Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis.
Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure.
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil.|Programa de Pos-Graduacao Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Sao Paulo, SP, Brazil.
Luis G V
LGV
Fernandes
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, SP, Brazil.
Antonio F S
AFS
Filho
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, SP, Brazil.
Gisele O
GO
Souza
Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, SP, Brazil.
Silvio A
SA
Vasconcellos
Centro de Bacteriologia, Instituto Adolfo Lutz, Avenida Dr Arnaldo, 355, CEP 01246-902, &nbsp;Sao Paulo, SP, Brazil.
Eliete C
EC
Romero
Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil.|Programa de Pos-Graduacao Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Sao Paulo, SP, Brazil.
Ana L T O
ALTO
Nascimento
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism*; D001422:Bacterial Adhesion / Q000502:physiology; D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000382:microbiology*; D006224:Cricetinae; D006470:Hemorrhage / Q000382:microbiology*; D006801:Humans; D007919:Leptospira / Q000378:metabolism; D007922:Leptospirosis / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin
D010446:Peptide Fragments; D011498:Protein Precursors; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D011516:Prothrombin