title: Concentration-dependent effect of hypocalcaemia on in vitro clot strength in patients at risk of bleeding: a retrospective cohort study.
abstract: OBJECTIVE
  It is uncertain whether hypocalcaemia is associated with an increased risk of bleeding. This study assessed the dose-related relationship between ionised calcium concentrations and in vitro clot strength measured by maximum amplitude (MA) on the thromboelastograph (TEG).
  
  
  METHODS
  A total of 610 patients who were at risk of bleeding or had active bleeding between 2010 and 2014 were considered in this retrospective cohort study. A scatter plot with Pearson correlation coefficient (r) and multiple linear regression was used to assess the dose-related relationship between ionised calcium concentrations and MA on the TEG.
  
  
  RESULTS
  The mean ionised calcium of the patients was 1·10 mmol L(-1) (interquartile range: 1·04-1·17) and 235 (38·5%) of them had hypocalcaemia (<1·1 mmol L(-1) ). Hypocalcaemia was more common in patients with significant coexisting coagulopathy. Ionised calcium concentrations (r = 0·285, 95% confidence interval (CI) 0·211-0·356, P = 0·001), as well as fibrinogen concentrations, platelet counts, international normalised ratio (INR) and activated Partial Thromboplastin Time (aPTT), had a significant linear correlation with the MA on the TEG. Ionised calcium concentrations and its interaction term with platelet count were both significantly associated with the MA on the TEG (slope of the regression line 1·1 per 0·1 mmol L(-1) increment, 95%CI 0·3 to 1·9, P = 0·011), after adjusting for fibrinogen concentrations, platelet counts, INR and aPTT.
  
  
  CONCLUSIONS
  Ionised calcium concentrations had a concentration-dependent association with in vitro clot strength after adjusting for other coagulation abnormalities in patients with coexisting coagulopathy. Maintaining a normal ionised calcium concentration, >1 mmol L(-1) , during critical bleeding is recommended.
authors.affiliation: Department of Intensive Care Medicine, Royal Perth Hospital, Perth, Western Australia, Australia.|School of Population Health, University of Western Australia, Perth, Western Australia, Australia.|School of Veterinary & Life Sciences, Murdoch University, Perth, Western Australia, Australia.
authors.forename: K M
authors.identifier: http://orcid.org/0000-0002-6705-6004
authors.initials: KM
authors.lastname: Ho
authors.affiliation: Department of Anaesthesiology, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: C B
authors.initials: CB
authors.lastname: Yip
mesh_terms: D000368:Aged; D002118:Calcium / Q000097:blood*; D005260:Female; D006470:Hemorrhage / Q000097:blood* / Q000209:etiology; D006801:Humans; D006996:Hypocalcemia / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time / Q000379:methods; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D002118:Calcium
keywords: calcium; clotting; coagulopathy; critical bleeding; dose-response relationship; haemorrhage