Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability.
OBJECTIVE
The endogenous thrombin potential (ETP) represents the balance between pro- and anti-coagulant forces operating in plasma and can be used to investigate hyper- and hypo-coagulability. As a preliminary step to larger clinical studies we investigated the effect on ETP of phospholipids, tissue factor (TF) and residual platelets in frozen plasma.


METHODS
We investigated platelet-poor and platelet-rich plasmas from healthy subjects, patients on oral anticoagulants (OA), or with hemophilia and women on oral contraceptives (OC), chosen as examples of the normal, hypo- and hyper-coagulable states in which ETP has been reported to be impaired.


RESULTS
Phospholipids had only a slight effect on ETP in all conditions except in women on OC, in whom the best diagnostic efficacy was observed at 0.5 microM. TF had only a slight effect in all conditions except hemophilia, in which an ETP impairment was observed only at low (1 pM) concentration. Residual platelets had considerable effects on ETP in frozen plasmas, but this was abrogated by filtration before freezing. ETP in platelet-rich plasma at 150x103/mm3 was similar to that obtained in filtered-plasma with 1.5 microM phospholipids in healthy subjects, patients on OA and patients with severe hemophilia, but not in those with mild- or moderate-hemophilia, where the ETP was higher in platelet-rich plasma.


CONCLUSIONS
The results suggest that the method can be used for investigations on the clinical value of ETP. Platelet-rich and platelet-poor plasma are suitable testing materials. The latter should be filtered before freezing to minimize the effect of residual platelets.
Chantarangkul
Veena
V
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, University and IRCCS Maggiore Hospital, Milano, Italy.
Clerici
Marigrazia
M
Bressi
Caterina
C
Giesen
Peter L A
PL
Tripodi
Armando
A
D000925:Anticoagulants / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000175:diagnosis*; D001780:Blood Coagulation Tests / Q000379:methods*; D001792:Blood Platelets / Q000502:physiology; D003276:Contraceptives, Oral; D004305:Dose-Response Relationship, Drug; D005260:Female; D005615:Freezing; D006467:Hemophilia A / Q000097:blood; D006801:Humans; D010743:Phospholipids / Q000494:pharmacology; D015203:Reproducibility of Results; D013917:Thrombin / Q000032:analysis* / Q000096:biosynthesis; D019851:Thrombophilia / Q000175:diagnosis*; D013925:Thromboplastin / Q000494:pharmacology
D000925:Anticoagulants; D003276:Contraceptives, Oral; D010743:Phospholipids; D013925:Thromboplastin; D013917:Thrombin