PMID- 29565968
OWN - NLM
STAT- MEDLINE
DCOM- 20180618
LR  - 20181114
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 12
IP  - 3
DP  - 2018 Mar
TI  - Blood coagulation abnormalities in multibacillary leprosy patients.
PG  - e0006214
LID - 10.1371/journal.pntd.0006214 [doi]
LID - e0006214
AB  - BACKGROUND: Leprosy is a chronic dermato-neurological disease caused by 
      Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy 
      were detected around the world, representing the most frequent cause of 
      infectious irreversible deformities and disabilities. PRINCIPAL FINDINGS: In the 
      present work, we demonstrate a consistent procoagulant profile on 40 reactional 
      and non-reactional multibacillary leprosy patients. A retrospective analysis in 
      search of signs of coagulation abnormalities among 638 leprosy patients 
      identified 35 leprosy patients (5.48%) which displayed a characteristic 
      lipid-like clot formed between blood clot and serum during serum harvesting, 
      herein named 'leprosum clot'. Most of these patients (n = 16, 45.7%) belonged to 
      the lepromatous leprosy pole of the disease. In addition, formation of the 
      leprosum clot was directly correlated with increased plasma levels of soluble 
      tissue factor and von Willebrand factor. High performance thin layer 
      chromatography demonstrated a high content of neutral lipids in the leprosum 
      clot, and proteomic analysis demonstrated that the leprosum clot presented in 
      these patients is highly enriched in fibrin. Remarkably, differential 
      2D-proteomics analysis between leprosum clots and control clots identified two 
      proteins present only in leprosy patients clots: complement component 3 and 4 and 
      inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In 
      agreement with those observations we demonstrated that M. leprae induces 
      hepatocytes release of IHRP in vitro. CONCLUSIONS: We demonstrated that leprosy 
      MB patients develop a procoagulant status due to high levels of plasmatic 
      fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue 
      factor. We propose that some of these components, fibrinogen for example, 
      presents potential as predictive biomarkers of leprosy reactions, generating 
      tools for earlier diagnosis and treatment of these events.
FAU - Silva, Debora Santos da
AU  - Silva DSD
AD  - Lab. of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 
      Rio de Janeiro, Brazil.
FAU - Teixeira, Lisandra Antonia Castro
AU  - Teixeira LAC
AD  - Lab. of Conjunctive Tissue, Institute of Medical Biochemistry, Federal University 
      of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Beghini, Daniela Gois
AU  - Beghini DG
AD  - Lab. of Toxinology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de 
      Janeiro, Brazil.
FAU - Ferreira, Andre Teixeira da Silva
AU  - Ferreira ATDS
AD  - Lab. of Toxinology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de 
      Janeiro, Brazil.
FAU - Pinho, Marcia de Berredo Moreira
AU  - Pinho MBM
AD  - Lab. of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 
      Rio de Janeiro, Brazil.
FAU - Rosa, Patricia Sammarco
AU  - Rosa PS
AD  - Department of Biology, Lauro de Souza Lima Institute, Bauru, Brazil.
FAU - Ribeiro, Marli Rambaldi
AU  - Ribeiro MR
AD  - Lab. Dr. Sergio Franco, Hematology Department, DASA, Rio de Janeiro, Brazil.
FAU - Freire, Monica Di Calafiori
AU  - Freire MDC
AD  - Lab. Dr. Sergio Franco, Hematology Department, DASA, Rio de Janeiro, Brazil.
FAU - Hacker, Mariana Andrea
AU  - Hacker MA
AD  - Lab. of Leprosy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 
      Brazil.
FAU - Nery, Jose Augusto da Costa
AU  - Nery JADC
AD  - Lab. of Leprosy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 
      Brazil.
FAU - Pessolani, Maria Cristina Vidal
AU  - Pessolani MCV
AD  - Lab. of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 
      Rio de Janeiro, Brazil.
FAU - Tovar, Ana Maria Freire
AU  - Tovar AMF
AD  - Lab. of Conjunctive Tissue, Institute of Medical Biochemistry, Federal University 
      of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Sarno, Euzenir Nunes
AU  - Sarno EN
AD  - Lab. of Leprosy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 
      Brazil.
FAU - Perales, Jonas
AU  - Perales J
AD  - Lab. of Toxinology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de 
      Janeiro, Brazil.
FAU - Bozza, Fernando Augusto
AU  - Bozza FA
AD  - Department of Critical Care, National Institute of Infectious Disease, Oswaldo 
      Cruz Foundation, Rio de Janeiro, Brazil.
FAU - Esquenazi, Danuza
AU  - Esquenazi D
AD  - Lab. of Leprosy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 
      Brazil.
FAU - Monteiro, Robson Queiroz
AU  - Monteiro RQ
AD  - Lab. of Hemostasis and Poisons, Institute of Medical Biochemistry, Federal 
      University of Rio de Janeiro, Rio de Janeiro, Brazil.
FAU - Lara, Flavio Alves
AU  - Lara FA
AUID- ORCID: 0000-0002-2717-6597
AD  - Lab. of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 
      Rio de Janeiro, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180322
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Blood Coagulation Disorders/*microbiology
MH  - Brazil
MH  - Child
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Erythema Nodosum/*blood/complications
MH  - Female
MH  - Humans
MH  - Leprosy, Lepromatous/*blood/complications
MH  - Linear Models
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Mycobacterium leprae/isolation & purification
MH  - Prospective Studies
MH  - Proteomics/methods
MH  - Retrospective Studies
MH  - Skin/*microbiology
MH  - Young Adult
PMC - PMC5863944
COIS- The authors declare that no competing interests exist.
EDAT- 2018/03/23 06:00
MHDA- 2018/06/19 06:00
PMCR- 2018/03/22
CRDT- 2018/03/23 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2018/01/05 00:00 [accepted]
PHST- 2018/03/23 06:00 [entrez]
PHST- 2018/03/23 06:00 [pubmed]
PHST- 2018/06/19 06:00 [medline]
PHST- 2018/03/22 00:00 [pmc-release]
AID - PNTD-D-17-01395 [pii]
AID - 10.1371/journal.pntd.0006214 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2018 Mar 22;12(3):e0006214. doi: 
      10.1371/journal.pntd.0006214. eCollection 2018 Mar.