Skip to main content
2024 AABB Annual Meeting Main banner
Icon Legend
This session is not in your favorites.
This session is in your favorites. Click again to remove it.
Presentation Icons
Live Stream Sessions
Live Stream Sessions

Cell Biology, Immunology and Biochemistry (basic and preclinical research)

(P-CB-10) Exploring the Efficacy of Continuous Whole Blood Exchange in Drug-Induced Hemolytic Anemia Rats: A Preclinical Study

Sunday, October 20, 2024
12:00 PM - 1:00 PM  
Background/Case Studies: Hemolytic anemia (HA) is characterized by the massive destruction of red blood cells (RBCs) and insufficient oxygen supply, which can be life-threatening(Dhaliwal et al., 2004; Noronha, 2016). Recent studies have preliminarily demonstrated the therapeutic effectiveness of whole blood exchange (WBE) in treating acute HA and have shown promise in reducing the duration of corticosteroid treatment(Barcellini & Fattizzo, 2021; Murki & Kumar, 2011), while underlying mechanism function of WBE therapy was not investigated in preclinical study. This study investigates the efficacy of WBE in phenylhydrazine hydrochloride (PHZ)-induced hemolytic anemia in rats to aid the development of therapeutics for severe HA such as drug-induced HA (DIHA).

Study

Design/Methods: An approach for continuous WBE in rats has been developed to study its therapeutic effects and mechanisms, investigating these through PHZ-induced rat model of hemolytic anemia (ethics approval number: CSU-2023-0065). This study randomized male Sprague-Dawley rats into Control, DIHA, WBE, and traditional blood transfusion (BT) groups, initiating WBE or BT on day 1 treatments post-DIHA (Fig-A b) induction with blood samples and organ tissue collected for analysis of hematological and biochemical parameters.

Results/Findings:

Throughout the 8-day monitoring period, research results demonstrate the efficacy of WBE therapy in significantly reducing mortality in DIHA rats, with a 100% survival rate observed in WBE group compared to lower rates (38.5%) in the DIHA group (Fig-A a, P=0.0185). Additionally, WBE led to significant improvements by day 2 post-treatment (Fig-A b) in hematological parameters such as RBCs (Fig-A c, Day2, P=0.01), hemoglobin (HGB) (Fig-A d, Day2, P=0.0099), and lactate dehydrogenase (LDH) levels (Fig-A e, Day2, P< 0.0001), compared with DIHA, in contrast to the BT group where levels remained elevated. WBE also effectively reduced oxidative stress as indicated by stabilized ROS levels (Fig-A f, Day2-8, P< 0.0009) and decreased inflammation by downregulating tumor necrosis factor-alpha (TNF-α) levels. (Fig-A g, Day4-6, P< 0.0001). And mitigated organ damage, particularly in the liver, where hepatic ferroportin (FPN) levels were significantly higher in the WBE group than in DIHA group (Fig-A h-i, P< 0.0483), whereas BT group showed no significant change. The DIHA model had increased liver iron compared to the control group(P< 0.001), but WBE treatment reduced hepatic iron accumulation (Fig-A j-k, P< 0.01).


Conclusions:

The results of this study underscore the efficacy of WBE as an innovative therapeutic strategy for HA, indicating that WBE may offer advantages over BT for treating cases of severe anemias. Utilizing WBE not only enhances the survival but also addresses the fundamental pathophysiological mechanisms of HA, providing preclinical evidence to support its potential as a primary treatment option in acute clinical scenarios.