Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin

Romy M. W. Kremers*, Stephane Zuily, Hilde Kelchtermans, Tessa C. Peters, Saartje Bloemen, Veronique Regnault, H. Coenraad Hemker, Philip G. de Groot, Denis Wahl, Bas de Laat

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Web of Science)

Abstract

Antiphospholipid syndrome (APS) is a condition in which the presence of antibodies against phospholipid-binding proteins is associated with thrombophilia and/or pregnancy morbidity. Although antiphospholipid antibodies have anticoagulant characteristics in vitro, they are associated with thromboembolic complications. Thrombin generation (TG) is a sensitive global test of coagulation, and elevated TG is associated with thrombosis. Increased TG can be caused by increased prothrombin conversion, decreased thrombin inactivation, or a combination of both. In this study, we measured TG in APS patients and healthy controls with and without vitamin K antagonist (VKA) treatment at 1 and 5 pMtissue factor andwith thrombomodulin. Prothrombin conversion and thrombin inactivation were determined by thrombin dynamics analysis. The TG peak was increased in nontreated APS patients at 1 pM TF compared with nontreated controls. Prothrombin conversion was significantly increased in nontreated APS patients. In contrast, prothrombin conversion did not differ in controls and patients that were on VKA therapy. Thrombin inactivation was comparable between controls and APS patients in the presence and absence of VKAs. Both TG (peak and ETP) and prothrombin conversion were significantly higher in APS patients with prior thrombosis compared with patients without a history of thrombosis. In this study, we demonstrate that in APS, the hemostatic balance shifts toward amore prothrombotic phenotype due to elevated prothrombin conversion but unchanged thrombin inactivation rates. Within the group of APS patients, increased TG and prothrombin conversion are associatedwith a history of thrombosis.
Original languageEnglish
Pages (from-to)1315-1324
Number of pages10
JournalBlood advances
Volume2
Issue number11
DOIs
Publication statusPublished - 12 Jun 2018

Keywords

  • ACTIVATED PROTEIN-C
  • THROMBIN GENERATION
  • LUPUS ANTICOAGULANTS
  • ACQUIRED-RESISTANCE
  • HEMOPHILIA-A
  • ANTIBODIES
  • RISK
  • UPDATE
  • ASSAY
  • HYPOCOAGULABILITY

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