Monitoring direct thrombin inhibitors with a plasma diluted thrombin time

Abstract

Activated partial thromboplastin time (aPTT) monitoring of direct thrombin inhibitors (DTIs) is vulnerable to interference from many sources. If the baseline aPTT is prolonged, as occurs with lupus inhibitors, alternative methods are required to monitor DTI levels. We compared the plasma diluted thrombin time (1:4 dilution of patient plasma with normal plasma) and the aPTT in patient samples spiked with argatroban, bivalirudin, or lepirudin at three concentration levels. Each drug was spiked into five samples with lupus inhibitors, five samples with deficient vitamin K-dependent factors, three samples with elevated D-dimers, and eight samples with normal baseline aPTT values. The aPTT overestimated the spiked DTI concentration in all samples with lupus inhibitors, low levels of vitamin K-dependent factors, and elevated D-dimers. In samples with normal baseline aPTTs, the aPTT failed to correctly estimate the spiked drug concentration in four of 24 samples spiked with argatroban, seven of 24 spiked with lepirudin, and three of 24 spiked with bivalirudin. The plasma diluted thrombin time was not affected by lupus inhibitors, low vitamin K-dependent factor levels or elevated D-dimer levels and correctly estimated the spiked drug level in 63 of 63 samples spiked with argatroban, 63 of 63 samples spiked with bivalirudin, and 62 of 63 samples spiked with lepirudin. In conclusion, the plasma diluted thrombin time appears to be a viable alternative to the aPTT for monitoring DTI levels, especially in patients with lupus inhibitors or low levels of vitamin K-dependent factors.

The Effects of Direct Thrombin Inhibition with Dabigatran on Plaque Formation and Endothelial Function in Apolipoprotein E-Deficient Mice

“…Under these concentrations a relevant increase in dTT could be observed ( Fig. 1) (Love et al, 2007) by using HEMOCLOT (Hyphen BioMed, Neuville-sur-Oise, France) as described previously (Stangier and Feuring, 2012). Atherosclerotic Plaque Formation.…”

Current knowledge on assessing the effects of and managing bleeding and urgent procedures with direct oral anticoagulants

“…Where available, hemodialysis has been used as a strategy to accelerate plasma clearance of dabigatran because of its relatively low (35%) protein binding. 27,[70][71][72][73][74][75][76][77] Initial pharmacokinetic assessments of the removal of single doses of dabigatran using dialysis in patients with stable chronic kidney disease have suggested that approximately two thirds of the drug could be removed in two hours. 78 However, this single-dose model, in which dialysis is performed shortly after the drug is administered, overestimates the extent of dialysis removal, as equilibrium and tissue uptake has not occurred.…”

Monitoring target-specific oral anticoagulants

“…In patients with therapeutic and higher range plasma concentrations, the TCT will often be prolonged above the upper limit of the laboratory's testing range. A modification of the TCT, the dilute thrombin time, can be used to assess the anticoagulant effect of direct thrombin inhibitors, 19 and a commercial assay, the HEMOCLOT (Hyphen BioMed), is approved for use in Europe and Canada and can be used for measurement of dabigatran levels. 20 In addition, an ecarin chromogenic assay or ecarin clotting time assay can be used for this purpose, although they are not widely available.…”