Influence of O₂‐carrying plasma hemoprotein “albumin‐heme” on complement system and platelet activation in vitro and physiological responses to exchange transfusion

Abstract

Recombinant human serum albumin (HSA) including the synthetic iron(II)-porphyrin (FeP), albumin-heme (HSA-FeP), is a unique O(2)-carrying plasma hemoprotein as a red blood cell substitute. We have investigated the possible influence of HSA-FeP on the complement system and platelet activation in vitro. The amounts of the serum complement titer CH(50) and terminal complement complex SC5b-9 of human blood serum, incubated with HSA-FeP (10, 20, and 40 vol %), were almost the same as those of the corresponding samples with HSA. The effect of HSA-FeP on the platelet reactivity has been demonstrated by conformational changes in the membrane glycoprotein IIb/IIIa and surface expression of an alpha-granule membrane protein P-selectin. Platelet activation in response to the ADP-stimulation was not influenced by the presence of HSA-FeP. It can be concluded that the albumin-heme solution does not facilitate the immunological reaction and platelet activation. Moreover, a 20% exchange transfusion with HSA-FeP into anesthetized rats has been performed to evaluate the circulation and blood parameters for 6 h. Time course changes in all parameters showed features identical to the control group (without infusion) and HSA group.

Artificial Oxygen Carriers, Hemoglobin Vesicles and Albumin−Hemes, Based on Bioconjugate Chemistry

“…The obtained solution showed a long shelf-life of over two years at room temperature . Furthermore, HSA-FeP 1 has no effect on the morphology of blood cell components and does not engender immunological reaction and platelet activation . Upon addition of O 2 gas through this solution, the visible absorption spectrum immediately changed to that of the O 2 adduct complex.…”

Linking Labile Heme with Thrombosis

“…In contrast, in 2000 a decreased platelet count (from 129000/mm 3 to 72000/mm 3 ) was determined in an AIP patient after hematin (Panhematin ® ; 4 mg/kg) administration [ 168 ]. At about the same time, an albumin (50 g/L)-heme (3 mM) mixture was demonstrated to have no effect on the platelet count of a blood suspension from rats [ 179 ] as well as on the ADP-stimulated activation of platelets as demonstrated by the proportion of PAC-1 positive platelets in human whole blood [ 194 ].…”

Structural and Mutagenic Approach to Create Human Serum Albumin-Based Oxygen Carrier and Photosensitizer

“…19) We investigated HSA incorporating synthetic Fe 2＋ porphyrin (FeP)``HSA-FeP'' as an entirely synthetic O2 transporter. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] A saline solution of HSA-FeP is a most promising material for RBC substitute. In this review, we describe very recent results on the O2 carrier formed by complexing natural Fe 2＋ protoporphyrin IX (heme) with genetically engineered HSA and on photosensitizer formed by complexing carboxy-C60-fullerene (CF) with HSA ( Fig.…”