Fibrinolysis in patients with chemotherapy-induced thrombocytopenia and the effect of platelet transfusion

Floor C. J. I. Heubel-Moenen*, Yvonne M. C. Henskens, Paul W. M. Verhezen, Rick J. H. Wetzels, Harry C. Schouten, Erik A. M. Beckers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Essentials

Bleeding in chemotherapy induced thrombocytopenia (CIT) might be influenced by hyperfibrinolysis. t-PA-thromboelastography is a fast and reliable assay for hyperfibrinolysis in CIT patients. Clots of CIT patients are more susceptible to t-PA induced lysis compared to healthy individuals. Besides platelets, other factors are likely to influence clot lysis in CIT patients. Background Bleeding events in chemotherapy-induced thrombocytopenic (CIT) patients with similar platelet counts might be influenced by changes in clot lysis potential. Objectives To investigate, in an observational study, thromboelastographic lysis parameters, alterations in clot strength and susceptibility to clot lysis in CIT patients. To identify factors associated with fibrinolytic profiles, and to evaluate the effects of platelet transfusions. Methods Independent determinants of tissue-type plasminogen activator (t-PA)-ROTEM lysis parameters were identified with multivariable linear regression. Clot formation, strength and lysis parameters were compared with the results of healthy individuals. Characteristics of CIT patients with and without hyperfibrinolytic profiles were compared. t-PA-ROTEM results before, 1 hour after and 24 hours after platelet transfusion were compared. Results A total of 72 consecutive CIT patients were included. t-PA-ROTEM lysis parameters correlated with changes in fibrinolytic proteins. Clot formation time was longer, maximum clot firmness was weaker and lysis times were shorter than in healthy individuals. CIT patients had low plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor levels, and 40% showed hyperfibrinolytic profiles. Platelet transfusions resulted in less hyperfibrinolytic profiles in many, but not all CIT patients. Patients without hyperfibrinolytic profiles had higher fibrinogen, factor VIII and alpha(2)-antiplasmin levels. Conclusions t-PA-ROTEM can be used as a fast and reliable assay to detect hyperfibrinolytic profiles in CIT patients. CIT patients have weaker clots, which are more susceptible to clot lysis, than healthy individuals. Besides platelets, other factors are likely to influence clot susceptibility to fibrinolysis in CIT patients. The impact of a hyperfibrinolytic t-PA-ROTEM profile on bleeding remains to be investigated.

Original languageEnglish
Pages (from-to)1073-1084
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • bleeding
  • fibrinolysis
  • platelet transfusion
  • thrombocytopenia
  • thromboelastography
  • TISSUE-PLASMINOGEN ACTIVATOR
  • MULTIPLE-MYELOMA PATIENTS
  • HEMATOLOGICAL MALIGNANCIES
  • IN-VITRO
  • INHIBIT FIBRINOLYSIS
  • FIBRINOGEN LEVELS
  • CANCER-PATIENTS
  • FACTOR-XIII
  • RICH CLOTS
  • PLASMA

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