title: Effects of plasma dilution on tissue-factor-induced thrombin generation and thromboelastography: partly compensating role of platelets.
abstract: BACKGROUND
  Bleeding upon major surgery or severe trauma is treated by transfusion with crystalloids, colloids, or plasma. This treatment, however, can lead to dilutional coagulopathy and impaired hemostasis. We investigated the suitability of two integrative coagulation tests to measure the hemostatic activity of diluted plasma.
  
  
  METHODS
  Plasma from healthy donors was diluted in vitro with saline or colloid (venofundin or gelofusin). Coagulant activity in response to tissue factor was monitored by calibrated automated thrombin (CAT) generation and rotational thromboelastography (TEG), detecting formation of elastic fibrin clots. Plasma from patients receiving fluid infusion during coronary artery bypass grafting (CABG) was analyzed with the same assays.
  
  
  RESULTS
  Optimal activity of CAT and TEG assays required the presence of 10 pmol per L tissue factor and 4 micromol per L phospholipid vesicles or 100 x 10(9) platelets (PLTs) per L. Strikingly, thrombin generation and clot formation became impaired at a higher extent of dilution with PLTs present (< or =40% plasma) than with phospholipid vesicles present (< or =60% plasma). Colloids aggravated the dilution effect on clot formation, but FFP antagonized the dilution effect on thrombin and clot formation. In contrast, fibrinogen and Factor (F)XIII only restored the impaired clot formation. In plasma samples from patients undergoing CABG, CAT and TEG assay variables were altered to an extent corresponding with the volume of fluid infusion.
  
  
  CONCLUSIONS
  Thrombin generation and clot formation are reduced at a plasma dilution of more than 40 percent. In either process, PLTs can partly compensate for the dilution effect. In vitro dilution with colloids impaired fibrin clot elasticity compared to saline.
authors.affiliation: Department of Biochemistry, Maastricht University and University Hospital, Maastricht, The Netherlands.
authors.forename: Saskia E M
authors.initials: SE
authors.lastname: Schols
authors.forename: Marion A H
authors.initials: MA
authors.lastname: Feijge
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Lancé
authors.forename: Karly
authors.initials: K
authors.lastname: Hamulyák
authors.forename: Hugo
authors.initials: H
authors.lastname: ten Cate
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
authors.forename: Elisabeth C M
authors.initials: EC
authors.lastname: van Pampus
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000502:physiology*; D003102:Colloids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D000077324:Crystalloid Solutions; D005780:Gelatin / Q000494:pharmacology / Q000627:therapeutic use; D006474:Hemorrhagic Disorders / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D007552:Isotonic Solutions / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D009994:Osmolar Concentration; D010949:Plasma; D010952:Plasma Substitutes / Q000009:adverse effects / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D003102:Colloids; D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; C082196:Innovin; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D011479:Protamines; D011994:Recombinant Proteins; D013386:Succinates; C060085:succinylated gelatin; D005780:Gelatin; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin