OPG and RANKL Plasma Level After Administration of Unfractionated Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in Hemodialysis
A randomised, prospective, cross over study will be done to determine whether the anticoagulation therapy with UFH or LMWH used for hemodialysis sessions modifies osteoprotegerin and RANKL plasma levels.
It's well known that treatment with heparin can lead to a reduction in bone density and the development of osteoporosis [ 1 ]. Until now, it's not clear the mechanism by which heparin produces this side effect, but several studies in animals [ 2,3] and in humans [ 4 ] have shown that LMWH may induce less osteoporosis than UFH.
Recently it was observed that heparin interferes with RANK/RANKL/POG system [5,6]. RANK, RANKL and OPG are members of TNF alfa receptor superfamily. The pathways involving them in conjunction with various cytokines and calciotrophic hormones play a pivotal role in bone remodelling. In addiction experimental and clinical studies established a consistent relationship between the RANK/RANKL/OPG pathway and both skeletal lesion related to disorders of mineral metabolism [7,8,9] and vascular calcification [7,10]. OPG exists either as active soluble form or is expressed by osteoblast, stromal and cardiovascular cells, acting as decoy receptor that competes with RANKL for RANK.
This interaction inhibits osteoclastic proliferation and differentiation and consequently prevents bone resorption . OPG is also produced by both endothelial cells (EC) and Vascular Smooth Muscle Cells (VSMCs ). EC-derived OPG seems to act as an important autocrine / paracrine factor able to protect against arterial calcification blocking the effects of RANKL that promotes monocytes differentiation in osteoclast -like cells and an osteogenic differentiation program in VSMC. This process leads to the synthesis of bone proteins and matrix calcification within the arterial vessel. OPG levels increase with aging and are higher in ESRD patient [11,12].
Recently it was demonstrated in cultures of murine bone marrow that the heparin inhibits osteoprotegerin activity binding OPG competitively and in this way inhibiting the interaction between OPG and RANKL .
On the other side heparin seems cause the mobilization of OPG into the circulation. It was reported that OPG is co-localized with vWF in Weibel Palade bodies in endothelial cells  and binds to Glucosaminoglycans (GAGs) at cellular membranes through its highly basic heparin binding domain [14,15]. Heparin treatment causes an immediate mobilization of these protein in to the circulation by displacement from the endothelial surface since they have higher affinity for heparins than GAGs at the endothelial surface[16,17]. UFH cause a more pronounced vascular mobilization of OPG than LMWH, indicating that UFH have an higher affinity for OPG than LMWH .
Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
law molecular weigth heparin, unfractioned heparin
St.Orsola University Hospital
St. Orsola Hospital
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00669721
- Information obtained from ClinicalTrials.gov on July 15, 2010
The purpose of this study is to determine whether low dose continuous infusion of unfractioned heparin (500 units/hour), in addition to the standard treatment, is efficacious as complement...
Recurrent implantation failure is the failure to achieve a pregnancy after multiple attempts with in vitro fertilization treatment. The reason is usually obscure. Many empirical treatments...
Patients at BWH receiving unfractionated heparin or enoxaparin who subsequently develop heparin induced thrombocytopenia will be identified via a computer generated report designed for the...
Conventional hemodialysis requires transient systemic anticoagulation to prevent blot clotting after contact with the extracorporeal circuit. However, low molecular weight heparin (LMWH) o...
Intensive care unit patients have multiple risk factors for venous thromboembolism. Venous thromboembolism leads to significant morbidity and can be fatal. Unfractionated heparin and low...
Both low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have been shown to be equivalent in efficacy and safety profiles for the management of pulmonary embolism (PE).
Heparin is a widely used drug for the control of blood coagulation. The majority of heparin that is produced commercially is derived from animal sources, is poly-disperse in nature and therefore ill-d...
Heparin-induced thrombocytopenia (HIT) is a potentially fatal clinical condition which can develop after exposure to unfractionated or low-molecular-weight heparins. Even small doses of heparin such a...
Thromboprophylaxis are routinely given to prevent venous thromboembolism (VTE) in patients after total hip and knee replacement surgeries. Low molecular weight heparin (LMWH) (fractioned heparin) is e...
Background: Proliferation and migration are the two main processes of intimal hyperplasia: the primary cause of intermediate and late vascular graft failure. Low-molecular-weight heparins (LMWHs) inhi...
Medical and Biotech [MESH] Definitions
Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism.
A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. (From Merck Index, 11th ed)
A heparin fraction with a mean molecular weight of 4500 daltons. It is isolated from porcine mucosal heparin and used as an antithrombotic agent. (From Merck Index, 11th ed)
Low-molecular-weight fragment of heparin, having a 4-enopyranosuronate sodium structure at the non-reducing end of the chain. It is prepared by depolymerization of the benzylic ester of porcine mucosal heparin. Therapeutically, it is used as an antithrombotic agent. (From Merck Index, 11th ed)
Coagulant substances inhibiting the anticoagulant action of heparin.