Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever.
A prospective cohort study was performed in 50 patients with dengue haemorrhagic fever (DHF) to determine the potential role of the contact activation system and factor XI activation (intrinsic pathway) in the coagulation disorders in DHF. To establish whether TAFI (thrombin-activatable fibrinolysis inhibitor) was involved in the severity of the coagulation disorders, the TAFI antigen and activity levels were also determined. Markers of contact activation (kallikrein--C1-inhibitor complexes), the intrinsic pathway of coagulation (factor XIa--C1-inhibitor complexes) and TAFI were measured and correlated to thrombin generation markers (thrombin--anti-thrombin complexes (TAT), prothrombin fragment 1+2 (F1+2)) and a marker for fibrinolysis [plasmin--alpha 2--anti-plasmin complexes (PAP)]. Activation of the intrinsic pathway of coagulation was clearly demonstrated by elevated levels of factor XIa--C1-inhibitor complexes, without evidence of contact activation, reflected by undetectable kallikrein--C1-inhibitor complexes. Both TAFI antigen and activity levels were decreased in all patients, which may contribute to the severity of bleeding complications in DHF because of the impaired capacity of the coagulation system to protect the fibrin clot from fibrinolysis. These findings in a human viral infection model are in accordance with earlier findings in bacterial sepsis.
van Gorp
E C
EC
Department of Internal Medicine Slotervaart Hospital, Amsterdam, The Netherlands. ecmvangorp@yahoo.com.uk
Minnema
M C
MC
Suharti
C
C
Mairuhu
A T
AT
Brandjes
D P
DP
ten Cate
H
H
Hack
C E
CE
Meijers
J C
JC
D001324:Autoantigens / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005172:Factor XI / Q000378:metabolism*; D005246:Feedback; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D019595:Severe Dengue / Q000097:blood*; D018709:Statistics, Nonparametric; D013917:Thrombin / Q000378:metabolism*
D001324:Autoantigens; D015415:Biomarkers; D005172:Factor XI; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D013917:Thrombin