Recombinant hirudin is a heparin alternative in cardiac surgery

Rieß, Friedrich-Christian; Bleese, Niels; Kormann, Joachim; Pötzsch, Bernd; Madlener, Katharina; Müller‐Berghaus, Gert; Greinacher, Andreas

doi:10.1016/s1053-0770(97)90088-4

Cited by 10 publications

(4 citation statements)

References 4 publications

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“…Recombinant hirudin is a suitable alternative for anticoagulation of CPB patients with HIT. The drug effect is easy to monitor (ecarin clotting time) and has a relatively short half‐life, which makes the control of the side‐effects much easier (59,60). There are ongoing studies using bivalirudin in this setting including the CHOOSE and EVOLUTION study.…”

Section: Treatmentmentioning

confidence: 99%

Heparin-induced thrombocytopenia (an overview)

Daneschvar

Daw

2006

International Journal of Clinical Practice

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Heparin induced thrombocytopenia is a serious side effect of a drug that is widely used in clinical practice. All patients exposed to heparin, administered by any route or at any dose, are at varying risk of developing HIT and its potentially devastating thrombotic complications. There are two clinical forms of HIT, type I and type II. Type I HIT, is a non-immunologic response, while type II HIT is an immunologic response to heparin therapy. Type I HIT is not associated with an increased risk of thrombosis and is characterized by reversible thrombocytopenia. Type II HIT occurs in approximately 1 to 3% of patients receiving unfractionated heparin. Type II HIT is more severe because of the increased risk of thrombotic events. Venous and arterial thromboembolic complications may lead to amputation, stroke, myocardial infarction, and death.

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Section: Treatmentmentioning

confidence: 99%

Heparin-induced thrombocytopenia (an overview)

Daneschvar

Daw

2006

International Journal of Clinical Practice

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“…In patients undergoing cardiac surgery with lepirudin (165, 199–201), close bedside monitoring using the ecarin clotting time (ECT) is essential (159, 160, 165, 201–204). A pre‐CPB lepirudin bolus of 0.25 mg/kg should be given and 0.2 mg/kg added to the priming solution.…”

Section: Heparin‐induced Thrombocytopeniamentioning

confidence: 99%

DRUG‐INDUCEDAND DRUG‐DEPENDENT IMMUNE THROMBOCYTOPENIAS

Greinacher¹,

Eichler²,

Lübenow³

et al. 2001

Rev Clin Exp Hematol

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Thrombocytopenia is a frequent comorbid condition in many in hospital patients. In some patients, drugs are the cause of low platelet counts. While cytotoxic effects of anti-tumor therapy are the most frequent cause, immune mechanisms should also be considered. This review addresses thrombocytopenias in four groups. Heparin-dependent thrombocytopenia (HIT), by far the most frequent drug-induced immune-mediated type of thrombocytopenia, has a unique pathogenesis and clinical consequences. HIT is a clinicopathological syndrome in which antibodies mostly directed against a multimolecular complex of platelet factor 4 and heparin cause paradoxical thromboembolic complications. The mechanisms through which heparin can enhance thrombin generation are discussed and treatment alternatives for affected patients are presented in detail. It is of primary importance to recognize these patients as early as possible and to substitute heparin with a compatible anticoagulatory drug, such as hirudin, danaparoid or argatroban. Patients seem to benefit from therapeutic doses of alternative treatment rather than from low-dose prophylactic doses. With the increasing use of glycoprotein (GP) IIb/IIIa inhibitors in patients with acute coronary syndromes, thrombocytopenias are increasingly recognized as an adverse effect of these drugs. Up to 4% of treated patients are affected. Most important, pseudothrombocytopenia, a laboratory artefact, is as frequent as real drug-induced thrombocytopenia and must be excluded before changes in treatment are considered. The pathogenesis of these thrombocytopenias is still debated; an immune mechanism involving preformed antibodies is likely. However, since these antibodies are also detectable in a high percentage of normal controls and of patients not developing thrombocytopenia, their impact is still unclear. Patients with real thrombocytopenia are at an increased risk of bleeding; treatment consists of cessation of the GP IIb/IIIa inhibitor and platelet transfusions in cases of severe hemorrhage. Classic immune thrombocytopenia can be induced by some drugs, e.g. gold, which trigger anti-platelet antibodies indistinguishable from platelet autoantibodies found in autoimmune thrombocytopenia. Drug-induced and drug-dependent immune thrombocytopenia is induced by antibodies recognizing an epitope on platelet GP formed after binding of a drug to a platelet glycoprotein. Still unresolved is whether antibody binding is the consequence of a conformational change of the antigen, the antibody, or both. These antibodies typically react with monomorphic epitopes on platelet GP, but only in the presence of the drug or a metabolite. Although several platelet GP have been identified as antibody target (GPIb/IX, GPV, GP IIb/IIIa), antibodies in an individual patient are highly specific for a single GP. Clinically, these patients present with very low platelet counts and acute, sometimes severe, hemorrhage. Treatment is restricted to withdrawal of the drug and symptomatic treatment of bleeding.

