Red cell-derived microparticles (RMP) as haemostatic agent

Wenche Jy, Max E. Johansen, Carlos Bidot, Lawrence L. Horstman, Yeon Ahn

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 μm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

Original languageEnglish
Pages (from-to)751-760
Number of pages10
JournalThrombosis and Haemostasis
Volume110
Issue number4
DOIs
StatePublished - Oct 7 2013

Fingerprint

Cell-Derived Microparticles
Hemostatics
Blood Platelets
Thrombelastography
Bleeding Time
clopidogrel
Thromboplastin
Thrombin
Flow Cytometry
Hemorrhage
Rabbits
Busulfan
Annexin A5
Proxy
Hemostasis
Platelet Aggregation
Adenosine Diphosphate
Phospholipids
Light
Pressure

Keywords

  • Animal bleeding models
  • Haemostatic agent
  • Red cell microparticles (RMP)
  • RMP-platelet interaction
  • Thromboelastography

ASJC Scopus subject areas

  • Hematology

Cite this

Jy, W., Johansen, M. E., Bidot, C., Horstman, L. L., & Ahn, Y. (2013). Red cell-derived microparticles (RMP) as haemostatic agent. Thrombosis and Haemostasis, 110(4), 751-760. https://doi.org/10.1160/TH12-12-0941

Red cell-derived microparticles (RMP) as haemostatic agent. / Jy, Wenche; Johansen, Max E.; Bidot, Carlos; Horstman, Lawrence L.; Ahn, Yeon.

In: Thrombosis and Haemostasis, Vol. 110, No. 4, 07.10.2013, p. 751-760.

Research output: Contribution to journalArticle

Jy, W, Johansen, ME, Bidot, C, Horstman, LL & Ahn, Y 2013, 'Red cell-derived microparticles (RMP) as haemostatic agent', Thrombosis and Haemostasis, vol. 110, no. 4, pp. 751-760. https://doi.org/10.1160/TH12-12-0941
Jy, Wenche ; Johansen, Max E. ; Bidot, Carlos ; Horstman, Lawrence L. ; Ahn, Yeon. / Red cell-derived microparticles (RMP) as haemostatic agent. In: Thrombosis and Haemostasis. 2013 ; Vol. 110, No. 4. pp. 751-760.
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