Künstliche Sauerstoffträger als Alternative zur Bluttransfusion

Abstract

The expected cost-explosion in transfusion medicine (increasing imbalance between donors and recipients, treatment of transfusion-associated complications) increases the socio-economic significance of the development of safe and effective synthetic oxygen carriers as an alternative to the transfusion of allogeneic red blood cells. Currently two types of artificial oxygen carriers have been tested for safety and efficacy in cases of severe anemia otherwise requiring transfusion. Solutions based on human or bovine hemoglobin (HBOC) possess vasoconstrictor properties in addition to their oxygen transport capacity. The impact of vasoconstriction on tissue perfusion and organ function is however not yet fully understood. Nevertheless, in 2001 the bovine HBOC Hemopure was approved in South Africa for treatment of acutely anemic surgical patients. The purely synthetic perfluorocarbon (PFC) emulsions increase the physically dissolved portion of arterial oxygen content. Due to their particulate nature (emulsion droplets) PFCs may only be infused in low doses to avoid overload and malfunction of phagocytic cells of the reticulo-endothelial system. As part of a multimodal blood conservation program (including normovolemic hemodilution and hyperoxia) the low-dose administration of Oxygent effectively increases intraoperative anemia tolerance. Although reduction of perioperative allogeneic blood transfusion has already been demonstrated for HBOC and PFC, the global clinical establishment of artificial oxygen carriers is not to be expected in the near future.

Blood Substitutes

“…Due to its large molecular size, this HBOC is void of nephrotoxic effects. Since prion-inactivation techniques have been implemented into the manufacturing process, the risk of bovine spongiform encephalopathy (BSE) seems to be extremely low, but is still a matter of concern [38]. Contrasting isolated human Hb, the O 2 -affinity of extracellular bovine Hb is not regulated by 2,3-DPG, but by chloride anions.…”

“…While the first-generation r-Hb 1.1 was structurally an analog to DCLHb and had identical side-effects, the second-generation r-Hb (r-Hb 2.0) was a PEG-conjugated Hb-polymer, which featured 20-30-fold less NO-scavenging [38]. An experimental shock-model in pigs yielded promising results: regarding hemodynamic stability and 6-days survival, r-Hb 2.0 was as effective as whole blood and superior to conventional fluid resuscitation with crystalloids and colloids [55].…”

“…The development of second-generation HBOCs aimed at optimizing O 2 -transport properties and attenuating undesirable effects [38,49]. These efforts included the development of innovative methods of hemolysis, dialysis, crystallization, and filtration.…”

“…Regarding O 2 -delivery to the tissues, it is discussed that PFC also facilitates the release of Hb-transported O 2 by lowering the diffusion-barrier between the erythrocyte and the plasma ("facilitated diffusion") [38].…”

Síntese e caracterização de copolímeros do tipo ABA para encapsulação de hemoglobina bovina

“…[1][2][3] Embora mais segura, a transfusão de sangue alogênico ainda está associada a riscos para o receptor; os mais graves são as reações alérgicas, lesão pulmonar associada à transfusão (TRALI), erro na compatibilidade sanguínea e transmissão de infecções virais e bacterianas (hepatite, HIV, vírus Epstein-Barr). 4,5 Os riscos de transmissão da doença de Chagas através da transfusão de sangue tornam-se evidentes quando arquivos de doadores de sangue são revistos para a infecção pelo T. cruzi.…”