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“…[48] Close bedside monitoring using the ECT is essential [48,[128][129][130][131][132][133][134] when lepirudin is used in humans undergoing cardiac surgery. [125][126][127][128] Pötzsch and Madlener [48] developed an algorithm suggesting a pre-CPB lepirudin bolus of 0.25 mg/kg with 0.2 mg/kg added to the priming solution. Plasma lepirudin concentrations at the start of CPB should be >2.5 %g/ml (if lower, an additional 10mg bolus should be given).…”

Section: Extracorporeal Circulationmentioning

confidence: 99%

Drugs for the Prevention and Treatment of Thrombosis in Patients with Heparin-Induced Thrombocytopenia

Lübenow

Greinacher

2001

American Journal of Cardiovascular Drugs

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Most patients with heparin-induced thrombocytopenia (HIT), a serious adverse effect of heparin mediated by platelet-activating heparin-dependent antibodies, require alternative anticoagulation. This is because HIT is highly prothrombotic and is characterized by markedly increased thrombin generation. Unfractionated heparins seem to induce HIT more often than low molecular weight heparins. There are three anticoagulants for which there is an emerging consensus for their efficacy in management of HIT, and which are currently approved for treatment of HIT in several countries: the recombinant hirudin, lepirudin, a direct thrombin inhibitor; the synthetic direct thrombin inhibitor, argatroban; and the heparinoid, danaparoid sodium, mainly exhibiting antifactor-Xa activity. Recommendations for optimal use of these drugs in HIT are given in this review stressing the need for immediate treatment of patients with HIT without awaiting laboratory diagnosis. Hirudin, the drug for which most data from prospective trials exists, can be safely and effectively used in patients with HIT, its dramatically increased elimination half-life in patients with renal failure being the most important drawback. Argatroban, which is mainly eliminated by the liver, could be used preferentially in such patients with renal impairment. Interference with the international normalized ratio makes oral anticoagulation, which is necessary in many patients with HIT, problematic. Activated partial thromboplastin time is sufficient to monitor lepirudin and argatroban treatment in most cases. Danaparoid sodium, with an antifactor-X activity half-life of about 24 hours seems to be best suited for thrombosis prophylaxis in patients with HIT. In some patients monitoring by determining antifactor-Xa activity is necessary. No antidote is available for any of the drugs discussed, and bleeding complications are the most important adverse effects. In situations such as hemodialysis or cardiopulmonary bypass, not only the characteristics of the drug in use itself, but also availability of monitoring methods play an important role. Adjunctive treatments have not been systematically evaluated and should be used cautiously. Recent data suggest that re-exposure of patients with a history of HIT with heparin, for example during cardiopulmonary bypass, can be well tolerated provided no circulating HIT antibodies are detectable at the time of re-exposure, and heparin is strictly avoided pre- and postoperatively.

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Recombinant hirudin is a heparin alternative in cardiac surgery

Cited by 10 publications

References 4 publications

Heparin-induced thrombocytopenia (an overview)

Heparin-induced thrombocytopenia (an overview)

DRUG‐INDUCEDAND DRUG‐DEPENDENT IMMUNE THROMBOCYTOPENIAS

Drugs for the Prevention and Treatment of Thrombosis in Patients with Heparin-Induced Thrombocytopenia

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