PMID- 15179449
OWN - NLM
STAT- MEDLINE
DCOM- 20041025
LR  - 20191108
IS  - 0897-5957 (Print)
IS  - 0897-5957 (Linking)
VI  - 22
IP  - 2
DP  - 2004 Summer
TI  - Low-molecular-weight heparins in thrombosis and cancer: emerging links.
PG  - 121-34
AB  - Heparin as well as low-molecular-weight heparins (LMWHs) have polypharmacological 
      actions at various levels. Earlier studies focused on the plasma anti-Xa and 
      anti-IIa pharmacodynamics (PD) for the different LMWHs. Other important PD 
      parameters for heparin and LMWHs might explain the diverse clinical impacts of 
      this class of agents in thrombosis and beyond: the release of the vascular tissue 
      factor pathway inhibitor (TFPI), inhibition of key matrix-degrading enzymes, and 
      other mechanisms. There is much evidence for the key role of LMWHs in 
      hypercoagulation in thrombosis and cancer, angiogenesis, and inflammatory 
      disorders. Many cancer patients reportedly have a hypercoaguable state, with 
      recurrent thrombosis due to the impact of cancer cells and chemotherapy or 
      radiotherapy on the coagulation cascade. Studies have demonstrated that 
      unfractionated heparin (UFH) or its low molecular weight fractions interfere with 
      various processes involved in tumor growth and metastasis. Clinical trials have 
      suggested a clinically relevant and improved efficacy of LMWHs, as compared to 
      UFH, on the survival of cancer patients with deep vein thrombosis. Our laboratory 
      has demonstrated a significant role for LMWHs and for LMWH-releasable TFPI on the 
      regulation of angiogenesis, tumor growth, and tumor metastasis; we have also seen 
      potent inhibition of matrix-degrading enzymes by LMWHs but not by TFPI. The 
      antiangiogenesis effect of LMWHs or non-anticoagulant LMWH derivatives was shown 
      to be reversed by anti-TFPI. Thus, modulation of tissue factor/VIIa noncoagulant 
      activities by LMWH-releasable TFPI and the inhibitory effects on matrix-degrading 
      enzymes beside the anticoagulant efficacy have provided an expanded clinical 
      utility for LMWHs in angiogenesis-associated disorders, including human tumor 
      growth and metastasis.
FAU - Mousa, Shaker A
AU  - Mousa SA
AD  - Pharmaceutical Research Institute at Albany College of Pharmacy, 106 New Scotland 
      Avenue, Albany, NY 12208, USA. mousas@acp.edu.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Cardiovasc Drug Rev
JT  - Cardiovascular drug reviews
JID - 9006912
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Anticoagulants/*therapeutic use
MH  - Blood Coagulation
MH  - Clinical Trials as Topic
MH  - Heparin, Low-Molecular-Weight/*therapeutic use
MH  - Humans
MH  - Neoplasms/blood/complications/*drug therapy
MH  - Thromboembolism/complications/*drug therapy/prevention & control
MH  - Treatment Outcome
MH  - Venous Thrombosis/complications/prevention & control
RF  - 47
EDAT- 2004/06/05 05:00
MHDA- 2004/10/27 09:00
CRDT- 2004/06/05 05:00
PHST- 2004/06/05 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/06/05 05:00 [entrez]
AID - 10.1111/j.1527-3466.2004.tb00135.x [doi]
PST - ppublish
SO  - Cardiovasc Drug Rev. 2004 Summer;22(2):121-34. doi: 
      10.1111/j.1527-3466.2004.tb00135.x.