Activation of the coagulation cascade in patients with leptospirosis.
BACKGROUND
Disseminated intravascular coagulation (DIC) is common among patients with sepsis. Leptospirosis is an important cause of sepsis in tropical areas, and pulmonary hemorrhage associated with thrombocytopenia is the major cause of death, but the coagulopathy in severe leptospirosis has not been further characterized. The aim of this study was to evaluate coagulation factors and the presence of DIC in patients with leptospirosis in northeast Thailand.


METHODS
We measured plasma concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 and evaluated the DIC score in 79 patients with culture-confirmed and/or serologically confirmed leptospirosis and in 33 healthy Thai control subjects.


RESULTS
The median concentrations of fibrinogen, D-dimer, thrombin-antithrombin III complexes, and prothrombin fragment 1,2 were significantly elevated in a cohort of 79 patients with leptospirosis, compared with healthy control subjects (P<or=.001 for all tests). Patients with leptospirosis had significantly longer prothrombin times, longer activated partial thromboplastin times, and lower platelet counts. Thrombocytopenia was present in 38% of case patients and occurred more frequently among patients with culture-negative leptospirosis; in multivariate analysis, it was the only hemostasis factor independently associated with clinical bleeding. Patients who were culture-negative for Leptospira species had higher Acute Physiology and Chronic Health Evaluation II and Sepsis-Related Organ Failure Assessment scores and more bleeding complications. Nearly one-half of patients with leptospirosis had overt DIC as defined by an International Society on Thrombosis and Hemostasis DIC score.


CONCLUSIONS
Activation of the coagulation system is an important feature of leptospirosis. Thrombocytopenia is an indicator of severe disease and risk of bleeding.
Chierakul
Wirongrong
W
Department of Clinical Tropical Medicine, Mahidol University, Bangkok, Thailand. tmwcr@mahidol.ac.th
Tientadakul
Panatsaya
P
Suputtamongkol
Yupin
Y
Wuthiekanun
Vanaporn
V
Phimda
Kriangsak
K
Limpaiboon
Roongrueng
R
Opartkiattikul
Nisarat
N
White
Nicholas J
NJ
Peacock
Sharon J
SJ
Day
Nicholas P
NP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000990:Antithrombin III; D001777:Blood Coagulation / Q000502:physiology*; D004211:Disseminated Intravascular Coagulation / Q000097:blood*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D006801:Humans; D007919:Leptospira / Q000302:isolation & purification*; D007922:Leptospirosis / Q000097:blood* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D010976:Platelet Count / Q000379:methods; D011446:Prospective Studies; D011516:Prothrombin; D011517:Prothrombin Time / Q000379:methods; D018805:Sepsis / Q000097:blood / Q000382:microbiology; D013921:Thrombocytopenia / Q000097:blood
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D010447:Peptide Hydrolases