PMID- 27622544
OWN - NLM
STAT- MEDLINE
DCOM- 20171225
LR  - 20230829
IS  - 1538-7836 (Electronic)
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 14
IP  - 12
DP  - 2016 Dec
TI  - Dexamethasone inhibits endotoxin-induced coagulopathy in human lungs.
PG  - 2471-2477
LID - 10.1111/jth.13504 [doi]
AB  - Essentials Glucocorticoids are associated with an increased risk of thrombosis. 
      Healthy volunteers received dexamethasone or placebo in an endotoxin lung 
      instillation model. Dexamethasone suppressed thrombin generation in 
      bronchoalveolar lavage. Glucocorticoids inhibit endotoxin induced pulmonary 
      coagulopathy. SUMMARY: Background Activation of local and systemic coagulation is 
      a common finding in patients with pneumonia. There is evidence that 
      glucocorticoids have procoagulant activity in the circulation, particularly in 
      the context of inflammation. The effects of glucocorticoids on local pulmonary 
      coagulation have not yet been investigated. Objective To use a human model of 
      lung inflammation based on the local instillation of endotoxin in order to 
      investigate whether glucocorticoids alter pulmonary coagulation. Methods 
      Twenty-four healthy volunteers were randomized to receive either dexamethasone or 
      placebo in a double-blind trial. Endotoxin was instilled via bronchoscope into 
      right or left lung segments, followed by saline into the contralateral site. Six 
      hours later, a bilateral bronchoalveolar lavage (BAL) was performed and 
      coagulation parameters were measured. Results Endotoxin induced activation of 
      coagulation in the bronchoalveolar compartment: the level of prothrombin fragment 
      1 + 2 (F(1 + 2) ) was increased three-fold (248 pmol L(-1) , 95% confidence 
      interval [CI] 43-454 versus 743 pmol L(-1) , 95% CI 437-1050) and the level of 
      thrombin-antithrombin complex (TATc) was increased by ~ 50% (31 mug L(-1) , 95% CI 
      18-45 versus 49 mug L(-1) , 95% CI 36-61) as compared with saline-challenged 
      segments. Dexamethasone reduced F(1 + 2) (284 pmol L(-1) , 95% CI 34-534) and 
      TATc (9 mug L(-1) , 95% CI 0.7-17) levels almost to those measured in BAL fluid 
      from the saline-instilled segments in the placebo group. Dexamethasone even 
      profoundly reduced F(1 + 2) levels (80%) in saline-instilled lung segments (50 
      pmol L(-1) , 95% CI 12-87). In contrast, dexamethasone had no effect on systemic 
      F(1 + 2) levels. Conclusions Dexamethasone inhibits endotoxin-induced 
      coagulopathy in lungs. This trial is the first to provide insights into the 
      effects of glucocorticoids on pulmonary coagulation in response to endotoxin.
CI  - (c) 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley 
      Periodicals, Inc. on behalf of International Society on Thrombosis and 
      Haemostasis.
FAU - Bartko, J
AU  - Bartko J
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Schoergenhofer, C
AU  - Schoergenhofer C
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Schwameis, M
AU  - Schwameis M
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Buchtele, N
AU  - Buchtele N
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Wojta, J
AU  - Wojta J
AD  - Department of Internal Medicine II, Medical University of Vienna, Vienna, 
      Austria.
FAU - Schabbauer, G
AU  - Schabbauer G
AD  - Institute of Physiology, Center for Physiology and Pharmacology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Stiebellehner, L
AU  - Stiebellehner L
AD  - Department of Internal Medicine II, Medical University of Vienna, Vienna, 
      Austria.
FAU - Jilma, B
AU  - Jilma B
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20161024
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Endotoxins)
RN  - 0 (Glucocorticoids)
RN  - 0 (antithrombin III-protease complex)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9000-94-6 (Antithrombin III)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Adult
MH  - Antithrombin III/chemistry
MH  - Blood Coagulation
MH  - Blood Coagulation Disorders/*drug therapy
MH  - Bronchoalveolar Lavage
MH  - Bronchoalveolar Lavage Fluid
MH  - Dexamethasone/*pharmacology
MH  - Double-Blind Method
MH  - Endotoxins/*adverse effects
MH  - Female
MH  - Glucocorticoids/*pharmacology
MH  - Healthy Volunteers
MH  - Humans
MH  - Inflammation
MH  - Lung/*drug effects
MH  - Male
MH  - Peptide Hydrolases/chemistry
MH  - Thrombosis
MH  - Young Adult
PMC - PMC5298044
OTO - NOTNLM
OT  - acute respiratory distress syndrome
OT  - coagulation
OT  - dexamethasone
OT  - lung
OT  - pneumonia
EDAT- 2016/10/25 06:00
MHDA- 2017/12/26 06:00
PMCR- 2017/02/08
CRDT- 2016/09/14 06:00
PHST- 2016/04/01 00:00 [received]
PHST- 2016/08/26 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/12/26 06:00 [medline]
PHST- 2016/09/14 06:00 [entrez]
PHST- 2017/02/08 00:00 [pmc-release]
AID - S1538-7836(22)02522-3 [pii]
AID - JTH13504 [pii]
AID - 10.1111/jth.13504 [doi]
PST - ppublish
SO  - J Thromb Haemost. 2016 Dec;14(12):2471-2477. doi: 10.1111/jth.13504. Epub 2016 
      Oct 24.