Gibt es eine Zukunft für künstliche Blutersatzstoffe?

Zusammenfassung

Künstliche Blutersatzstoffe der früheren Generationen sollten, wie die gebrauchte Abkürzung „artificial oxygen carriers” (AOC) impliziert, die Sauerstofftransportfunktion des Blutes möglichst ohne Nebenwirkungen, ohne Blutgruppeninkompatibilitäten und Übertragungsrisiko für Infektionen ersetzen. Sie nutzten entweder die konventionelle Sauerstoffbindung an Hämoglobin: HBOC- „hemoglobin based oxygen carriers” oder die physikalische Lösung des Sauerstoffs im Plasma in den sogenannten Perfluorkarbon (PFC)-Emulsionen. Heutzutage hat man eingesehen, dass der Sauerstofftransport nicht ohne weiteres von weiteren, physiologisch gekoppelten Aufgaben des Blutes losgelöst werden kann. Heutige Blutersatzstoffe sollen auch die Kapillarperfusion aufrecht erhalten, den Gefäßtonus regulieren bzw. die organspezifische Autoregulationsfähigkeit, die Gerinnung und das Immunsystem aufrechterhalten. Weil dieses Konzept aber gegenüber den früheren Bestrebungen relativ jung ist, gestaltet sich die klinische Einführung dieser neuen Generation von Blutersatzstoffen schwierig.

Nichtsdestotrotz existieren erhebliche Forschungsaktivitäten und neue Produkte. Neuere Generationen von künstlichen Sauerstoffträgern werden heute in der dritten und vierten Generation als Spielarten und Mischformen durch Imitation der Erythrozytenfunktion als Mizellen, Nanokapseln (ABC- artifical blood cells) [43] oder Gasblasen (Microbubbles), oder Zumischung von Hydroxyäthylstärke, Gelatine oder Albumin [42]und hyperbarer Oxigenierung [38]erforscht. Selbst künstliche Thrombozyten sind bereits am Menschen bis in die Phasen der klinischen Erprobung IIa vorgedrungen [12,17]

Diese Übersicht fasst die bisherigen Erkenntnisse der Erforschung der Blutersatzmittel zusammen und betont neue Erkenntnisse und Möglichkeiten, die sich aus der Erforschung der AOC ergeben. Sie schließt mit der Schlussfolgerung – ja, höchstwahrscheinlich wird es eine Zukunft für künstliche Blutersatzstoffe geben. Offen bleibt, welches der Konzepte, Ansätze und Produkte sich klinisch durchsetzen wird und vor allem wann.

Abstract

Formerly developed resuscitation fluids solely imitated the main function of the blood -oxygen transport. A research driven by the army requested an oxygen carrier that does not need cross typing and cooled storage . Artificial oxygen carriers (AOC) use either the molecular oxygen bondage to hemoglobin: HBOC- „hemoglobin based oxygen carriers” or the physical dissolution of oxygen in the blood plasma compartment by hyperbaric pressure in perfluorocarbon emulsions (PFC). Decades of preclinical and clinical research did pass but the results were disappointing- in Russia, a not well designed PFC is available locally and the only approved HBOC in South Africa is not being used much. Other products, just prior to filing for FDA approval, did not achieve convincing study results and research and production was stopped. Some trials have been stopped by the FDA for safety reasons, half of trials with the primary endpoint reduction of allogeneic transfusion requirement were unsuccessful or offset by an increased blood requirement later.

However, some ventures currently are trying to use the knowledge gained so far and are investigating third and fourth generation products of artificial blood components. These imitate the cellular structure of red cells as micells, nanocapsules, (ABC- artifical blood cells) or gas bubbles (microbubbles), admixture of volume substitutes such as starches, gelatin or albumin or use hyperbaric oxygenation [38]. Artificial platelets are in clinical phase IIa, recombinant albumin in phase III.

In this article, a short overview about the current situation on artifical blood products is given. The critical point for the break through for artificial blood products did not come yet but could be ahead-

künstliche Sauerstoffträger - Hämoglobine - Perfluorkarbone - Blutersatz - Transfusion - Perfusion - Hypertension

artificial oxygen carriers - hemoglobin-based - perfluorocarbon - artificial blood - transfusion - perfusion - hypertension

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