Low molecular weight heparin half life is prolonged in haemodialysed patients

Goudable, C.; That, H. Ton; Damani, A.; Durand, Dominique; Caranobe, C; Sié, P.; Boneu, B

doi:10.1016/0049-3848(86)90039-3

Cited by 42 publications

(13 citation statements)

References 6 publications

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“…Hirudin and its recombinant analogs produce their effect through the direct inhibition of thrombin (76,78). This effect appears to be specific, with little or no effect on other clotting factors including factor Xa.…”

Section: Pharmacologymentioning

confidence: 91%

See 1 more Smart Citation

State-of-the-Art Review: Pharmacology and Pharmacokinetics of Antithrombotic Agents

Kandrotas

1997

Clin Appl Thromb Hemost

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To prevent blood loss, a complex and dynamic system has evolved in humans that is activated when blood vessels are damaged. The lumen of each blood vessel is lined with a layer of endothelial cells. Directly below the endothelial layer is the basement membrane. The subendothelial layer is composed of collagen, connective tissue, fibronectin and smooth muscle. Upon injury to the endothelial lining, platelets and clotting factors are activated, resulting in stimulation of the clotting cascade and platelet aggregation at the site of injury. ' Under normal conditions, platelets do not adhere to the vessel wall but when they come in contact with the subendothelial cell components they become activated and adhere to the wall (1,2). Once the platelets adhere to the vessel wall they change shape, which facilitates aggregation and formation of a platelet plug. Platelets also provide receptor sites for binding of activated clotting factors (3).Once the platelet plug is formed, hemostasis stabilizes it into an organized clot. This coagulation process is illustrated by the traditional coagulation cascade (Fig. 1).The cascade can be broken down into three separate parts: the intrinsic, extrinsic and common pathways.The intrinsic is so named because activation of these clotting factors does not require exposure to substances that are not normally found in blood. Factor XII is activated by contact with a charged surface such as collagen. Then, in the presence of prekallikrein (PK), highmolecular weight kininogen (HMWK), factor XIIa stimulates the conversion of XI to XIa. Activated factor XI then stimulates the activation of factor IX that, in the off factor VRI, platelet factor 3 (PF3), and cdcium, facilitates the conversion of factor X to Xa.The second arm of the coagulation cascade is the expathway. It its because tissue thromboplastin (a substance not normally found in blood) is required for activation. When factor VII comes in contact with thromboplastin in the presence of calcium it is activated. Activated factor VII then stimulates the conversion of factor X to Xa.The point at which the intrinsic and extrinsic pathways produce the same result (i.e., the activation of factor X) is the common pathway. Activated factor X combines with PF3, factor V and calcium to form a complex called prothrombinase. Prothrombinase stimulates the conversion of prothrombin to thrombin. Thrombin causes the conversion of fibrinogen to fibrin and the activation of factor XIII. Factor XIIIa stabilizes the fibrin into an organized clot.Eventually, as the damage to the vessel is repaired, the clot is lysed and broken down by the fibrinolytic system. This occurs through the release of tissue plasminogen activator (t-PA) from the vessel wall. The t-PA causes the conversion of plasminogen to plasmin, which breaks down fibrin, fibrinogen, and factors V and VIII (Fig. 2). WARFARINIn 1922 a report appeared in the literature of a hemorrhagic &dquo;disease&dquo; in cattle that had ingested hay laced with sweet clover (4). Bis-hydroxy coumarin was found t...

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Section: Pharmacologymentioning

confidence: 91%

“…The half-life of LMWHs in patients with chronic endstage renal disease is approximately double the half-life in patients with normal renal function (75,76). This would suggest that the dose and/or dosing interval may require adjustment in these patients.…”

Section: Clinical Considerationsmentioning

confidence: 97%

State-of-the-Art Review: Pharmacology and Pharmacokinetics of Antithrombotic Agents

Kandrotas

1997

Clin Appl Thromb Hemost

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“…In another study, the anticoagulant effect of the LMWH CY222 after intravenous injection in five hemodialysis patients was nearly double that of six healthy controls (13) (CY222 is not commercially available). Therefore monitoring antifactor Xa levels (target level is 0.5–1.0 IU/ml for systemic therapeutic anticoagulation) in patients with CKD receiving LMWH has been recommended by some authors (14).…”

Section: Pharmacokinetic Studies Of Lmwh In Patients With Impaired Gfrmentioning

confidence: 96%

Use of Low Molecular Weight Heparins and Glycoprotein IIb/IIIa Inhibitors in Patients with Chronic Kidney Disease

Perazella¹,

Mosenkis

Berns

2004

Seminars in Dialysis

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Despite aggressive intervention, cardiac causes of death, including acute coronary syndrome (ACS), continue to be a major source of mortality in patients with chronic kidney disease (CKD), including end-stage renal disease (ESRD). Multiple large prospective trials have demonstrated the clinical benefits of both low molecular weight heparin (LMWH) and glycoprotein (Gp) IIb/IIIa inhibitors in treating patients with ACS. Unfortunately patients with significant impairment of kidney function have generally been excluded from these major clinical trials. Consequently relatively little is known about the pharmacokinetics, appropriate dosing, efficacy, and safety of these medications in patients with CKD of various stages. This article examines the available literature regarding the pharmacokinetics, dosing, efficacy, and safety of LMWH and Gp IIb/IIIa inhibitors in patients with CKD.

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“…The prolonged half-life of LMWH suggested a theoretical advantage of a more stable anticoagulant treatment as compared to heparin [ 161. Furthermore, in view of the considerably reduced elimination of LMWH in patients with renal insufficiency [21], accumulation of anti-Xa activity may occur, resulting in increased plasma anti-Xa levels between dialyses. Therefore, LMWH, with a relatively long elimination half-life, are unlikely candidates for replacement of heparin in patients with stable chronic renal failure.…”

Section: Hemodialysismentioning

confidence: 99%

Clinical studies with low‐molecular‐weight heparin(oid)s: An interim analysis

et al. 1988

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In this review an interim analysis was made of all clinical studies performed with low-molecular-weight heparin(oid)s (LMWH) up to January 1987. Thus far, many experimental studies on LMWH show these substances to have an increased benefit/risk ratio concerning efficacy and bleeding as compared to standard heparin. In man, this increased ratio was verified in some small open studies. However, until the present day, controversy still exists. Some of the difficulties in assessing the results of different investigations include the existence of various kinds of LMWH and the lack of a consensus as to the unitage in which they are expressed. Furthermore, no international agreement exists as to the test measuring dosage/effect and its standard. In the following review all published clinical studies were analyzed for patient groups. Important issues concerning controversy with regard to efficacy, bleeding risk, diagnosis, and testing are discussed. In general, it may be concluded that LMWH have an antithrombotic potential comparable to that of heparin, and that the benefit/risk ratio i.e., decreased bleeding potential when compared to standard heparin, as found in animal experiments, has not been clearly demonstrated in man.

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Low molecular weight heparin half life is prolonged in haemodialysed patients

Cited by 42 publications

References 6 publications

State-of-the-Art Review: Pharmacology and Pharmacokinetics of Antithrombotic Agents

State-of-the-Art Review: Pharmacology and Pharmacokinetics of Antithrombotic Agents

Use of Low Molecular Weight Heparins and Glycoprotein IIb/IIIa Inhibitors in Patients with Chronic Kidney Disease

Clinical studies with low‐molecular‐weight heparin(oid)s: An interim analysis

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