title: Coagulation disorders in patients with severe leptospirosis are associated with severe bleeding and mortality.
abstract: 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, P = 0.04). Bleeding occurred in 31 subjects (60%). Of these, 24 had mild bleeding and seven had severe haemorrhages. Thrombocytopenia (platelets </=100 x 10(9)/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, P = 0.05) and the TAT/PAP ratio (OR 1.3, 95% CI: 1.0-1.6, P = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. jfpwagenaar@hotmail.com
authors.forename: J F P
authors.initials: JF
authors.lastname: Wagenaar
authors.forename: M G A
authors.initials: MG
authors.lastname: Goris
authors.forename: D L
authors.initials: DL
authors.lastname: Partiningrum
authors.forename: B
authors.initials: B
authors.lastname: Isbandrio
authors.forename: R A
authors.initials: RA
authors.lastname: Hartskeerl
authors.forename: D P M
authors.initials: DP
authors.lastname: Brandjes
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: M H
authors.initials: MH
authors.lastname: Gasem
authors.forename: E C M
authors.initials: EC
authors.lastname: van Gorp
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000469:parasitology*; D001780:Blood Coagulation Tests / Q000379:methods; D004211:Disseminated Intravascular Coagulation / Q000469:parasitology; D004812:Epidemiologic Methods; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007922:Leptospirosis / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D011379:Prognosis; D011517:Prothrombin Time