Plasmatic Coagulation Capacity Correlates With Inflammation and Abacavir Use During Chronic HIV Infection

Wouter A. van der Heijden*, Jun Wan, Lisa Van de Wijer, Martin Jaeger, Mihai G. Netea, Andre J. van der Ven, Philip G. de Groot, Mark Roest, Quirijn de Mast

*Corresponding author for this work

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Abstract

Background: D-dimer concentrations in people living with HIV (PLHIV) on combination antiretroviral therapy (cART) are increased and have been linked to mortality. D-dimer is a biomarker of in vivo coagulation. In contrast to reports on D-dimer, data on coagulation capacity in PLHIV are conflicting. In this study, we assessed the effect of cART and inflammation on coagulation capacity. Setting: We explored coagulation capacity using calibrated thrombin generation (TG) and linked this to persistent inflammation and cART in a cross-sectional study including PLHIV with viral suppression and uninfected controls. Methods: We used multivariate analyses to identify independent factors influencing in vivo coagulation (D-dimer) and ex vivo coagulation capacity (TG). Results: Among 208 PLHIV, 94 (45%) were on an abacavir-containing regimen. D-dimer levels (219.1 vs 170.5 ng/mL, P = 0.001) and inflammatory makers (sCD14, sCD163, and high-sensitive C-reactive protein) were increased in PLHIV compared with those in controls (n = 56). PLHIV experienced lower TG (reflected by endogenous thrombin potential [ETP]) when compared with controls, after correction for age, sex, and antiretroviral therapy. Abacavir use was independently associated with increased ETP. Prothrombin concentrations were strongly associated with ETP and lower in PLHIV on a non-abacavir-containing regimen compared with those in controls, suggesting consumption as a possible mechanism for HIV-associated reduction in TG. D-dimer concentrations were associated with inflammation, but not TG. Conclusions: Abacavir use was associated with increased TG and could serve as an additional factor in the reported increase in thrombotic events during abacavir use. Increased exposure to triggers that propagate coagulation, such as inflammation, likely underlie increased D-dimer concentrations found in most PLHIV.

Original languageEnglish
Pages (from-to)711-719
Number of pages9
JournalJaids-journal of Acquired Immune Deficiency Syndromes
Volume87
Issue number1
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • D-dimer
  • thrombin generation
  • abacavir
  • inflammation
  • coagulation
  • thrombosis
  • MYOCARDIAL-INFARCTION
  • THROMBIN GENERATION
  • ANTIRETROVIRAL THERAPY
  • PLATELET REACTIVITY
  • RISK
  • MORTALITY
  • INDIVIDUALS
  • ASSOCIATION
  • DISEASE
  • MARKERS

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