PMID- 15783242
OWN - NLM
STAT- MEDLINE
DCOM- 20050517
LR  - 20220318
IS  - 0114-5916 (Print)
IS  - 0114-5916 (Linking)
VI  - 28
IP  - 4
DP  - 2005
TI  - Safety profile of different low-molecular weight heparins used at therapeutic 
      dose.
PG  - 333-49
AB  - Low-molecular weight heparins (LMWHs) have been shown to be as safe and effective 
      as unfractionated heparin (UFH) for the treatment of acute venous thrombosis and 
      non-life-threatening pulmonary embolism. Different reports have shown that LMWHs 
      may also be used to treat patients with unstable angina or non-Q-wave infarction. 
      The safety of LMWHs used at therapeutic dose has been widely studied in pivotal 
      clinical trials and analysed in several meta-analyses. However, despite the wide 
      development and use of LMWHs, several issues regarding the safety and optimal use 
      of LMWHs remain unanswered. The main adverse effect of LMWHs is bleeding and it 
      is uncertain whether a weight-adjusted dosage regimen without laboratory 
      monitoring can be used in patients with a high risk of bleeding, such as patients 
      with renal failure, elderly patients, obese patients or pregnant women. These 
      patients are usually excluded from clinical trials and only a few studies, not 
      sufficiently powered to estimate efficacy and safety, have been carried out in 
      these special populations. Most of the available data comes from pharmacokinetic 
      or population pharmacodynamic studies or clinical reports. Results in patients 
      with renal impairment who are not undergoing haemodialysis suggest that a 
      reduction in calculated creatinine clearance levels is associated with an 
      increased risk of accumulation of anti-Xa activity, the extent of which differs 
      depending on the individual LMWH and the extent to which the compound is cleared 
      by the kidney. The limited data available regarding the use of therapeutic doses 
      of LMWHs in obese patients suggest that there is no need to cap the dose at a 
      maximal allowable dose. Long-term (3-month) treatment with LMWHs appears to be as 
      effective and safe as oral anticoagulant therapy for the treatment of venous 
      thromboembolism. It appears that each LMWH is a distinct compound with unique 
      pharmacokinetic and pharmacodynamic profiles. Until more data are available 
      regarding these special populations, periodic monitoring of anti-Xa activity 
      levels may be recommended to detect accumulation and/or an overdose and minimise 
      the bleeding risk. The non-haemorrhagic adverse effects of the LMWHs include 
      heparin-induced thrombocytopenia (HIT) and osteoporosis. The incidence of HIT 
      appears to be lower with LMWHs than with UFH; there is currently not enough data 
      to compare the frequency of HIT between the various LMWHs. LMWHs also appear to 
      carry a lower risk of causing osteoporosis than UFH. In conclusion, studies that 
      include special population patients are required to make conclusive 
      recommendations concerning the safety and monitoring of the different LMWHs.
FAU - Gouin-Thibault, Isabelle
AU  - Gouin-Thibault I
AD  - Laboratoire d'Hematologie, Hopital Charles Foix (University Hospital of Paris), 
      Ivry/Seine, France. isabelle.gouin@cfx.aphp.fr
FAU - Pautas, Eric
AU  - Pautas E
FAU - Siguret, Virginie
AU  - Siguret V
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Anticoagulants/adverse effects/pharmacokinetics/therapeutic use
MH  - Area Under Curve
MH  - Clinical Trials as Topic
MH  - Female
MH  - Hemorrhage/*chemically induced
MH  - *Heparin, Low-Molecular-Weight/adverse effects/pharmacokinetics/therapeutic use
MH  - Humans
MH  - Kidney Failure, Chronic/metabolism
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Pregnancy
MH  - Thrombocytopenia/chemically induced
MH  - Venous Thrombosis/*drug therapy/prevention & control
RF  - 95
EDAT- 2005/03/24 09:00
MHDA- 2005/05/18 09:00
CRDT- 2005/03/24 09:00
PHST- 2005/03/24 09:00 [pubmed]
PHST- 2005/05/18 09:00 [medline]
PHST- 2005/03/24 09:00 [entrez]
AID - 2845 [pii]
AID - 10.2165/00002018-200528040-00005 [doi]
PST - ppublish
SO  - Drug Saf. 2005;28(4):333-49. doi: 10.2165/00002018-200528040-00005.