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.