Affordable Access

deepdyve-link
Publisher Website

Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists.

Authors
  • Garabet, Lamya1, 2, 3
  • Ghanima, Waleed3, 4
  • Hellum, Marit3, 5
  • Sandset, Per Morten3, 6, 7
  • Bussel, James B8
  • Tran, Hoa9
  • Henriksson, Carola E3, 5
  • 1 Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Lørenskog, Norway. , (Norway)
  • 2 Center for Laboratory Medicine, Østfold Hospital Trust, Grålum, Norway. , (Norway)
  • 3 Institute of Clinical Medicine, University of Oslo, Norway. , (Norway)
  • 4 Department of Research, Østfold Hospital Trust, Grålum, Norway. , (Norway)
  • 5 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. , (Norway)
  • 6 Department of Haematology, Oslo University Hospital, Oslo, Norway. , (Norway)
  • 7 Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway. , (Norway)
  • 8 Department of Pediatrics, Division of Hematology, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA.
  • 9 Department of Haematology, Akershus University Hospital, Lørenskog, Norway. , (Norway)
Type
Published Article
Journal
Platelets
Publisher
Informa UK (Taylor & Francis)
Publication Date
Jan 01, 2020
Volume
31
Issue
3
Pages
322–328
Identifiers
DOI: 10.1080/09537104.2019.1639655
PMID: 31280643
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Immune thrombocytopenia (ITP) patients have thrombocytopenia and increased bleeding risk, but, conversely, they also have increased thrombotic risk which appears to be exacerbated by thrombopoietin-receptor agonist (TPO-RA)-treatment. Microvesicles (MVs) released from activated/apoptotic cells are prothrombotic due to exposure of phosphatidylserine (PS) and tissue factor (TF). MVs are increased in ITP patients, but their prothrombotic effect, before and during treatment with TPO-RAs, is unclear.We studied the effect of TPO-RAs on the procoagulant activity of MVs in 11 ITP patients, before, and two and six weeks after initiation of treatment, and in 15 healthy controls. MV-associated PS-activity, TF-activity and the capacity of isolated MVs and plasma to generate thrombin in a phospholipid-dependent manner were measured.Before treatment with TPO-RAs, prothrombotic markers in ITP patients were comparable to levels found in healthy controls. After both two and six weeks of TPO-RA-treatment, ITP patients had higher MV-associated PS-activity and phospholipid-dependent thrombin generation in plasma than controls. In addition, ITP patients had increased phospholipid-dependent MV-associated thrombin generation two weeks after initiation of TPO-RA-treatment compared with controls and pre-treatment levels. MV-associated TF-activity was low in controls and in ITP patients before and after initiation of TPO-RA-treatment.In conclusion, TPO-RAs increase phospholipid-dependent MV-associated thrombin generation in ITP patients. This could contribute to or exacerbate a pre-existing hypercoagulable state. Phospholipid-dependent thrombin generation generated by isolated MVs, or measured directly in plasma, may be potential tools that could help in the risk-assessment of future thromboembolic events in ITP patients, both before and after initiation of TPO-RA-treatment.

Report this publication

Statistics

Seen <100 times