PB1016 - Argatroban Monitoring in Critically Ill Patients and correlation with Thrombin Generation

Background: Argatroban is a parenteral direct thrombin inhibitor used for anticoagulation in patients suffering from heparin induced thrombocytopenia (HIT). There is increasing evidence suggesting that inter-individual differences are poorly reflected by argatroban plasma concentration in critically ill patients.

Aims: The aim of the study was to investigate the correlation of argatroban plasma concentration with blood coagulation activity when using standardized thrombin generation assay (TGA) measurement in individual patients.

Methods: Four patients who developed a HIT and were treated with argatroban at individual doses, samples were taken on five consecutive days. The argatroban concentration was determined with Technoclot DTI assay (Technoclone). Fully automated thrombin generation was determined with Ceveron RC High kit. All measurements were made on a Ceveron s100 analyzer (Technoclone). Calibration curves were made at the beginning of the study using the standard analyzer settings for the argatroban assay, and for the TGA.

Results: Patients 1, 2 and 3 were diagnosed with thrombosis on day 1. Patient 1 was treated with a constant dose of argatroban, his initially high TGA Peak of 461 nM thrombin normalized over time. Patients 2 and 3 had increasing doses of argatroban, but the peak thrombin level of patient 2 continued to show hypercoagulability, whereas the peak thrombin level of patient 3 was normalized. Patient 4 with an initially borderline peak thrombin value and increasing argatroban dose, showed increasing peak thrombin values and developed a thrombosis on day 4. The results are shown in Figure 1.

Conclusion(s): These data show that patient care may be individualized when coagulation activity, as determined by thrombin generation, is used as additional parameter in adjusting argatroban dose for prevention of a thrombosis. Thrombin generation measurement complements estimation of argatroban concentration, a static marker, because it additionally reflects the fluctuating hemostatic landscape in critically ill patients.