title: Effects of naturopathic medicines on Multiplate and ROTEM: a prospective experimental pilot study in healthy volunteers.
abstract: BACKGROUND
  Of patients undergoing surgery, 22 to 57% have been reported to be using naturopathic medicines. Several of these medicines have been reported to increase bleeding or enhance the effect of other drugs that increase bleeding. The Swedish Medical Products Agency recommends cessation of the use of the naturopathic medicines echinacea, fish oil, ginkgo biloba, ginseng, St. John's wort, valeriana and garlic 2 weeks before surgery. The aim of this pilot study was to examine the effects of these 7 naturopathic medicines in healthy humans by utilising multiple electrode aggregometer (Multiplate) and viscoelastic rotational thromboelastometer (ROTEM) to obtain data for sample size calculation before a larger trial.
  
  
  METHODS
  Thirty-five healthy volunteers ingested one of the listed naturopathic medicines for 7 days. Each naturopathic medicine was taken in a recommended standard dose by 5 volunteers. ROTEM clot initiation (CT), clot formation (CFT), α-angle (AA) and clot structure (MCF) were analysed with tissue factor activated (EXTEM) and native (NATEM) assays. The Multiplate platelet aggregation area under curve (AUC) was measured with adenosine diphosphate (ADP), collagen (COL) and arachidonic acid (ASPI) assays.
  
  
  RESULTS
  Multiplate with ADP agonist decreased from 73 ± 8.7 AUC to 60 ± 5.9 AUC (P = 0.003, 95% confidence interval (CI) -19.2 to -7.6) after medication with fish oil, but fish oil had no effect on COL or ASPI reagents. None of the other naturopathic medicines had any effect on Multiplate aggregometry. ROTEM NATEM-CFT increased from 217 ± 32 s to 283 ± 20 (P = 0.009, 95% CI 26.8 to 107), and NATEM-AA decreased from 52 ± 3.9° to 44 ± 2.3° (P = 0.009, 95 % CI -12.0 to -3.2) after medication with fish oil. There were no significant changes in the other NATEM or EXTEM parameters. The other naturopathic medicines had no significant effects on ROTEM or Multiplate aggregometry.
  
  
  CONCLUSIONS
  We have demonstrated that a recommended standard intake of 1260 mg Ω-3 polyunsaturated fatty acids (fish oil) daily - but not echinacea, ginkgo biloba, ginseng, St. John's wort, valeriana or garlic - may decrease platelet aggregation and clot formation. A larger trial in this setting would be meaningful to perform.
  
  
  BACKGROUND
  Trial registration ISRCTN78027929. Registered 19 May 2015.
authors.affiliation: Medical Faculty, University of Lund, Box 117, 221 00, Lund, Sweden.
authors.forename: August
authors.initials: A
authors.lastname: Bagge
authors.affiliation: Department of Clinical Sciences, University of Lund, Box 188, SE-221 00, Lund, Sweden.|Department of Intensive and Perioperative Care, Skåne University Hospital Lund, 22185, Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schött
authors.affiliation: Department of Clinical Sciences, University of Lund, Box 188, SE-221 00, Lund, Sweden. thomas.kander@med.lu.se.|Department of Intensive and Perioperative Care, Skåne University Hospital Lund, 22185, Lund, Sweden. thomas.kander@med.lu.se.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kander
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D020900:Echinacea; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use*; D020441:Ginkgo biloba; D006801:Humans; D020902:Hypericum; D008297:Male; D008875:Middle Aged; D009324:Naturopathy; D005894:Panax; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D011446:Prospective Studies; D012717:Sesquiterpenes; D014632:Valerian; D055815:Young Adult
chemical_list: D005395:Fish Oils; D012717:Sesquiterpenes; C414950:viscosumic acid