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


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.


CONCLUSIONS
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.
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Hilda
H
Luna-Záizar
UMAE, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
Ana Isabel
AI
González-Moncada
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Emily Lizbeth
EL
Padilla-López
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Ana Cristina
AC
Ramírez-Anguiano
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Fermín Paul
FP
Pacheco-Moisés
Departamento de Química, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Sandra Fabiola
SF
Velasco-Ramírez
División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México; Doctorado en Genética Humana, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, México.
María Guadalupe Zavelia
MG
Padilla-Romo
UMAE, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México; Doctorado en Genética Humana, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Cesar
C
Borjas-Gutierrez
División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México. Electronic address: arjaloma@gmail.com.
Ana Rebeca
AR
Jaloma-Cruz
D000328:Adult; D000925:Anticoagulants / Q000737:chemistry; D002138:Calibration; D015331:Cohort Studies; D005260:Female; D064368:Healthy Volunteers; D006470:Hemorrhage / Q000150:complications; D006579:Heterozygote; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D012372:ROC Curve; D012307:Risk Factors; D013916:Thrombelastography; D013917:Thrombin / Q000737:chemistry*; D019851:Thrombophilia / Q000235:genetics* / Q000517:prevention & control*; D013927:Thrombosis / Q000150:complications; D014812:Vitamin K / Q000037:antagonists & inhibitors; D055815:Young Adult
D000925:Anticoagulants; D014812:Vitamin K; D013917:Thrombin
Endogenous thrombin potential; International normalized ratio; Thrombin generation; Thrombophilia; Thromboprophylactic therapy; Thrombotic and hemorrhagic risk