Racial differences in endotoxin-induced tissue factor-triggered coagulation.
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.


OBJECTIVE
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.


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 (F1+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).


CONCLUSIONS
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.
Mayr
F B
FB
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Spiel
A O
AO
Leitner
J M
JM
Firbas
C
C
Jilma-Stohlawetz
P
P
Chang
J-Y
JY
Key
N S
NS
Jilma
B
B
D000328:Adult; D015415:Biomarkers / Q000097:blood; D044383:Black People; D001777:Blood Coagulation / Q000187:drug effects*; D004375:Duffy Blood-Group System / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D044469:Racial Groups; D019851:Thrombophilia / Q000453:epidemiology*; D013925:Thromboplastin / Q000494:pharmacology; D044465:White People; D055815:Young Adult
D015415:Biomarkers; D004375:Duffy Blood-Group System; D004731:Endotoxins; D008070:Lipopolysaccharides; D013925:Thromboplastin