Laboratory Assessment of Antithrombotic Therapy: What Tests and If So Why?

Abstract

A critical review is given of the tests available for the assessment of the action of anticoagulants, such as heparins, oral anticoagulants and direct thrombin inhibitors, in patients under antithrombotic therapy. The principle of action and the performance of the thromboplastm time (PT), the activated partial thromboplastin time (aPTT), the whole blood clotting time, the thrombin time, the ecarin clotting time and the endogenous thrombin potential (ETP) is discussed, as well as the evidence behind the accepted therapeutic ranges. The two most common tests, PT and aPTT, respond in an essentially different way to clinically effective anticoagulation with hepa-rin and with oral anticoagulants. This means that they covar-iate with, but do not themselves represent the essential parameter influenced by anticoagulation. The experimental basis for the widely accepted two times prolongation of the aPTT as an indicator for adequate anticoagulation is shown to be meagre in the case of unfractionated heparin and lacking for the other anticoagulants. Common sources for error in the interpretation of anti-factor Xa- and anti-thrombin activity of heparins are indicated. Extensive experience with new tests like the ecarin clotting time and the ETP is still lacking. On the basis of preliminary data and in view of the importance of the enzymatic action of thrombin in the pathogenesis of thrombosis, the ETP is considered a possible candidate for a common parameter to assess different types of anticoagulants.

Pilot dose‐finding and safety study of bivalirudin in infants <6 months of age with thrombosis

“…It should be noted that the APTT has significant limitations when it comes to assessing the degree of anticoagulation for all anticoagulants including bivalirudin [ref]. While the ecarin clotting time (ECT) has been shown to correlate more linearly with plasma bivalirudin levels [16], this assay is commercially unavailable and was not made available to us for use in this clinical trial. Thus, until better assays are developed, the APTT is the best available assay to determine the degree of anticoagulation with bivalirudin.…”

Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time

“…There is bad correlation between the prolongation of the APTT and the heparin level or clinical course under heparin treatment [23]. The rationale behind the traditional therapeutic aim of a prolongation of the APTT to 1.5–2.5 times the normal value is questionable (see Kher [24] and references therein). One cannot but conclude that the APTT appears a poor means to assess heparin pharmacodynamics.…”

Population modelling of the effect of inogatran, at thrombin inhibitor, on ex vivo coagulation time (APTT) in healthy subjects and patients with coronary artery disease

“…For this class of drugs it is important that an optimal degree of anticoagulation is attained that gives the desired antithrombotic effect without increasing the risk for adverse effects, such as bleeding complications, to an unacceptable level. One common surrogate marker for the degree of anticoagulation is the activated partial thromboplastin time (APTT), which has long been used to monitor treatment with heparin [3] and more recently in the clinical evaluation of direct thrombin inhibitors, e.g. hirudin, hirulog and argatroban [4–10].…”