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Racial differences in endotoxin‐induced tissue factor‐triggered coagulation
Author(s) -
MAYR F. B.,
SPIEL A. O.,
LEITNER J. M.,
FIRBAS C.,
JILMASTOHLAWETZ P.,
CHANG J.Y.,
KEY N. S.,
JILMA B.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03307.x
Subject(s) - tissue factor , coagulation , fibrin , medicine , immunology , antigen , thrombin , antithrombin , lipopolysaccharide , endocrinology , platelet , heparin
Summary. Background: Racial differences in coagulation are poorly understood. While some studies suggest a ‘prothrombotic’ coagulation profile in blacks compared with whites, others report an increased bleeding risk for blacks in various clinical settings. Moreover, preclinical data suggest a link between the Duffy antigen (= DARC, Duffy antigen receptor of chemokines) and coagulation. Objectives: Based on our previous research in Duffy antigen negative Africans, we hypothesized that Africans have an attenuated procoagulant response compared with Caucasians in a model of lipopolysaccharide (LPS)‐induced, tissue factor (TF)‐triggered coagulation activation. Patients/methods: Healthy male volunteers (16 Duffy‐negative Africans, 16 Duffy‐positive Caucasians) received 2 ng kg −1 LPS, and outcome parameters were measured using enzyme immunoassays and real‐time polymerase chain reaction (RT‐PCR, Taqman). Results: LPS increased microparticle (MP)‐associated TF procoagulant activity (PCA) less in Africans than Caucasians. Africans had reduced in vivo thrombin formation compared with Caucasians: they generated less thrombin–antithrombin (TAT) complexes (10.4 pg mL −1 vs. 23.0 pg mL −1 , P < 0.0001) and less prothrombin fragments (F 1+2 ) (337 pmol mL −1 vs. 819 pmol mL −1 , P < 0.0001). Consistently, Africans also had decreased fibrin formation ( d ‐dimer: 0.3 pg mL −1 vs. 0.5 pg mL −1 , P = 0.02). Conclusion: Duffy‐negative subjects of African descent have a markedly reduced procoagulant response in a model of LPS‐induced, TF‐triggered coagulation activation compared with Duffy‐positive healthy Caucasians.