PMID- 32402428
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20200914
IS  - 2542-4513 (Print)
IS  - 2542-4513 (Linking)
VI  - 45
IP  - 3
DP  - 2020 May
TI  - Anticoagulant activity and pleiotropic effects of heparin.
PG  - 147-157
LID - S2542-4513(20)30228-5 [pii]
LID - 10.1016/j.jdmv.2020.03.002 [doi]
AB  - The recognized therapeutic effect of heparins is an anticoagulant activity 
      (anti-Xa and anti-IIa) acting in an indirect manner (cofactor of antithrombin) 
      but which is carried by only 20% at best of the glycan chains composing any 
      commercial preparation of heparin, whether unfractionated or low molecular 
      weight. However, the effects of glycan chains that participate in the therapeutic 
      but also potentially adverse effects of heparin preparations must also be 
      considered. These specific effects of glycans are potentially different for each 
      commercial preparation of heparins and, in particular, low molecular weight 
      heparins (LMWH) compared with unfractionated heparin (UFH) and LMWH between them. 
      The glycanic nature of heparin is responsible for its very particular 
      pharmacology: exchange with the glycocalyx of cells in particular endothelial. 
      Exchanges which depend on the length and structure of the glycan chains therefore 
      different between UFH and LMWH between the different heparin preparations between 
      them but also according to the state of glycocalyx differently altered according 
      to the underlying diseases and their degree of evolution. If the anticoagulant 
      effects of heparins can potentially be replaced with those of new oral 
      anticoagulants, the glycan effects of heparins cannot be replaced by synthetic 
      non-glycan molecules. This replacement will undoubtedly limit certain risks such 
      as heparin-induced thrombocytopenia (HIT) but other beneficial effects 
      participating to the overall efficacy of heparin (whose relative importance 
      remains to be ascertained), will also disappear: effects on surfaces, 
      anti-inflammatory effects, antineoplastic and anti-metastatic effects, ancillary 
      anticoagulant effects (not dependent on antithrombin), effect on endothelial 
      dysfunction. This review will be focused on all of these related/pleiotropic 
      effects of heparins that are in fact the effects of the glycan nature of heparin. 
      Among the antithrombotic effects not dependent on antithrombin one has been more 
      recently highlighted: the passivation/neutralization of the positively charged 
      fibrils of Netosis, by the negatively charged glycan chains of heparin. This also 
      has clinical implications: in the era of generics and biosimilars where 
      biosimilar heparins begin to appear, it is important to know that accordingly to 
      FDA and EMEA rules: their biosimilarity is judged only on the "classical" 
      anticoagulation effect cofactor of antithrombin (anti-IIa/anti-Xa) but that all 
      glycan effects that are potentially beneficial or potentially deleterious are not 
      taken into consideration in their assessment.
CI  - Copyright (c) 2020 Elsevier Masson SAS. All rights reserved.
FAU - Bal Dit Sollier, C
AU  - Bal Dit Sollier C
AD  - CREATIF (Centre de Reference et d'Education aux AntiThrombotiques d'Ile de 
      France), Lariboisiere Hospital, 2, rue Ambroise Pare, 75475 Paris cedex 10, 
      France; Department of Cardiology, Lariboisiere Hospital, 2, rue Ambroise Pare, 
      75475 Paris cedex 10, France.
FAU - Dillinger, J-G
AU  - Dillinger JG
AD  - CREATIF (Centre de Reference et d'Education aux AntiThrombotiques d'Ile de 
      France), Lariboisiere Hospital, 2, rue Ambroise Pare, 75475 Paris cedex 10, 
      France; Department of Cardiology, Lariboisiere Hospital, 2, rue Ambroise Pare, 
      75475 Paris cedex 10, France.
FAU - Drouet, L
AU  - Drouet L
AD  - CREATIF (Centre de Reference et d'Education aux AntiThrombotiques d'Ile de 
      France), Lariboisiere Hospital, 2, rue Ambroise Pare, 75475 Paris cedex 10, 
      France; Department of Cardiology, Lariboisiere Hospital, 2, rue Ambroise Pare, 
      75475 Paris cedex 10, France. Electronic address: ludovic.drouet@aphp.fr.
LA  - eng
PT  - Journal Article
DEP - 20200417
PL  - France
TA  - J Med Vasc
JT  - Journal de medecine vasculaire
JID - 101709200
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Anticoagulants)
RN  - 0 (Antineoplastic Agents)
RN  - 9005-49-6 (Heparin)
SB  - IM
CIN - J Med Vasc. 2020 May;45(3):103-104. PMID: 32402422
MH  - Animals
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Anticoagulants/adverse effects/chemistry/metabolism/*therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - Blood Coagulation/*drug effects
MH  - Endothelial Cells/metabolism
MH  - Glycocalyx/metabolism
MH  - Hemorrhage/chemically induced
MH  - Heparin/adverse effects/chemistry/metabolism/*therapeutic use
MH  - Humans
MH  - Molecular Weight
MH  - Protein Conformation
MH  - Risk Assessment
MH  - Risk Factors
MH  - Structure-Activity Relationship
MH  - Thrombocytopenia/blood/chemically induced
OTO - NOTNLM
OT  - Glycanes
OT  - Glycocalyx
OT  - Heparin
OT  - Low molecular weight heparin
OT  - Netosis
OT  - Non-fractionated heparin
EDAT- 2020/05/14 06:00
MHDA- 2020/09/15 06:00
CRDT- 2020/05/14 06:00
PHST- 2019/11/12 00:00 [received]
PHST- 2020/01/23 00:00 [accepted]
PHST- 2020/05/14 06:00 [entrez]
PHST- 2020/05/14 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
AID - S2542-4513(20)30228-5 [pii]
AID - 10.1016/j.jdmv.2020.03.002 [doi]
PST - ppublish
SO  - J Med Vasc. 2020 May;45(3):147-157. doi: 10.1016/j.jdmv.2020.03.002. Epub 2020 
      Apr 17.