Thrombin generation and international normalized ratio in inherited thrombophilia patients receiving thromboprophylactic therapy.

Abstract

BACKGROUND:

Thrombin generation assay (TGA) is useful as a global functional test for assessing bleeding or thrombotic risk and its modification with therapy. We investigated TGA to assess anticoagulation status compared with the international normalized ratio (INR) system in patients with primary thrombophilia receiving and not undergoing thromboprophylaxis.

MATERIALS AND METHODS:

We studied 50 patients with at least one thrombotic event and a confirmed diagnosis of inherited thrombophilia. Thrombin generation was measured in platelet-poor plasma by calibrated automated thrombography (CAT).

RESULTS:

Patients in optimal anticoagulation (INR: 2.0-3.0) showed an endogenous thrombin potential (ETP) of 14-56% of normal and a peak of 18-55% of normal. A significant inverse relationship between INR and thrombin generation parameters (ETP, peak and velocity index) and a linear correlation for lag time was found in patients treated with vitamin-K antagonists (VKA). Receiver-operating characteristics (ROC) analysis showed that the optimal cutoff for ETP was 1600.2 nM · min (111.6% of normal, with a sensitivity of 96.6% and a specificity of 92.9%) and for the peak was 298.3 nM (112.1% of normal, with a sensitivity of 96.4% and a specificity of 100%). According to this analysis, ETP was able to identify patients with increased thrombotic and hemorrhagic risk, correlating with severe clinical complications.

CONCLUSION:

TGA showed excellent sensitivity and specificity for assessing anticoagulation status in patients with primary thrombophilia receiving VKA, with significant advantages with regard to INR. Clinical data strongly support ETP as a valuable indicator of thrombotic or hemorrhagic risk in patients receiving or not receiving thromboprophylaxis.

• Authors: Hilda Luna-Záizar, Ana Isabel González-Moncada, Emily Lizbeth Padilla-López, Ana Cristina Ramírez-Anguiano, Fermín Paul Pacheco-Moisés, Sandra Fabiola Velasco-Ramírez, María Guadalupe Zavelia Padilla-Romo, Cesar Borjas-Gutierrez, Ana Rebeca Jaloma-Cruz
• Journal: Thrombosis research (Thromb Res) Vol. 136 Issue 6 Pg. 1291-8 (Dec 2015) ISSN: 1879-2472 [Electronic] United States
• PMID: 26493603 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Anticoagulants
• Vitamin K
• Thrombin

Topics

• Adult
• Anticoagulants (chemistry)
• Calibration
• Cohort Studies
• Female
• Healthy Volunteers
• Hemorrhage (complications)
• Heterozygote
• Humans
• International Normalized Ratio
• Male
• Middle Aged
• Partial Thromboplastin Time
• Prothrombin Time
• ROC Curve
• Risk Factors
• Thrombelastography
• Thrombin (chemistry)
• Thrombophilia (genetics, prevention & control)
• Thrombosis (complications)
• Vitamin K (antagonists & inhibitors)
• Young Adult