Thromboplastin-thrombomodulin-mediated time: a new global test sensitive to protein S deficiency and increased levels of factors II, V, VII and X.
OBJECTIVE
A new test for screening the procoagulant capacity of plasma is described and evaluated. This test is based on the coagulation of plasma initiated by thromboplastin (Tp) in the presence of thrombomodulin (TM). In a previous paper we reported that this test had a significant phenotypic and genetic correlation with thrombosis susceptibility. The present report describes the characteristics of the test and its sensitivity to the concentration of some hemostasis factors.


METHODS
Plasma from normal subjects, from individuals with various disorders of hemostasis and plasma with different concentrations of factors II, V, VII, VIII, X, fibrinogen, protein C and protein S were studied. The thromboplastin-thrombomodulin-mediated time (Tp-TMT) is measured after mixing 100 mL of plasma diluted 1/10 at 37 C with 100 mL of a solution composed of 2 parts of thromboplastin, 1 part of thrombomodulin at 30 U/mL and 1 part of Owren's buffer. The results are expressed as the ratio of the patient's clotting time to that of the control. Values were compared with Student's t test and the Mann-Whitney test. Differences were considered statistically significant when p<0.05.


RESULTS
In the control group women showed significantly lower values than men. Raised levels of factors II, V, VII and X reduced the coagulation time obtained with Tp-TM. Elevated concentrations of fibrinogen and factor VIII did not influence the test. The Tp-TMT was sensitive to protein S deficiencies, but not to protein C deficiencies.


CONCLUSIONS
These results indicate that the effect of protein S on the test is through its anti-prothrombinase activity.


CONCLUSIONS
Tp-TMT, which is correlated with thrombosis susceptibility, is sensitive to raised levels of factors II, V, VII and X, as well as to low levels of protein S, and may be an indicator of thrombosis risk.
Borrell
Montserrat
M
Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Avgda San Antoni M  Claret 167, 08025 Barcelona, Spain. mborrell@hsp.santpau.es
Llobet
Dolors
D
Ortín
Rosa
R
Felices
Rosa
R
Vallvé
Cristina
C
Mateo
José
J
Souto
Joan
J
Fontcuberta
Jordi
J
D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology; D001780:Blood Coagulation Tests / Q000379:methods* / Q000592:standards; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D018455:Protein S Deficiency / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D018180:Thrombomodulin; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis; D013925:Thromboplastin / Q000494:pharmacology / Q000592:standards
D001779:Blood Coagulation Factors; D018180:Thrombomodulin; D013925:Thromboplastin