Leytin Valery, Mazer David, Mody Meera, Garvey Bernadette, Freedman John
Department of Transfusion Medicine, St. Michael's Hospital, Toronto, Canada.
Br J Haematol. 2003 Feb;120(3):535-41. doi: 10.1046/j.1365-2141.2003.04068.x.
Haemoglobin-based oxygen carriers (HBOCs) are anticipated to be safe and efficient alternatives to RBC transfusions. Haemoglobin (Hb) raffimer (Hemolink; Hemosol, Toronto, ON, Canada) is polymerized human Hb, cross-linked with o-raffinose. As administration of cell-free Hb may affect blood cells and tissues, this study was focused on evaluating effects of Hb raffimer on human platelets in whole blood in vitro. Citrated blood from healthy donors was incubated with Hb raffimer to achieve raffimer concentrations of 2-50 vol percentage (2-50 g/l). Platelet activation, phosphatidylserine exposure and microparticle generation were measured by flow cytometry. Aperture closure time on collagen/ADP- and collagen/epinephrine-coated membranes was determined by a platelet function analyser (PFA-100). We found that addition of Hb raffimer to blood samples up to 50 vol % did not affect human platelets as measured by various markers of platelet activation (CD42b, CD41, PAC-1, CD62, CD63), procoagulant activity (annexin V) and microparticle formation; differences between Hb raffimer- and lactated Ringer's-diluted blood were not significant. Similarly, no adverse effect of Hb raffimer on closure time was observed at concentrations up to 50 vol %, in comparison with Ringer's solution. These data indicate that exposure of human blood to high concentrations of Hb raffimer in vitro did not cause platelet activation nor affect platelet function.
基于血红蛋白的氧载体(HBOCs)有望成为红细胞输血安全有效的替代品。血红蛋白(Hb) raffimer(Hemolink;Hemosol,加拿大安大略省多伦多市)是与人血红蛋白交联的聚合人血红蛋白。由于无细胞血红蛋白的给药可能会影响血细胞和组织,本研究重点评估了Hb raffimer在体外对全血中人类血小板的影响。将健康供体的枸橼酸盐血与Hb raffimer孵育,使raffimer浓度达到2 - 50体积百分比(2 - 50 g/l)。通过流式细胞术测量血小板活化、磷脂酰丝氨酸暴露和微粒生成。通过血小板功能分析仪(PFA - 100)测定胶原/ADP和胶原/肾上腺素包被膜上的孔径闭合时间。我们发现,在高达50体积%的血样中添加Hb raffimer,通过血小板活化的各种标志物(CD42b、CD41、PAC - 1、CD62、CD63)、促凝活性(膜联蛋白V)和微粒形成来衡量,对人类血小板没有影响;Hb raffimer稀释血与乳酸林格氏液稀释血之间的差异不显著。同样,与林格氏液相比,在高达50体积%的浓度下,未观察到Hb raffimer对闭合时间有不良影响。这些数据表明,体外将人类血液暴露于高浓度的Hb raffimer不会引起血小板活化,也不会影响血小板功能。