title: Laboratory and therapeutic control in the Thrombosis Centre Rotterdam using chromogenic prothrombin time tests.
abstract: Growing interest is observed in chromogenic substrate assays, because of their better precision, performance and possibilities for automation. Applied to a Cobas Bio centrifugal analyzer, we compared Nycotest-Chrom (N-test) and Thromboquant-PT (Tbq) with Thrombotest (TT). Precision tests were performed with samples from 4 plasma pools: normal (45 sec), low (100 sec), middle (150 sec) and high (200 sec) segments of the therapeutic range of TT. N-test had the best precision profile in both intraassay and interassay determinations compared with Tbq. Both chromogenic substrate assays were better than TT in this respect. By orthogonal regression a provisional therapeutic range was calculated from 312 determinations and later adjusted in a confirmation experiment with natural logarithm regression in 946 determinations. Compared with a TT range of 105-180 sec, the therapeutic ranges were 71-120 sec for N-test and 63-103 sec for Tbq. In a clinical therapeutic control phase, 110 patients were randomized in equal proportions to two groups A and B. Every 2 weeks for a period of 16 weeks, blood samples were tested for N-test, Tbq and TT. In group A, dose adjustment was based on N-test, and in group B on Tbq. The monitoring physician was blinded for Tbq and TT in group A and for N-test and TT in group B. No differences were found between the groups for mean TT, N-test, Tbq or mean dosage, nor differences were found in complication rate. A definite therapeutic range was complied using sensitivity/specificity curves together with their 95% confidence limits. Given TT 105-180 sec, the therapeutic range of N-test is from 80 (95% confidence limits: 77-82) to 110 (95% confidence limits: 108-115) sec, and of Tbq from 68 (95% confidence limits: 66-71) to 95 (95% confidence limits: 91-98) sec. It was concluded that the two chromogenic substrate assays performed equally safe in the monitoring of patients on oral anticoagulant therapy, despite differences in diagnostic correspondence with the reference TT.
authors.affiliation: Thrombosis Centre, Rotterdam.
authors.forename: J J
authors.initials: JJ
authors.lastname: Jonker
authors.forename: A J
authors.initials: AJ
authors.lastname: Azar
authors.forename: P F
authors.initials: PF
authors.lastname: van Bergen
authors.forename: R A
authors.initials: RA
authors.lastname: Klarenberg
authors.forename: E F
authors.initials: EF
authors.lastname: Przespolewski
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D002863:Chromogenic Compounds; D005069:Evaluation Studies as Topic; D006801:Humans; D009426:Netherlands; D011517:Prothrombin Time; D011786:Quality Control
chemical_list: D000925:Anticoagulants; D002863:Chromogenic Compounds