PMID- 18624976
OWN - NLM
STAT- MEDLINE
DCOM- 20090205
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
VI  - 6
IP  - 9
DP  - 2008 Sep
TI  - Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced 
      plasma fibrinolytic potential.
PG  - 1571-7
LID - 10.1111/j.1538-7836.2008.03070.x [doi]
AB  - BACKGROUND: Mild hyperhomocysteinemia (HHcy) has been shown to be associated with 
      impaired fibrinolysis, but some aspects of this association are unclear. 
      OBJECTIVE: Using an in vitro model of physiological relevance, we investigated 
      whether and how HHcy influences plasma fibrinolytic potential. PATIENTS/METHODS: 
      We studied 176 patients with previous venous thromboembolism, 58 with HHcy, 118 
      with normal total homocysteine (tHcy) levels (NHcy), at least 3 months after 
      withdrawal of anticoagulant therapy. Plasma fibrinolytic potential was measured 
      as the fibrinolysis time of tissue factor (TF)-induced clots exposed to 15 ng 
      mL(-1) t-PA. RESULTS: Fibrinolysis time was longer in HHcy than in NHcy patients, 
      but this difference disappeared when the assay was performed in the presence of 
      the TAFIa inhibitor, PTCI. Plasma levels of thrombin activatable fibrinolysis 
      inhibitor (TAFI) and factor VIII (FVIII) were higher in HHcy than NHcy, whereas 
      PAI-1, fibrinogen and endogenous thrombin potential were similar. Using 
      multivariate analysis, plasma tHcy was identified as an independent predictor of 
      fibrinolysis time. Experiments in which native fibrinogen was replaced by 
      purified fibrinogen suggested that alterations of fibrinogen structure did not 
      contribute appreciably to the hypofibrinolysis of HHcy plasma samples. The acute 
      increase of tHcy either in vivo (after an oral methionine load) or in vitro 
      (after incubation of normal plasma with 0.5 mm DL-Hcy) had no effects on 
      fibrinolysis or TAFI levels. CONCLUSIONS: We describe an enhanced TAFI-related 
      antifibrinolytic activity in mild HHcy, which might account for the reported 
      heightened thrombosis risk; however, it is unknown whether HHcy is causally 
      related to hypofibrinolysis or an associated bystander.
FAU - Colucci, M
AU  - Colucci M
AD  - Department of Biomedical Sciences and Human Oncology, Section of General and 
      Experimental Pathology, University of Bari, Bari, Italy. 
      mario.colucci@dimo.uniba.it
FAU - Cattaneo, M
AU  - Cattaneo M
FAU - Martinelli, I
AU  - Martinelli I
FAU - Semeraro, F
AU  - Semeraro F
FAU - Binetti, B M
AU  - Binetti BM
FAU - Semeraro, N
AU  - Semeraro N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080704
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - EC 3.4.17.20 (Carboxypeptidase B2)
SB  - IM
MH  - Adult
MH  - Blood Coagulation
MH  - Carboxypeptidase B2/*blood
MH  - Chromatography, High Pressure Liquid
MH  - Female
MH  - *Fibrinolysis
MH  - Humans
MH  - Hyperhomocysteinemia/*blood
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Thromboembolism/blood
EDAT- 2008/07/16 09:00
MHDA- 2009/02/06 09:00
CRDT- 2008/07/16 09:00
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2009/02/06 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
AID - S1538-7836(22)13255-1 [pii]
AID - 10.1111/j.1538-7836.2008.03070.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2008 Sep;6(9):1571-7. doi: 10.1111/j.1538-7836.2008.03070.x. 
      Epub 2008 Jul 4.