Pharmacology of r-hirudin in renal impairment

Nowak, G; Bucha, Elke; Gööck, Th.; Thieler, H; Markwardt, Fritz

doi:10.1016/0049-3848(92)90046-d

Cited by 88 publications

(61 citation statements)

References 6 publications

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“…This also became obvious in patients suffering from chronic renal malfunction in whom a prolonged elimination phase was found. There was a significant correlation between half-lives of hirudin and creatinine clearance (102).…”

Section: Pharmacokineticsmentioning

confidence: 98%

Hirudin: The Promising Antithrombotic

Markwardt

1992

Cardiovascular Drug Reviews

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It has long been known that medicinal leeches (Hirudo medicinalis) contain a substance with anticoagulant properties. In early studies, aqueous extracts and dry preparations from leeches containing minute amounts of the active substance were used to prevent blood from clotting. Only after the development of protein chemistry and the elucidation of the biochemistry of blood coagulation was the anticoagulant agent, hirudin, isolated and its chemical nature and mode of action clarified.The historical background of hirudin isolation as well as the individual steps of its biochemical and pharmacological characterization have been described in several reviews (36,68,70,72,74,79). BIOCHEMISTRYHirudin is extracted from the homogenized heads of medicinal leeches and enriched by precipitation procedures followed by ion-exchange chromatography and gel filtration (2,65,98,137). Affinity chromatography on matrix-bound thrombin can be used to obtain highly purified hirudin preparations (139,140). The pure anticoagulant agent obtained is a carboxyhydrate-free single chain miniprotein containing 65 amino acids with a molecular weight of about 7 kDa. The amino acid composition is characterized by a remarkably high content of acidic amino acids at the C-terminal, the absence of arginine, methionine, and tryptophan, and the presence of a sulfated tyrosine residue and three intramolecular disulfide bridges (62,65,70).Considerable progress in the isolation, purification, and analysis of hirudin has shown the medicinal leech generates several variants of the miniprotein in trace amounts. The isoinhibitor forms share 85-90% amino acid sequence homology. Their main structural elements, which include N-terminal hydrophobic amino acids, followed by a core region linked by three disulfide bridges and the unique clustering of acidic amino acid residues in the C-terminal portion remain constant (4,17,18,113). The N-terminal amino acids Val-Val can be replaced by Ile-Thr (Fig. 1).

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Section: Pharmacokineticsmentioning

confidence: 98%

Hirudin: The Promising Antithrombotic

Markwardt

1992

Cardiovascular Drug Reviews

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“…Generally, lepirudin is not recommended for patients with renal insufficiency or on hemodialysis, because the half-life of lepirudin reaches up to 316 hours with hemodialysis, 88 and proper monitoring with aPTT is flawed when concentration exceeds 0.5 g/mL. 74 The ecarin clotting time can provide a better guide for lepirudin dosing, but this method is only available in a few centers.…”

Section: Lepirudinmentioning

confidence: 99%

Heparin-Induced Thrombocytopenia in Cardiovascular Patients

Yoon

Jang²

2011

Cardiology in Review

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Heparin-induced thrombocytopenia is a life-threatening immune-mediated platelet activation condition that can cause arterial and venous thromboembolism. The triggering complex, platelet factor 4/heparin antibody, has several unique immunologic characteristics that have not been well elucidated until recently. In patients undergoing cardiovascular procedures such as percutaneous coronary intervention and coronary artery bypass graft surgery, the prevalence of platelet factor 4/heparin antibody is significantly higher than that in the general population. The acuity and graveness of the thromboembolic phenomenon requires early diagnosis and empirical initiation of treatment, even before confirmatory test results are available. Also, although multiple therapeutic modalities exist, the safety and efficacy of each option depends upon the clinical setting. Therefore, this review will focus on the updated pathophysiology of heparin-induced thrombocytopenia, new diagnostic criteria, and the various treatment options for cardiovascular patients with different conditions.

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“…A significant correlation between creatinine clearance and lepirudin clearance has been described in patients with varying degrees of renal failure. [8][9][10] Significant dosage adjustments will be required based not only on residual function at the start of therapy but also to account for recovery of renal function that may ensue. 10 The mode of dialysis (hemodialysis vs. hemofiltration) and the type of dialysis filter (low flux vs. high flux) also needs to be considered.…”

Section: Discussionmentioning

confidence: 99%

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

Abraham

Uber

Lazarchick

et al. 2002

Congestive Heart Failure

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Heparin‐induced thrombocytopenia with associated thrombosis is a potentially catastrophic complication of heparin therapy. Heart failure patients often require heparin therapy in the setting of multiple comorbidities, particularly renal insufficiency. The authors report a case of heparin‐induced thrombocytopenia with associated thrombosis in a patient with multisystem organ failure and discuss dosing regimens using lepirudin for the treatment of this disorder. The potential risk for excessive anticoagulation is highlighted and a conservative dosing strategy with frequent monitoring of this agent in the presence of renal failure is emphasized.

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Pharmacology of r-hirudin in renal impairment

Cited by 88 publications

References 6 publications

Hirudin: The Promising Antithrombotic

Hirudin: The Promising Antithrombotic

Heparin-Induced Thrombocytopenia in Cardiovascular Patients

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

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