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Free Content Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality

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Abstract:

Summary Objective  To determine the involvement of coagulation in bleeding and poor outcome in patients with severe leptospirosis. Methods  In a prospective study, parameters of the coagulation system were measured on admission and during follow-up in 52 consecutive patients with severe leptospirosis. Results  All patients showed coagulation disorders, such as prolonged prothrombin time (PT) and activated partial thromboplastin time, marked procoagulant activity [thrombin–antithrombin (TAT) complexes, prothrombin fragment 1+2, D-dimer], reduced levels of anticoagulant markers (protein C, antithrombin) and increased (anti-) fibrinolytic activity [plasmin–antiplasmin (PAP) complexes, plasminogen activator inhibitor-1]. These disorders were more pronounced in patients who died eventually. PT prolongation was associated with mortality (OR 1.4, 95% CI: 1.0–1.8,  = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets ≤100 × 10/l) was significantly associated with clinical bleeding (OR 4.6, 95% CI: 1.3–16). A subanalysis of patients with and without severe bleeding revealed a more pronounced imbalance of the coagulation system in patients with severe bleeding, as reflected by a significant association with PT (OR 1.4, 95% CI: 1.0–1.8,  = 0.05) and the TAT/PAP ratio (OR 1.3, 95% CI: 1.0–1.6,  = 0.05), which is an indicator of the balance between coagulation and fibrinolysis. Overt disseminated intravascular coagulation (DIC) was found in 10 (22%) of the 46 patients for whom the score could be calculated. There was no significant association between DIC scores, bleeding diathesis or poor outcome. Conclusion  The coagulation system was strongly activated in patients with leptospirosis. This was more pronounced in the deceased and in patients with severe bleeding than in than the survivors and in those without severe bleeding.

French
Objectif: 

Déterminer l’implication du système de la coagulation dans l’hémorragie et un mauvais pronostic chez les patients atteints de leptospirose sévère. Méthodes: 

Dans une étude prospective, les paramètres du système de coagulation ont été mesurés à l’admission et durant le suivi, chez 52 patients consécutifs atteints de leptospirose sévère. Résultats: 

Tous les patients présentaient des troubles de la coagulation tels que: une prolongation du temps de prothrombine (TP) et du temps de la céphaline partielle activée, une activité pro-coagulante marquée (complexes thrombine-antithrombine (TAT), fragments 1 + 2 de la prothrombine, dimères D), des taux réduits des marqueurs anticoagulants (protéine C, antithrombine) et une augmentation de l’activité des complexes (anti-) fibrinolytique (plasmine-antiplasmine (PAP), activateur/inhibiteur-1 du plasminogène).

Ces troubles étaient plus prononcés chez les patients décédés par la suite. La prolongation du TP était associée à la mortalité (OR: 1,4, IC95%: 1,0-1,8; p  =  .04). Des saignements sont survenus chez 31 sujets (60%). Parmi eux, 24 avaient des saignements légers et 7 avaient des hémorragies graves. La thrombocytopénie (numération plaquettaire ≤ 100x109/L) était significativement associée à un saignement clinique (OR: 4,6; IC95%: 1,3-16). Une sous-analyse des patients avec ou sans saignement grave a révélé un déséquilibre plus marqué du système de coagulation chez les patients présentant une hémorragie sévère, reflété par une association significative avec le TP (OR: 1,4; IC95%: 1,0-1,8; p = 0.05) et le rapport TAT/PAP (OR: 1,3; IC95%: 1,0-1,6; p  =  .05), qui est un indicateur de l’équilibre entre la coagulation et la fibrinolyse. De façon manifeste, une coagulation intravasculaire disséminée (CIVD) a été trouvée chez 10 (22%) des 46 patients pour lesquels le score pouvait être calculé. Il n’y avait aucune association significative entre les scores CIVD, la diathèse hémorragique ou un mauvais pronostic. Conclusion: 

Le système de la coagulation était fortement activé chez les patients atteints de leptospirose. Cela était plus prononcé chez les personnes décédées et chez les patients présentant une hémorragie sévère que chez les survivants et les personnes sans saignement grave.

Keywords: Leptospira; Leptospirosis; coagulación; coagulación intravascular diseminada; coagulation; coagulation intravasculaire disséminée; disseminated intravascular coagulation; fibrinolyse; fibrinolysis; fibrinólisis; leptospirose; leptospirosis; sepsis; septicémie

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1365-3156.2009.02434.x

Affiliations: 1:  Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands 2:  KIT Biomedical Research, Royal Tropical Institute (KIT), Amsterdam, The Netherlands 3:  Department of Internal Medicine Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia 4:  Leptospirosis Laboratory, Department of Microbiology Faculty of Medicine, Diponegoro University, Semarang, Indonesia 5:  Departments of Vascular Medicine and Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Publication date: 2010-02-01

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