Coagulation disorders in patients with severe hemophagocytic lymphohistiocytosis.
ADAMTS13 Protein
/ blood
Adult
Aged
Biomarkers
/ blood
Blood Coagulation Disorders
/ blood
Female
Fibrin Fibrinogen Degradation Products
/ metabolism
France
/ epidemiology
Hemorrhage
/ blood
Hospital Mortality
Humans
Lymphohistiocytosis, Hemophagocytic
/ blood
Male
Middle Aged
Plasminogen Activator Inhibitor 1
/ blood
Prospective Studies
Severity of Illness Index
Tissue Plasminogen Activator
/ blood
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
15
04
2021
accepted:
14
06
2021
entrez:
3
8
2021
pubmed:
4
8
2021
medline:
25
11
2021
Statut:
epublish
Résumé
Coagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH. We prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) <50% and/or fibrinogen <2g/L. HLH aetiology was mostly ascribed to haematological malignancies (74% of patients). Coagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2∙65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p = 0∙021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], p<0∙001) were independently associated with hospital mortality. No early biological marker was associated with severe bleeding. Hyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.
Sections du résumé
BACKGROUND
Coagulation disorders are common in patients with hemophagocytic lymphohistiocytosis (HLH), associated with an increased risk of bleeding and death. We aim to investigate coagulation disorders and their outcome implications in critically ill patients with HLH.
METHODS
We prospectively evaluated 47 critically ill patients with HLH (median age of 54 years [42-67]) between April 2015 and December 2018. Coagulation assessments were performed at day 1. Abnormal standard coagulation was defined as prothrombin time (PT) <50% and/or fibrinogen <2g/L. HLH aetiology was mostly ascribed to haematological malignancies (74% of patients).
RESULTS
Coagulation disorders and severe bleeding events were frequent, occurring in 30 (64%) and 11 (23%) patients respectively. At day 1, median fibrinogen level was 2∙65g/L [1.61-5.66]. Fibrinolytic activity was high as suggested by increased median levels of D-dimers, fibrin monomers, PAI-1 (plasminogen activator inhibitor) and tPA (tissue plasminogen activator). Forty-one (91%) patients had a decreased ADAMTS13 activity (A Disintegrin-like And Metalloproteinase with ThromboSpondin type 1 repeats, member 13). By multivariable analysis, the occurrence of a severe bleeding (OR 3.215 [1.194-8.653], p = 0∙021) and SOFA score (Sepsis-Related Organ Failure Assessment) at day 1 (OR 1.305 per point [1.146-1.485], p<0∙001) were independently associated with hospital mortality. No early biological marker was associated with severe bleeding.
CONCLUSIONS
Hyperfibrinolysis may be the primary mechanism responsible for hypofibrinogenemia and may also participate in ADAMTS13 degradation. Targeting the plasmin system appears as a promising approach in severe HLH-related coagulation disorders.
Identifiants
pubmed: 34343182
doi: 10.1371/journal.pone.0251216
pii: PONE-D-21-12544
pmc: PMC8330932
doi:
Substances chimiques
Biomarkers
0
Fibrin Fibrinogen Degradation Products
0
Plasminogen Activator Inhibitor 1
0
SERPINE1 protein, human
0
fibrin fragment D
0
Tissue Plasminogen Activator
EC 3.4.21.68
ADAMTS13 Protein
EC 3.4.24.87
ADAMTS13 protein, human
EC 3.4.24.87
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0251216Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Crit Care Clin. 2020 Apr;36(2):415-426
pubmed: 32172822
Medicine (Baltimore). 2014 Mar;93(2):100-105
pubmed: 24646466
Blood. 2005 Feb 1;105(3):1085-93
pubmed: 15388580
Crit Care. 2013 Nov 18;17(6):R273
pubmed: 24238574
Medicine (Baltimore). 2016 Apr;95(16):e3374
pubmed: 27100422
Blood. 2017 May 25;129(21):2836-2846
pubmed: 28416507
Intensive Care Med. 2008 Jul;34(7):1177-87
pubmed: 18427781
J Intensive Care Med. 2020 Feb;35(2):118-127
pubmed: 30384814
Ann Hematol. 2007 Jul;86(7):493-8
pubmed: 17347847
Mayo Clin Proc. 2014 Apr;89(4):484-92
pubmed: 24581757
Medicine (Baltimore). 2004 Jul;83(4):233-244
pubmed: 15232311
Blood Adv. 2017 Jan 16;1(5):293-305
pubmed: 29296945
Br J Haematol. 2015 Jan;168(1):63-8
pubmed: 25157895
World J Crit Care Med. 2018 Nov 30;7(6):73-83
pubmed: 30596029
Am J Hematol. 2015 Mar;90(3):220-4
pubmed: 25469675
J Natl Cancer Inst. 2014 Sep 29;106(9):
pubmed: 25265940
Cytokine. 2018 Oct;110:459-465
pubmed: 29801971
J Thromb Haemost. 2017 Dec;15(12):2432-2442
pubmed: 28981198
Am J Pediatr Hematol Oncol. 1993 Feb;15(1):92-8
pubmed: 8447564
J Biochem. 2018 May 1;163(5):381-389
pubmed: 29228282
Intensive Care Med. 2010 Oct;36(10):1695-702
pubmed: 20532477
Scand J Clin Lab Invest Suppl. 2002;237:29-33
pubmed: 12570164
Indian J Crit Care Med. 2012 Oct;16(4):198-203
pubmed: 23559726
Intensive Care Med. 2003 Apr;29(4):530-8
pubmed: 12664219
Lancet. 2014 Apr 26;383(9927):1503-1516
pubmed: 24290661
J Blood Med. 2016 Oct 11;7:227-231
pubmed: 27785117
Thromb Haemost. 2018 Apr;118(4):676-687
pubmed: 29618154
Blood Rev. 2007 Sep;21(5):245-53
pubmed: 17590250
Eur J Haematol. 2005 Jan;74(1):6-10
pubmed: 15613100
JAMA. 2018 Nov 27;320(20):2099-2107
pubmed: 30357270
Blood. 2017 Jul 6;130(1):59-72
pubmed: 28325863
Ann Hematol. 2012 Jun;91(6):897-904
pubmed: 22147006
N Engl J Med. 1998 Nov 26;339(22):1578-84
pubmed: 9828245
Hematol Oncol Clin North Am. 2015 Oct;29(5):895-902
pubmed: 26461149
Cytokine. 2016 Sep;85:14-7
pubmed: 27269180
Medicine (Baltimore). 2015 Oct;94(40):e1692
pubmed: 26448017
Lancet Haematol. 2016 May;3(5):e237-45
pubmed: 27132698
J Exp Med. 1974 Apr 1;139(4):834-50
pubmed: 4816302
Intensive Care Med. 1996 Jul;22(7):707-10
pubmed: 8844239
Orphanet J Rare Dis. 2015 Feb 15;10:20
pubmed: 25757854