PMID- 27898513
OWN - NLM
STAT- MEDLINE
DCOM- 20180606
LR  - 20180606
IS  - 1473-5733 (Electronic)
IS  - 0957-5235 (Linking)
VI  - 28
IP  - 6
DP  - 2017 Sep
TI  - Inhibition of plasmin generation in plasma by heparin, low molecular weight 
      heparin, and a covalent antithrombin-heparin complex.
PG  - 431-437
LID - 10.1097/MBC.0000000000000611 [doi]
AB  - : The clinical limitations of unfractionated heparin (UFH) and low molecular 
      weight heparin (LMWH) led to the development of an antithrombin-heparin covalent 
      complex (ATH), which displays superior anticoagulant abilities compared with UFH. 
      A recent study investigating its interaction with fibrinolysis showed that ATH 
      inhibited free and fibrin bound plasmin and decreased plasmin generation on 
      fibrin clots. These studies were conducted using purified components and did not 
      elucidate the interaction of ATH with plasmin in the presence of its natural 
      inhibitors alpha2-antiplasmin (alpha2-AP) and alpha2-macroglobulin (alpha2-M). The aim of this 
      study was to determine the effects of ATH, UFH, and LMWH on plasmin generation in 
      plasma, under more physiological conditions. Plasmin generation in plasma in the 
      absence and presence of anticoagulants was initiated by tissue plasminogen 
      activator and soluble fibrin fragments, and plasmin and plasmin-alpha2-M complexes 
      generated over time were quantified chromogenically. Generation of plasmin-alpha2-AP 
      complexes and consumption of plasminogen were quantified by ELISA. Plasmin 
      generation was decreased in the presence of UFH and ATH, whereas LMWH had no 
      effect. Neither plasminogen consumption nor generation of plasmin-alpha2-AP complexes 
      were affected by UFH or ATH. However, plasmin-alpha2-M complexes were slightly 
      reduced by ATH suggesting that ATH may be able to compete with alpha2-M for plasmin. 
      Plasmin generation may be mildly inhibited by heparin-based anticoagulants; 
      however, heparin-catalyzed antithrombin activity is not a major inhibitor of 
      plasmin, as compared to its natural inhibitors alpha2-AP and alpha2-M. This adds to our 
      understanding of ATH mechanisms of action and aids in its development for 
      clinical use.
FAU - Chang, Gabriela M T
AU  - Chang GMT
AD  - Department of Pediatrics, Thrombosis and Atherosclerosis Research Institute, 
      McMaster University, Hamilton, Ontario, Canada.
FAU - Atkinson, Helen M
AU  - Atkinson HM
FAU - Berry, Leslie R
AU  - Berry LR
FAU - Chan, Anthony K C
AU  - Chan AKC
LA  - eng
PT  - Journal Article
PL  - England
TA  - Blood Coagul Fibrinolysis
JT  - Blood coagulation & fibrinolysis : an international journal in haemostasis and 
      thrombosis
JID - 9102551
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Antithrombins)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Pregnancy-Associated alpha 2-Macroglobulins)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.7 (Fibrinolysin)
SB  - IM
MH  - Antifibrinolytic Agents/metabolism
MH  - Antithrombins/chemistry/*pharmacology
MH  - Fibrinolysin/*antagonists & inhibitors/metabolism
MH  - Heparin/chemistry/*pharmacology
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - Multiprotein Complexes/chemistry/pharmacology
MH  - Plasma/metabolism
MH  - Pregnancy-Associated alpha 2-Macroglobulins/metabolism
EDAT- 2016/11/30 06:00
MHDA- 2018/06/07 06:00
CRDT- 2016/11/30 06:00
PHST- 2016/11/30 06:00 [pubmed]
PHST- 2018/06/07 06:00 [medline]
PHST- 2016/11/30 06:00 [entrez]
AID - 10.1097/MBC.0000000000000611 [doi]
PST - ppublish
SO  - Blood Coagul Fibrinolysis. 2017 Sep;28(6):431-437. doi: 
      10.1097/MBC.0000000000000611.