Monitoring of Recombinant Hirudin: Assessment of a Plasma-Based Ecarin Clotting Time Assay

Pötzsch, Bernd; Hund, Simone; Madlener, Katharina; Unkrig, Christoph; Müller‐Berghaus, Gert

doi:10.1016/s0049-3848(97)00082-0

Cited by 115 publications

(69 citation statements)

References 12 publications

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“…Antihirudin antibodies in patients with heparin-induced thrombocy- They put forward the suggestion that it may be time to consider abandoning the bovine route of ISI calibration and rely on the rabbit route of international sensitivity index (ISI) calibration for thromboplastins of bovine origin [1]. In view of the smaller demand and theoretical risk of virus transmission with bovine brain it is not unnatural that the need for the provision of this material should be questioned by Drs van den Besselaar and Tripodi.…”

Section: Mg Kgmentioning

confidence: 99%

Lepirudin: is the approved dosing schedule too high?

Hacquard

Maistre

Lecompte

2005

Journal of Thrombosis and Haemostasis

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Section: Mg Kgmentioning

confidence: 99%

Lepirudin: is the approved dosing schedule too high?

Hacquard

Maistre

Lecompte

2005

Journal of Thrombosis and Haemostasis

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“…Hirudin inhibits meizothrombin. The degree of prolongation of the resulting clotting (44,46). This linear correlation can be found in a wide range of concentrations (0.05 to 5 g/ml), and thus no dilution procedures are necessary for measurement of subtherapeutic, therapeutic, or toxic concentrations.…”

Section: Alternative Anticoagulants In Hit II Therapymentioning

confidence: 88%

“…In a study with healthy volunteers, the aPTT was doubled by 0.4 g of recombinant hirudin (r-hirudin) per ml of plasma, and in a case report on a patient awaiting surgery for aortic valve replacement, a prolonged aPTT of between 60 and 80 s was associated with a plasma r-hirudin concentration of 1 to 1.5 g/ml (8, 48). Potzsch et al found a correlation coefficient of 0.61 between prolongation of the aPTT and the plasma r-hirudin concentration in r-hirudintreated patients (44). An aPTT exceeding 70 s is increasingly insensitive to increasing concentrations of r-hirudin and therefore is not suitable for procedures and clinical settings with the need for high concentrations of hirudin (e.g., cardiopulmonary bypass surgery [CPB]) (18).…”

Section: Alternative Anticoagulants In Hit II Therapymentioning

confidence: 99%

Laboratory Diagnosis of Heparin-Induced Thrombocytopenia and Monitoring of Alternative Anticoagulants

Leo

Winteroll

2003

Clin Vaccine Immunol

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The major complication in the therapeutic or prophylactic use of heparin in medical treatment is type II heparin-induced thrombocytopenia (HIT II), a unique form of drug-induced immune-mediated thrombocytopenia. Due to the extensive use of heparin, this side effect is widespread; up to 3% of patients treated with unfractionated heparin (UFH) develop HIT II (69). Clinically, HIT II is characterized by thrombocytopenia which paradoxically is associated with thrombosis (HIT IIinduced thrombosis [HITTS]) (i.e., deep vein thrombosis, pulmonary embolism, and venous gangrene) in about 50% of the cases.In the pathogenesis of HIT II, the formation of platelet factor 4 (PF4)/heparin complexes seems to be the major determinant (2, 3, 20). The binding of PF4 to heparin induces antibody production directed against a neoepitope created by the three-dimensional assembly of PF4 and heparin. Subsequently, PF4/heparin-antibody complexes induce platelet activation, followed by the shedding of platelet microparticles, thrombin generation, and the involvement of endothelial cells (Fig. 1).Remarkably, the incidence of HIT II, HIT II-associated thrombotic complications, and PF4/heparin-antibodies (HIT II antibodies) in patients receiving therapy with UFH is clearly dependent on the clinical setting of the patient. Cardiosurgical patients are at a high risk to develop HIT II antibodies, while orthopedic patients undergoing hip replacement have a high risk for developing thromboembolic complications (Iceberg model [66]). In medical patients the risk for developing HIT II is substantially lower. Comparing low-molecular-weight heparins (LMWH) with UFH, the use of LMWH coincides with a substantially lower risk of HIT II, but this effect holds true only within the same group of patients (77,78).It is generally accepted that the clinical diagnosis of HIT II should be followed by immediate cessation of heparin therapy and initiation of therapy with alternative anticoagulants. Negative results in the concomitant laboratory testing should not serve as the sole criterion for restarting heparin therapy.In almost every case of HIT II, administration of alternative anticoagulants is essential either to continue prophylactic anticoagulation or to treat and prevent thrombotic complications due to HIT II. Three substances (danaparoid, hirudin, and argatroban) are available. Since these substances have not been compared directly with each other in the treatment of HIT II, criteria such as half-life and/or route of excretion should be considered for selection. This review focuses on (i) the present laboratory methods for diagnosing HIT II, including their principles, time consumption, and significance, and (ii) the alternative anticoagulants, including their characteristics and indications in certain clinical settings. LABORATORY ASSAYS FOR HIT II DIAGNOSISLaboratory testing in the diagnosis of HIT II is based on either the immunological detection of antibodies directed against the PF4/heparin complex or the functional plateletactivating potential of t...

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“…18 Clinical use of the ECT has been reported. One study 19 examined the precision of the ECT method compared with the aPTT method of monitoring lepirudin in 10 patients undergoing open heart surgery who had a current or past history of heparin-induced thrombocytopenia (HIT). An ECT reference range of 35.3-39.9 seconds was determined from plasma samples drawn from 50 healthy individuals.…”

mentioning

confidence: 99%

“…29 One limitation of the ECT (as well as the aPTT) is reduced accuracy in plasma that is depleted of prothrombin or fibrinogen. 19,21 The clinical impact of varying concentrations of prothrombin and fibrinogen on ECT remains to be established. This may be relevant in patients with liver disease who have low levels of prothrombin or in patients receiving the non-fibrin-specific thrombolytic streptokinase in DIRECT THROMBIN INHIBITORS AND ECARIN CLOTTING TIME de Denus and Spinler whom fibrinogen depletion may occur, as found in the recently published Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial.…”

mentioning

confidence: 99%

Clinical Monitoring of Direct Thrombin Inhibitors Using the Ecarin Clotting Time

Denus¹,

Spinler²

2002

Pharmacotherapy

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(Pharmacotherapy 2002;22(4):433-435)Direct thrombin inhibitors such as lepirudin, bivalirudin, and argatroban constitute a novel class of anticoagulants. The mechanism of action of these agents differs from heparin in that they directly inhibit the active site of thrombin, and they do not require an interaction with antithrombin III to produce their anticoagulant effect.1 Furthermore, contrary to heparin, these agents inhibit only the activity of thrombin whereas heparin, through its activation of antithrombin III, indirectly inhibits factors IIa (thrombin), Xa, IXa, XIa and XIIa.

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Monitoring of Recombinant Hirudin: Assessment of a Plasma-Based Ecarin Clotting Time Assay

Cited by 115 publications

References 12 publications

Lepirudin: is the approved dosing schedule too high?

Lepirudin: is the approved dosing schedule too high?

Laboratory Diagnosis of Heparin-Induced Thrombocytopenia and Monitoring of Alternative Anticoagulants

Clinical Monitoring of Direct Thrombin Inhibitors Using the Ecarin Clotting Time

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