Discrepant coagulation profile in HIV infection: Elevated D-dimer but impaired platelet aggregation and clot initiation

摘要

Objectives: In HIV infection, cardiovascular disease (CVD) has emerged as a clinical problem, and elevated D-dimer has been reported. The pathophysiologic mechanisms underlying this remain unclear. We aimed to investigate whether untreated HIVinfected individuals display evidence of functional coagulopathy and whether this was associated with microbial translocation. Design: The study population consisted of 50 HIV-infected untreated individuals and 50 HIV-infected individuals on combination antiretroviral therapy (cART). Groups were matched for age, sex and current CD4cell count. Methods: Coagulation analyses included D-dimer and the functional haemostatic whole blood tests, thromboelastography (TEG) and platelet aggregation (Multiplate, impedance aggregometry). Microbial translocation was assessed by plasma levels of lipopolysaccharide (LPS). Results: A larger proportion of untreated individuals compared with treated individuals had D-dimer above normal reference range (27.7 vs. 2.2%, P=0.001). In both treated and untreated individuals, delayed clot initiation with TEG R-time above upper reference range (18 and 28%, respectively, both P<0.001) and TEG angle below lower reference range [14% (P=0.004) and 24% (P<0.001), respectively] was found. In untreated individuals, 64.6% had aggregation response below threshold in at least two of four tests compared with 36.7% in treated individuals (P=0.010). Untreated individuals with increased D-dimer levels were relatively hypercoagulable by thromboelastography. Furthermore, in untreated patients, a negative association between microbial translocation and platelet aggregation was found. Conclusion: Elevated D-dimer in untreated HIV-infected individuals was confirmed. However, in both untreated and treated individuals, reduced platelet aggregation and clot initiation was found. The impact of reduced platelet function in HIV infection and a potential role of microbial translocation warrant further investigation.