Thromboelastography on plasma in virologically suppressed HIV-positive patients compared with healthy controls

Abstract

BackgroundCardiovascular events in people infected with HIV are an emerging clinical problem and the underlying mechanisms are poorly understood. We examined functional plasma coagulation in HIV-infected people compared with healthy individuals on the basis of the hypothesis that plasma samples from HIV-infected people display hypocoagulable properties as an adaptive response to ensure blood flow through an activated, procoagulant endothelium. MethodsThis cross-sectional study was done at Rigshospitalet (Copenhagen, Denmark). The study population comprised 67 HIV-infected people (97% white, 91% men, median age 55 years) who had received continuous combination antiretroviral treatment for a median of 12·5 years. 15 age-matched and sex-matched blood donors who were negative for HIV and viral hepatitis served as controls (median age 57 years; 87% men). All participants gave written informed consent. The study was approved by the local ethics committee. The clotting potential of plasma (pure fibrin clot) was assessed by thromboelastography. Thawed EDTA plasma was recalcified, activated with tissue factor, and analysed immediately at 37°C. To assess the clot resistance to fibrinolysis, the samples were analysed both with and without addition of tissue-type plasminogen activator. The indices recorded were reaction time (time until initial fibrin clot formation), angle (rapidity of fibrin clot build-up), maximum amplitude (strength of the fibrin clot), lysis after 30 and 60 min (percentage amplitude reduction after 30 and 60 min), and clot lysis time (time between maximal amplitude and 2 mm amplitude). Results are presented as medians with IQRs. Groups were compared with the Mann-Whitney test. FindingsCompared with healthy individuals (n=15), HIV-infected people (n=67) had delayed clot formation with a longer clot reaction time (14·1 min [12·2–17·4] vs 11·2 min [9·2–13·1]; p=0·0007) and a smaller angle on thromboelastography tracing curve (22·9° [19·3–30·0] vs 48·6° [40·8–56·7]; p<0·0001), indicative of reduced clot initiation and thrombin generation. Furthermore, HIV-infected people had reduced resistance to tissue-type plasminogen activator induced clot lysis (reduction of amplitude after 30 min of 53·6% [38·1–67·5] vs 24·2% [11·1–34·3], p<0·0001; and reduction at 60 min of 76·9% [68·1–84·6] vs 59·9% [47·3–65·6], p<0·0001). In addition they had a shortened clot lysis time (23·2 min [17·6–32·3] vs 37·3 min [33·1–45·5]; p=0·0003), indicative of altered fibrin clot structure. Clot strength as measured by maximal amplitude was similar between groups (25·4 mm [21·9–32·3] vs 24·9 mm [23·7–31·3], p=0·99). InterpretationPeople infected with HIV displayed altered functional plasma coagulation compared with healthy individuals, which could be associated with their increased cardiovascular risk. This study is limited by the small number of healthy individuals, and the lack of information on cardiovascular risk factors—such as smoking—in the study population. The strengths of the study are the long follow-up of uninterrupted treatment and the substantial number of patients. This is, to our knowledge, the first study examining the clotting potential of plasma in HIV infected people and the results call for larger studies to determine the clinical implications of this finding. FundingThis work was supported by the Danish Medical Research Council, The Danish AIDS Foundation, AP Møller and wife Chastine Mc-Kinney Møller's Foundation (Fonden til Lægevidenskabens Fremme), the Augustinus Foundation, Grosser LF Foght's Foundation, Bjørn Aastrup's Foundation for AIDS research, Alfred Helsted's and Eli Møller's grant, and Rigshospitalet's Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the abstract.