title: Enhanced thrombin generation and reduced intact protein S in processed solvent detergent plasma.
abstract: BACKGROUND
  Standardized solvent/detergent (S/D)-treated plasma has been developed as an improved alternative to fresh frozen-plasma (FFP) in the management of severe bleeds. This study aimed at exploring compositional modifications that may influence the general applicability of S/D-treated plasma.
  
  
  METHODS
  S/D-treated plasma and FFP were compared in procoagulant microparticles and concentration of coagulation factors and inhibitors. Compositional differences were correlated with hemostatic and fibrinolytic characteristics as measured by PT, APTT, thrombin generation and thromboelastography.
  
  
  RESULTS
  Procoagulant microparticles were absent in S/D-treated plasma. Procoagulant factors were within the normal range. Antithrombin, TFPI and protein S antigen may be normal or slightly reduced depending on the duration of the S/D-treatment, but S/D-treated plasmas had only 12-14% intact functional protein S. Thrombin generation was subsequently increased, especially at low tissue factor concentration (1 pM). Plasma coagulation times in PT and APTT were normal, but 1.5-fold reduced in thromboelastography at low TF (1 pM). α2-antiplasmin was reduced with a concomitant 3-4 fold shortened clot lysis time measured by thromboelastography in the presence of TF (10 pM) and tissue-type plasminogen activator (0.2μg/ml). Enhanced fibrin degradation could be normalised with tranexamic acid.
  
  
  CONCLUSIONS
  S/D-treatment seems to induce a procoagulant phenotype that results from a strongly reduced level of intact single chain protein S. Whether this may correct the apparent hemostatic imbalance as suggested from the increased fibrinolysis remains to be established. Our findings may bear implications in patients with deficiencies of natural anticoagulants. Co-administration of tranexamic acid appears beneficial to control enhanced fibrinolysis.
authors.affiliation: Helsinki University Central Hospital Research Institute, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Pitkänen
authors.affiliation: Helsinki University Central Hospital Research Institute, Helsinki, Finland.
authors.forename: Annukka
authors.initials: A
authors.lastname: Jouppila
authors.affiliation: Department of Hematology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mowinckel
authors.affiliation: Coagulation Disorder Unit, Cancer Center, HUSLAB and Laboratory Services HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Lemponen
authors.affiliation: Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Patiwael
authors.affiliation: Department of Hematology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
authors.affiliation: Coagulation Disorder Unit, Cancer Center, HUSLAB and Laboratory Services HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
authors.affiliation: Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands. Electronic address: h.brinkman@sanquin.nl.
authors.forename: Herm Jan M
authors.initials: HJ
authors.lastname: Brinkman
mesh_terms: D000925:Anticoagulants / Q000737:chemistry; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000737:chemistry; D003029:Coagulants / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D010641:Phenotype; D017293:Protein S / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013916:Thrombelastography; D013917:Thrombin / Q000737:chemistry*; D014148:Tranexamic Acid / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D003029:Coagulants; D003902:Detergents; D017293:Protein S; D012997:Solvents; D014148:Tranexamic Acid; D005337:Fibrin; D013917:Thrombin
keywords: Fibrinolysis; Plasma transfusion; Protein S; S/D-treated plasma; Thrombin generation