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

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 HIV-infected 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 CD4(+)cell 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.