org_t)

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In:Platelets: Taylor & Francis32:1, s. 90-960953-71041369-1635

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