PMID- 31533230
OWN - NLM
STAT- MEDLINE
DCOM- 20200210
LR  - 20200210
IS  - 1660-3397 (Electronic)
IS  - 1660-3397 (Linking)
VI  - 17
IP  - 9
DP  - 2019 Sep 17
TI  - The Inhibitory Effect of Protamine on Platelets is Attenuated by Heparin without 
      Inducing Thrombocytopenia in Rodents.
LID - 10.3390/md17090539 [doi]
LID - 539
AB  - Protamine sulfate (PS) is a polycationic protein drug obtained from the sperm of 
      fish, and is used to reverse the anticoagulant effect of unfractionated heparin 
      (UFH). However, the interactions between PS, UFH, and platelets are still not 
      clear. We measured the platelet numbers and collagen-induced aggregation, 
      P-selectin, platelet factor 4, beta-thromboglobulin, prostacyclin metabolite, 
      D-dimers, activated partial thromboplastin time, prothrombin time, anti-factor 
      Xa, fibrinogen, thrombus weight and megakaryocytopoiesis in blood collected from 
      mice and rats in different time points.. All of the groups were treated 
      intravenously with vehicle, UFH, PS, or UFH with PS. We found a short-term 
      antiplatelet activity of PS in mice and rats, and long-term platelet-independent 
      antithrombotic activity in rats with electrically-induced thrombosis. The 
      antiplatelet and antithrombotic potential of PS may contribute to bleeding risk 
      in PS-overdosed patients. The inhibitory effect of PS on the platelets was 
      attenuated by UFH without inducing thrombocytopenia. Treatment with UFH and PS 
      did not affect the formation, number, or activation of platelets, or the 
      thrombosis development in rodents.
FAU - Miklosz, Joanna
AU  - Miklosz J
AUID- ORCID: 0000-0003-0958-0454
AD  - Department of Pharmacodynamics, Medical University of Bialystok, 15-222 
      Bialystok, Poland.
FAU - Kalaska, Bartlomiej
AU  - Kalaska B
AUID- ORCID: 0000-0002-4968-4429
AD  - Department of Pharmacodynamics, Medical University of Bialystok, 15-222 
      Bialystok, Poland.
FAU - Kaminski, Kamil
AU  - Kaminski K
AUID- ORCID: 0000-0002-7421-6758
AD  - Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, 
      30-387 Krakow, Poland.
FAU - Rusak, Malgorzata
AU  - Rusak M
AD  - Department of Haematological Diagnostics, Medical University of Bialystok, 15-269 
      Bialystok, Poland.
FAU - Szczubialka, Krzysztof
AU  - Szczubialka K
AUID- ORCID: 0000-0001-6612-1102
AD  - Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, 
      30-387 Krakow, Poland.
FAU - Nowakowska, Maria
AU  - Nowakowska M
AUID- ORCID: 0000-0001-6456-5463
AD  - Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, 
      30-387 Krakow, Poland.
FAU - Pawlak, Dariusz
AU  - Pawlak D
AD  - Department of Pharmacodynamics, Medical University of Bialystok, 15-222 
      Bialystok, Poland.
FAU - Mogielnicki, Andrzej
AU  - Mogielnicki A
AUID- ORCID: 0000-0003-2406-5290
AD  - Department of Pharmacodynamics, Medical University of Bialystok, 15-222 
      Bialystok, Poland. andrzej.mogielnicki@umb.edu.pl.
LA  - eng
GR  - 2016/23/N/NZ7/00442/Narodowe Centrum Nauki/
GR  - N/ST/MN/17/002/2211/Uniwersytet Medyczny w Bialymstoku/
PT  - Journal Article
DEP - 20190917
PL  - Switzerland
TA  - Mar Drugs
JT  - Marine drugs
JID - 101213729
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Protamines)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/administration & dosage/*adverse effects
MH  - Blood Platelets/drug effects
MH  - Disease Models, Animal
MH  - Hemorrhage/blood/chemically induced/prevention & control
MH  - Heparin/administration & dosage/*adverse effects
MH  - Heparin Antagonists/administration & dosage/*adverse effects
MH  - Humans
MH  - Male
MH  - Mice
MH  - Partial Thromboplastin Time
MH  - Platelet Aggregation/drug effects
MH  - Protamines/administration & dosage/*adverse effects
MH  - Rats
MH  - Thrombocytopenia/blood/chemically induced/*diagnosis
MH  - Time Factors
PMC - PMC6780366
OTO - NOTNLM
OT  - animal models
OT  - heparin
OT  - platelets
OT  - protamine
OT  - thrombocytopenia
OT  - thrombosis
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2019/09/20 06:00
MHDA- 2020/02/11 06:00
PMCR- 2019/09/01
CRDT- 2019/09/20 06:00
PHST- 2019/08/22 00:00 [received]
PHST- 2019/09/11 00:00 [revised]
PHST- 2019/09/13 00:00 [accepted]
PHST- 2019/09/20 06:00 [entrez]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/02/11 06:00 [medline]
PHST- 2019/09/01 00:00 [pmc-release]
AID - md17090539 [pii]
AID - marinedrugs-17-00539 [pii]
AID - 10.3390/md17090539 [doi]
PST - epublish
SO  - Mar Drugs. 2019 Sep 17;17(9):539. doi: 10.3390/md17090539.