Mechanical circulatory device thrombosis: A new paradigm linking hypercoagulation and hypofibrinolysis

Vance G. Nielsen, James K. Kirklin, William L. Holman, Brad L. Steenwyk, James F. George, Fen Zhou, Dale A. Parks, Truitt C. Ellis

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


This review considers the perhaps unappreciated role of contact pathway proteins in the pathogenesis of thrombotic/thromboembolic morbidity associated with mechanical circulatory support. Placement of ventricular assist devices (VADs) has been associated with consumption of circulating contact proteins and persistent generation of activated contact proteins such as Factor XII and high molecular weight kininogen. Importantly, activated contact proteins are absorbed to the surface of VADs via the Vroman effect. Further, hyperfibrinogenemia and persistent platelet activation exist in patients with VADs, likely contributing to speed of clot growth. Using thrombelastographic-based analyses, it has been determined that contact pathway protein activated coagulation results in a thrombus that develops strength at a significantly faster rate that tissue factor initiated coagulation. Further, thrombelastographic analyses that include the addition of tissue-type plasminogen activator have demonstrated that contact protein pathway activation results in thrombin activatable fibrinolysis inhibitor activation to a far greater extent than that observed with tissue factor initiated coagulation, resulting in a thrombus that takes significantly longer to lyse. These observations serve as the rational basis for clinical investigation to determine if regional suppression of thrombin generation with FXII/high molecular weight kininogen inhibition in concert with thrombin-activatable fibrinolysis inhibitor inhibition may decrease mechanical circulatory support-associated thrombotic morbidity.

Original languageEnglish (US)
Pages (from-to)351-358
Number of pages8
JournalASAIO Journal
Issue number4
StatePublished - Jul 2008

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering


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