PMID- 15383472
OWN - NLM
STAT- MEDLINE
DCOM- 20041026
LR  - 20220408
IS  - 0012-3692 (Print)
IS  - 0012-3692 (Linking)
VI  - 126
IP  - 3 Suppl
DP  - 2004 Sep
TI  - Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on 
      Antithrombotic and Thrombolytic Therapy.
PG  - 188S-203S
AB  - This article about unfractionated heparin (UFH) and low-molecular-weight heparin 
      (LMWH) is part of the Seventh American College of Chest Physicians Conference on 
      Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. UFH is a 
      heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a 
      pentasaccharide, catalyzing the inactivation of thrombin and other clotting 
      factors. UFH also binds endothelial cells, platelet factor 4, and platelets, 
      leading to rather unpredictable pharmacokinetic and pharmacodynamic properties. 
      Variability in activated partial thromboplastin time (aPTT) reagents necessitates 
      site-specific validation of the aPTT therapeutic range in order to properly 
      monitor UFH therapy. Lack of validation has been an oversight in many clinical 
      trials comparing UFH to LMWH. In patients with apparent heparin resistance, 
      anti-factor Xa monitoring may be superior to measurement of aPTT. LMWHs lack the 
      nonspecific binding affinities of UFH, and, as a result, LMWH preparations have 
      more predictable pharmacokinetic and pharmacodynamic properties. LMWHs have 
      replaced UFH for most clinical indications for the following reasons: (1) these 
      properties allow LMWHs to be administered subcutaneously, once daily without 
      laboratory monitoring; and (2) the evidence from clinical trials that LMWH is as 
      least as effective as and is safer than UFH. Several clinical issues regarding 
      the use of LMWHs remain unanswered. These relate to the need for monitoring with 
      an anti-factor Xa assay in patients with severe obesity or renal insufficiency. 
      The therapeutic range for anti-factor Xa activity depends on the dosing interval. 
      Anti-factor Xa monitoring is prudent when administering weight-based doses of 
      LMWH to patients who weigh > 150 kg. It has been determined that UFH infusion is 
      preferable to LMWH injection in patients with creatinine clearance of < 25 
      mL/min, until further data on therapeutic dosing of LMWHs in renal failure have 
      been published. However, when administered in low doses prophylactically, LMWH is 
      safe for therapy in patients with renal failure. Protamine may help to reverse 
      bleeding related to LWMH, although anti-factor Xa activity is not fully 
      normalized by protamine. The synthetic pentasaccharide fondaparinux is a 
      promising new antithrombotic agent for the prevention and treatment of venous 
      thromboembolism.
FAU - Hirsh, Jack
AU  - Hirsh J
AD  - Henderson Research Centre, 711 Concession St, Hamilton, ON L8V 1C3, Canada. 
      jhirsh@thrombosis.hhscr.org
FAU - Raschke, Robert
AU  - Raschke R
LA  - eng
PT  - Guideline
PT  - Journal Article
PT  - Practice Guideline
PL  - United States
TA  - Chest
JT  - Chest
JID - 0231335
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Protamines)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Antithrombin III/metabolism
MH  - Biological Availability
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Evidence-Based Medicine
MH  - Fibrinolytic Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Hemorrhage/blood/chemically induced/drug therapy
MH  - Heparin/adverse effects/pharmacokinetics/*therapeutic use
MH  - Heparin Antagonists/therapeutic use
MH  - Heparin, Low-Molecular-Weight/adverse effects/*therapeutic use
MH  - Humans
MH  - Kidney Failure, Chronic/blood
MH  - Metabolic Clearance Rate/physiology
MH  - Partial Thromboplastin Time
MH  - Protamines/therapeutic use
EDAT- 2004/09/24 05:00
MHDA- 2004/10/27 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - S0012-3692(15)31491-4 [pii]
AID - 10.1378/chest.126.3_suppl.188S [doi]
PST - ppublish
SO  - Chest. 2004 Sep;126(3 Suppl):188S-203S. doi: 10.1378/chest.126.3_suppl.188S.