Racial differences in endotoxin-induced tissue factor-triggered coagulation |
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Authors: | F B MAYR§ A O SPIEL J M LEITNER C FIRBAS P JILMA-STOHLAWETZ† J-Y CHANG‡ N S KEY‡ B JILMA¶ |
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Institution: | Departments of Clinical Pharmacology;;Blood Group Serology &Transfusion Medicine, Medical University of Vienna, Austria;;Division of Hematology, Oncology, and Transplantation, University of North Carolina, Chapel Hill, NC;;CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA;;and Department of Pharmaceutics, College of Pharmacy, University of Florida Gainesville, FL, USA |
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Abstract: | 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 (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). 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. |
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Keywords: | coagulation Duffy antigen endotoxin MCP-1 tissue factor |
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