Prothrombin, alone or in complex concentrates or plasma, reduces bleeding in a mouse model of blood exchange-induced coagulopathy

Scientific Reports

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[1] 0000 0001 0285 1288, grid.423370.1, Centre for Innovation, Canadian Blood Services, Hamilton, ON, Canada;0000 0001 0285 1288, grid.423370.1, Centre for Innovation, Canadian Blood Services, Hamilton, ON, Canada;0000 0004 1936 8227, grid.25073.33, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada;0000 0001 0285 1288, grid.423370.1, Centre for Innovation, Canadian Blood Services, Hamilton, ON, Canada;0000 0004 1936 8227, grid.25073.33, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada;Faculty of Health Sciences, Ontario Tech University, Oshawa, ON, Canada;0000 0001 0285 1288, grid.423370.1, Centre for Innovation, Canadian Blood Services, Toronto, ON, Canada;grid.415502.7, Department of Laboratory Medicine, University of Toronto and Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, ON, Canada;0000 0001 0285 1288, grid.423370.1, Centre for Innovation, Canadian Blood Services, Vancouver, BC, Canada;0000 0001 2288 9830, grid.17091.3e, Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada;0000 0004 5879 2987, grid.282569.2, IONIS Pharmaceuticals, Carlsbad, CA, United States;

DOI  :  10.1038/s41598-019-49552-9

来源: publisher

【 摘 要 】

Prothrombin complex concentrates (PCC) are fractionated plasma protein drugs that reverse warfarin anticoagulation. PCC may control more general bleeding. We sought to identify the dominant procoagulant factor in PCC in vivo. We tested PCC or coagulation factor (F) treatment in CD1 mice made coagulopathic by exchange of whole blood for washed red cells. Anesthetized mice were transfused with murine fresh-frozen plasma (mFFP), PCC, mixtures of human vitamin K-dependent proteins (VKDP) (prothrombin, FVII, FIX, or FX), or purified single human VKDP, immediately prior to tail transection (TT), liver laceration (LL), or intravascular laser injury (ILI). Plasma donor mice were treated with vehicle or control antisense oligonucleotide (ASO-CON) or ASO specific for prothrombin (FII) (ASO-FII) to yield mFFP or ASO-CON mFFP or ASO-FII mFFP. Blood losses were determined spectrophotometrically (TT) or gravimetrically (LL). Thrombus formation was quantified by intravital microscopy of laser-injured arterioles. PCC or four factor- (4F-) VKDP or prothrombin significantly reduced bleeding from TT or LL. Omission of prothrombin from 4F-VKDP significantly reduced its ability to limit bleeding. Mice transfused with ASO-FII mFFP demonstrated inferior haemostasis versus those transfused with ASO-FII following TT, LL, or ILI. Prothrombin is the dominant procoagulant component of PCC and could limit bleeding in trauma.

【 授权许可】

CC BY