Summary
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.
Keywords
Directthrombin inhibitors - therapeutic drug monitoring - lupus inhibitors
