Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing

Robert C. Gosselin, Jeffrey H. King, Kim A. Janatpour, William E. Dager, Edward C. Larkin, John T Owings

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1-1.2 μg/mL) and high (1.5-8.0 μg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 μg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 μg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 μg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.

Original languageEnglish (US)
Pages (from-to)1383-1388
Number of pages6
JournalAnnals of Pharmacotherapy
Volume38
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

Thrombin Time
Antithrombins
Partial Thromboplastin Time
Pharmaceutical Preparations
ecarin
Thrombin
Thrombocytopenia
Heparin
Actins

Keywords

  • Activated partial thromboplastin time
  • Anticoagulation
  • Direct thrombin inhibitors

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing. / Gosselin, Robert C.; King, Jeffrey H.; Janatpour, Kim A.; Dager, William E.; Larkin, Edward C.; Owings, John T.

In: Annals of Pharmacotherapy, Vol. 38, No. 9, 09.2004, p. 1383-1388.

Research output: Contribution to journalArticle

Gosselin, Robert C. ; King, Jeffrey H. ; Janatpour, Kim A. ; Dager, William E. ; Larkin, Edward C. ; Owings, John T. / Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing. In: Annals of Pharmacotherapy. 2004 ; Vol. 38, No. 9. pp. 1383-1388.
@article{1fdd442351c44c89aac47132a6aa4b0e,
title = "Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing",
abstract = "BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1-1.2 μg/mL) and high (1.5-8.0 μg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 μg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 μg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 μg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.",
keywords = "Activated partial thromboplastin time, Anticoagulation, Direct thrombin inhibitors",
author = "Gosselin, {Robert C.} and King, {Jeffrey H.} and Janatpour, {Kim A.} and Dager, {William E.} and Larkin, {Edward C.} and Owings, {John T}",
year = "2004",
month = "9",
doi = "10.1345/aph.1D565",
language = "English (US)",
volume = "38",
pages = "1383--1388",
journal = "Annals of Pharmacotherapy",
issn = "1060-0280",
publisher = "Harvey Whitney Books Company",
number = "9",

}

TY - JOUR

T1 - Comparing direct thrombin inhibitors using aPTT, ecarin clotting times, and thrombin inhibitor management testing

AU - Gosselin, Robert C.

AU - King, Jeffrey H.

AU - Janatpour, Kim A.

AU - Dager, William E.

AU - Larkin, Edward C.

AU - Owings, John T

PY - 2004/9

Y1 - 2004/9

N2 - BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1-1.2 μg/mL) and high (1.5-8.0 μg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 μg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 μg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 μg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.

AB - BACKGROUND: Patients with heparin-induced thrombocytopenia and thrombosis may be acutely anticoagulated with direct thrombin inhibitors (DTIs). The anticoagulation is typically monitored using the activated partial thromboplastin time (aPTT) or ecarin clotting time (ECT). OBJECTIVE: To compare 14 methods for measuring aPTT, as well as ECT and thrombin inhibitor management test (TIM), in samples containing DTIs. METHODS: DTIs were added to pooled normal plasma to achieve low (0.1-1.2 μg/mL) and high (1.5-8.0 μg/mL) drug concentrations. Each low-concentration DTI sample was tested using all aPTT reagents, while each low- and high-concentration DTI was tested using the ECT and TIM. RESULTS: All aPTT reagents had a significant dose-dependent correlation with drug concentration. Only Actin FSL and APTT-S demonstrated equivalent aPTT ratios obtained from any DTI. The TAS-aPTT was the most sensitive aPTT reagent to argatroban, with the aPTT ranging from 52.7 to 121.2 seconds corresponding to 0.1 to 1.2 μg/mL of drug concentration. The TAS-aPTT and Pathromtin were the most sensitive aPTT reagents to bivalirudin, with aPTTs of 87.4 seconds and 101.5 seconds, respectively, at 1.2 μg/mL of drug. Pathromtin was the most sensitive aPTT reagent to lepirudin, with a maximum aPTT of 108.9 seconds at 1.2 μg/mL of drug. There was no statistically significant difference between the TIM and ECT clotting times for each DTI. Lepirudin and bivalirudin ECT and TIM clotting times were equivalent. CONCLUSIONS: There are unique differences between reagent manufacturers in the monitoring of DTIs. Acceptable alternatives to aPTT monitoring of DTI anticoagulation include the ECT and TIM.

KW - Activated partial thromboplastin time

KW - Anticoagulation

KW - Direct thrombin inhibitors

UR - http://www.scopus.com/inward/record.url?scp=4143113354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4143113354&partnerID=8YFLogxK

U2 - 10.1345/aph.1D565

DO - 10.1345/aph.1D565

M3 - Article

C2 - 15238620

AN - SCOPUS:4143113354

VL - 38

SP - 1383

EP - 1388

JO - Annals of Pharmacotherapy

JF - Annals of Pharmacotherapy

SN - 1060-0280

IS - 9

ER -