Hemostatic system in Takotsubo patients at long-term follow-up: A hidden activation?

Int J Cardiol. 2023 Nov 1:390:131229. doi: 10.1016/j.ijcard.2023.131229. Epub 2023 Jul 30.

Abstract

Background: Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients.

Methods: We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit.

Results: Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase.

Conclusions: The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes.

Keywords: BDNF; Coagulation; Fibrinogen; PAI-1; TF; Takotsubo cardiomyopathy.

MeSH terms

  • Brain-Derived Neurotrophic Factor
  • Female
  • Fibrin
  • Fibrinogen
  • Hemostatics*
  • Humans
  • Plasminogen Activator Inhibitor 1
  • Takotsubo Cardiomyopathy* / diagnosis

Substances

  • Plasminogen Activator Inhibitor 1
  • Brain-Derived Neurotrophic Factor
  • Hemostatics
  • Fibrinogen
  • Fibrin