title: Changes in molecular markers of hemostatic and fibrinolytic activation under various sampling conditions using vacuum tube samples from healthy volunteers.
abstract: Molecular makers such as thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), and D-dimer, are useful markers in the diagnosis and assessment of various thrombotic conditions. These markers are measured in plasma after blood sampling. Difficult blood sampling is known to falsely elevate plasma TAT levels. However, it is not known exactly why this occurs. In the present study, we examined how levels of molecular markers of haemostatic and fibrinolytic activation change under various sampling conditions using vacuum tube samples from healthy volunteers. When blood was sampled continuously by taking 10 consecutive vacuum tube samples following application of a tourniquet, blood sampling resulted in an accurate assessment of these molecular makers. When blood was sampled continuously by taking vacuum tube samples every one minute over a total of 9 minutes to investigate possible changes in the levels of the molecular markers over time, plasma levels of TAT, SF, and F1+2 gradually increased with time. Plasma levels of TAT, F1+2, and SF increased beyond the normal range over the course of nine minutes. When blood was sampled using three alternative methods, which varied in terms of the duration of needle puncture (sampling B), duration of tourniquet use (sampling C), or both (sampling A), plasma TAT and SF levels were significantly increased with all three methods, compared to control samples. Plasma F1+2 levels were significantly increased with sampling methods A and B, compared to control samples, but not with sampling method C. On the other hand, plasma D-dimer levels were not significantly altered by any of the sampling methods. In conclusion, the results suggest that molecular markers of haemostatic and fibrinolytic activation, except for D-dimer, may be affected by sampling method, particularly the duration of needle puncturing. Therefore, care needs to be taken when using TAT, F1+2, and SF levels to diagnose and estimate activation of the coagulation system.
authors.affiliation: Department of Clinical Laboratory, Kanazawa University School of Medicine, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Omote
authors.forename: Hidesaku
authors.initials: H
authors.lastname: Asakura
authors.forename: Sayuri
authors.initials: S
authors.lastname: Takamichi
authors.forename: Masami
authors.initials: M
authors.lastname: Shibayama
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kadohira
authors.forename: Mio
authors.initials: M
authors.lastname: Maekawa
authors.forename: Masahide
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Morishita
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D001800:Blood Specimen Collection; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006487:Hemostasis; D006490:Hemostatics / Q000097:blood*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D011516:Prothrombin; D012995:Solubility; D013997:Time Factors; D014618:Vacuum
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D006490:Hemostatics; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases