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 journalArticle

24 Citations (Scopus)

Abstract

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
Volume54
Issue number4
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Thrombosis
Proteins
Equipment and Supplies
Heart-Assist Devices
Carboxypeptidase B2
Coagulation
High Molecular Weight Kininogens
Chemical activation
Thromboplastin
Tissue
Molecular weight
Factor XII
Morbidity
Platelet Activation
Tissue Plasminogen Activator
Platelets
Thrombin
Growth

ASJC Scopus subject areas

  • Biophysics
  • Biomaterials
  • Bioengineering
  • Biomedical Engineering
  • Medicine(all)

Cite this

Nielsen, V. G., Kirklin, J. K., Holman, W. L., Steenwyk, B. L., George, J. F., Zhou, F., ... Ellis, T. C. (2008). Mechanical circulatory device thrombosis: A new paradigm linking hypercoagulation and hypofibrinolysis. ASAIO Journal, 54(4), 351-358. https://doi.org/10.1097/MAT.0b013e31817f3e03

Mechanical circulatory device thrombosis : A new paradigm linking hypercoagulation and hypofibrinolysis. / Nielsen, Vance G; Kirklin, James K.; Holman, William L.; Steenwyk, Brad L.; George, James F.; Zhou, Fen; Parks, Dale A.; Ellis, Truitt C.

In: ASAIO Journal, Vol. 54, No. 4, 07.2008, p. 351-358.

Research output: Contribution to journalArticle

Nielsen, VG, Kirklin, JK, Holman, WL, Steenwyk, BL, George, JF, Zhou, F, Parks, DA & Ellis, TC 2008, 'Mechanical circulatory device thrombosis: A new paradigm linking hypercoagulation and hypofibrinolysis', ASAIO Journal, vol. 54, no. 4, pp. 351-358. https://doi.org/10.1097/MAT.0b013e31817f3e03
Nielsen, Vance G ; Kirklin, James K. ; Holman, William L. ; Steenwyk, Brad L. ; George, James F. ; Zhou, Fen ; Parks, Dale A. ; Ellis, Truitt C. / Mechanical circulatory device thrombosis : A new paradigm linking hypercoagulation and hypofibrinolysis. In: ASAIO Journal. 2008 ; Vol. 54, No. 4. pp. 351-358.
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