Die Plasma-Sensibilität auf Heparin und Enoxaparin

Unfraktioniertes Heparin (UFH) und niedermolekulares Heparin (NMH) sind die am häufigsten verwendeten klinischen Antikoagulantien zur Therapie von Patienten mit venösen Thromboembolien (VTE), akutem Koronarsyndrom (ACS) und für Thromboseprophylaxe in Krankenhäusern. Die klinische Tendenz favorisi...

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Bibliographic Details
Main Author: Ajib, Salem Abdulfatah
Contributors: Stief, T. (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2013
Online Access:PDF Full Text
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Unfractionated heparin (UFH) and low-molecular-weight-heparin (LMWH) are the most common used clinical anticoagulants for treatment of patients with venous thromboembolism (VTE) or acute coronary syndrome (ACS) and for antithrombotic prophylaxis within hospitals. The clinical tendency increasingly favours LMWH, even intravenously, e.g. in ST elevation myocardial infarction (STEMI). To test the anticoagulant action of the heparins in the major part of the work, the extrinsic coagulation activity assay (EXCA) was performed with 51 normal citrated plasmas or 213 patient plasmas (with normal PT and APTT in absence of LMWH) after 50 μl sample supplementation with 0-1 IU/ml UFH or LMWH. To test the procoagulant action of the heparins in the minor part of the work, the recalcified coagulation activity assay (RECA) was performed with 10 normal citrated plasmas or 32 patient plasmas, after 50 μl sample supplementation with 0-10 mIU/ml UFH or LMWH. 1 IU/ml enoxaparin reduced the normal thrombin generation in EXCA to about 13 % of normal, whereas at 1 IU/ml heparin the normal thrombin generation was completely suppressed. This means that 1 IU/ml enoxaparin is a strongly therapeutic anticoagulant, whereas 1 IU/ml UFH is in the toxic range. 0.01 IU/ml heparin or enoxaparin reduced the normal thrombin generation in EXCA only by about 10 % or 20 %, respectively. Heparin at 0.1 mIU/ml does not reduce thrombin generation in RECA; instead it even increased the thrombin generation in RECA by about 20 %, whereas 0.1 mIU/ml enoxaparin significantly decreased the thrombin generation by about 30%-60%. This means that in ultra-low concentrations, as e.g. occurring in the end of heparin infusion, heparin might be dangerous especially for patients with susceptible intrinsic hemostasis. It is suggested to add enoxaparin at the end of heparin infusion or to replace heparin by enoxaparin. These results support the concept that the LMWH dosage of each individual patient should be adjusted with an ultra-specific thrombin generation assay as EXCA or INCA (intrinsic coagulation activity assay). The dosing of LMWH-enoxaparin must be individualized according to the patient´s need (prophylactic or therapeutic) and anticoagulant response as reflected by trigger-induced thrombin generation. Target for therapeutic or prophylactic anticoagulation is 10-20 % or 20-40 % of normal triggerinduced thrombin generation, respectively. The adequate dosage of enoxaparin in the individual patient should be monitored by a specific thrombin generation assay.