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Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.

ABSTRACT: The current global shortage of organ resources, the imbalance in donor-recipient demand and the increasing number of high-risk donors make organ preservation a necessity to consider appropriate storage options. The current method of use often has risks such as blood group mismatch, short shelf life, and susceptibility. HBOCs have positive effects such as anti-apoptotic, anti-inflammatory, antioxidant and anti-proliferative, which have significant advantages in organ storage. Therefore, it is the common pursuit of researchers to design and synthesize HBOCs with safety, ideal oxygen-carrying capacity, easy storage, etc. that are widely applicable and optimal for different organs. There has been a recent advancement in understanding HBOCs mechanisms, which is discussed in this review.

SUBMITTER: Ma Y

PROVIDER: S-EPMC10558499 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.

Ma Yuexiang Y Zhang Qi Q Dai Zheng Z Li Jing J Li Wenxiu W Fu Chuanqing C Wang Qianmei Q Yin Wen W

Heliyon 20230829 9

The current global shortage of organ resources, the imbalance in donor-recipient demand and the increasing number of high-risk donors make organ preservation a necessity to consider appropriate storage options. The current method of use often has risks such as blood group mismatch, short shelf life, and susceptibility. HBOCs have positive effects such as anti-apoptotic, anti-inflammatory, antioxidant and anti-proliferative, which have significant advantages in organ storage. Therefore, it is the ...[more]

PMID: 37809714

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Project description:BackgroundHyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy. Recent data demonstrate that red blood cell lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOCs) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy because of the presence of free hemoglobin.Materials and methodsWB was sampled from healthy donors (n = 6). The clotting profile of each citrated sample was evaluated using native thromboelastography. Serial titrations were performed using both HBOC (PolyHeme) and normal saline (NS; 5%, 25%, and 50%) and evaluated both with and without a 75-ng/mL tissue plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin-dependent fibrinolysis. Fibrinolysis was measured and recorded as lysis at 30 min (LY30), the percentage of clot LY30 after maximal clot strength. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman rho coefficients. Groups were also compared using a Friedman test and post hoc analysis with a Bonferroni adjustment.ResultstPA-provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, and 50% titrations: 11%, 21%, and 44%, respectively; Spearman = 0.94; P < 0.001) and NS (11%, 28%, and 58%, respectively; Spearman = 0.790; P < 0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%, 4%, 5%; Spearman = 0.735; P = 0.001) and NS did not (1%, 2%, 1%; r = 0.300; P = 0.186. Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB versus 50% HBOC: 1.8% versus 5.7%, P = 0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC versus 50% HBOC + TXA: 5.6% versus 5.7%, P = 0.92). In addition, the increased fibrinolysis seen with NS was reversed when TXA was present (WB versus 50% NS: 1.8% versus 1.7%, P = 1.0).ConclusionsHBOCs enhance fibrinolysis both with and without addition of tPA; moreover, this mechanism is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings indicate the hemoglobin molecule or its components stimulate fibrinolysis by both tPA-dependent and innate mechanisms.

Dataset Information

Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.

Publications

Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.

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