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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.