title: Abnormal Protac-induced coagulation inhibition chromogenic assay results are associated with an increased risk of recurrent venous thromboembolism.
abstract: Evaluation of the risk of recurrent venous thromboembolism (VTE) is required to determine the optimal duration of secondary prophylaxis. Application of global assays reflecting the pro- versus anti-coagulant balance in vivo would be desirable. We aimed at investigating the relationship between recurrent VTE and the Protac-induced coagulation inhibition (PICI) assay, which is based on tissue factor-induced thrombin generation measured by a chromogenic substrate. One-hundred-ninety patients were followed-up after a first episode of unprovoked, objectively documented VTE for 2.7 years after stopping treatment with vitamin K antagonists (VKA). PICI was measured 1 month after stopping treatment as the percentage of the OD values recorded without or with Protac. The lower the PICI%, the greater the pro- versus anti-coagulant imbalance. The study outcome was objectively-documented symptomatic recurrent VTE. Patients with PICI% <or= 74% had crude hazard-ratios (HR) (95% CI) for recurrent VTE of 2.86 (1.01-8.12) as compared to those with PICI% > 87%. After adjustment for age, gender, type of index event, VKA duration and normal/abnormal D-Dimer, HR (95% CI) were substantially unchanged [2.91 (1.01-8.38)]. The corresponding values after further adjustment for the above variables plus the absence/presence of the most frequent thrombophilic alterations were 3.38 (1.16-9.84). These HR values compare favorably with those obtained in a previous study investigating the thrombin generation test performed in the presence of thrombomodulin. In conclusion, the measurement of PICI helps to identify patients at higher risk of VTE recurrence. Advantages of PICI over thrombin generation tests are easy performance in general clinical laboratories, easy standardization and no special equipment.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Università degli Studi di Milano, Via Pace 9, 20122 Milan, Italy. armando.tripodi@unimi.it
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Cristina
authors.initials: C
authors.lastname: Legnani
authors.forename: Laura
authors.initials: L
authors.lastname: Lemma
authors.forename: Benilde
authors.initials: B
authors.lastname: Cosmi
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Palareti
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D002863:Chromogenic Compounds; D004334:Drug Administration Schedule; D005260:Female; D005343:Fibrinolytic Agents; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010455:Peptides; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D002863:Chromogenic Compounds; D005343:Fibrinolytic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011486:Protein C; C049647:snake venom protein C activator; D014812:Vitamin K; D013925:Thromboplastin; D013917:Thrombin